Thomas Kickler

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.

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.

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...

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.

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...

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...

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.

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...

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.

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 ...

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 ...

This case report describes a patient who presented with Stage IV B Hodgkin'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's disease and autoimmune thrombocytopenia is reviewed.

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 <100 x 109/L, serum creatinine…

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...

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,...

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...

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.

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…

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.