Location via proxy:   [ UP ]  
[Report a bug]   [Manage cookies]                
Skip to main content
Joan Carles Reverter

    Joan Carles Reverter

    Thromboprophylaxis is not well defined after liver transplantation (LT). The aim of this study was to evaluate the incidence of splanchnic vein thrombosis (SVT) and nonsplanchnic vein thrombosis (NSVT) after LT. Liver transplantations... more
    Thromboprophylaxis is not well defined after liver transplantation (LT). The aim of this study was to evaluate the incidence of splanchnic vein thrombosis (SVT) and nonsplanchnic vein thrombosis (NSVT) after LT. Liver transplantations performed between 2009 and 2013 in our institution were reviewed. Demographic, intraoperative, and postoperative data were recorded. Low-molecular-weight heparin was only administered postoperatively if intraoperative thrombectomy was performed or in patients preoperatively anticoagulated. Of a total of 328 patients, 72% were male with a median age of 56 years, score of model for end-stage liver disease 18 (11-23), and 88% had liver cirrhosis. The incidence of postoperative venous thrombotic events was 4.6%: 8 (2.4%) patients had SVT and 7 (2.1%) patients had NSVT. After logistic regression analysis, intraoperative thrombectomy and Child A classification emerged as risk factors for SVT (odds ratio [OR]: 77, 95% confidence interval [95% CI]: 14-421) and...
    The pathogenesis of thrombosis in heparin-induced thrombocytopenia (HIT) was studied by investigating whether antibodies to heparin-platelet factor 4 (H-PF4) induced tissue factor (TF) synthesis by monocytes. Plasma from 5 patients with... more
    The pathogenesis of thrombosis in heparin-induced thrombocytopenia (HIT) was studied by investigating whether antibodies to heparin-platelet factor 4 (H-PF4) induced tissue factor (TF) synthesis by monocytes. Plasma from 5 patients with HIT containing IgG to H-PF4 was incubated with peripheral blood mononuclear cells without or with purified PF4 and heparin. Significant TF-dependent procoagulant activity (PCA) expressed by monocytes, measured with a factor Xa-based chromogenic assay, was induced after incubation of each HIT plasma sample. This monocyte PCA required the presence of PF4 and was inhibited by high concentrations of heparin. Furthermore, purified HIT IgG added to whole blood with PF4 and heparin also provoked significant synthesis of TF mRNA by monocytes, demonstrated by RT-PCR, and this effect was not observed with normal IgG. These findings strongly support the hypothesis that antibodies to PF4 developed in HIT trigger the production of tissue factor by monocytes, and ...
    Intraalveolar fibrin deposition found in neonates with respiratory distress syndrome (RDS) is explained by the activation of the coagulation system and inefficient fibrinolysis. However, thrombin activatable fibrinolysis inhibitor... more
    Intraalveolar fibrin deposition found in neonates with respiratory distress syndrome (RDS) is explained by the activation of the coagulation system and inefficient fibrinolysis. However, thrombin activatable fibrinolysis inhibitor activity (TAFIa), an inhibitor of fibrinolysis, and the ratio of D‐dimer to thrombin–antithrombin complex (D‐dimer/TAT), an index of fibrinolytic activity, have not been reported previously in neonatal RDS. Aim of this study is to evaluate the influence of plasma TAFIa levels on the fibrinolytic state in neonatal RDS. The RDS group (Group 1) consisted of 29 neonates, and 18 neonates served as the control group (Group 2). Plasma TAFIa levels and D‐dimer/TAT ratios were evaluated in all neonates in the first 6 hr of life. Neonates in the RDS group were further divided into two subgroups; Group 1a consisted of 12 neonates with evidence of mild asphyxia (Apgar score at 5 min <7 and cord pH <7.26), and Group 1b consisted of 17 nonasphyxiated neonates. No ...
    Mechanisms of action of direct oral anticoagulants (DOAC) suggest a potential therapeutic use in the prevention of thrombotic complications in arterial territories. However, effects of DOACs on platelet activation and aggregation have not... more
    Mechanisms of action of direct oral anticoagulants (DOAC) suggest a potential therapeutic use in the prevention of thrombotic complications in arterial territories. However, effects of DOACs on platelet activation and aggregation have not been explored in detail. We have investigated the effects of apixaban on platelet and fibrin components of thrombus formation under static and flow conditions. We assessed the effects of apixaban (10, 40 and 160 ng/mL) on: 1) platelet deposition and fibrin formation onto a thrombogenic surface, with blood circulating at arterial shear-rates; 2) viscoelastic properties of forming clots, and 3) thrombin generation in a cell-model of coagulation primed by platelets. In studies with flowing blood, only the highest concentration of apixaban, equivalent to the therapeutic Cmax, was capable to significantly reduce thrombus formation, fibrin association and platelet-aggregate formation. Apixaban significantly prolonged thromboelastometry parameters, but di...
    In cirrhosis, increased intrahepatic vascular resistance (IHVR) is the primary factor for portal hypertension (PH) development. Hepatic stellate cells (HSCs) play a major role increasing IHVR because, when activated, they are contractile... more
    In cirrhosis, increased intrahepatic vascular resistance (IHVR) is the primary factor for portal hypertension (PH) development. Hepatic stellate cells (HSCs) play a major role increasing IHVR because, when activated, they are contractile and promote fibrogenesis. Protease‐activated receptors (PARs) can activate HSCs through thrombin and factor Xa, which are known PAR agonists, and cause microthrombosis in liver microcirculation. This study investigates the effects of the oral anticoagulant, rivaroxaban (RVXB), a direct antifactor Xa, on HSC phenotype, liver fibrosis (LF), liver microthrombosis, and PH in cirrhotic rats. Hepatic and systemic hemodynamic, nitric oxide (NO) bioavailability, LF, HSC activation, and microthrombosis were evaluated in CCl4 and thioacetamide‐cirrhotic rats treated with RVXB (20 mg/kg/day) or its vehicle for 2 weeks. RVXB significantly decreased portal pressure (PP) in both models of cirrhosis without changes in portal blood flow, suggesting a reduction in I...
    Cell-derived microparticles (cMPs) are small membrane vesicles that are released from many different cell types in response to cellular activation or apoptosis. Elevated cMP counts have been found in almost all thrombotic diseases and... more
    Cell-derived microparticles (cMPs) are small membrane vesicles that are released from many different cell types in response to cellular activation or apoptosis. Elevated cMP counts have been found in almost all thrombotic diseases and pregnancy wastage, such as recurrent spontaneous abortion and in a number of conditions associated with inflammation, cellular activation and angiogenesis. cMP count was investigated in patients experiencing unexplained recurrent implantation failure (RIF). The study group was composed of 30 women diagnosed with RIF (RIF group). The first control group (IVF group) (n = 30) comprised patients undergoing a first successful IVF cycle. The second control group (FER group) included 30 healthy women who had at least one child born at term and no history of infertility or obstetric complications. cMP count was significantly higher in the RIF group compared with the IVF and FER groups (P < 0.05 and P < 0.01, respectively) (RIF group: 15.8 ± 6.2 nM phosph...
    Thromboembolic events were described in patients with Chagas disease without cardiomyopathy. We aim to confirm if there is a hypercoagulable state in these patients and to determine if there is an early normalization of hemostasis factors... more
    Thromboembolic events were described in patients with Chagas disease without cardiomyopathy. We aim to confirm if there is a hypercoagulable state in these patients and to determine if there is an early normalization of hemostasis factors after antiparasitic treatment. Ninety-nine individuals from Chagas disease-endemic areas were classified in two groups: G1, with T.cruzi infection (n = 56); G2, healthy individuals (n = 43). Twenty-four hemostasis factors were measured at baseline. G1 patients treated with benznidazole were followed for 36 months, recording clinical parameters and performance of conventional serology, chemiluminescent enzyme-linked immunosorbent assay (trypomastigote-derived glycosylphosphatidylinositol-anchored mucins), quantitative polymerase chain reaction, and hemostasis tests every 6-month visits. Prothrombin fragment 1+2 (F1+2) and endogenous thrombin potential (ETP) were abnormally expressed in 77% and 50% of infected patients at baseline but returned to and...
    The possible platelet-aggregating effect of plasma from systemic lupus erythematosus (SLE) patients (n = 19) was investigated under flow conditions. Aliquots of the SLE plasmas with (n = 10) or without (n = 9) anticardiolipin antibodies... more
    The possible platelet-aggregating effect of plasma from systemic lupus erythematosus (SLE) patients (n = 19) was investigated under flow conditions. Aliquots of the SLE plasmas with (n = 10) or without (n = 9) anticardiolipin antibodies (ACAs) were added to anticoagulated blood (1:20, vol/vol). Plasma from normal donors was used as a control. Blood was incubated for 15 minutes at 37 degrees C and then perfused through annular chambers containing denuded arterial segments. Perfusions were performed for 10 minutes at a shear rate of 800 sec-1. The interaction of platelets with vessel subendothelium (SE) was morphometrically evaluated in thin sections. In control experiments, the percentage of the SE covered with platelets was 23.6 +/- 4.3% (mean +/- SD). Large aggregates (more than 5 microns in height) covering 11.8 +/- 5.7% of the exposed SE were noted. The deposition of platelets was statistically increased (38.5 +/- 7.6%, p less than 0.01 versus control) in the presence of SLE plas...
    Objective— Thrombin is a multifunctional serine protease that promotes vascular proinflammatory responses whose effect on endothelial MMP-10 expression has not previously been evaluated. Methods and Results— Thrombin induced endothelial... more
    Objective— Thrombin is a multifunctional serine protease that promotes vascular proinflammatory responses whose effect on endothelial MMP-10 expression has not previously been evaluated. Methods and Results— Thrombin induced endothelial MMP-10 mRNA and protein levels, through a protease-activated receptor-1 (PAR-1)–dependent mechanism, in a dose- and time-dependent manner. This effect was mimicked by a PAR-1 agonist peptide (TRAP-1) and antagonized by an anti–PAR-1 blocking antibody. MMP-10 induction was dependent on extracellular regulated kinase1/2 (ERK1/2) and c-jun N-terminal kinase (JNK) pathways. By serial deletion analysis, site-directed mutagenesis and electrophoretic mobility shift assay an AP-1 site in the proximal region of MMP-10 promoter was found to be critical for thrombin-induced MMP-10 transcriptional activity. Thrombin and TRAP-1 upregulated MMP-10 in murine endothelial cells in culture and in vivo in mouse aorta. This effect of thrombin was not observed in PAR-1–d...
    ObjectiveTo investigate whether patients having antiphospholipid syndrome (APS) as the only aetiological factor for recurrent spontaneous abortion (RSA) are at increased risk of thrombosis later in life.MethodsA case–control study at a... more
    ObjectiveTo investigate whether patients having antiphospholipid syndrome (APS) as the only aetiological factor for recurrent spontaneous abortion (RSA) are at increased risk of thrombosis later in life.MethodsA case–control study at a tertiary university referral centre. The study group consisted of 57 primary APS and RSA women (APS–RSA group). Control groups included: 86 patients with RSA of unknown aetiology (uRSA group), 42 patients with RSA and thrombophilic genetic defects as the only aetiologic factor for RSA (tRSA group) and 30 antiphospholipid antibody (aPL) positive but otherwise healthy women (aPL group). The main measurement was the thrombosis rate after long-term follow-up.ResultsAPS–RSA patients had a significantly higher 12-year cumulative thrombotic incidence rate compared with the three comparator groups (19.3% vs 4.8%, 0.0% and 0.0%, respectively (log rank), p<0.001). Patients in the APS–RSA group had 25.6 thrombotic events per 1000 patient-years (95% CI 12.8 to...
    To analyse the relationship between an automated thrombin generation test, the endogenous thrombin potential (ETP), and other hypercoagulability markers, with vascular involvement in patients with Behçet's disease (BD). Patients and... more
    To analyse the relationship between an automated thrombin generation test, the endogenous thrombin potential (ETP), and other hypercoagulability markers, with vascular involvement in patients with Behçet's disease (BD). Patients and methods. We analysed 56 BD patients (30 men; mean age, 34.4 ± 14.3 years) without any known thrombophilic factor, of which 17 had previously suffered from thrombosis (deep venous thrombosis in 14 and ischaemic stroke in 3), and 56 controls matched for age and sex. Additionally, we also evaluated 20 plasma samples with an international normalised ratio (INR) between 1.5 and 5.0 obtained from patients with atrial fibrillation but without a history of embolic events that were under treatment with acenocumarol. Thrombin generation was measured as ETP with a chromogenic assay in an automated analyser. Factor VIII, von Willebrand factor antigen, prothrombin fragment 1.2, D-dimer and plasmin-antiplasmin complexes were also measured. BD patients showed highe...
    Studies dealing with the number or size of individual adipose cells in abnormal human bone marrow are lacking. To ascertain whether variations in fat tissue fraction depend on the size of individual adipocytes or their number or both, a... more
    Studies dealing with the number or size of individual adipose cells in abnormal human bone marrow are lacking. To ascertain whether variations in fat tissue fraction depend on the size of individual adipocytes or their number or both, a stereologic study of 30 human bone marrow specimens (10 with aplasia, 10 with hyperplasia, and 10 with dysplasia) was performed. A total of 23,435 adipocyte profiles were measured and two stereologic parameters were obtained in each specimen: mean diameter and number of cells per mm3 of bone marrow. The fat tissue fraction correlated positively with the size (r = .79; P less than .001) and the number/volume (r = .77; P less than .001) of adipocytes. The significance of both adipocyte size and adipocyte number/volume was confirmed by stepwise multiple regression, in which the size alone explained 62.5% of fat tissue fraction and both size and number/volume explained 95.8% of fat tissue fraction. These results are discussed from a pathophysiologic poin...
    ABSTRACT Objective To determine practices related to control of perioperative hemostasis and transfusion in patients undergoing cardiac surgery in Spain, including the extent to which protocols are being used. Methods A questionnaire was... more
    ABSTRACT Objective To determine practices related to control of perioperative hemostasis and transfusion in patients undergoing cardiac surgery in Spain, including the extent to which protocols are being used. Methods A questionnaire was created to collect information from physicians in anesthesiology and postoperative recovery care between July 1 and September 20, 2007. The physicians were asked about practice in the 12 months prior to the survey. Results Thirty-four hospitals responded. Seventy percent reported that they did not have protocols or guidelines for the control of hemostasis during cardiac surgery. Forty-four percent did not have information on the proportion of patients who received transfusions; 47% gave transfusions to 75% of patients. The standard preoperative tests were platelet counts, activated partial thromboplastin time, and prothrombin time. Acetylsalicylic acid and clopidogrel were suspended before surgery at 15 (44%) and 25 (73%) hospitals, respectively. In cases of resistance to heparin, additional doses of the drug were injected, in combination with plasma or antithrombin in 29% and 12% of the hospitals, respectively. In the intensive postoperative recovery care unit, only 1 hospital used thromboelastography. Only 1 other hospital used a platelet function analyzer. Conclusions Hemostasis, perioperative coagulation, and criteria for transfusion vary widely among the hospitals surveyed. Few guidelines are available and they are not often being followed. A high percentage of patients receive transfusions, although not all hospitals can cite a figure. New technology has not been widely applied.
    Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity... more
    Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity exhibit a thrombotic risk. We examined the ADAMTS13 activity in systemic lupus erythematosus (SLE) and its value as a thrombotic biomarker. ADAMTS13 activity, VWF antigen and multimeric structure, and vascular cell adhesion molecule 1 (VCAM-1) were measured in plasma samples from 50 SLE patients and 50 healthy donors. Disease activity (systemic lupus erythematosus disease activity index; SLEDAI) and organ damage (systemic lupus international collaborating clinics) scores, thrombotic events, antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPLs) were registered. SLE patients showed decreased ADAMTS13 activity and high VWF levels compared with controls (66 ± 27% vs. 101 ± 8%, P < 0.01, and 325 ± 151% vs. 81 ± 14%, P < 0.001). VCA...
    Cytochrome P4502C9 (CYP2C9) is the main enzyme implicated in coumarinic metabolism. Variant alleles, CYP2C9*2 and CYP2C9*3, have been related to decreased enzymatic activity, but their clinical relevance in acenocoumarol metabolism has... more
    Cytochrome P4502C9 (CYP2C9) is the main enzyme implicated in coumarinic metabolism. Variant alleles, CYP2C9*2 and CYP2C9*3, have been related to decreased enzymatic activity, but their clinical relevance in acenocoumarol metabolism has not been established. We investigated CYP2C9 polymorphisms in relation to acenocoumarol dose requirement, stability of anticoagulation and bleeding. CYP2C9 genotyping was performed in 325 acenocoumarol-treated patients (INR target between 2.0 and 3.0) and in an additional group of 84 patients with repeated bleeding. Patients with the wild-type CYP2C9*1/*1 genotype (n=169) required a higher maintenance dose of acenocoumarol (17.1 8.7 mg/week) than did patients with the CYP2C9*2 (14.6 6.4 mg/week, p<0.05, N=97) or the CYP2C9*3 allele (11.2 6.2 mg/week, p<0.001, n=59). Out of 170 patients requiring a low-dose of acenocoumarol (<or= 2 mg/day), 27.1% carried the CYP2C9*3 allele, while among the patients requiring higher doses, 8.4% had CYP2C9*3 (O...
    The possibility of developing synthetic platelet substitutes is a subject of current interest. We explored the possible hemostatic effect of synthetic phospholipid incorporated in multilamellar vesicles (MLVs) or intermediate unilamellar... more
    The possibility of developing synthetic platelet substitutes is a subject of current interest. We explored the possible hemostatic effect of synthetic phospholipid incorporated in multilamellar vesicles (MLVs) or intermediate unilamellar vesicles (IUVs) using a well-characterized experimental system with circulating human thrombocytopenic blood (10 min, 250 s(-1)). The ability of the liposomes containing different combinations of dipalmitoylphosphatidylcholine (DPPC), phosphatidylethanolamine (PE) and dipalmitoylphosphatidylserine (DPPS) to promote fibrin formation (%F) on the damaged subendothelium was morphometrically evaluated. Generation of thrombin in the system was monitored through prothrombin fragment F1+2 determination. IUV liposomes containing DPPC, 1DPPS:9DPPC, 1DPPS:3DPPC, 1PE:1DPPC increased fibrin deposition on the subendothelium (53.87 +/- 11.0%; 39.76 +/- 6.75%; 40.69 +/- 10.54% and 32.22 +/- 7.35%, respectively vs. thrombocytopenic blood 11.5 +/- 1.2%; p<0.05), w...
    Editor: Francesc Cardellach Editor asociado: Òscar Miró Caso: 161-.
    SummaryRecent reports have described the factor XIII A subunit (FXIII-A) Val34Leu polymorphism as a protective factor against venous and arterial thrombosis. The aim of this study was to investigate the association between the FXIII-A... more
    SummaryRecent reports have described the factor XIII A subunit (FXIII-A) Val34Leu polymorphism as a protective factor against venous and arterial thrombosis. The aim of this study was to investigate the association between the FXIII-A Val34Leu polymorphism, its interaction with fibrinogen concentration, and thrombosis in patients with antiphospholipid antibodies (aPL). We included 172 consecutive patients with aPL: 88 with primary antiphospholipid syndrome (APS), 38 with APS associated with systemic lupus erythematosus (APS-SLE), 32 with SLE and aPL but without APS (SLE-aPL), and 14 asymptomatic individuals with aPL (A-aPL). The FXIII-A Val34Leu polymorphism was assessed by polymerase chain reaction techniques. We found no significant differences in FXIII-A Leu34 allele frequencies between primary APS (allele frequency 0.22), APS-SLE (0.23), SLE-aPL (0.22) and A-aPL (0.32) patients, or between patients with (0.21) and without thrombosis (0.26). FXIII-A Leu34 allele frequencies were ...
    SummaryThere is a current controversy over the hypothesis that a number of thromboembolic events could be related to hypercoagulable state in patients with chronic Chagas disease. This study was designed to determine whether a... more
    SummaryThere is a current controversy over the hypothesis that a number of thromboembolic events could be related to hypercoagulable state in patients with chronic Chagas disease. This study was designed to determine whether a prothrombotic state existed in chronic Trypanosoma cruzi-infected patients and, if so, to describe its evolution after treatment with Benznidazole. Twenty-five patients with chronic Chagas disease and 18 controls were evaluated. The markers used were prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, plasminogen, protein C, total protein S, free protein S, factor VIII, D-dimer, activated factor VIIa, tissue-type plasminogen activator inhibitor-1, prothrombin fragment 1+2 (F1+2), plasmin-antiplasmin complexes, soluble P-selectin and endogenous thrombin potential (ETP). Despite statistically significant differences between cases and controls in several markers, only ETP (which quantifies the ability of plasma to generate thrombin ...
    To study the clinical characteristics at diagnosis and during follow-up of patients with the antiphospholipid syndrome (APS) and to analyze the influence of treatment on their outcome. One hundred patients with APS were included (86%... more
    To study the clinical characteristics at diagnosis and during follow-up of patients with the antiphospholipid syndrome (APS) and to analyze the influence of treatment on their outcome. One hundred patients with APS were included (86% female and 14% male; mean age, 36 years). Sixty-two percent had primary APS and 38% had APS associated with systemic lupus erythematosus (SLE). The median length of follow-up was 49 months. Fifty-three percent of the patients had thromboses, 52% had thrombocytopenia, and 60% of the women had pregnancy losses. Patients with APS associated with SLE had a higher prevalence of hemolytic anemia (P = .02), thrombocytopenia (platelet count lower than 100 x 10(9)/L) (P = .004), antinuclear antibodies (P = .0002), and low complement levels. Fifty-three percent of the patients with thrombosis had recurrent episodes (86% in the same site as the previous thrombotic event). Recurrences were observed in 19% of the episodes treated with long-term oral anticoagulation, in 42% treated prophylactically with aspirin, and in 91% in which anticoagulant/antiaggregant treatment was discontinued (P = .0007). Multivariate analysis showed that prophylactic treatment and older age had an independent predictive value for rethrombosis. Prophylactic treatment during pregnancy (usually with aspirin) increased the live birth rate from 38% to 72% (P = .0002). Patients with APS have a high risk of recurrent thromboses. Long-term oral anticoagulation seems to be the best prophylactic treatment to prevent recurrences. Prophylactic treatment with aspirin during pregnancy reduced the rate of miscarriages remarkably.
    Several methods are available for estimating size distributions of spherical objects in tissue sections. In this article a comparative study of four stereological techniques applied to human bone marrow adipocytes was carried out. In the... more
    Several methods are available for estimating size distributions of spherical objects in tissue sections. In this article a comparative study of four stereological techniques applied to human bone marrow adipocytes was carried out. In the first part, four stereological methods (Giger-Riedwyl, Saltykov, Wicksell, and Cruz-Orive) were used for the evaluation of adipocyte size in a set of 50 human bone marrow specimens (20 normal controls, 10 aplastic, 10 hyperplastic and 10 dysplastic bone marrows). In the second part, a computer simulation model was employed for generating both control and test populations. The latter were analyzed by means of the four stereological methods and compared to the control. When applied to bone marrow specimens, no statistically significant differences were seen among the four methods. Results were very close between the Giger-Riedwyl and Saltykov methods, and between the Wicksell and Cruz-Orive methods. In the simulation model, Saltykov's method was the most accurate stereological technique for the studied conditions. Additional advantages of this method are that the assumption of Gaussian distribution is not required, and that a higher relative weight is assigned to the largest classes, in which accurate definition is easier in the microphotographs. However, since the differences among the four methods are very small, they may all be considered as valid for the stereological study of human bone marrow adipocytes.

    And 10 more