Thrombocytopenia is a common clinical feature of HIV infection. Given the number of possible etiologies of thrombocytopenia in a patient with known HIV, a peripheral blood test effective in determining the likely pathophysiologic basis of... more
Thrombocytopenia is a common clinical feature of HIV infection. Given the number of possible etiologies of thrombocytopenia in a patient with known HIV, a peripheral blood test effective in determining the likely pathophysiologic basis of the thrombocytopenia would be a valuable clinical tool. Immature platelets are released early from the bone marrow in response to increased platelet turnover. These platelets contain residual megakaryocyte mRNA and have been termed reticulated platelets. A new assay, the Immature Platelet Fraction (IPF), measures the reticulated platelet count in peripheral blood. Patients with increased destruction of platelets from such conditions as ITP consistently have a higher IPF percent, while patients with decreased platelet production have a low or normal IPF percent. The goal of our study was to determine the performance characteristics of the IPF assay in HIV patients with thrombocytopenia and to see if the IPF percent could be used to help elucidate the etiology of low platelet counts in this group of patients. All adult patients admitted to the Johns Hopkins Hospital with a diagnosis of HIV and a platelet count less than 150,000 were eligible for enrollment. 62 patients were identified from February 2007 to June 2007. 34 control samples were obtained from inpatients with HIV who were not thrombocytopenic. In addition, 81 samples were available from non-HIV historical controls with normal platelet counts. The mean platelet count in the HIV thrombocytopenic group was 92,000 while the mean platelet count in the HIV control group was 254,000 (p value <.001). The mean platelet count in the non-HIV historical control group was 274 (p=.34 when compared to the HIV control group). The mean IPF percent in the HIV thrombocytopenic group was 10.2% as compared to 6.8% in the HIV control group (p=.001). The mean IPF in historical non-HIV controls was 3.1% (p<.001 for both the HIV thrombocytopenic and the HIV control group). Univariate analyses were conducted to identify potential individual predictors of a high IPF percent. Backward selection was then performed using multivariate linear models with a threshold Wald test p-value of 0.05. ITP, diabetes mellitus and cirrhosis were significantly associated with a higher IPF percent with a co-efficient (95% confidence interval) of 6.98 (3.05–10.91), 4.73 (1.39–8.06), and 14.18 (9.7–18.66), respectively. CD4 count, HIV viral load, hepatitis C and reticulocyte count were not correlated with IPF percent. Our results suggest that patients with HIV have increased platelet turnover as compared to patients without HIV. Thrombocytopenic patients with HIV have increased platelet turnover relative to both non-thrombocytopenic HIV patients and to historical non-HIV controls. History of ITP, diabetes mellitus, and cirrhosis are predictive of an elevated IPF percent. Reticulocyte count is not correlated to IPF percent, suggesting that a low reticulocyte count is not a reliable marker for decreased bone marrow production in HIV thrombocytopenia. It is unlikely that the IPF assay alone can be used to determine the pathophysiologic basis of thrombocytopenia in any single patient with HIV. Further work needs to be done to clarify the utility of the IPF assay in this group of patients.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Cardiology, Medicine, Platelet, Humans, Internal Medicine, and 15 morePlatelet aggregation, Female, Male, Aspirin, Clinical Sciences, Aged, Middle Aged, Myocardial Infarction, Circulation, Coronary Artery Disease, Creatinine, Arachidonic Acid, Blood platelets, Cardiovascular medicine and haematology, and Cyclooxygenase
To assess whether HIV infection directly or indirectly promotes coronary artery disease (CAD) volume progression in a longitudinal study of African Americans. We randomly selected 300 individuals with subclinical CAD (210 male; age: 48.0... more
To assess whether HIV infection directly or indirectly promotes coronary artery disease (CAD) volume progression in a longitudinal study of African Americans. We randomly selected 300 individuals with subclinical CAD (210 male; age: 48.0 ± 7.2 years; 226 HIV infected, 174 cocaine users) from 1429 cardiovascularly asymptomatic participants of a prospective epidemiological study between May 2004 and August 2015. Individuals underwent coronary CT angiography at two time points (mean follow-up: 4.0 ± 2.3 years). We quantified noncalcified (NCP: −100–350HU), low-attenuation noncalcified (LA-NCP: −100-30HU), and calcified (CP: ≥ 351 HU) plaque volumes. Linear mixed models were used to assess the effects of HIV infection, atherosclerotic cardiovascular disease (ASCVD) risk, and years of cocaine use on plaque volumes. There was no significant difference in annual progression rates between HIV-infected and HIV-uninfected regarding NCP (8.7 [IQR: 3.0–19.4] mm3/year vs. 4.9 [IQR: 1.5–18.3] mm3/year, p = 0.14), LA-NCP (0.2 [IQR: 0.0–1.6] mm3/year vs. 0.2 [IQR: 0.0–0.9] mm3/year, p = 0.07) or CP volumes (0.3 [IQR: 0.0–3.4] mm3/year vs. 0.1 [IQR: 0.0–3.2] mm3/year, p = 0.30). Multivariately, HIV infection was not associated with NCP (−6.9mm3, CI: [−32.8–19.0], p = 0.60), LA-NCP (−0.1mm3, CI: [−2.6–2.4], p = 0.92), or CP volumes (−0.3mm3, CI: [−9.3–8.6], p = 0.96). However, each percentage of ASCVD and each year of cocaine use significantly increased total, NCP, and CP volumes among HIV-infected individuals, but not among HIV-uninfected. Importantly, none of the HIV-associated medications had any effect on plaque volumes (p > 0.05 for all). The more profound adverse effect of risk factors in HIV-infected individuals may explain the accelerated progression of CAD in these people, as HIV infection was not independently associated with any coronary plaque volume. • Human immunodeficiency virus–infected individuals may have similar subclinical coronary artery disease, as the infection is not independently associated with coronary plaque volumes. • However, cardiovascular risk factors and illicit drug use may have a more profound effect on atherosclerosis progression in those with human immunodeficiency virus infection, which may explain the accelerated progression of CAD in these people. • Nevertheless, through rigorous prevention and abstinence from illicit drugs, these individuals may experience similar cardiovascular outcomes as -uninfected individuals.
Research Interests:
Cardiovascular disease is a leading cause of death in survivors of immune‐mediated thrombotic thrombocytopenic purpura (iTTP), but the epidemiology of major adverse cardiovascular events (MACE) in iTTP survivors is unknown. We evaluated... more
Cardiovascular disease is a leading cause of death in survivors of immune‐mediated thrombotic thrombocytopenic purpura (iTTP), but the epidemiology of major adverse cardiovascular events (MACE) in iTTP survivors is unknown. We evaluated the prevalence and risk factors for MACE, defined as the composite of non‐fatal or fatal myocardial infarction (MI), stroke, and cardiac revascularization, during clinical remission in two large iTTP cohorts (Johns Hopkins University and Ohio State University). Of 181 patients followed for ≥ 3 months after recovery from acute iTTP, 28.6% had a MACE event over a median follow up of 7.6 years. Stroke was the most common type of MACE (18.2%), followed by non‐fatal MI (6.6%), cardiac revascularization (4.9%) and fatal MI (0.6%). Compared to the general United States population, iTTP survivors were younger at first stroke in remission (males [56.5 years vs. 68.6 years, p = 0.031], females [49.7 years vs. 72.9 years, p < 0.001]) or MI in remission (mal...
Research Interests:
Background Various cardiovascular risk factors are thought to modify atherosclerosis in a similar fashion (ie, by increasing the magnitude of coronary artery disease [CAD]). However, coronary CT angiography allows precision phenotyping of... more
Background Various cardiovascular risk factors are thought to modify atherosclerosis in a similar fashion (ie, by increasing the magnitude of coronary artery disease [CAD]). However, coronary CT angiography allows precision phenotyping of plaque characteristics through use of radiomics. Purpose To assess whether different cardiovascular risk factors have distinctive contributions to the changes in plaque morphologic features over time. Materials and Methods Individuals with or without HIV infection and cocaine use and without cardiovascular symptoms underwent coronary CT angiography between May 2004 and August 2015. In the current HIPAA-compliant study, the effects of cocaine use, HIV infection, and atherosclerotic cardiovascular disease (ASCVD) risk on the temporal changes (mean ± standard deviation, 4.0 years ± 2.3 between CT angiographic examinations) in CAD structure were analyzed by using radiomic analysis. The changes in radiomic features were analyzed by using linear mixed models, with correction for factors that may change plaque structure: high-sensitivity C-reactive protein level, statin use, positive family history of CAD, and total plaque volume to account for any potential intrinsic correlation between volume and morphologic features. Clusters among significant radiomic features were identified by using hierarchical clustering. Bonferroni-corrected P values less than .00004 (.05 divided by 1276) were considered to indicate significant differences. Results Of 1429 participants, 300 with CAD confirmed at coronary CT angiography were randomly selected (mean age, 48 years ± 7; 210 men, 226 people infected with HIV, 174 people who use cocaine) and 1276 radiomic features were quantified for each plaque. Cocaine use was significantly associated with 23.7% (303 of 1276) of the radiomic features, HIV infection was significantly associated with 1.3% (17 of 1276), and elevated ASCVD risk was significantly associated with 8.2% (104 of 1276) (P < .00004 for all). Parameters associated with elevated ASCVD risk or cocaine use and HIV infection did not overlap. There were 13 clusters among the 409 parameters, eight of which were affected only by cocaine use and three of which were affected only by ASCVD risk. Conclusion Radiomics-based precision phenotyping indicated that conventional risk factors, cocaine use, and HIV infection each had different effects on CT angiographic morphologic changes in coronary atherosclerosis over 4 years. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Schoepf and Emrich in this issue.
Research Interests:
Background/Introduction Cross-sectional studies are inconsistent on the potential independent adverse effects of human immunodeficiency virus (HIV)-infection on coronary artery disease (CAD). Furthermore, there is no information on the... more
Background/Introduction Cross-sectional studies are inconsistent on the potential independent adverse effects of human immunodeficiency virus (HIV)-infection on coronary artery disease (CAD). Furthermore, there is no information on the potential effects of HIV-infection on plaque volumes. Also, only the independent effects of HIV-infection on CAD have been investigated. Purpose In a prospective longitudinal observational cohort, we wished to assess whether HIV-infection accelerates CAD independently, or by acting in synergistic fashion with conventional and nonconventional cardiovascular risk factors to accelerate disease progression as assessed by clinical and volumetric parameters of CAD on coronary CT angiography (CCTA). Methods Overall, 300 asymptomatic individuals without cardiovascular symptoms but with CCTA-confirmed coronary plaques (210 males, age: 48.0±7.2 years) with or without HIV (226 HIV-infected) prospectively underwent CCTA at two time points (mean follow-up: 4.0±2.3...
Research Interests:
Acute Promyelocytic Leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML), classified by a translocation between chromosomes 15 and 17 [t(15;17)], that is notably distinguished clinically by a rapidly progressive and fatal course.... more
Acute Promyelocytic Leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML), classified by a translocation between chromosomes 15 and 17 [t(15;17)], that is notably distinguished clinically by a rapidly progressive and fatal course. Due to the acute nature of its presentation, prompt and accurate diagnosis is required to initiate appropriate therapy that can be curative. However, the gold standard genetic tests can take days to confirm a diagnosis and thus therapy is often initiated on high clinical suspicion based on both clinical presentation as well as direct visualization of the peripheral smear. While there are described cellular morphological features that distinguish APL, there is still considerable difficulty in diagnosing APL from direct visualization of a peripheral smear by a hematopathologist. We hypothesized that deep learning pattern recognition would have greater discriminatory power and consistency compared to humans to distinguish t(15;17) translocation positive...
Research Interests:
Research Interests:
Background: Only the independent effect of human immunodeficiency virus (HIV)-infection on coronary artery disease (CAD) has been investigated in cross-section studies, while rather than directly, HIV-infection may accelerate CAD through... more
Background: Only the independent effect of human immunodeficiency virus (HIV)-infection on coronary artery disease (CAD) has been investigated in cross-section studies, while rather than directly, HIV-infection may accelerate CAD through promoting the effects of risk factors. Furthermore, there is no information on the potential effects of HIV-infection on coronary plaque volumes. Therefore, we investigated whether HIV-infection directly or indirectly promotes clinical and volumetric characteristics of CAD in a observational longitudinal study. Methods: 300 individuals without cardiovascular symptoms (210 male; age: 48·0±7·2 years; 226 HIV-infected) underwent coronary CT angiography at two time points (mean follow-up: 4·0±2·3 years). We quantified Agatston-score, number of coronary plaques, segment stenosis score, and also segmented the coronary plaques to enumerate total, noncalcified (-100–350HU) and calcified (≥351HU) plaque volumes. Linear mixed models were used to assess the effects of HIV-infection, atherosclerotic cardiovascular disease (ASCVD) risk, years of cocaine use and high-sensitivity C-reactive protein on CT markers of CAD. Findings: There was no significant difference in annual progression rates between HIV-infected and -uninfected (p>0·05 for all). Multivariately, HIV-infection was not associated with any CAD parameter (p>0·05 for all). However, among HIV-infected individuals, each year of cocaine use significantly increased all CAD parameters (p<0·05 for all), while ASCVD risk score was significantly associated with CAD parameters except for Agatston-score (p<0·05). However, these associations were only apparent among HIV-infected individuals. Importantly, none of the HIV-medications were associated with any of the CAD outcomes. Interpretation: HIV-infection is not directly associated with CAD and therefore HIV-infected are not destined to have worse CAD profiles as compared to uninfected individuals. However, more aggressive management of conventional cardiovascular risk factors and abstinence from illicit drugs may be needed to achieve similar CAD status. Funding Statement: Procedures and tests were funded by the National Institute on Drug Abuse, and the National Institutes of Health (NIH R01DA12777, R01DA15020, R01DA25524, R21DA048780 and U01DA040325). Declaration of Interests: None. Ethics Approval Statement: The Committee on Human Research at the Johns Hopkins School of Medicine (Baltimore, MD) approved the study protocol, and all study participants provided written informed consent. All procedures used in this study were in accordance with HIPAA, local and federal regulations, and the Declaration of Helsinki.
Research Interests:
Type II heparin-induced thrombocytopenia (HIT) is an antibody-mediated complication of heparin therapy that is associated with a consumptive thrombocytopenia and a high risk of thromboembolism. It is now known that antibodies associated... more
Type II heparin-induced thrombocytopenia (HIT) is an antibody-mediated complication of heparin therapy that is associated with a consumptive thrombocytopenia and a high risk of thromboembolism. It is now known that antibodies associated with type II HIT recognize sites on PF4 when complexed with heparin. Due to technical challenges associated with the serotonin release assay, most clinicians rely on the PF4 ELISA to establish a laboratory diagnosis of HIT. However, it is unclear whether the ELISA has predictive value in identifying those patients who have clinically apparent disease and whether ELISA optical density (OD) measurements correlate with the development of thrombosis. We retrospectively reviewed the medical records of 103 sequential patients who tested positive for HIT by a commercial PF4 ELISA from 2000–2002. While blinded to ELISA OD values, we recorded patient age and gender, admission diagnosis, hospital course, type of heparin administered, route of administration, b...
Research Interests:
Levels of platelet-associated IgG (PA-IgG) were studied in 72 patients with Hodgkin–s (HD) and non-Hodgkin–s lymphoma (NHL). Thirty-nine percent of patients with HD and 20% of patients with NHL had elevated PA-IgG levels. There was a... more
Levels of platelet-associated IgG (PA-IgG) were studied in 72 patients with Hodgkin–s (HD) and non-Hodgkin–s lymphoma (NHL). Thirty-nine percent of patients with HD and 20% of patients with NHL had elevated PA-IgG levels. There was a positive correlation between disease activity and the presence of PA-IgG in HD and NHL. In patients with HD, PA-IgG strongly correlated with extent of disease and may serve as a marker of disease activity. PA-IgG may have facilitated platelet destruction in 5 of 11 thrombocytopenic patients with HD and increased PA-IgG and in 2 patients with HD and increased PA-IgG who developed severe thrombocytopenia when treated with chemotherapy.
Research Interests: Medicine, Platelet, Lymphoma, Humans, Internal Medicine, and 14 moreFemale, Blood, Male, Thrombocytopenia, Clinical Sciences, Aged, Middle Aged, Adult, Thrombotic Thrombocytopenic Purpura, Hodgkin disease, immunoglobulin G, Blood platelets, Cardiovascular medicine and haematology, and Paediatrics and reproductive medicine
Despite the use of HLA-matched platelets for alloimmunized recipients, transfusion failures occur. In order to reduce these failures, we investigated the use of a radiolabeled antiglobulin technique for platelet crossmatching. The... more
Despite the use of HLA-matched platelets for alloimmunized recipients, transfusion failures occur. In order to reduce these failures, we investigated the use of a radiolabeled antiglobulin technique for platelet crossmatching. The principle of the test is that of an indirect Coombs test using 125I labeled goat anti-human IgG. Incompatibility is determined by calculating a radioactivity antiglobulin test (RAGT) index. Using this technique, we performed 89 crossmatches on 19 leukemic or aplastic patients who were refractory to random donor platelets and receiving varying degrees of HLA-matched platelets. Effectiveness of the transfusion was assessed from the posttransfusion corrected platelet count increment (CCI) determined at 1 and 20 hr. When the RAGT index was 1.9 or less, the mean CCI at 1 lhr was 17,570 +/- 7003/cu mm, n = 55. When the RAGT index was 2.0 or greater, the mean CCI was 4237 +/- 4100/cu mm, n = 34. At 20 hr when the RAGT index was 1.9 or less, the mean CCI was 8722 ...
Research Interests: Adolescent, Medicine, Platelet, Acute Myeloid Leukemia, Humans, and 14 moreChild, Female, Blood, Male, Clinical Sciences, Middle Aged, Aplastic Anemia, Bone Marrow Transplantation, Adult, Blood Transfusion, Child preschool, Platelet transfusion, Cardiovascular medicine and haematology, and Paediatrics and reproductive medicine
This study shows that the increased occurrence of stroke in thrombotic thrombocytopenic purpura (TTP) during remission is associated with low ADAMTS13 values.
Research Interests:
BACKGROUNDAmerican Association of Blood Banks (AABB) guidelines suggest that packed red blood cells (PRBCs) be administered through a dedicated intravenous (IV) catheter. Literature supporting this broad‐scope declaration are scarce.... more
BACKGROUNDAmerican Association of Blood Banks (AABB) guidelines suggest that packed red blood cells (PRBCs) be administered through a dedicated intravenous (IV) catheter. Literature supporting this broad‐scope declaration are scarce. Obtaining additional IV access is painful, costly, and an infectious risk. We evaluated the effect of co‐incubating PRBCs with crystalloids and medications on PRBC hemolysis, membrane deformability, and aggregation, as well as medication concentration.METHODSPRBCs were co‐incubated 5 minutes with plasma, normal saline (NS), 5% dextrose in water (D5W), Plasmalyte, epinephrine (epi), norepinephrine (norepi), dopamine (dopa), or Propofol (prop). Samples were then assessed for hemolysis (free hemoglobin, serum potassium), membrane deformability (elongation index [EI]), aggregation (smear, critical shear stress [mPa]) and drug concentration (High Performance Liquid Chromatography/Tandem Mass Spectrometry [LCMS‐MS]). Significance (p ≤ 0.05) was determined by ...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
This case report describes a patient who presented with Stage IV B Hodgkin&#39;s disease and autoimmune thrombocytopenia. Prior to the institution of therapy the presence of platelet-associated IgG was documented. When the patient was... more
This case report describes a patient who presented with Stage IV B Hodgkin&#39;s disease and autoimmune thrombocytopenia. Prior to the institution of therapy the presence of platelet-associated IgG was documented. When the patient was treated with steroids and chemotherapy, the thrombocytopenia resolved and platelet-associated IgG disappeared. Splenectomy alone did not correct the thrombocytopenia. The literature on Hodgkin&#39;s disease and autoimmune thrombocytopenia is reviewed.
Research Interests:
Research Interests:
Introduction: Atypical hemolytic uremic syndrome (aHUS) is a disease of excessive alternative pathway of complement (APC) activation that can be treated with eculizumab. Clinicians have been hesitant to administer eculizumab because of... more
Introduction: Atypical hemolytic uremic syndrome (aHUS) is a disease of excessive alternative pathway of complement (APC) activation that can be treated with eculizumab. Clinicians have been hesitant to administer eculizumab because of the lack of a diagnostic assay for aHUS and the expense of the drug. Mutations in genes that regulate the APC (factor H/CFH, I/CFI, CD46, etc.) underlie up to 50% of aHUS patients, but the clinical relevance of these mutations is often unclear. We developed the modified Ham test to distinguish aHUS from thrombotic thrombocytopenic purpura (TTP). This functional assay measures cell viability (WST-1) of a PIGA mutant cell line following exposure to patient serum. The cells are more sensitive to APC killing because complement regulators CD55 and CD59 are absent from the cell surface. CD46 is a transmembrane APC regulator that remains on the surface of the PIGA- null TF1 cells. Here, we show that the modified Ham test predicts response to eculizumab and can be adapted to assess the contribution of APC mutations to clinical phenotype. Method: We studied adult patients with thrombotic microangiopathies (TMA) who presented to our hospital from July 2014 through June 2015 and two patients from outside institutions. aHUS was defined by the presence of a TMA with platelet count &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;100 x 109/L, serum creatinine…
Research Interests:
Research Interests:
Research Interests:
Background We sought to determine the prevalence and sociodemographic and clinical correlates of acute and convalescent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hepatitis C virus (HCV), and human immunodeficiency... more
Background We sought to determine the prevalence and sociodemographic and clinical correlates of acute and convalescent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections among emergency department (ED) patients in Baltimore. Methods Remnant blood samples from 7450 unique patients were collected over 4 months in 2020 for SARS-CoV-2 antibody (Ab), HCV Ab, and HIV-1/2 antigen and Ab. Among them, 5012 patients were tested by polymerase chain reaction for SARS-CoV-2 based on clinical suspicion. Sociodemographics, ED clinical presentations, and outcomes associated with coinfections were assessed. Results Overall, 729 (9.8%) patients had SARS-CoV-2 (acute or convalescent), 934 (12.5%) HCV, 372 (5.0%) HIV infection, and 211 patients (2.8%) had evidence of any coinfection (HCV/HIV, 1.5%; SARS-CoV-2/HCV, 0.7%; SARS-CoV-2/HIV, 0.3%; SARS-CoV-2/HCV/HIV, 0.3%). The prevalence of SARS-CoV-2 (acute or convalesce...
Research Interests:
affecting post-transfusion platelet increments, platelet refractori-
Research Interests:
Research Interests:
Introduction: Patients with malignant gliomas are at high risk for venous thromboembolism (VTE). The reason for this association is unclear. We sought to identify clinical and laboratory risk factors for VTE in adult patients with... more
Introduction: Patients with malignant gliomas are at high risk for venous thromboembolism (VTE). The reason for this association is unclear. We sought to identify clinical and laboratory risk factors for VTE in adult patients with high-grade gliomas. Methods: The NABTT CNS Consortium prospectively enrolled patients with newly-diagnosed grade 3 or 4 malignant glioma prior to anti-neoplastic therapy. Patients with a previous history of VTE, anti-neoplastic therapy or on chronic anticoagulation were excluded. At enrollment, we collected demographic and clinical information (age, gender, ethnicity, tumor histopathology and grade, Karnofsky Performance Status (KPS), and ABO blood group) and blood samples for measurement of factor VIII activity (FVIII), fibrinogen, and quantitative D dimer using standard laboratory assays. Endogenous thrombin potential (ETP) was measured using Innovin® and a synthetic chromagenic thrombin substrate on a BCS® coagulation analyzer (Dade Behring Inc. Newark,...
Research Interests:
The human platelet alloantigen 1 system (HPA-1) is determined by a polymorphism at position 33 in the N-terminus of human glycoprotein IIIa (GPIIIa). This naturally occurring substitution creates a conformation in the HPA-1a allelic form... more
The human platelet alloantigen 1 system (HPA-1) is determined by a polymorphism at position 33 in the N-terminus of human glycoprotein IIIa (GPIIIa). This naturally occurring substitution creates a conformation in the HPA-1a allelic form that can be antigenic when presented to an individual expressing the HPA-1b form. Anti–HPA-1a antibodies generated by this immune response can lead to the destruction of platelets, as seen in the clinical disorders, neonatal alloimmune thrombocytopenia (NAIT) and posttransfusion purpura (PTP). To understand better the structural requirements for recognition by these pathogenic antibodies, we investigated the N-terminal 66 amino acids from the HPA-1a form of human GPIIIa and the analogous amino acids from the nonimmunogenic murine homolog. Our objectives were to define further the boundaries of the HPA-1a epitope(s) in the N-terminus of human GPIIIa, to isolate the murine 5’ nucleotide sequence and compare the deduced murine N-terminal sequence to th...
Research Interests: Chemistry, Biology, Medicine, Humans, Sequence alignment, and 15 moreMice, Animals, Blood, Monoclonal Antibodies, Clinical Sciences, Antibody, Protein Conformation, Amino Acid Sequence, Amino Acid Substitution Rates, Recombinant Proteins, Epitopes, Molecular Sequence Data, epitope, Cardiovascular medicine and haematology, and Paediatrics and reproductive medicine
Research Interests:
The survival time of transfused red cells antigenically distinct from the recipient's red cells was determined using an indirect enzyme linked antiglobulin test. These results were then compared to those determined by Cr-51 labeling.... more
The survival time of transfused red cells antigenically distinct from the recipient's red cells was determined using an indirect enzyme linked antiglobulin test. These results were then compared to those determined by Cr-51 labeling. Three patients with hypoproliferative anemias and one patient (2 studies) with traumatic hemolytic anemia caused by a prosthetic heart valve were studied. Survival times were performed by transfusing a 5cc aliquot of Cr-51 labeled cells along with the remaining unit. One hour post transfusion, a blood sample was drawn and used as the 100% value. Subsequent samples drawn over a 2-3 week period were then compared to the initial sample to determine percent survival for both methods. The ELISA method for measuring red cell survival in antigenically distinct cells is in close agreement with the Cr-51 method. Although CR-51 labeling is the accepted method for red cell survival determination the ELISA method can be used when radioisotopes are unavailable or contraindicated or when the decision to estimate red cell survival is made after transfusion.
Research Interests:
Research Interests:
Research Interests:
Research Interests: Functional Analysis, Clinical Trial, Biology, Medicine, Platelet, and 13 moreDiscriminant Analysis, Humans, Standard Deviation, Follow-up studies, Triglycerides, Time Factors, Fatty Acid, Monounsaturated Fatty Acid, Physical Properties, Platelet Count, Fatty Acid Composition, Blood platelets, and Drug combinations
Research Interests:
Research Interests:
Research Interests: Chemistry, Immunology, Clinical Trial, Filtration, Medicine, and 14 morePlatelet, Humans, Clinical Sciences, Reproducibility of Results, Apheresis, Erythrocytes, Leukocytes, Transfusion, Plateletpheresis, Ultraviolet Rays, Blood platelets, Platelet transfusion, Cardiovascular medicine and haematology, and leukocyte Count
Research Interests:
Unlike the pretransfusion testing of RBCs, there are no accepted standards for the selection of platelets for transfusion to patients with alloantibodies to platelets. Despite four decades of managing patients with alloimmune-mediated... more
Unlike the pretransfusion testing of RBCs, there are no accepted standards for the selection of platelets for transfusion to patients with alloantibodies to platelets. Despite four decades of managing patients with alloimmune-mediated platelet refractoriness, there has been no real sense of urgency in standardizing the platelet selection process for the alloimmunized patient. A variety of reasons exist for this inconsistency in blood bank laboratories’ approaches to platelet and RBC selections. Perhaps because immune destruction of platelets does not cause clinically severe reactions as does that of RBCs, the added effort and cost of pretransfusion platelet testing has not been seen as worthwhile. To realize the need for developing standards in selecting platelets, however, one needs only to consider the possible morbidity and mortality in thrombocytopenic patients not promptly achieving a good transfusion outcome, the possible increased risk of viral disease or microbial transmission, and the increased costs and the waste of a valuable resource when platelet transfusions fail to increase the patient’s platelet count. For HLA phenotyping and antibody identification, HLA typing reagents and typed lymphocyte panels have been widely used in organ transplantation. This permits the phenotyping of donors and recipients and identification of the specificity of antibodies. The standardization of the anti-human globulin-enhanced microlymphoctyotoxicity test has allowed increased sensitivity and accuracy of HLA antibody identification.1 Reliable, commercially available methods for platelet compatibility testing have been available for at least a decade.2 Thus, we have the same tools for selecting platelets as we do for RBCs: namely, typing reagents, antibody panel identification, and a technique for direct compatibility testing. Various approaches to selecting platelets by HLA matching, HLA antibody identification, or platelet crossmatching have been reported in a series of studies. The article by Petz et al.3 in this issue of TRANSFUSION documents the utility of HLA antibody identification in the selection of platelets for transfusion. This approach permitted accurate identification of donors and increased the availability of potential donors who are ordinarily excluded by reliance solely on HLA matching. Soon after the introduction of prophylactic platelet transfusion, it became apparent that serial transfusions resulted in decreasing effectiveness. Yankee and coworkers4 showed that platelet transfusion failure results from the induction of alloantibodies to HLA. In those early studies, matching for class I HLA-A and -B loci antigens was found necessary. Depending upon the HLA type of an individual, one may have little difficulty in locating platelets that are identical, whereas, in some patients with unusual HLA types, HLA matching is difficult.5 As HLA matching for platelets became more widely available, it became evident that there were shortcomings. In evaluating HLA matching as the sole method of platelet selection for alloimmunized patients, investigators found that HLA-identical platelet transfusions still occurred in up to 20 percent of transfusions. Of the transfusions selected on the basis of HLA crossreactivities of public specificities, 40 percent failed to increase the recipient’s platelet count. With the use of one or two antigen-mismatched platelets, approximately onethird of transfusions failed.6 These observations suggested that selecting platelets on the basis of HLA matching did not provide the degree of accuracy that we needed. In many cases, reliance solely upon HLA matching might eliminate donors who may in fact be compatible. For these reasons, refining the process of selecting platelets for alloimmunized patients has been the subject of much investigation. Numerous investigators evaluated the usefulness of crossmatching a recipient’s serum against potential donor platelets.7-9 Because of the multiplicity of nonimmune factors that affect platelet transfusion outcome, the evaluation of platelet crossmatch techniques has not been straightforward. Recently, a commercially available platelet compatibility test has resulted in the wider use of platelet crossmatching.2 Platelet crossmatching has its shortcomings in the severally alloimmunized patient with high levels of platelet-reactive antibody. If one relies only upon platelet crossmatching and does not take into account the HLA phenotype of the patient and the antibody specificities present, one may have to do a large number of crossmatches for patients with high antiplatelet reactivity.10 The approach taken by Petz et al. provides a direct approach by identifying the HLA antibody specificity and then selecting the appropriate phenotype. Their observations found that the predictive value of HLA antibody specificity identification was similar to that of platelet crossmatching or HLA matching and that it allowed for the efficient identification…
Research Interests:
Thrombocytopenia is a common finding in normal pregnancy. The introduction of routine automated complete blood counting has clearly documented this. In the past, these patients would go undetected and be spared unnecessary testing,... more
Thrombocytopenia is a common finding in normal pregnancy. The introduction of routine automated complete blood counting has clearly documented this. In the past, these patients would go undetected and be spared unnecessary testing, procedures, or medications. This article reviews the common causes of thrombocytopenia and offers criteria on which the diagnosis of clinically significant thrombocytopenia can be made. In addition, we will discuss therapeutic approaches to manage patients with pathologic thrombocytopenia.
Research Interests:
Research Interests: Medicine, Platelet, Humans, Internal Medicine, Platelet aggregation, and 15 moreEpinephrine, Female, Male, Aspirin, Clinical Sciences, Aged, Middle Aged, Acute Coronary Syndrome, Coronary Artery Disease, Chest Pain, Arachidonic Acid, Case Control Studies, Blood platelets, Platelet Aggregation Inhibitors, and biological effect
Research Interests: Medicine, Humans, Monoclonal Antibodies, Tandem Mass Spectrometry, Haemostasis and Thrombosis, and 9 moreUrine, Risk factors, Clinical Sciences, High Pressure Liquid Chromatography, Cardiovascular Diseases, Risk Factors, Sensitivity and Specificity, Enzyme Linked Immunosorbent Assay, and Cardiovascular medicine and haematology
Research Interests: Medicine, Critical Care, Platelet, Stroke, Internal Medicine, and 13 morePlatelets, Sample Size, Ct Scan, Platelet function, Clinical Sciences, Neuromuscular Disease, Computerized tomography, Intracerebral Hemorrhage, Bleeding Time, Neurosciences, Prospective Study, Arachidonic Acid, and Mean platelet volume
Research Interests:
Research Interests:
ABSTRACT
Research Interests:
Research Interests: Cardiology, Medicine, Transplantation, Prospective studies, Humans, and 12 moreInternal Medicine, Female, Male, Aged, Middle Aged, Biological markers, Disease Progression, Coronary Artery Disease, Heart Transplantation, Fibrinolysis, Predictive value of tests, and Cardiovascular medicine and haematology
Acquired von Willebrand disease (aVWD) is a rare disorder associated with a reduction in von Willebrand factor (VWF) activity, leading to increased bleeding risk. Monoclonal gammopathy of undetermined significance (MGUS) is the most... more
Acquired von Willebrand disease (aVWD) is a rare disorder associated with a reduction in von Willebrand factor (VWF) activity, leading to increased bleeding risk. Monoclonal gammopathy of undetermined significance (MGUS) is the most common cause of lymphoproliferative disorder-associated aVWD and is caused by accelerated clearance of circulating VWF. Standard VWF replacement protocols for congenital VWD based on intermittent bolus dosing are typically less effective for aVWD because of antibody-mediated clearance. Intermittent bolus dosing of VWF concentrates often leads to inadequate peak response and profoundly shortened VWF half-life in aVWD. Intravenous immune globulin (IVIG) has demonstrated efficacy in aVWD; however, treatment effect is delayed up to 4 days, limiting its efficacy in acutely bleeding patients. We report the successful use of continuous-infusion VWF concentrate (with or without concomitant IVIG) in 3 patients with MGUS-associated aVWD who had demonstrated an ina...
Research Interests:
Research Interests:
HIV infection and/or antiretroviral therapy may increase the risk of subclinical coronary atherosclerosis. However, patients with chronic kidney disease (CKD) and those without IV access cannot undergo contrast-enhanced coronary CT... more
HIV infection and/or antiretroviral therapy may increase the risk of subclinical coronary atherosclerosis. However, patients with chronic kidney disease (CKD) and those without IV access cannot undergo contrast-enhanced coronary CT angiography (CCTA). This study was to explore the relationship between cardiac troponin T (cTnT) levels and the extent of coronary plaque burden, as assessed by CCTA in those with HIV infection. Between June and September 2017, 58 HIV-infected participants were recruited and underwent contrast-enhanced CCTA. cTnT was measured with the Elecsys Troponin T Gen 5 STAT assay, and noncalcified plaque burden was quantified using coronary plaque analysis. Robust regression model was employed to perform primary statistical analysis. Univariate robust regression analysis indicated that male gender, cardiovascular risk score defined by the 2013 ACC/AHA cardiovascular risk score algorithm, and cTnT levels were significantly associated with noncalcified plaque volume ...
Research Interests:
It has been recognized that myocardial and hepatic steatosis may be more prevalent in HIV-infected individuals on antiretroviral therapy (ART); however, factors associated with these conditions have not been thoroughly investigated. The... more
It has been recognized that myocardial and hepatic steatosis may be more prevalent in HIV-infected individuals on antiretroviral therapy (ART); however, factors associated with these conditions have not been thoroughly investigated. The goals of this study were (1) to identify the risk factors for myocardial and hepatic steatosis in HIV-infected African Americans (AAs) and explore whether ART use is independently associated with myocardial and hepatic steatosis, and (2) to examine whether and how cocaine use influences any associations of ART use with myocardial and hepatic steatosis. Between June 2010 and December 2013, 220 HIV-infected AAs in Baltimore, Maryland, were enrolled in a study investigating HIV/ART-associated myocardial and hepatic damage. Proton magnetic resonance spectroscopy was performed to quantify myocardial and hepatic triglyceride contents. Sociodemographic, medical and laboratory data were also obtained. Robust regression model was employed to perform primary s...
Research Interests: Medicine, Humans, Internal Medicine, Baltimore, Female, and 15 moreMale, Risk factors, African Americans, Middle Aged, Fatty Liver, Adult, Myocardium, Highly Active Antiretroviral Therapy, Risk Factors, Cross Sectional Studies, Steatosis, proton magnetic resonance spectroscopy, Psychology and Cognitive Sciences, Medical and Health Sciences, and HIV infections
Research Interests:
BackgroundEmergency Departments (EDs) can serve as surveillance sites for infectious diseases. Our purpose was to determine the burden of SARS-CoV-2 infection and prevalence of vaccination against COVID-19 among patients attending an... more
BackgroundEmergency Departments (EDs) can serve as surveillance sites for infectious diseases. Our purpose was to determine the burden of SARS-CoV-2 infection and prevalence of vaccination against COVID-19 among patients attending an urban ED in Baltimore City.MethodsUsing 1914 samples of known exposure status, we developed an algorithm to differentiate previously infected, vaccinated, and unexposed individuals using a combination of antibody assays. We applied this testing algorithm to 4360 samples ED patients obtained in the springs of 2020 and 2021. Using multinomial logistic regression, we determined factors associated with infection and vaccination.ResultsFor the algorithm, sensitivity and specificity for identifying vaccinated individuals was 100% and 99%, respectively, and 84% and 100% for naturally infected individuals. Among the ED subjects, seroprevalence to SARS-CoV-2 increased from 2% to 24% between April 2020 and March 2021. Vaccination prevalence rose to 11% by mid-Mar...
Research Interests:
BACKGROUND The prevalence of heparin-induced thrombocytopenia (HIT) varies by population and the type and duration of heparinoid exposure; however, the association with unfractionated heparin (UFH) dose, route, timing, and duration has... more
BACKGROUND The prevalence of heparin-induced thrombocytopenia (HIT) varies by population and the type and duration of heparinoid exposure; however, the association with unfractionated heparin (UFH) dose, route, timing, and duration has not been evaluated in cardiac surgery patients. METHODS A retrospective case-control study matched HIT-positive adult cardiac surgery patients (positive platelet factor 4 immunoglobulin G and serotonin release assays) 1:1 with HIT-negative controls. Total UFH dose, route, timing, and duration were compared between groups. RESULTS The study included 124 patients, 92(74%) males, with mean(standard deviation) age 65(11) years. Significantly more HIT-positive patients received intravenous UFH preoperatively and/or postoperatively compared to patients without HIT [55(88.7%) vs. 23(37.1%), p<0.001]. There were no significant differences regarding intraoperative or subcutaneous UFH dose or duration. When controlling for obesity and cardiopulmonary bypass duration using multivariable conditional logistic regression, the odds of HIT were increased ten-fold in patients who received preoperative and/or postoperative IV UFH continuous infusion (odds ratio 10.2, 95% confidence interval 3.1-33.7, p<0.001). Receiver operating characteristic curves demonstrated that receiving preoperative and/or postoperative intravenous UFH infusion total dose >32,000 units (sensitivity 82%, specificity 74%, area under curve 0.78) or >7 hours (sensitivity 87%, specificity 68%, area under curve 0.77) was associated with HIT. CONCLUSIONS Odds of HIT were increased ten-fold in adult cardiac surgery patients receiving preoperative and/or postoperative intravenous UFH infusion. Intraoperative UFH dose and subcutaneous route were not associated with HIT. Future study should evaluate incorporation of IV UFH administration, dose, and duration in HIT scoring tools for cardiac surgery patients.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Immunology, Medicine, Pregnancy, Humans, Cord Blood, and 14 moreFemale, Lectins, Plant Lectins, Clinical Sciences, Newborn Infant, Soybeans, Gestational Age, Arachis Hypogaea, Hemagglutination, Transfusion, Maternal-fetal exchange, Random Allocation, Cardiovascular medicine and haematology, and blood group antigens
Research Interests:
The rate of alloimmunization to platelet-specific antigens associated with platelet glycoproteins (GPs) IIb-IIIa and Ib/IX was studied in 293 multiply transfused thrombocytopenic patients. Antibodies to platelet-specific antigens were... more
The rate of alloimmunization to platelet-specific antigens associated with platelet glycoproteins (GPs) IIb-IIIa and Ib/IX was studied in 293 multiply transfused thrombocytopenic patients. Antibodies to platelet-specific antigens were measured with a solid-phase assay using platelet GP IIb-IIIa or Ib/IX as the antigenic targets. Nine patients were found to have antibodies to platelet GP IIb-IIIa, and no patients had antibodies to platelet GP Ib/IX. In six of these nine patients, the specificity of the antibody was shown by using GP IIb-IIIa from donors with different platelet-specific antigen phenotypes. In the remaining three patients with antibodies to platelet GP IIb-IIIa, no specificity could be identified. These patients had autoimmune thrombocytopenia in association with lymphoma. The alloimmunization rate to platelet-specific antigens associated with GP IIb-IIIa was 2 percent, whereas the rate of alloimmunization to HLA antigens was 23 percent. Of the patients alloimmunized to HLA antigens, 9 percent also had antibodies to platelet-specific antigens. A poor response to HLA-identical platelet transfusions was observed only in those patients with positive assays in the solid-phase test. These results suggest that the incidence of antibodies to platelet-specific antigens carried on GP IIb-IIIa is low. Platelet-specific antibodies may be found more frequently in patients alloimmunized to HLA antigens than in those not so alloimmunized.
Research Interests:
The long-term survival of serologically incompatible red cell units was measured in five patients with antibodies to high-frequency antigens. Initially, the survival of 1 ml of 51Cr-labeled incompatible red cells was measured over 1 hour.... more
The long-term survival of serologically incompatible red cell units was measured in five patients with antibodies to high-frequency antigens. Initially, the survival of 1 ml of 51Cr-labeled incompatible red cells was measured over 1 hour. After demonstrating that the 1-hour survival times were successful (greater than 70%), each patient then received 5 ml of the same 51Cr-labeled red cells followed by the transfusion of the remainder of the red cell unit. The long-term T 1/2Cr survival for each case was patient 1 (anti-McCa), 15 days; patient 2 (anti-JMH), 12 days; patient 3 (anti-Kna), 31 days; patient 4 (anti-McCa), 12 days; and patient 5 (anti-Hya), 14 days. Each antibody tested in an in vitro homologous macrophage assay showed less than 5 percent phagocytosis. Anti-JMH was the only antibody to react with IgG subclass antisera and was determined to be IgG4. The macrophage assay, IgG subclass testing, and short-term (1 hour, 1 ml) 51Cr survival studies all indicated that the short-term survival was good. However, only the measurement of long-term survival with transfused units of serologically incompatible red cells was able to determine the actual survival, and &quot;clinical significance&quot; of the alloantibodies. Determining the actual long-term survival by the method described here can be of importance for patients requiring chronic red cell transfusion.
Research Interests:
Research Interests:
Research Interests: Immunology, Medicine, Humans, Beta decay, Blood groups, and 14 moreAnemia, Chromium, Clinical Sciences, Blood Transfusion, Erythrocytes, Cell Survival, Enzyme Linked Immunosorbent Assay, Transfusion, Blood cells, Enzyme Immunoassay, Erythrocyte Count, Erythrocyte transfusion, Cardiovascular medicine and haematology, and blood group antigens
Research Interests:
Removal of white cells (WBCs) from platelets may reduce alloimmunization to WBC antigens, prevent febrile reactions, and improve platelet increments in multiply transfused patients receiving HLA-matched platelets. A new surface-modified... more
Removal of white cells (WBCs) from platelets may reduce alloimmunization to WBC antigens, prevent febrile reactions, and improve platelet increments in multiply transfused patients receiving HLA-matched platelets. A new surface-modified fibrous polyester filter was evaluated; it requires no special processing of pooled platelet concentrates and can be used at the patient&#39;s bedside. The studies were designed to measure WBC removal, platelet function, in vitro platelet recovery, and in vivo platelet survival. WBC mean removal was 99.8 percent +/- 0.56 (n = 37) when a pool similar in volume to 6 platelet concentrates was tested. The mean number of residual WBCs after filtration was 5.6 x 10(5). In vitro mean platelet recovery was 86.9 percent for a pool size of 6 units (n = 37). Clot retraction and platelet aggregation were unaffected by filtration. Survival studies of 111Indium-labeled platelets done with filtered autologous platelets showed no reduction in the normally expected survival. These studies indicated that the filter efficiently removes WBCs without substantially decreasing platelet number, survival, or function. This device offers the potential of considerably improving platelet transfusion therapy.
Research Interests: Chemistry, Immunology, Kinetics, Biology, Cell Adhesion, and 14 moreMedicine, Cell separation, Adsorption, Platelet, Humans, Clinical Sciences, Blood Transfusion, Cell Survival, Leukocytes, Platelet Count, Transfusion, Blood platelets, Platelet transfusion, and Cardiovascular medicine and haematology
Research Interests:
Research Interests:
Research Interests:
Amino acid substitutions in platelet membrane glycoproteins result in alloantigens implicated in neonatal alloimmune thrombocytopenia. We report the use of the reverse dot blot technique to genotype the five major fetal platelet... more
Amino acid substitutions in platelet membrane glycoproteins result in alloantigens implicated in neonatal alloimmune thrombocytopenia. We report the use of the reverse dot blot technique to genotype the five major fetal platelet alloantigens from amniotic fluid cells. We evaluated a patient with Bakb platelet antibodies who had a previous pregnancy complicated by fetal intracranial hemorrhage. The father was heterozygous Baka/Bakb, giving the pregnancy a 50% risk for platelet incompatibility between mother and fetus. Amniotic fluid was obtained at 16 weeks. Deoxyribonuleic acid was extracted from uncultured amniocytes and amplified with polymerase chain reaction. These products were hybridized to filters containing oligonucleotides specific for each of the 10 different platelet antigen alleles. Reactivity was detected with a chromogenic substrate. The reverse dot blot genotyping of uncultured amniocytes revealed the fetus to be Baka/Baka, thus not at risk for neonatal alloimmune thrombocytopenia. Precise knowledge of fetal platelet type by amniocentesis could obviate the need for fetal blood sampling and significantly alter prenatal management of neonatal alloimmune thrombocytopenia.
Research Interests: Medicine, Platelet, Pregnancy, Humans, Female, and 15 moreBlood sampling, Deoxyribonucleic Acid, Polymerase Chain Reaction, American, Amniotic Fluid, Genotype, Foetus, Adult, Fetus, Amino Acid Substitution Rates, Gestation, Intracranial Hemorrhage, alleles, Blood platelets, and Paediatrics and reproductive medicine
Research Interests:
Research Interests:
Research Interests:
P106 Objectives: Impaired platelet function has been associated with increased propensity for ICH. Our objective is to demonstrate that patients with larger ICH volume have abnormal platelet function. Methods: This is a prospective cohort... more
P106 Objectives: Impaired platelet function has been associated with increased propensity for ICH. Our objective is to demonstrate that patients with larger ICH volume have abnormal platelet function. Methods: This is a prospective cohort study. Platelet function was measured by a standard set of tests within one week of ICH. CT scans were performed within 24 hours of the event and ICH volume determined by the ABC/2 method. Results: 12 patients were enrolled (5/12 female, 7/12 male). The mean age was 64 years (range 40–85). Four patients were on ASA. Platelet count ranged from 76 to 315 KU/mm 3 . Patients were divided into two subgroups based on ICH size: ≤30cc and >30cc. The two CT subgroups were similar with respect to age, sex, race, history of hypertension and alcohol abuse. We report in Table 1 the distribution of specific platelet abnormalities among the two ICH groups. Conclusions: Large spontaneous ICH (>30cc) is associated with evidence of platelet hypoactivity which ...
Research Interests:
Background: Point-of-care testing (POCT) can provide rapid test results, but its impact on patient care is not well documented. We investigated the ability of POCT to decrease inpatient and outpatient waiting times for cardiovascular... more
Background: Point-of-care testing (POCT) can provide rapid test results, but its impact on patient care is not well documented. We investigated the ability of POCT to decrease inpatient and outpatient waiting times for cardiovascular procedures. Methods: We prospectively studied, over a 7-month period, 216 patients requiring diagnostic laboratory testing for coagulation (prothrombin time/activated partial thromboplastin time) and/or renal function (urea nitrogen, creatinine, sodium, and potassium) before elective invasive cardiac and radiologic procedures. Overall patient management and workflow were examined in the initial phase. In phase 2, we implemented POCT but utilized central laboratory results for patient management. In phase 3, therapeutic decisions were based on POCT results. The final phase, phase 4, sought to optimize workflow around the availability of POCT. Patient wait and timing of phlebotomy, availability of laboratory results, and therapeutic action were monitored....
Research Interests: Cardiology, Medicine, Clinical Chemistry, Humans, Medical Biotechnology, and 15 moreInterventional Radiology, Potassium, Renal Function, Clinical Sciences, Time Factors, Patient Care, Point of Care Testing, Waiting Time, Laboratory Tests, Prospective Study, Diagnostic and Interventional Radiology, Activated partial thromboplastin time, Outcome assessment (Health care), Medical biochemistry and metabolomics, and Kidney function tests
Amino acid substitutions in platelet membrane glycoproteins result in alloantigens. Identifying these polymorphisms is important in alloimmune-mediated platelet disorders. Immunophenotyping platelet antigens can be limited by the... more
Amino acid substitutions in platelet membrane glycoproteins result in alloantigens. Identifying these polymorphisms is important in alloimmune-mediated platelet disorders. Immunophenotyping platelet antigens can be limited by the unavailability of specific antisera. The goal of this work was to identify human platelet antigen genotypes in individuals using a technique that would circumvent the limitations of immunophenotyping and be clinically applicable. We have successfully applied the reverse dot-blot (RDB) technique to the genotyping of the five major human platelet alloantigen systems. Allele-specific oligonucleotides (ASOs) representing each allele of these alloantigens were covalently linked to a filter. Biotinylated oligonucleotides flanking the polymorphic sequences in genomic DNA were used to amplify genomic DNA by the polymerase chain reaction (PCR), and these products were hybridized to the filters containing the ASOs. Reactivity was detected with a chromogenic substrate...
Research Interests: Genetics, Biology, Medicine, Humans, Female, and 15 moreBlood, Nucleic acid hybridization, Male, Polymerase Chain Reaction, Amniocentesis, Clinical Sciences, Genotype, Immunophenotyping, Blood Transfusion, Base Sequence, Enzyme Linked Immunosorbent Assay, Molecular Sequence Data, alleles, Cardiovascular medicine and haematology, and Paediatrics and reproductive medicine
Tracking cells and proteins' phenotypic changes in deep suspensions is critical for the direct imaging of blood-related phenomena in replica of cardiovascular systems and blood-handling devices. This paper introduces fluorescence... more
Tracking cells and proteins' phenotypic changes in deep suspensions is critical for the direct imaging of blood-related phenomena in replica of cardiovascular systems and blood-handling devices. This paper introduces fluorescence imaging techniques for space and time resolved detection of platelet activation, von Willebrand factor (VWF) conformational changes, and VWF-platelet interaction in deep suspensions. Labeled VWF, platelets, and VWF-platelet strands are suspended in deep cuvettes, illuminated, and imaged with a high-sensitivity EM-CCD camera, allowing detection using an exposure time of 1 ms. In-house postprocessing algorithms identify and track the moving signals. Recombinant VWF-eGFP (rVWF-eGFP) and VWF labeled with an FITC-conjugated polyclonal antibody are employed. Anti-P-Selectin FITC-conjugated antibodies and the calcium-sensitive probe Indo-1 are used to detect activated platelets. A positive correlation between the mean number of platelets detected per image and...
Research Interests:
Although cocaine use may induce/accelerate HIV-associated comorbidities in HIV-infected individuals on antiretroviral therapy (ART), and that HIV itself may accelerate aging, the issue of whether cocaine use plays a role in HIV-associated... more
Although cocaine use may induce/accelerate HIV-associated comorbidities in HIV-infected individuals on antiretroviral therapy (ART), and that HIV itself may accelerate aging, the issue of whether cocaine use plays a role in HIV-associated aging in HIV-infected cocaine users has not been reported. The goals of this study were (1) to explore factor(s) associated with peripheral blood leukocyte telomere length, a marker of cellular replicative history, and telomere shortening in HIV-infected individuals, and (2) to assess whether cocaine use plays a role in accelerating telomere shortening in cocaine users with HIV infection. Between June 2010 and December 2016, 147 HIV-infected participants in Baltimore, Maryland, were enrolled in a cross-sectional study investigating factor(s) associated with telomere length. Of these 147, 93 participated in a follow-up study to examine factor(s) associated with telomere shortening. Robust regression model was used to analyze cross-sectional data and...
Research Interests:
Systemic thromboxane generation, not suppressible by standard aspirin therapy and likely arising from nonplatelet sources, increases the risk of atherothrombosis and death in patients with cardiovascular disease. In the RIGOR (Reduction... more
Systemic thromboxane generation, not suppressible by standard aspirin therapy and likely arising from nonplatelet sources, increases the risk of atherothrombosis and death in patients with cardiovascular disease. In the RIGOR (Reduction in Graft Occlusion Rates) study, greater nonplatelet thromboxane generation occurred early compared with late after coronary artery bypass graft surgery, although only the latter correlated with graft failure. We hypothesize that a similar differential association exists between nonplatelet thromboxane generation and long-term clinical outcome. Five-year outcome data were analyzed for 290 RIGOR subjects taking aspirin with suppressed platelet thromboxane generation. Multivariable modeling was performed to define the relative predictive value of the urine thromboxane metabolite, 11-dehydrothromboxane B2 (11-dhTXB2), measured 3 days versus 6 months after surgery on the composite end point of death, myocardial infarction, revascularization or stroke, an...
Research Interests: Cardiology, Surgery, Biomarkers, Medicine, Multivariate Analysis, and 15 moreStroke, Humans, Female, Male, Risk factors, Aspirin, Aged, Middle Aged, Myocardial Infarction, Risk Factors, Proportional Hazards Models, Predictive value of tests, Cause of death, Platelet Aggregation Inhibitors, and Coronary Artery Bypass
Fentanyl is a potent opiate commonly administered during cardiac catheterization procedures in North America. The question of whether fentanyl could have adverse consequences in patients undergoing percutaneous coronary intervention (PCI)... more
Fentanyl is a potent opiate commonly administered during cardiac catheterization procedures in North America. The question of whether fentanyl could have adverse consequences in patients undergoing percutaneous coronary intervention (PCI) is raised by recent research demonstrating that intravenous morphine significantly delays the absorption of oral P2Y12 platelet inhibitors. The presumed mechanism is slowed gastric emptying. The single-center Platelet Aggregation with tiCagrelor Inhibition and FentanYl (PACIFY) trial randomized adults undergoing clinically-indicated elective coronary angiography to receive the procedure with or without intravenous fentanyl (NCT02683707). The study was approved by the Johns Hopkins Medicine Institutional Review Board and all participants provided written informed consent. Eligible adults had not received P2Y12 inhibitors for 14 days prior to enrollment. Other exclusion criteria included: pre-procedural treatment with oral anticoagulants or opiates; ...
Research Interests:
Ethylenediaminetetraacetic acid (EDTA)-dependent pseudothrombocytopenia is the occurrence of a falsely low platelet count caused by antibodies that agglutinate platelets in the presence of EDTA. If unrecognized, it may result in the... more
Ethylenediaminetetraacetic acid (EDTA)-dependent pseudothrombocytopenia is the occurrence of a falsely low platelet count caused by antibodies that agglutinate platelets in the presence of EDTA. If unrecognized, it may result in the erroneous diagnosis of thrombocytopenia and possible inappropriate therapy. It has been noted that this phenomenon tends to appear in hospitalized patients after an initially normal platelet count, but sequential measurements of anti-platelet antibody have not been reported. The case of a patient who developed EDTA-dependent pseudothrombocytopenia approximately 1 week after being hospitalized for severe trauma is described. Anti-platelet antibodies were not detected on admission by a radiolabeled antiglobulin technique but were shown to increase in titer concurrent with the appearance of EDTA-dependent pseudothrombocytopenia.
Research Interests:
The key objectives of this study were to examine whether HIV infection itself is associated with subclinical coronary atherosclerosis and the potential contributions of cocaine use and antiretroviral therapies (ARTs) to subclinical... more
The key objectives of this study were to examine whether HIV infection itself is associated with subclinical coronary atherosclerosis and the potential contributions of cocaine use and antiretroviral therapies (ARTs) to subclinical coronary artery disease (CAD) in HIV-infected persons. Between June 2004 and February 2015, 1429 African American (AA) adults with/without HIV infection in Baltimore, Maryland, were enrolled in an observational study of the effects of HIV infection, exposure to ART, and cocaine use on subclinical CAD. The prevalence of subclinical coronary atherosclerosis was 30.0% in HIV-uninfected and 33.7% in HIV-infected (P=0.17). Stratified analyses revealed that compared to HIV-uninfected, HIV-infected ART naïve were at significantly lower risk for subclinical coronary atherosclerosis, whereas HIV-infected long-term ART users (≥36 months) were at significantly higher risk. Thus, an overall nonsignificant association between subclinical coronary atherosclerosis and H...
Research Interests: Risk assessment, Medicine, Humans, Internal Medicine, Baltimore, and 15 moreFemale, Male, Risk factors, African Americans, Prevalence, Middle Aged, Coronary Angiography, Adult, Time Factors, Risk Factors, Risk Assessment, Coronary Artery Disease, Multidetector Computed Tomography, Asymptomatic Diseases., and HIV infections
Research Interests:
Research Interests:
Objective. We present the case of a 73-year-old female, with no family or personal history of a bleeding disorder, who had a classic presentation for acquired hemophilia A. Factor VIII activity was low but detectable and a factor VIII... more
Objective. We present the case of a 73-year-old female, with no family or personal history of a bleeding disorder, who had a classic presentation for acquired hemophilia A. Factor VIII activity was low but detectable and a factor VIII inhibitor was undetectable. Methods. The patient's plasma was comprehensively studied to determine the cause of the acquired coagulopathy. Using the Nijmegen modification of the Bethesda assay, no factor VIII autoantibody was measureable despite varying the incubation time from 1 to 3 hours. Results. The aPTT was prolonged at 46.8 seconds, which did not correct in the 4 : 1 mix but did with 1 : 1 mix. Using a one stage factor VIII activity assay, the FVIII activity was 16% and chromogenic FVIII activity was also 16%. The patient was treated with recombinant FVII and transfusion, significantly reducing bleeding. Long-term therapy was initiated with cyclophosphamide and prednisone with normalization of FVIII activity. Conclusions. Physicians can be p...
Research Interests:
Antibodies to beta2-glycoprotein I (anti-beta2-GPI) are found in a large percentage of patients with primary or secondary antiphospholipid syndrome (APS). Our aim was to identify the prevalence and clinical correlation of these antibodies... more
Antibodies to beta2-glycoprotein I (anti-beta2-GPI) are found in a large percentage of patients with primary or secondary antiphospholipid syndrome (APS). Our aim was to identify the prevalence and clinical correlation of these antibodies in patients with APS and systemic lupus erythematosus (SLE), in comparison to anticardiolipin (aCL) and the lupus anticoagulant (LAC). We investigated whether serial samples improve clinical utility. Serum samples for anti-beta2-GPI (IgG, IgM, IgA), aCL (IgG, IgM, IgA), and LAC (by dilute Russell viper venom time; RVVT) were collected from 418 consecutive patients with SLE or APS between October 2002 and March 2003. Clinical and serologic data of these patients were analyzed. A total of 185 (44.5%) patients were positive for anti-beta2-GPI, 55.3% were positive for aCL, and 31.1% for LAC. Anti-beta2-GPI was more common in Caucasians than in African Americans (p = 0.098). IgM and IgA were the most frequent isotypes of anti-beta2-GPI. aCL and anti-bet...
Research Interests: Rheumatology, Immunology, Risk assessment, Medicine, Comorbidity, and 15 moreHumans, Systemic Lupus Erythematosus, Female, Male, Risk factors, Maryland, Clinical Sciences, Prevalence, Reproducibility of Results, Biological markers, Risk Factors, Risk Assessment, Sensitivity and Specificity, Autoantibodies, and Antiphospholipid Syndrome
The VerifyNow P2Y12 assay assesses the adequacy of clopidogrel therapy by measuring ADP-induced platelet activation in whole blood. Low hematocrit is associated with high clopidogrel on-treatment platelet reactivity (HTPR) defined by this... more
The VerifyNow P2Y12 assay assesses the adequacy of clopidogrel therapy by measuring ADP-induced platelet activation in whole blood. Low hematocrit is associated with high clopidogrel on-treatment platelet reactivity (HTPR) defined by this assay. To characterize the effect of hematocrit on VerifyNow values and determine if it is due to hematocrit-dependent changes in intrinsic platelet reactivity or an in vitro assay phenomenon. Adenosine diphosphate-induced platelet activation was measured using the VerifyNow P2Y12 assay, whole blood impedance and light transmission platelet aggregometry (LTA) before and after clopidogrel loading in 113 patients undergoing elective cardiac catheterization. Iso-TRAP-induced platelet activation was additionally measured using the VerifyNow device. Multivariate modeling employing clinical and laboratory variables was used to investigate the association between hematocrit and VerifyNow values. VerifyNow P2Y12 reaction units (PRU) and iso-TRAP Base units before and after clopidogrel loading, but not their relative change, exhibited strong negative correlation with hematocrit (P ≤ 0.0005 for both). While hematocrit remained a strong predictor of post-clopidogrel PRU (P = 0.001) in multivariate modeling, it was independent of post-clopidogrel ADP-induced platelet reactivity as measured by LTA (P = 0.001). Correcting for the effects of hematocrit resulted in a 15-39% reduction in the prevalence of HTPR defined by thresholds of 208-236 PRU. The effect of hematocrit on VerifyNow PRU values is an in vitro phenomenon that is independent of intrinsic change in ADP-induced platelet reactivity and clopidogrel responsiveness. Correcting for hematocrit when using this assay may more accurately identify patients with HTPR that may benefit from alternative antiplatelet therapy.
Research Interests:
Research Interests:
Chlamydia pneumoniae has been associated with atherosclerosis, although its role in the process is not clearly defined. Heart transplant recipients are known to have high titers of antibodies to C. pneumoniae, and the organism has been... more
Chlamydia pneumoniae has been associated with atherosclerosis, although its role in the process is not clearly defined. Heart transplant recipients are known to have high titers of antibodies to C. pneumoniae, and the organism has been recovered from the coronary arteries of both transplant recipients and donors. This study evaluated association between C. pneumoniae infection and accelerated graft arteriosclerosis (AGA), also known as cardiac allograft vasculopathy (CAV), after cardiac transplantation. A case-control study was performed with 54 heart transplant recipients at the Johns Hopkins Hospital. Severe cases had &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50% luminal narrowing on cardiac catheterization, mild cases &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;50% narrowing, and controls were free of arteriosclerotic disease. Blood specimens were examined for C. pneumoniae serology and DNA detection by polymerase chain reaction (PCR) assays. For every twofold increase in geometric mean C. pneumoniae immunoglobulin (Ig)G titer, the odds ratio for severe AGA versus controls was 3.13 (P=0.03) and for mild AGA versus control patients was 1.61 (P=0.45). On Kaplan-Meier survival analysis there was a nonsignificant trend toward faster development of CAV in patients with higher C. pneumoniae antibody titers. Overall, 29% of heart transplant patients evaluated had evidence of circulating C. pneumoniae DNA by PCR, without a statistical difference between groups. C. pneumoniae IgG titer correlates with severity of allograft arteriosclerosis after cardiac transplantation. Circulating C. pneumoniae DNA is detectable by PCR in up to 30% of cardiac transplant recipients, but this does not correlate with severity of allograft vasculopathy.
Research Interests:
SUMMARY Understanding the biology of platelet is important for one to treat patients with acquired or inherited platelet disorders. Platelets provide primary hemostasis by performing five primary functions: adhesion, aggregation,... more
SUMMARY Understanding the biology of platelet is important for one to treat patients with acquired or inherited platelet disorders. Platelets provide primary hemostasis by performing five primary functions: adhesion, aggregation, secretion, and providing procoagulant surface and clot retraction. The elucidation of the molecular mechanisms carrying out these functions has led to a better understanding of the pathophysiology of bleeding and the development of new approaches in treating patients with qualitative and quantitative platelet disorders. The purpose of this review is to provide a foundation for understanding the other papers in this publication on the treatment of platelet disorders.
Research Interests:
SUMMARY Alternatives to platelet transfusions are important in preventing the adverse events associated with platelet transfusions. The use of platelet alternatives has not been extensively compared with platelet transfusions, although... more
SUMMARY Alternatives to platelet transfusions are important in preventing the adverse events associated with platelet transfusions. The use of platelet alternatives has not been extensively compared with platelet transfusions, although studies suggest that bleeding can be controlled and transfusions prevented. A variety of pharmacologic agents are available, which generally work by augmenting different hemostatic mechanisms. In addition to pharmacologic agents, recombinant activated factor VII is available for controlling inherited qualitative platelet disorders such as Glanzmann’s thrombasthenia. For the treatment of chemotherapy-induced thrombocytopenia, the use of growth factors may shorten the duration of thrombocytopenia and prove to be an approach for reducing or preventing platelet transfusions. Although interesting research has been carried out for several decades in the aim of developing a platelet substitute, it is unlikely that a platelet substitute will be available for clinical use in the near future.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
There is little doubt about the therapeutic effectiveness of platelets stored at room temperature. Nonetheless, questions remain about whether platelet viability, structure, and function can be improved. The quest for such improvements is... more
There is little doubt about the therapeutic effectiveness of platelets stored at room temperature. Nonetheless, questions remain about whether platelet viability, structure, and function can be improved. The quest for such improvements is stimulated by the several biochemical and functional abnormalities found in stored A limited number of in vivo studies also suggest transient functional impairment of stored platelets and somewhat diminished survival for platelets stored for long periods of time.3-s New approaches to improving the quality of stored platelets are currently the subject of much investigation. Besides the development of new storage media, the detrimental effects of plasma and white cell contamination are being investigated. Determination of whether any of these innovations will lead to improved clinical hemostasis will require careful clinica1 investigation. When platelets are removed from the circulation and exposed to the foreign conditions of even the most carefully designed collection and storage system, various changes collectively referred to as platelet activation begin. A bewildering number of variables may produce minimal changes that perpetuate the process as more platelets are recruited into the activated state. These activation changes may be reflected in platelet shape change, platelet aggregation, secretion of platelet granular contents, and expression of activation antigens. The challenge in preparing platelets for transfusion has been the effort to minimize the damaging effects of preparation and storage. The major advance in improving stored platelets was the elucidation of the metabolic factors that lead to a deleterious fall in the pH. Early in the development of platelet storage, it was recognized that a decline in pH was associated with a reduction in platelet viability.6 Seminal research showed that the drop in pH was caused by an accumulation of lactic acid through glycolysis and was promoted by the relative hypoxic storage conditions found in the older generation of platelet storage bags.’ With improved transmission of oxygen through gasJ I
Research Interests:
Research Interests:
To the Editor: Adrenoleukodystrophy is a sex-linked disorder in which very-long-chain fatty acids accumulate in all body tissues1. For this reason, a variety of diets have been formulated to lower the levels of these acids. One diet... more
To the Editor: Adrenoleukodystrophy is a sex-linked disorder in which very-long-chain fatty acids accumulate in all body tissues1. For this reason, a variety of diets have been formulated to lower the levels of these acids. One diet includes Lorenzo's Oil, a product that contains 20 percent erucic acid (22:1) and 80 percent oleic acid (18:1). During the past two years, 40 male and 6 female patients have received Lorenzo's Oil according to a protocol calculated to provide 20 percent of daily caloric intake. In 19 of these patients the platelet count has decreased significantly (Table 1). The degree of . . .
Research Interests:
Research Interests:
Research Interests:
Research Interests: Treatment Outcome, Medicine, Prospective studies, Humans, Heparin, and 15 moreFemale, Male, Thrombocytopenia, Haemostasis and Thrombosis, Risk factors, Clinical Sciences, Aged, Middle Aged, Adult, Thrombosis, Risk Factors, SAPHENOUS VEIN, Coronary artery bypass surgery, Cardiovascular medicine and haematology, and Coronary Artery Bypass
Research Interests: Cardiovascular, Medicine, Electrocardiography, Humans, Platelets, and 15 moreCocaine, Male, Drug abuse, Recurrence, Clinical Sciences, Cardiac Catheterization, Coronary Angiography, Myocardial Infarction, Adult, Public health systems and services research, Normal, Coronary artery bypass surgery, Coronary artery, Cardiovascular medicine and haematology, and Coronary Artery Bypass
Research Interests:
Research Interests:
This article discusses the causes and management of platelet refractoriness. Improvements in the quality of platelets and leukoreduction have reduced the morbidity and mortality related to alloimmunization and refractoriness of patients... more
This article discusses the causes and management of platelet refractoriness. Improvements in the quality of platelets and leukoreduction have reduced the morbidity and mortality related to alloimmunization and refractoriness of patients to platelet transfusion. Alloimmunization can be distinguished from other causes of poor post-transfusion platelet increments by the measurement of platelet alloantibodies. Options for managing platelet refractoriness caused by alloimmunization include platelet transfusion from human leukocyte antigen-matched or donor-recipient cross-matched platelets. Prevention strategies include efforts to limit recipients&amp;amp;#39; exposure to human leukocyte antigen specificities by using single-donor platelets, filtration to reduce the number of human leukocyte antigen-bearing leukocytes, and pretransfusion ultraviolet B irradiation to decrease their immunogenicity. For appropriate management of patients refractory to platelets, close cooperation and good communication are necessary between clinicians and blood centers.
Research Interests:
To determine the medical and laboratory characteristics of bacteremia secondary to transfusion of microbiologically contaminated platelet concentrates. Febrile transfusion reactions were prospectively monitored over 42 months. Units... more
To determine the medical and laboratory characteristics of bacteremia secondary to transfusion of microbiologically contaminated platelet concentrates. Febrile transfusion reactions were prospectively monitored over 42 months. Units involved in reactions were evaluated with Gram&amp;amp;#39;s stain and culture tests. Comprehensive cancer center. Patients receiving platelet transfusions for thrombocytopenia secondary to bone marrow failure. Seven cases of transfusion-associated sepsis were observed. Multidonor platelet products stored for 5 days resulted in an incidence of sepsis five times higher than those stored for 4 days or less (P less than .01). Investigation indicates that contamination most likely occurred at the time of blood collection. Clinically, septic reactions were associated with greater temperature elevations (average increase, 2.0 degrees C) than febrile reactions to sterile products. Contamination of platelet concentrates remains a significant clinical problem. Septic episodes may be reduced by transfusion of platelets with shorter storage intervals.
Research Interests:
To the Editor. — The recent study of the human erythropoietin response to autologous donation1concluded that the current guidelines for autologous blood banking (hematocrit >0.34) do not allow a significant degree of anemia to develop... more
To the Editor. — The recent study of the human erythropoietin response to autologous donation1concluded that the current guidelines for autologous blood banking (hematocrit >0.34) do not allow a significant degree of anemia to develop in patients. Increased levels of erythropoietin and erythropoiesis were not observed, implying that preoperative autologous storage may not increase the total red blood cell mass at the time of surgery. These findings may be methodological artifacts typical of suboptimal clinical predonation programs. Most patients deposited 3 U or less at three-day intervals over a short period (nine to 12 days). The spontaneous erythropoietic response to sustained phlebotomy-induced anemia requires seven to nine days to initiate and becomes maximal at three weeks, with adequate iron stores.2Phlebotomy is best begun four to five weeks from the date of planned surgery. This maximizes the preoperative period of increased erythropoiesis, within the limits of liquid
Research Interests:
Research Interests:
Research Interests:
Research Interests:
To the Editor. —In the article entitled "Hereditary Hemorrhagic Telangiectasia and Factor VIII Deficiency" in the August issue, Esham et al describe a patient with a case of severe hemorrhagic disorder. An important... more
To the Editor. —In the article entitled "Hereditary Hemorrhagic Telangiectasia and Factor VIII Deficiency" in the August issue, Esham et al describe a patient with a case of severe hemorrhagic disorder. An important consideration, which the authors apparently failed to recognize, is that this patient may also have a circulating anticoagulant. This is suggested by the severity of the patient's bleeding tendency despite a factor VIII value of 28% and the development of an abnormal partial thromboplastin time after a bleeding episode that may represent an amnestic increase in the circulating anticoagulant level after therapeutic administration of factor VIII. The lack of response to plasma components containing factor VIII also suggest the presence of an inhibitor to factor VIII. Despite the authors' claim of presenting the first case of hereditary telangiectasia and factor VIII deficiency, Quick has previously described the cases of two patients with these defects.1 In these patients,
Research Interests:
Research Interests:
Research Interests:
Research Interests: RNA, Medicine, Humans, Diabetes mellitus, Female, and 14 moreInfection, Male, Thrombocytopenia, Platelet activation mechanism, African Americans, Middle Aged, Adult, chronic hepatitis C, Platelet Count, Predictive value of tests, Viral Load, Blood platelets, Cardiovascular medicine and haematology, and HIV infections
Research Interests:
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), classified by a translocation between chromosomes 15 and 17 [t(15;17)], that is considered a true oncologic emergency though appropriate therapy is... more
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), classified by a translocation between chromosomes 15 and 17 [t(15;17)], that is considered a true oncologic emergency though appropriate therapy is considered curative. Therapy is often initiated on clinical suspicion, informed by both clinical presentation as well as direct visualization of the peripheral smear. We hypothesized that genomic imprinting of morphologic features learned by deep learning pattern recognition would have greater discriminatory power and consistency compared to humans, thereby facilitating identification of t(15;17) positive APL. By applying both cell-level and patient-level classification linked to t(15;17) PML/RARA ground-truth, we demonstrate that deep learning is capable of distinguishing APL in both discovery and prospective independent cohort of patients. Furthermore, we extract learned information from the trained network to identify previously undescribed morphological ...
Background: Emergency Departments (EDs) can serve as surveillance sites for infectious diseases. The objective of this study was to determine the burden of SARS-CoV-2 infection and to monitor the prevalence of vaccination against COVID-19... more
Background: Emergency Departments (EDs) can serve as surveillance sites for infectious diseases. The objective of this study was to determine the burden of SARS-CoV-2 infection and to monitor the prevalence of vaccination against COVID-19 among patients attending an urban ED in Baltimore City. Methods: Using 1,914 samples of known exposure status, we developed an algorithm to differentiate previously infected, vaccinated, and unexposed individuals using a combination of antibody assays. We applied this testing algorithm to 4,360 samples ED patients obtained in the spring of 2020 and 2021. Using multinomial logistic regression, we determined factors associated with infection and vaccination. Results: For the algorithm, sensitivity and specificity for identifying vaccinated individuals was 100% and 99%, respectively, and 84% and 100% for previously infected individuals. Among the ED subjects, seroprevalence to SARS-CoV-2 increased from 2% to 24% between April 2020 and March 2021. Vacc...
Research Interests:
ABSTRACT During the recent years considerable advances in the clinical and laboratory diagnosis of alloimmune thrombocytopenia have been done. Feto-maternal alloimmunization is the commonest cause of severe isolated fetal and neonatal... more
ABSTRACT During the recent years considerable advances in the clinical and laboratory diagnosis of alloimmune thrombocytopenia have been done. Feto-maternal alloimmunization is the commonest cause of severe isolated fetal and neonatal thrombocytopenia. The condition results from maternal immunization against specific fetal platelet antigens (HPA). Unlike the haemolytic disease of the fetus and newborn the first newborn was found to be affected. The diagnosis is usually made at birth when an otherwise ‘well’ term infant exhibits bleeding at delivery or few hours afterwards. The most feared complication of this disorder is the occurrence of intracranial haemorrhage (ICH) as a result of severe thrombocytopenia leading to death or neurological sequelae. The diagnosis of alloimmune thrombocytopenia enables appropriate management of the index case and future pregnancies. The diagnosis is confirmed by laboratory testing with the identification of the maternal alloantibody and the offending antigen present in the fetus or neonate that is absent in the mother. In a recent retrospective study concerning 75 HPA-1b1b women, we have shown that the diagnosis of maternal alloimmunization was mostly established at delivery and the women were primigravida in 51% of the cases. The deleterious consequence of this severity was evidenced by in utero or postnatal ICH. Subsequent pregnancies were managed according to three different protocols, steroids only, intravenous immunoglobulin (IVIG) or IVIG and steroids. We found that the most efficacious antenatal therapy for fetal alloimmune thrombocytopenia is maternal treatment with IVIG and steroids. In summary, this study shows (1) that the morbidity linked with this condition is important to be considered for further antenatal screening (2) that antenatal management in referral centers should be suggested to high-risk pregnant women.
Research Interests:
In this study, we propose the use of surface-enhanced Raman spectroscopy (SERS) to determine spectral markers that can aid in the recognition of heparin-induced thrombocytopenia (HIT), a difficult-to-diagnose immune-related complication... more
In this study, we propose the use of surface-enhanced Raman spectroscopy (SERS) to determine spectral markers that can aid in the recognition of heparin-induced thrombocytopenia (HIT), a difficult-to-diagnose immune-related complication that often leads to limb ischemia and thromboembolism . The ability to produce distinct molecular signatures without requiring addition of exogenous labels enables unbiased inquiry and makes SERS an attractive complementary diagnostic tool for various complex pathologies. Specifically, we have designed a new plasmonic capillary flow platform that offers ultrasensitive , label-free measurement capability as well as efficient handling of blood serum samples. The optimized capillary channel shows excellent reproducibility and long-term stability and, crucially, provides an alternative diagnostic rubric for determination of HIT by leveraging machine-learning based classification of the spectroscopic data. With further refinement, we envision that a portable Raman instrument could be combined with the capillary-based SERS analytical tool for rapid, non-destructive determination of HIT in the clinical laboratory, without perturbing the existing diagnostic workflow.
Research Interests:
Morphine delays oral P2Y platelet inhibitor absorption and is associated with adverse outcomes after myocardial infarction. Consequently, many physicians and first responders are now considering fentanyl as an alternative. We conducted a... more
Morphine delays oral P2Y platelet inhibitor absorption and is associated with adverse outcomes after myocardial infarction. Consequently, many physicians and first responders are now considering fentanyl as an alternative. We conducted a single-centre trial randomizing cardiac patients undergoing coronary angiography to intravenous fentanyl or not. All participants received local anaesthetic and intravenous midazolam. Those requiring percutaneous coronary intervention (PCI) with stenting received 180 mg oral ticagrelor intra-procedurally. The primary outcome was area under the ticagrelor plasma concentration-time curve (AUC). The secondary outcomes were platelet function assessed at 2 hours after loading, measured by P2Y reaction units (PRUs) and light transmission platelet aggregometry. Troponin-I was measured post-PCI using a high-sensitivity troponin-I assay (hs-TnI). All participants completed a survey of pain and anxiety. Of the 212 randomized, 70 patients required coronary ste...
Research Interests:
Background: A number of assays have evolved to assess platelet reactivity and identify patients on dual antiplatelet therapy who remain at risk of thrombotic events. The goal of this study was to a...
Research Interests: Medicine and Circulation
Introduction: Platelet activation via thromboxane A2 (TXA2) is fundamental to thrombus formation in acute coronary syndrome (ACS) patients. Aspirin inhibits platelet TXA 2 production by inhibiting the cyclooxygenase (COX-1) enzyme in... more
Introduction: Platelet activation via thromboxane A2 (TXA2) is fundamental to thrombus formation in acute coronary syndrome (ACS) patients. Aspirin inhibits platelet TXA 2 production by inhibiting the cyclooxygenase (COX-1) enzyme in platelets. Emerging data suggest, however, that ACS patients continue to generate TXA2 despite aspirin therapy, but it is unclear whether this TXA2 is from a failure of aspirin to inhibit platelet COX-1 or from platelet COX-1 independent sources. Hypothesis: Persistent TXA2 generation during ACS is derived from platelet COX-1 independent sources. Methods: Platelet COX-1 independent TXA2 generation was evaluated in 25 patients on aspirin undergoing coronary angiography for stable and unstable angina. Platelet COX-1 activity was assessed by light transmission aggregation to 0.5mmol L−1 of arachidonic acid (<10% aggregation defines appropriate aspirin inhibition of platelet COX-1 activity). TXA2 was evaluated by ELISA measurement of urine 11-dehydro thromboxane B2 (UTXB2), a sta...
Research Interests: Medicine and Circulation
High circulating levels of the procoagulant molecule tissue factor (TF) are associated with thrombosis in a variety of diseases including unstable angina, cancer, and sepsis. Currently, there are no clinical assays to measure the level of... more
High circulating levels of the procoagulant molecule tissue factor (TF) are associated with thrombosis in a variety of diseases including unstable angina, cancer, and sepsis. Currently, there are no clinical assays to measure the level of TF activity in whole blood. We present an assay called Tissue Factor Clotting Time ("TiFaCT") that detects fibrin formation in human blood. The mean baseline clotting time in a healthy population was 472 +/- 94 s (mean +/- SD, n = 150). Bacterial lipopolysaccharide (LPS or endotoxin) shortened the clotting time in a time-dependent manner. Inhibitory anti-TF antibodies prolonged the clotting time of LPS-stimulated blood, indicating that the shortened clotting time was due to induction of TF expression. Patients with unstable angina had shortened mean baseline clotting time (284 +/- 86, n = 13) compared with healthy volunteers (474 +/- 98, n = 30), suggesting that these patients had elevated levels of circulating TF. The TiFaCT assay should...
Research Interests:
Selection of platelets for alloimmunized, thrombocytopenic patients has traditionally been based on HLA matching. This approach is indirect and may not adequately recognize incompatibility between the recipient and the platelet donor. The... more
Selection of platelets for alloimmunized, thrombocytopenic patients has traditionally been based on HLA matching. This approach is indirect and may not adequately recognize incompatibility between the recipient and the platelet donor. The authors evaluated the usefulness of directly showing donor-recipient compatibility by crossmatching the patient's serum with prospective platelet donors who were not preselected on the basis of their HLA type. Eleven alloimmunized patients were chosen for study, and crossmatching was done by a radiolabeled antiglobulin test. These patients had high levels of HLA alloantibody, and their unusual HLA types made the provision of HLA-matched platelets difficult. When the crossmatch was compatible, the mean one-hour corrected count increment was 18,379 +/- 4,670 (1 standard deviation), n = 22, and at 18-24 hours, 7,318 +/- 3,317. If the crossmatch was positive, the mean one-hour corrected increment was 2,536 +/- 3,057, and at 18-24 hours, 227 +/- 657...
Research Interests:
Research Interests: Engineering, Algorithms, Chemistry, Mass Spectrometry, Biology, and 15 moreKidney diseases, Cardiovascular disease, Medicine, Multidisciplinary, Humans, Female, Male, Lung Diseases, Middle Aged, Diabetes complications, Expression analysis, Enzyme Linked Immunosorbent Assay, Cohort Studies, Heart Diseases, and latex agglutination
Acute cellular rejection in cardiac allografts is a major cause of graft loss, and is associated with activation of the coagulation system. We investigated whether plasma markers of coagulation predict the presence of allograft rejection.... more
Acute cellular rejection in cardiac allografts is a major cause of graft loss, and is associated with activation of the coagulation system. We investigated whether plasma markers of coagulation predict the presence of allograft rejection. A total of 132 blood specimens and endomyocardial biopsies were collected from 35 patients, between February of 1997 and May of 1998. We measured plasma prothrombin fragment 1.2 (PF1.2) and p-selectin, fibrinogen, thrombomodulin, and d-dimer. Biopsies were graded according to the International Society of Heart and Lung Transplantation system, with a range of 0 to 4. Grades 0 and 1A were grouped as &quot;no rejection,&quot; and the higher grades as &quot;rejection.&quot; Linear and logistic regression, accounting for longitudinal data, were the principal analytic tools. p-Selectin level increased progressively with increasing rejection grade (P&lt;0.001). With multivariate analysis, both p-selectin and prothrombin fragment levels significantly predicted rejection. p-Selectin levels were predictive of prothrombin fragment levels (P&lt;0.0001) but not of d-dimer, fibrinogen, or thrombomodulin levels. This model allowed correct prediction of rejection, based on p-selectin and prothrombin fragment values, up to 85% of the time. Dichotomizing patients by a p-selectin level of 65 ng/ml resulted in an odds of rejection of 21.4 [95% C.I. 7.1-64.7] for the patients in the high- compared with the lower risk group. In heart transplant recipients, p-selectin levels and PF 1.2 levels are highly predictive of organ rejection. The elevation of PF 1.2 suggests that there is systemic generation of thrombin generation. These markers may be useful for noninvasively monitoring patients for organ rejection or for after response to treatment.
Research Interests: Surgery, Medicine, Probability, Humans, Method, and 15 moreSystem, Cell, Regression Analysis, Heart, Blood Coagulation, Association, Time Factors, Prognosis, Biological markers, Graft Rejection, Heart Transplantation, Predictive value of tests, Prothrombin, Cardiac Transplantation, and Medical and Health Sciences
Research Interests:
Research Interests:
Research Interests:
Research Interests:
A s a hematologist, I have always thought the phrase bloodless medicine to be an enigmatic way to describe an important medical approach. Goethe regarded blood to be “ein ganz besondrer Saft” (blood is a very special juice). Poets... more
A s a hematologist, I have always thought the phrase bloodless medicine to be an enigmatic way to describe an important medical approach. Goethe regarded blood to be “ein ganz besondrer Saft” (blood is a very special juice). Poets associate blood with being pure and eloquent, if not always royal and blue. Hematologists are fascinated by the study of blood. We look at it under the microscope with awe; we understand that the “life of the flesh is in the blood.” We value it therapeutically. But, bloodless suggests lifeless, unremarkable, and perhaps valueless. However, there can be no doubt about the value and need for advanced transfusion practices that avoid the use of allogeneic blood transfusions. There are many bloodless medicine programs throughout the Americas, Asia, and Europe, and the number is growing. Even in remote areas of Siberia, physicians and patients know about bloodless medicine. If one types “bloodless medicine” into an Internet search engine, 12,000 hits are obtained, and hundreds of programs are listed. This all suggests a strong interest in bloodless medicine. I do not wish to discuss the advantages or disadvantages of bloodless medicine. This has already been done by Goodnough and colleagues1 in this issue of TRANSFUSION. My purpose is to present some ideas that might be useful in establishing these services and to review some lessons from establishing our hospital’s bloodless medicine program. Bloodless medicine program objectives must include providing leadership within an institution for bloodless medicine and being the advocate for patients not accepting transfusions. Bloodless medicine programs require an administrative structure to coordinate services across a variety of departments. The preoperative and perioperative management of an anemic patient who does not accept transfusions for elective surgery may require cooperation between outpatient scheduling, surgical and anesthesia physicians and their clinic personnel, operating room scheduling, intensivists and hematologists to get the patient prepared, and the billing office to try to determine reimbursement issues (far too many phone calls for a busy surgeon or physicians in training unless these interactions are coordinated through a bloodless medicine program). In contrast, if one wants a transfusion, this can usually be accomplished with one phone call. Effective cooperation between multiple hospital departments is a feature of transfusion medicine programs. In many institutions, transfusion medicine specialists are also the strongest proponents of blood conservation and are knowledgeable in transfusion alternatives. Not including transfusion medical specialists in the function of bloodless medicine programs omits a key specialist. In encouraging patients and physicians to embrace bloodless medicine a balanced approach is needed. Enthusiasts for bloodless medicine must realize that the relative safety and efficacy of all transfusion alternatives have not been thoroughly tested in large populations. The patient’s choice of nonblood management through advanced transfusion practices is medically reasonable in many instances and legally protected for competent adult patients. However, for some very complicated risky procedures, some patients may have unrealistic expectations that are based on anecdotal information. For a bloodless medicine to thrive, vigorous testing of new treatment modalities, in well-designed clinical trials, is needed. One cannot expect bloodless medicine to be widely accepted unless it is based upon the principles that guide other aspects of medical discovery. The strongest argument for having a bloodless medicine program is to respect the rights of patients who refuse transfusion. The right of competent adult patients to refuse medical treatment is well established and has been upheld by several judicial decisions.2,3 This right is based on the ethical value of autonomy or selfdetermination, and medical institutions have a responsibility to respond to this need. Jehovah’s Witnesses have deep religious convictions against accepting primary blood components. Members of this religion seek the best possible medical care but believe that transfusion of primary blood components is forbidden for them by biblical passages. Working closely with the Jehovah’s Witnesses, especially through their hospital liaison committee, is invaluable. This interaction will improve one’s understanding about the concerns of Jehovah’s Witness patients and permit treating the Jehovah’s Witness patient in accordance with their beliefs. To establish guidelines concerning patient autonomy and transfusion, the institutional ethics committees should be involved. Consulting with other established bloodless medicine programs and representatives of the Jehovah’s Witness community is very useful. One particularly important aspect of establishing a bloodless medicine program is careful consideration of pediatric issues of treating children of…
Research Interests:
A microtiter plate assay is described for platelet serologic studies. The assay is based on an indirect radiolabeled antiglobulin test. The test was performed in microtiter wells of 400 microliter capacity manufactured to form strips that... more
A microtiter plate assay is described for platelet serologic studies. The assay is based on an indirect radiolabeled antiglobulin test. The test was performed in microtiter wells of 400 microliter capacity manufactured to form strips that fit into a standard 96-well carrier. The strips were broken apart and placed into tubes for counting in a gamma counter. The technique does not require fixation of the platelets to the wells. Freshly collected platelets or platelets that have been stored frozen in 5 percent dimethylsulfoxide can be used. Results are presented using the technique for platelet alloantibody identification, platelet antigen typing, and platelet crossmatching.
Research Interests:
Acquired inhibitors of coagulation factors, particularly to factor V (FV) and thrombin, after topical bovine thrombin exposure may result in clinically important coagulopathies. While bovine thrombin is commonly used in pediatric patients... more
Acquired inhibitors of coagulation factors, particularly to factor V (FV) and thrombin, after topical bovine thrombin exposure may result in clinically important coagulopathies. While bovine thrombin is commonly used in pediatric patients for surgical hemostasis, the reported cases of acquired inhibitors in children are few. We report two cases of children who developed factor inhibitors after bovine thrombin exposure. One child developed a FV inhibitor at 3 months of age after exposure to bovine thrombin during cardiac surgery. The inhibitor resolved with intravenous immunoglobulin (IVIG) and steroids. The other child developed concomitant FV and bovine thrombin inhibitors after cardiac surgery at age 11 years. The presence of these inhibitors complicated post-operative anti-coagulation management, but the inhibitors were transient. In addition to these two cases, we identified all the pediatric patients with bovine thrombin-induced inhibitors who were reported in the world&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s literature, and reviewed their clinical characteristics. These cases underscore the fact that bovine thrombin can be antigenic in infants and children and can result in significant coagulopathies.
Research Interests:
Research Interests:
... 1977; 50:317–25. Web of Science | Medline. 13. Conley CL. ... New England Journal of Medicine 346:13, 995-1008 Full Text. 3. Lian Mo, Sy-Jye C. Leu, Charles Berry, Fumin Liu, Tsaiwei Olee, Yi-Yuan Yang, Diana S. Beardsley, Robert... more
... 1977; 50:317–25. Web of Science | Medline. 13. Conley CL. ... New England Journal of Medicine 346:13, 995-1008 Full Text. 3. Lian Mo, Sy-Jye C. Leu, Charles Berry, Fumin Liu, Tsaiwei Olee, Yi-Yuan Yang, Diana S. Beardsley, Robert McMillan, Virgil L. Woods, Projen P. Chen. ...
Research Interests:
Research Interests: Genetics, Genomics, Biology, Cytokines, Medicine, and 15 moreBiological Sciences, Cell Differentiation, Humans, Hormones, Cluster Analysis, Karyotype, Erythropoiesis, Cell Proliferation, Molecular Targeted Therapy, Diploidy, Hemoglobins, Gene Expression Regulation, Gene expression profiling, erythroblasts, and Medical and Health Sciences
Central nervous system hemorrhage is a well-recognized complication of neonatal alloimmune thrombocytopenia attributed to perinatal trauma from passage through the birth canal. That central nervous system (CNS) hemorrhage can occur in... more
Central nervous system hemorrhage is a well-recognized complication of neonatal alloimmune thrombocytopenia attributed to perinatal trauma from passage through the birth canal. That central nervous system (CNS) hemorrhage can occur in utero is not as well recognized, and congenital CNS lesions have only circumstantially been linked to thrombocytopenia. We report two cases of intrauterine CNS hemorrhage shown to have occurred prenatally, resulting in porencephaly. The second case is unique in that the necropsy finding of a porencephalic cyst arising from an old hemorrhagic site pathologically confirms that the etiology of congenital CNS lesions in alloimmune thrombocytopenia is due to hemorrhage. This second case received close prenatal monitoring and yet died as a result of hemorrhage that was not detected until emergency operative delivery. A review of the literature revealed 10 cases, including two other pairs of siblings, who had CNS damage attributable to intrauterine hemorrhage. These findings indicate that congenital CNS lesions in alloimmune thrombocytopenia are due to intrauterine hemorrhage that careful obstetric and prenatal care may not identify or prevent. This fact should be included when genetic counseling is offered to alloimmunized mothers.
Research Interests:
Research Interests:
Research Interests:
Research Interests: Vitamin D, Biological Sciences, Humans, Baltimore, Female, and 12 moreMale, African Americans, Middle Aged, Coronary Angiography, Adult, Coronary Artery Disease, X ray Computed Tomography, Vitamin D Deficiency, Clinical Infectious Diseases, Asymptomatic Diseases., Medical and Health Sciences, and HIV infections
Research Interests: Surgery, Humans, Blood sampling, Statistical Significance, Heart, and 15 moreSerum Creatinine, Clinical Sciences, C reactive protein, Biological markers, Graft Rejection, Heart Transplantation, Cross Sectional Studies, Renal disease, Positive predictive value, Inflammatory response, False Positive, Lung Transplantation, Negative predictive value, renal insufficiency, and Cardiac Troponin T
Research Interests:
Research Interests:
Thrombocytopenia has been documented infrequently in association with congenital heart block or lupus dermatitis in the neonatal lupus erythematosus syndrome. We report the cases of two infants with transient neonatal thrombocytopenia... more
Thrombocytopenia has been documented infrequently in association with congenital heart block or lupus dermatitis in the neonatal lupus erythematosus syndrome. We report the cases of two infants with transient neonatal thrombocytopenia born to mothers with connective-tissue disease. Both mother/infant pairs were Ro(SS-A) antibody positive. Although the finding of neonatal thrombocytopenia in the presence of maternal connective-tissue disease suggests an autoimmune thrombocytopenia, platelet antibody studies were negative in both mother/infant pairs. We have found the Ro (SS-A) antibody with increased frequency in idiopathic thrombocytopenic purpura and thrombocytopenia associated with Sjögren&#39;s syndrome, but the nature of the association is unknown. We suggest that thrombocytopenia in our patients is a manifestation of the neonatal lupus erythematosus syndrome. This syndrome should be included in the differential diagnosis of neonatal thrombocytopenia.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Vitamin D, Biological Sciences, Humans, Baltimore, Female, and 12 moreMale, African Americans, Middle Aged, Coronary Angiography, Adult, Coronary Artery Disease, X ray Computed Tomography, Vitamin D Deficiency, Clinical Infectious Diseases, Asymptomatic Diseases., Medical and Health Sciences, and HIV infections
Research Interests: Engineering, Algorithms, Chemistry, Mass Spectrometry, Biology, and 15 moreKidney diseases, Cardiovascular disease, Medicine, Multidisciplinary, Humans, Female, Male, Lung Diseases, Middle Aged, Diabetes complications, Expression analysis, Enzyme Linked Immunosorbent Assay, Cohort Studies, Heart Diseases, and latex agglutination
Research Interests:
Research Interests: Sickle Cell Anemia, Stem Cell, Medicine, Linear models, Hematopoiesis, and 15 moreSpleen, Liver, Mice, Female, Animals, Blood, Male, Animal Model, Chimerism, Clinical Sciences, Mouse Model, Bone Marrow Transplantation, Cardiovascular medicine and haematology, Paediatrics and reproductive medicine, and leukocyte Count
Research Interests:
Research Interests: Medicine, Serotonin, Humans, Heparin, Female, and 14 moreMale, Follow-up studies, Risk factors, Platelet activation mechanism, Recurrence, Aged, Middle Aged, Myocardial Infarction, Coronary heart disease, Survival Rate, Angina pectoris, Risk Factors, The American, and Cardiovascular medicine and haematology
Critical Care Medicine Copyright © 1993 by Williams & Wilkins Vol. 21, No. 7 Printed in I JHA Effect of extracorporeal membrane oxygenation on platelets in newborns TONI M. ROBINSON, MD; THOMAS S. KICKLER, MD; LINDA KYLE WALKER, MD; PAUL... more
Critical Care Medicine Copyright © 1993 by Williams & Wilkins Vol. 21, No. 7 Printed in I JHA Effect of extracorporeal membrane oxygenation on platelets in newborns TONI M. ROBINSON, MD; THOMAS S. KICKLER, MD; LINDA KYLE WALKER, MD; PAUL NESS, ...
Research Interests:
The best method of monitoring anticoagulation during extracorporeal membrane oxygenation (ECMO) is unknown. We conducted a prospective observational study in a tertiary pediatric intensive care unit. Antifactor Xa, antithrombin (AT), and... more
The best method of monitoring anticoagulation during extracorporeal membrane oxygenation (ECMO) is unknown. We conducted a prospective observational study in a tertiary pediatric intensive care unit. Antifactor Xa, antithrombin (AT), and factor VIII activity (FVIII) were measured in blood samples collected at 6, 12, and every 24 hours, respectively, of ECMO. We enrolled 34 children who underwent 35 ECMO runs from April 2008 to September 2010. Activated clotting time (ACT) and heparin doses were higher, whereas ...
Research Interests:
Research Interests:
Results The prevalence of Pl A 2 was 2.1 times higher among the case patients than among the controls (39.4 percent vs. 19.1 percent, P = 0.01). In a subgroup of patients whose disease began before the age of 60 years, the prevalence ...
Research Interests: Polymorphism, Platelet, Humans, Female, Male, and 15 moreExploration, Risk factors, Clinical Sciences, Middle Aged, Risk Factor, Genotype, Myocardial Infarction, Genetic Polymorphism, Receptor, Risk Factors, Receiver, Logistic Models, Case Control Studies, Acute Disease, and Medical and Health Sciences
A variety of patientand product-related factors influenced the outcome of 6379 transfusions given to 533 patients in the Trial to Reduce Alloimmunization to Platelets (TRAP). Responses measured were platelet increments, interval between... more
A variety of patientand product-related factors influenced the outcome of 6379 transfusions given to 533 patients in the Trial to Reduce Alloimmunization to Platelets (TRAP). Responses measured were platelet increments, interval between platelet transfusions, and platelet ...
Research Interests:
ABSTRACTBACKGROUNDNeurological complications occur in COVID-19. We aimed to examine cerebrospinal fluid (CSF) of COVID-19 subjects with neurological complications and determine presence of neuroinflammatory changes implicated in... more
ABSTRACTBACKGROUNDNeurological complications occur in COVID-19. We aimed to examine cerebrospinal fluid (CSF) of COVID-19 subjects with neurological complications and determine presence of neuroinflammatory changes implicated in pathogenesis.METHODSCross-sectional study of CSF neuroinflammatory profiles from 18 COVID-19 subjects with neurological complications categorized by diagnosis (stroke, encephalopathy, headache) and illness severity (critical, severe, moderate, mild). COVID-19 CSF was compared with CSF from healthy, infectious and neuroinflammatory disorders and stroke controls (n=82). Cytokines (IL-6, TNFα, IFNγ, IL-10, IL-12p70, IL-17A), inflammation and coagulation markers (high-sensitivity-C Reactive Protein [hsCRP], ferritin, fibrinogen, D-dimer, Factor VIII) and neurofilament light chain (NF-L), were quantified. SARS-CoV2 RNA and SARS-CoV2 IgG and IgA antibodies in CSF were tested with RT-PCR and ELISA.RESULTSCSF from COVID-19 subjects showed a paucity of neuroinflammat...
Heparin-induced thrombocytopenia (HIT) remains diagnostically challenging. Immunoassays including PF4/heparin enzyme-linked immunosorbent assay (ELISA) have high sensitivity but low specificity. Whether the heparin neutralization assay... more
Heparin-induced thrombocytopenia (HIT) remains diagnostically challenging. Immunoassays including PF4/heparin enzyme-linked immunosorbent assay (ELISA) have high sensitivity but low specificity. Whether the heparin neutralization assay (HNA) improves the diagnostic accuracy of the PF4/heparin ELISA for HIT is uncertain. In this study, to assess its clinical utility and evaluate whether it improves the diagnostic accuracy for HIT, we implemented HNA in conjunction with PF4/heparin ELISA over a 1-year period. A total of 1194 patient samples were submitted to the laboratory for testing from December 2015 to November 2016. Heparin neutralization assay alone is a poor predictor for HIT, but it has high negative predictive value (NPV): Cases with %inhibition <70% are always negative for serotonin release assay. It improves the diagnostic positive predictive value (PPV) of ELISA without compromising sensitivity: ELISA optical density (OD) ≥1.4 alone has a sensitivity of 88% (14/16) and ...
Research Interests:
Although rapid progression of coronary atherosclerosis was observed in chronic cocaine users, it is unknown whether reduced cocaine use retards the progression of atherosclerosis. We investigated whether reduced cocaine use over a... more
Although rapid progression of coronary atherosclerosis was observed in chronic cocaine users, it is unknown whether reduced cocaine use retards the progression of atherosclerosis. We investigated whether reduced cocaine use over a 12-month period was associated with coronary plaque regression in cocaine users. Fifteen African American chronic cocaine users with previously coronary computed tomography angiography (CCTA)-confirmed >50% coronary stenosis in Baltimore, Maryland, were enrolled in a study to investigate whether reduced cocaine use is associated with changes in coronary plaque burden over a 12-month period of cash-based incentive intervention, which was implemented to systematically reinforce cocaine abstinence. In addition to previous CCTA (preintervention), CCTA was performed at the intervention baseline and at postintervention. Plaque analyses were performed to determine the trajectory of plaque changes in the absence of intervention by comparing the preintervention ...
Research Interests:
Persistent thromboxane (TX) generation while receiving aspirin therapy is associated with an increased risk of cardiovascular events. The Reduction in Graft Occlusion Rates (RIGOR) study found that aspirin-insensitive TXA2 generation,... more
Persistent thromboxane (TX) generation while receiving aspirin therapy is associated with an increased risk of cardiovascular events. The Reduction in Graft Occlusion Rates (RIGOR) study found that aspirin-insensitive TXA2 generation, indicated by elevated urine 11-dehydro-TXB2 (UTXB2) 6 months after coronary artery bypass graft surgery, was a potent risk factor for vein graft thrombosis and originated predominantly from nonplatelet sources. Our goal was to identify risks factors for nonplatelet TXA2 generation. Multivariable modeling was performed by using clinical and laboratory variables obtained from 260 RIGOR subjects with verified aspirin-mediated inhibition of platelet TXA2 generation. The strongest variable associated with UTXB2 6 months after surgery, accounting for 47.2% of the modeled effect, was urine 8-iso-prostaglandin (PG)F2α, an arachidonic acid metabolite generated nonenzymatically by oxidative stress (standardized coefficient 0.442, P<0.001). Age, sex, race, lip...
Research Interests: Biomarkers, Treatment Outcome, Oxidative Stress, Risk assessment, Multivariate Analysis, and 14 moreHumans, United States, Female, Male, Risk factors, Aged, Middle Aged, Time Factors, Risk Factors, Risk Assessment, SAPHENOUS VEIN, Platelet Aggregation Inhibitors, Human Umbilical Vein Endothelial Cells, and Coronary Artery Bypass
The long-term survival of serologically incompatible red cell units was measured in five patients with antibodies to high-frequency antigens. Initially, the survival of 1 ml of âµÂ¹Cr-labeled incompatible red cells was measured over 1... more
The long-term survival of serologically incompatible red cell units was measured in five patients with antibodies to high-frequency antigens. Initially, the survival of 1 ml of âµÂ¹Cr-labeled incompatible red cells was measured over 1 hour. After demonstrating that the 1-hour survival times were successful (greater than 70%), each patient then received 5 ml of the same âµÂ¹Cr-labeled red cells followed
Research Interests:
Platelets are implicated as etiologic agents in cerebral ischemia and as modulators of neural injury following an ischemic insult. We examined the effects of severe, transient global ischemia on platelet aggregation during 45-min ischemia... more
Platelets are implicated as etiologic agents in cerebral ischemia and as modulators of neural injury following an ischemic insult. We examined the effects of severe, transient global ischemia on platelet aggregation during 45-min ischemia and 30-, 60-, and 120-min reperfusion in adult and neonatal lambs. We also examined postischemic platelet deposition in brain and other tissues (120-min reperfusion) using indium-111-labeled platelets. Ischemic cerebral blood flow fell to 5 +/- 1 and 5 +/- 2 ml.min-1.100 g-1 in lambs and sheep, respectively. During ischemia, platelet counts fell to 47.5 +/- 5.1% of control (P < 0.05) in lambs and 59 +/- 4.9% of control in sheep (P < 0.05). Ischemia depressed platelet aggregation response (P < 0.01) to 4 micrograms collagen in lambs and sheep (20.4 +/- 29.2 and 26 +/- 44.7% of control, respectively). Marked platelet deposition occurred in brain and spleen in sheep, whereas significant platelet entrapment occurred only in brain in lambs. Our...
Research Interests:
The study of the immunogenetics of the human platelet antigens is important to the improvement of diagnosis and genetic counseling and to the development of screening programs for women at risk of having babies with neonatal alloimmune... more
The study of the immunogenetics of the human platelet antigens is important to the improvement of diagnosis and genetic counseling and to the development of screening programs for women at risk of having babies with neonatal alloimmune thrombocytopenia. Description of the immunogenetics of the human platelet antigens in some racial groups has been incomplete. A reverse dot blot technique employing polymerase chain reaction-amplified genomic DNA was applied in genotyping the five major human platelet antigens in the following populations: 100 African American and 100 white women admitted to the obstetric unit at Johns Hopkins Hospital (Baltimore, MD) and 100 inpatients at Yonsei University (Seoul, Korea). The gene frequencies of HPA-2b (Koa) and HPA-5b (Bra) in African Americans were twice those in whites (African Americans: 0.18 and 0.21, respectively; whites: 0.09 and 0.11, respectively). There is a very low gene frequency of the HPA-1b (PIA2) allele in Koreans (0.005). No signific...
Research Interests: Immunology, DNA, Humans, Korea, African American, and 11 moreUnited States, Female, Nucleic acid hybridization, Polymerase Chain Reaction, Clinical Sciences, Genotype, European Continental Ancestry Group, Asian Continental Ancestry Group, Transfusion, Gene frequency, and Cardiovascular medicine and haematology
Research Interests:
The limiting factor in platelet transfusion therapy is the development of alloimmunization. Although using HLA matched platelets may be effective in reducing the problem of alloimmune platelet transfusion refractoriness, relying solely... more
The limiting factor in platelet transfusion therapy is the development of alloimmunization. Although using HLA matched platelets may be effective in reducing the problem of alloimmune platelet transfusion refractoriness, relying solely upon HLA matching has its shortcomings. The selection of compatible platelet transfusions can be improved by compatibility testing. Despite these maneuvers, compatible platelets may not be found for some patients. When faced with these difficult patients there are few effective alternatives. The preventive measures of leukocyte depletion or ultraviolet irradiation of platelets promise to reduce or prevent alloimmunization.
Research Interests:
D-negative patients may be divided into responders and nonresponders when immunized with D-positive red cells (RBC). Forty-nine D-negative oncology patients who received D-positive RBCs via platelet and white cell transfusions were... more
D-negative patients may be divided into responders and nonresponders when immunized with D-positive red cells (RBC). Forty-nine D-negative oncology patients who received D-positive RBCs via platelet and white cell transfusions were studied to determine if nonresponders to D were likely to form lymphocytotoxic antibody (LCA). Nine patients developed anti-D in 16 to 390 days (mean = 112) after 2.6 to 481 ml (mean = 106) of D-positive RBCs. Forty patients had no evidence of anti-D after 0.8 to 535 ml (mean = 98) of D-positive RBCs and were followed for 14 to 1275 days (mean = 192). The anti-D group had no prior D-positive RBC transfusions, and two of five women making anti-D had previous pregnancies but no record of anti-D. LCA was found in four of nine (44%) patients with anti-D and in 12 of 40 (30%) patients without anti-D (p less than 0.50). Since both D and antigens HLA are considered highly immunogenic, it is of interest that the ability to form anti-D or LCA does not correlate. In fact, more patients (16/49; 32%) made LCA than anti-D (9/49; 18%). Of the 21 alloimmunized patients, 4 made both antibodies, while 17 had selective alloimmunization. It would thus appear that alloimmunization to D and HLA are not strongly linked and may indeed be unrelated.
Research Interests:
Research Interests:
Serologic identification of anti-PLAl and other platelet specific antibodies is difficult because other platelet reactive antibodies (e.g. anti-HLA) are commonly found in the samples. We have developed and evaluated a method using Western... more
Serologic identification of anti-PLAl and other platelet specific antibodies is difficult because other platelet reactive antibodies (e.g. anti-HLA) are commonly found in the samples. We have developed and evaluated a method using Western blotting to identify platelet specific antibodies. Since anti-PLAl is the most frequently encountered antibody, we used this antibody to validate the method. The PLAl antigen was found on a 95,000 Dalton protein, confirmed as glycoprotein IIIa by two-dimensional electrophoresis. The usefulness of Western blotting in resolving difficult platelet serologic problems was compared to a radiolabeled antiglobulin test using intact platelets. Our results showed that all sera with anti-PLAl identified by serology were confirmed by Western blotting. In addition, one anti-PLAl was detectable only by the proposed method. Western blotting was also as useful as a serologic method to PLAl type platelets. HLA antibodies were not demonstrable by this technique. In summary, Western blotting is a highly specific and sensitive way of identifying anti-PLAl in a variety of clinical situations. This approach may be used to identify antibodies to other platelet specific antigens and to standardize platelet antigen typing sera.
Research Interests:
Research Interests:
SummaryThe clinical relevance of heparin-induced antibodies (HIA) in the absence of thrombocytopenia remains to be defined. The aims of this study were (i) to determine the prevalence of HIA in patients treated by dialysis, (ii) to... more
SummaryThe clinical relevance of heparin-induced antibodies (HIA) in the absence of thrombocytopenia remains to be defined. The aims of this study were (i) to determine the prevalence of HIA in patients treated by dialysis, (ii) to determine the prevalence of thrombocytopenia and heparin-induced thrombocytopenia (HIT), and (iii) to test whether HIA are associated with adverse outcomes. Sera from 740 patients treated by hemodialysis (HD, n=596) and peritoneal dialysis (PD, n=144) were tested for HIA (IgG, IgA or IgM) by masked investigators at approximately six months after enrolment in the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) study. We assessed, with time-to-event Cox proportional hazards models, whether the presence of HIA predicted any of four clinical outcomes: arterial cardiovascular events, venous thromboembolism, vascular access occlusion and mortality. HIA prevalence was 10.3% overall. HIA positivity did not predict development of thromb...
Research Interests: Risk, Cardiovascular Risk, Antibodies, Humans, Heparin, and 15 moreFemale, Male, Thrombocytopenia, Clinical Sciences, Aged, Middle Aged, Adult, Peritoneal Dialysis, Cardiovascular Diseases, Platelet Count, Renal Dialysis, immunoglobulin G, Immunoglobulin A, immunoglobulin M, and Cardiovascular medicine and haematology
Research Interests:
Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, central nervous system abnormalities, and renal dysfunction. In early reports the... more
Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, fever, central nervous system abnormalities, and renal dysfunction. In early reports the mortality approached 100 percent. A treatment protocol was introduced in 1979 for patients admitted to Johns Hopkins Hospital with the diagnosis of TTP-HUS. Treatment regimens included 200 mg of prednisone a day, for patients with minimal symptoms and no central nervous system symptoms, and prednisone plus plasma exchange, for patients with rapid clinical deterioration who did not improve after 48 hours of prednisone alone and for patients presenting with central nervous system symptoms and rapidly declining hematocrit values and platelet counts. A total of 108 patients were treated, and 91 percent survived. Prednisone alone was judged to be effective in 30 patients with mild TTP-HUS (two relapses and two deaths). Plasma exchange plus prednisone was given to 78 patients with complicated TTP-HUS, resulting in 67 relapses and 8 deaths. Relapses occurred in 22 of 36 patients given maintenance plasma infusions. Neither splenectomy nor treatment with aspirin and dipyridamole was effective in those with a poor response to plasma exchange. None of the 71 patients tested had positive cultures for O157:H7 Escherichia coli. Nine percent of the patients were pregnant, and none gave birth to infants with TTP-HUS. Effective treatment with 91 percent survival is available for patients with TTP-HUS.
Research Interests: Research Design, Adolescent, Pregnancy, Humans, Female, and 15 moreMale, Plasma, Aspirin, Hemolytic Uremic Syndrome, Aged, Middle Aged, Adult, New England, Blood Transfusion, Thrombotic Thrombocytopenic Purpura, New England Journalof Medicine, Splenectomy, Prednisone, Plasma exchange, and Medical and Health Sciences
Research Interests: Treatment Outcome, Humans, Female, Male, The, and 15 moreAspirin, Platelet activation mechanism, Aged, Middle Aged, Coronary Angiography, Public health systems and services research, Time Factors, SAPHENOUS VEIN, Coronary artery bypass surgery, X ray Computed Tomography, Platelet Count, Adenosine Diphosphate, Platelet Aggregation Inhibitors, Cardiovascular medicine and haematology, and Coronary Artery Bypass
Research Interests:
This report illustrates the importance of serologic techniques for defining the etiology of neonatal thrombocytopenia. In Case 1 the maternal count was low normal to normal during the first postpartum week. Several weeks later the... more
This report illustrates the importance of serologic techniques for defining the etiology of neonatal thrombocytopenia. In Case 1 the maternal count was low normal to normal during the first postpartum week. Several weeks later the appearance of persistent maternal thrombocytopenia led to the demonstration of anti-GP IIb-IIIa in stored and freshly obtained maternal sera, suggesting that the mother had an autoimmune type of thrombocytopenia. The mother of Case 2 had systemic lupus erythematosus. However, serologic testing revealed that the infant&amp;amp;amp;amp;amp;amp;amp;amp;#39;s thrombocytopenia was not related to the mother&amp;amp;amp;amp;amp;amp;amp;amp;#39;s lupus but was secondary to alloimmunization with the PlA1 antigen. An algorithm for defining etiologic mechanisms in infants with antibody-mediated forms of thrombocytopenia is presented.
Research Interests:
Research Interests:
The effect of repeated phlebotomy on serum immunoreactive erythropoietin levels was studied prospectively in 69 autologous blood donors. At the time of the initial phlebotomy, 11 men (33%) and two women (6%) were anemic; during the course... more
The effect of repeated phlebotomy on serum immunoreactive erythropoietin levels was studied prospectively in 69 autologous blood donors. At the time of the initial phlebotomy, 11 men (33%) and two women (6%) were anemic; during the course of blood donations, anemia (defined as a hematocrit less than 0.41 for men and less than 0.36 for women) developed in an additional 17 men (71%) and 14 women (45%). Although there was an increase in the level of serum immunoreactive erythropoietin with successive phlebotomies, the increase was not substantially out of the normal range. The lack of an erythropoietic response to repeated phlebotomies in association with the small increment in the serum erythropoietin level was not due to iron deficiency, since the level of red-cell free protoporphyrin did not increase in these patients. We conclude that within the hematocrit range permissible for autologous blood donation, the degree of anemia experienced is insufficient to initiate an adequate increase in erythropoietin production; as a consequence, mild anemia develops in a majority of donors, and the volume of blood donated is inadequate to meet their operative needs.
Research Interests:
Background —Both inherited predisposition and platelet hyperreactivity have been associated with ischemic coronary events, but mechanisms that support genetic differences among platelets from different subjects are generally lacking.... more
Background —Both inherited predisposition and platelet hyperreactivity have been associated with ischemic coronary events, but mechanisms that support genetic differences among platelets from different subjects are generally lacking. Associations between the platelet Pl A2 polymorphism of GP IIIa and coronary syndromes raise the question as to whether this inherited variation may contribute to platelet hyperreactivity. Methods and Results —In this study, we characterized functional parameters in platelets from healthy donors with the Pl A (HPA-1) polymorphism, a Leu (Pl A1 ) to Pro (Pl A2 ) substitution at position 33 of the GP IIIa subunit of the platelet GP IIb/IIIa receptor (integrin α IIb β 3 ). We studied 56 normal donors (20 Pl A1,A1 , 20 Pl A1,A2 , and 16 Pl A2,A2 ). Compared with Pl A1,A1 platelets, Pl A2 -positive platelets showed a gene dosage effect for significantly greater surface-expressed P-selectin, GP IIb/IIIa–bound fibrinogen, and activated GP IIb/IIIa in response ...
Research Interests:
Research Interests:
Background A hemostatic monitor capable of rapid, accurate detection of clinical coagulopathy within the operating room could improve management of bleeding after cardiopulmonary bypass (CPB). The Clot Signature Analyzer is a... more
Background A hemostatic monitor capable of rapid, accurate detection of clinical coagulopathy within the operating room could improve management of bleeding after cardiopulmonary bypass (CPB). The Clot Signature Analyzer is a hemostatometer that measures global hemostasis in whole blood. The authors hypothesized that point-of-care hemostatometry could detect a clinical coagulopathic state in cardiac surgical patients. Methods Fifty-seven adult patients scheduled for a variety of elective cardiac surgical procedures were studied. Anesthesia, CPB, heparin anticoagulation, protamine reversal, and transfusion for post-CPB bleeding were all managed by standardized protocol. Clinical coagulopathy was defined by the need for platelet or fresh frozen plasma transfusion. The Clot Signature Analyzer collagen-induced thrombus formation (CITF) assay measured platelet-mediated hemostasis in vitro. The activated clotting time, platelet count, prothrombin time, activated partial thromboplastin tim...
Research Interests: Algorithms, Anesthesiology, Cardiac Surgery, Prospective studies, Humans, and 14 moreCollagen, Female, Male, Anesthesia, Clinical Sciences, Middle Aged, Hemostasis, Suction, Predictive value of tests, Intraoperative Neurophysiological Monitoring, Cardiopulmonary bypass, Blood coagulation disorders, Platelet transfusion, and Intraoperative complications
To determine the utility and limitations of D-dimer testing for the evaluation of venous thromboembolism in hospitalized patients. We performed D-dimer testing by four different methods in unselected inpatients undergoing radiologic... more
To determine the utility and limitations of D-dimer testing for the evaluation of venous thromboembolism in hospitalized patients. We performed D-dimer testing by four different methods in unselected inpatients undergoing radiologic evaluation for possible venous thromboembolism. We included patients with a history of malignancy, recent surgery, thrombosis, and anticoagulation treatment. C-reactive protein levels were assayed as a measure of inflammation. Of 45 patients with radiographically proven proximal deep venous thrombosis or pulmonary embolism, 43 had elevated D-dimer levels by enzyme-linked immunosorbent assay (ELISA) (sensitivity, 96%); the specificity of the test was 23% (36/157). The qualitative non-ELISA tests had higher specificities, but their sensitivities were &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;70%. Nineteen patients (42%) with thrombosis had false-negative D-dimer tests by at least one assay. The specificity of the tests decreased with increasing duration of hospitalization, increasing age, and increasing C-reactive protein levels. D-dimer testing had little or no utility in distinguishing patients with thrombosis from those without in patients who had been hospitalized for more than 3 days, were older than 60 years, or had C-reactive protein levels in the highest quartile. In unselected inpatients, D-dimer testing has limited clinical utility because of its poor specificity. This is particularly true for older patients, those who have undergone prolonged hospitalization, and those with markedly elevated C-reactive protein levels. In some patient subsets, a negative non-ELISA D-dimer test cannot discriminate between inpatients with and without thrombosis.
Research Interests: Risk assessment, Risk Analysis, Prospective studies, Humans, Female, and 15 morePulmonary Embolism, Male, ROC Curve, Aged, Middle Aged, Adult, Prognosis, Age Factors, Biological markers, Chi Square Distribution, Risk Assessment, Inpatients, Enzyme Linked Immunosorbent Assay, Case Control Studies, and Medical and Health Sciences
Research Interests:
Research Interests:
The presence of both complete IgM autoagglutinins and IgG autoantibodies in warm autoimmune hemolytic anemia (AIHA) is an uncommon finding. Over a 6-year period, only 5 of 115 (4.1%) patients with AIHA had IgM and IgG autoantibodies. In 3... more
The presence of both complete IgM autoagglutinins and IgG autoantibodies in warm autoimmune hemolytic anemia (AIHA) is an uncommon finding. Over a 6-year period, only 5 of 115 (4.1%) patients with AIHA had IgM and IgG autoantibodies. In 3 of the 5 cases, the complete IgM autoagglutinins reacted up to 30 degrees C and these patients responded well to corticosteroid or other therapies for warm AIHA. The 2 patients who had warm (37 degrees C) reactive IgM autoagglutinins, were refractory to corticosteroids, splenectomy and cytotoxic drugs, and died due to the complications of hemolytic anemia. The data in these 5 cases suggest that the thermal amplitude of the IgM antibody in these unusual AIHA cases may be predictive of refractoriness to therapy and poor clinical outcome.
Research Interests:
Research Interests:
Key Points GPI-anchor–deficient cell lines are more vulnerable to complement C5b-9 deposition and cell killing from aHUS serum. PIGA-null reagent cell lines can be used to rapidly and reliably distinguish aHUS from other thrombotic... more
Key Points GPI-anchor–deficient cell lines are more vulnerable to complement C5b-9 deposition and cell killing from aHUS serum. PIGA-null reagent cell lines can be used to rapidly and reliably distinguish aHUS from other thrombotic microangiopathies.