Fresh frozen plasma transfusion in patients with cirrhosis and coagulopathy: Effect on conventional coagulation tests and thrombomodulin-modified thrombin generation.

BACKGROUND & AIMS: The efficacy of fresh frozen plasma (FFP) transfusion in enhancing thrombin generation in patients with cirrhosis and impaired conventional coagulation tests has not been sufficiently explored. Thus, we aimed to assess the effect of FFP transfusion on thrombin generation in these patients. METHODS: Fifty-three consecutive patients receiving a standard dose of FFP to treat bleeding and/or before invasive procedures - if international normalized ratio (INR)/prothrombin time (PT) ratio were ≥1.5 - were prospectively enrolled. The primary endpoint was the amelioration of endogenous thrombin potential (ETP) with thrombomodulin (ETP-TM) after transfusion, which corresponds to the total amount of generated thrombin. INR/PT ratio and activated partial thromboplastin time (aPTT) were also assessed before and after transfusion. RESULTS: FFP enhanced ETP-TM by 5.7%, from 973 (731-1,258) to 1,028 (885-1,343 nM × min; p = 0.019). Before transfusion, evidence of normal or high ETP-TM was found in 94% of patients, even in those with bacterial infections. Only 1 (1.9%) patient had ETP-TM values reverting to the normal range after transfusion. Notably, no patients with low ETP-TM had bleeding. The median decrease in ETP-TM was 8.3% and the mean was 12.8% in 18 (34%) patients after transfusion (from 1,225 [1,071-1,537] to 1,124 [812-1,370] nM × min; p ≤0.0001). Similar responses to FFP transfusion were observed in patients with compensated and acute decompensated cirrhosis, acute-on-chronic liver failure, infection or shock. FFP significantly ameliorated INR and aPTT values (p <0.0001), but in a minority of patients the values were reduced to less than the cut-off point of 1.5. CONCLUSIONS: FFP transfusion enhanced thrombin generation and ameliorated conventional coagulation tests to normal values in a limited number of patients, and slightly decreased thrombin generation in 34% of cases. LAY SUMMARY: Transfusion of fresh frozen plasma in patients with cirrhosis only slightly improves coagulation test values in a limited number of patients and even appears to worsen them in a third of cases. Transfusion for the purpose of preventing or treating bleeding events could cause inherent risks and costs without clear benefits.

Preservation of platelet function in patients with cirrhosis and thrombocytopenia undergoing esophageal variceal ligation.

BACKGROUND: Thrombocytopenia is a possible risk factor for bleeding after band ligation of esophageal varices. However, elevated von Willebrand factor (VWF) in cirrhosis improves platelet function and could decrease this risk. Our objective was to assess platelet function in patients with cirrhosis undergoing esophageal variceal ligation (EVL). METHODS: The assessment consisted of platelet count, antigen and activity of VWF and VWF-cleaving protease ADAMTS-13 activity, and a platelet adhesion and aggregation test simulating vascular flow in vivo (Impact-RⓇ) prior to EVL. RESULTS: Totally 111 patients were divided into three groups according to platelet count: (1) < 50 × 109/L (n = 38, 34.2%); (2) 50 × 109/L to 100 × 109/L (n = 47, 42.3%); and (3) > 100 × 109/L (n = 26, 23.4%). No statistically significant difference was found in the aggregate size of platelets [group 1: 41.0 (31.8-67.3) µm2; group 2: 47.0 (33.8-71.3) µm2; and group 3: 47.0 (34.0-66.0) µm2; P = 0.60] and no significant correlation was found between aggregate size and platelet count (Spearman r = 0.07; P = 0.47). Surface coverage was 4.1% (2.8%-6.7%), 8.5% (4.0%-10.0%), and 9.0% (7.1%-12.0%) (P < 0.001) in groups 1, 2 and 3, respectively and correlated with platelet count (Spearman r = 0.39; P < 0.0001). There was no significant difference between groups in VWF or ADAMTS-13. Post-EVL bleeding occurred in six (5.4%) patients (n = 2 in group 1, n = 1 in group 2, and n = 3 in group 3; P = 0.32). Patients with bleeding had higher MELD scores [15.0 (11.3-20.3) versus 12.0 (10.0-15.0); P = 0.025], but no difference was demonstrated for platelet function parameters. CONCLUSION: Platelet function is preserved even in the presence of thrombocytopenia, including in the patients with post-EVL bleeding.

Difficult clinical situations in the antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is characterized by antiphospholipid antibodies (aPL) associated with thrombosis and/or pregnancy morbidity. However, there is a range of other manifestations associated with APS, called non-criteria manifestations that add significant morbidity to this syndrome and, some of them, represent difficult clinical situations to deal with. Other issues such as refractory treatment also represent challenging situations poorly addressed in the literature. Therefore, the purpose of this article is to review the management of difficult clinical situations in APS and provide information to help the readers in their decision-making process.

Arthroscopic partial anterior synovectomy of the knee on patients with haemophilia.

PURPOSE: This study assessed the results of two-portal knee arthroscopic synovectomy in terms of bleeding recurrence, knee function, quality of life (QOL), and radiographic staging in a prospective case series of patients with haemophilia. METHODS: Nine knees from eight patients (median age 16.1 years; range 9.6-25 years) with haemophilia and recurrent knee haemarthrosis were prospectively evaluated. Yearly recurrence of bleeding was evaluated once a year for 5 years postoperatively. Range of motion (ROM) and radiographic staging, as well as results of the short form (SF)-36 and subjective knee form of the International Knee Documentation Committee (IKDC) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaires, were evaluated before surgery and at the end of follow-up. RESULTS: Mean bleeding recurrence was significantly reduced during the 5-year follow-up period. Questionnaire results showed significant improvements (IKDC P = 0.015, WOMAC P = 0.011, and SF-36 P = 0.023), whereas ROM was not significantly affected. Arthropathy progressed from Arnold-Hilgartner radiographic stage III to stage IV (P = 0.0082). CONCLUSIONS: Two-portal knee arthroscopic synovectomy was effective at reducing bleeding recurrence and improving knee function and QOL in patients with haemophilia, but did not interrupt the progression of radiographic changes.

Aspirin responsiveness safely lowers perioperative cardiovascular risk.

INTRODUCTION: Vascular surgeries are related to high cardiac morbidity and mortality, and the maintenance of aspirin in the perioperative period has a protective effect. The purpose of this study was to evaluate the association between preoperative platelet aggregability and perioperative cardiovascular (CV) events. METHODS: A preoperative platelet aggregation test was performed on an impedance aggregometer in response to collagen and to arachidonic acid (AA) for 191 vascular surgery patients under chronic use of aspirin. We analyzed the following CV events: acute myocardial infarction, unstable angina, isolated troponin elevation, acute ischemic stroke, reoperation, and cardiac death. Hemorrhagic events were also evaluated and classified according to the Thrombolysis In Myocardial Infarction criteria. RESULTS: The incidence of CV events was 22% (n = 42). Higher platelet response to AA was associated with CV events, so that patients in the fourth quartile (higher than 11Ω) had almost twice the incidence of CV events when compared with the three lower quartiles: 35% vs 19%; P = .025. The independent predictors of CV events were hemodynamic instability during anesthesia (odds ratio [OR], 4.12; 95% confidence interval [CI], 1.87-9.06; P < .001), dyslipidemia (OR, 3.9; 95% CI, 1.32-11.51; P = .014), preoperative anemia (OR, 2.64; 95% CI, 1.19-5.85; P = .017), and AA platelet aggregability in the upper quartile (OR, 2.48; 95% CI, 1.07-5.76; P = .034). Platelet aggregability was not associated with hemorrhagic events, even when we compared the lowest quartile of AA platelet aggregability (0-1.00 Ω) with the three upper quartiles (>1.00 Ω; OR, 0.77; 95% CI, 0.43-1.37; P = .377). CONCLUSIONS: The degree of aspirin effect on platelet aggregability maybe important in the management of perioperative CV morbidity, without increment in the bleeding toll.

Preservation of thrombin generation in cirrhosis despite abnormal results of international normalized ratio: implications for invasive procedures.

Thrombin generation is normal or elevated in patients with cirrhosis when tested in the presence of thrombomodulin, the activator of the main natural anticoagulant protein C. However, the relationship between thrombin generation with bleeding has been little explored in literature. 97 Consecutive patients with cirrhosis were prospectively included (58 men; 54 ±â€Š10 years) and divided into two groups international normalized ratio (INR) less than 1.5 (n = 72) or INR at least 1.5 (n = 25). 46 Healthy individuals were tested as controls. Endogenous thrombin potential (ETP) was measured without and with the addition of thrombomodulin. ETP measured without thrombomodulin was reduced in patients with cirrhosis when compared with controls, but no significant difference was found between the INR less than 1.5 and INR at least 1.5 groups (1250 ±â€Š315.7 versus 1186 ±â€Š238 nmol/l × min; P = 0.3572). After the addition of thrombomodulin, both groups generated thrombin comparable with controls (INR ≥ 1.5: 965.9 ±â€Š232.3; INR < 1.5: 893.0 ±â€Š368.6; controls: 915.0 ±â€Š458 nmol/l × min). 80% of patients had high ETP without/with thrombomodulin ratio, demonstrating the resistance to the anticoagulant action of thrombomodulin for both groups. This was more marked in the INR at least 1.5 group (0.81 ±â€Š0.1 versus 0.69 ±â€Š0.2; P = 0.0042). Postligation of esophageal varices bleeding occurred in 5.2% of patients (INR < 1.5, n = 3; INR ≥ 1.5, n = 2), all of them with ETP without/with thrombomodulin ratio ranging from 0.72 to 0.90 (controls 0.57 ±â€Š0.21). This study confirms that thrombin generation in the presence of thrombomodulin was normal in most patients with cirrhosis, including those with high INR value, but did not correlate with postligation of esophageal varices bleeding.

Immunogenicity, long term protection and safety of subcutaneous administration of hepatitis A vaccine in patients with hemophilia and other bleeding disorders: A randomized study.

Hepatitis A vaccine is recommended for all individuals with hemophilia, although patients with bleeding disorders should avoid intramuscular (IM) injections. To date, only few studies showed subcutaneous (SC) route immunogenicity is comparable with the IM route. Therefore, this randomized study compared immunogenicity, long term protection and safety of hepatitis A vaccine administered by SC route with the IM route in 78 children and adults with hemophilia and other bleeding disorders. Thirty-eight patients had serology performed after first vaccine dose, determining seroconversion rates of 83.3% and 90.0% for the SC and the IM group, respectively (p = 0.5). Median IgG CO/OD value for the SC group was almost the double compared with the IM group (4.4 vs 2.6, p = 0.2). After second vaccine dose, seroconversion rates for the SC group was 97.5% and for the IM group was 97.4% (p = 1.0). Of the two patients who did not have seroconversion, interval between vaccine dose and serology was only one and two days for the SC and the IM group, respectively and in the following routine antibody dosage they presented seroconversion (100% for both groups). Median IgG CO/OD value for the SC group was greater than the IM group (72.5 vs. 58.0, p = 0.2). In a median of nine years after second vaccine dose, median IgG S/CO value for the SC group was slightly greater than the IM group (7.6 vs. 7.4, p = 0.8). There were no serious adverse events in both groups. Five (12.5%) patients of the SC group and seven (18.4%) of the IM group presented adverse events (p = 0.5). Twice as many patients of the IM group had clotting factor concentrates need for adverse events (15.8% vs. 7.5%, p = 0.3). Therefore, hepatitis A vaccine administered subcutaneously is as immunogenic, long term protective and even safer than the intramuscular route.

Heparin Therapy Improving Hypoxia in COVID-19 Patients - A Case Series.

INTRODUCTION: Elevated D-dimer is a predictor of severity and mortality in COVID-19 patients, and heparin use during in-hospital stay has been associated with decreased mortality. COVID-19 patient autopsies have revealed thrombi in the microvasculature, suggesting that hypercoagulability is a prominent feature of organ failure in these patients. Interestingly, in COVID-19, pulmonary compliance is preserved despite severe hypoxemia corroborating the hypothesis that perfusion mismatch may play a significant role in the development of respiratory failure. METHODS: We describe a series of 27 consecutive COVID-19 patients admitted to Sirio-Libanes Hospital in São Paulo-Brazil and treated with heparin in therapeutic doses tailored to clinical severity. RESULTS: PaO2/FiO2 ratio increased significantly over the 72 h following the start of anticoagulation, from 254(±90) to 325(±80), p = 0.013, and 92% of the patients were discharged home within a median time of 11 days. There were no bleeding complications or fatal events. DISCUSSION: Even though this uncontrolled case series does not offer absolute proof that micro thrombosis in the pulmonary circulation is the underlying mechanism of respiratory failure in COVID-19, patient's positive response to heparinization contributes to the understanding of the pathophysiological mechanism of the disease and provides valuable information for the treatment of these patients while we await the results of further prospective controlled studies.

Endoscopic activity, tissue factor and Crohn's disease: findings in clinical remission patients.

BACKGROUND: As Crohn's disease (CD) is associated with a high risk of thromboembolic events (TE), including patients with subclinical inflammation, we aim to evaluate the correlation between the impact of endoscopic activity (EA) in the coagulation profiling of CD patients while in clinical remission. METHODS: From 164 consecutive CD patients included in clinical remission [Crohn's disease activity index (CDAI) < 150], 75 were in the EA group [Simplified Endoscopic Score for CD (SES-CD) ⩾ 7], 89 were in the endoscopic remission (ER) group (SES-CD ⩽ 2), and 50 were included as healthy controls in the study. Blood samples were analyzed for tissue factor (TF), factor VIII (FVIII), thrombomodulin (TM), ADAMTS-13, von Willebrand factor (VWF), and endogenous thrombin potential (ETP), as well as collecting data regarding risk factors for TE and CD profile. RESULTS: Mean plasma TF activity showed significantly higher levels in the EA group when compared with the ER and control groups (127 pM versus 103 pM versus 84 pM; p = 0.001), although the VWF:Ag (160% versus 168% versus 110%; p = 0.001), VWF/ADAMTS-13 (191 versus 219 versus 138; p = 0.003), FVIII (150% versus 144% versus 90%; p = 0.001) and TM (5.13 ng/ml versus 4.91 ng/mL versus 3.81 ng/ml; p < 0.001) were only increased in CD regardless of EA status when compared with controls. Lastly, ETP with and without TM remained the same in all three groups. CONCLUSIONS: CD patients in clinical remission with EA present endothelial lesion inducing TF exposure and subsequent coagulation cascade activation. Recommended thromboprophylaxis for EA outpatient subgroups will require additional investigation in order to be validated.

A prospective study of conventional and expanded coagulation indices in predicting ulcer bleeding after variceal band ligation.

BACKGROUND & AIMS: There is controversy over whether coagulation status predicts bleeding caused by ulceration after esophageal varices band ligation (EVL). METHODS: EVL was performed for primary (n = 45) or secondary (n = 105) prophylaxis in 150 patients with cirrhosis (Child A, n = 74, 49%; Child B, n = 42, 28%; Child C, n = 34, 23%). International normalized ratio (INR) and platelet counts were assessed in all. In 92 patients, levels of factor V, fibrinogen, D-dimer, protein C and protein S, von Willebrand factor, and thromboelastography (TEG) were assessed. Platelet count <50 x 10(3)/mm(3) and INR >1.5 were considered high-risk cutoff for bleeding. Conversely, platelet count >or=50 x 10(3)/mm(3) with INR

Highlights from the I international symposium of thrombosis and anticoagulation in internal medicine, October 23-25, 2008, Sao Paulo, Brazil.

The importance of thrombosis and anticoagulation in clinical practice is rooted firmly in several fundamental constructs that can be applied both broadly and globally. Awareness and the appropriate use of anticoagulant therapy remain the keys to prevention and treatment. However, to assure maximal efficacy and safety, the clinician must, according to the available evidence, choose the right drug, at the right dose, for the right patient, under the right indication, and for the right duration of time. The first International Symposium of Thrombosis and Anticoagulation in Internal Medicine was a scientific program developed by clinicians for clinicians. The primary objective of the meeting was to educate, motivate and inspire internists, cardiologists and hematologists by convening national and international visionaries, thought-leaders and dedicated clinician-scientists in Sao Paulo, Brazil. This article is a focused summary of the symposium proceedings.

Estrogen treatment improves arterial distensibility, fibrinolysis, and metabolic profile in postmenopausal women with type 2 diabetes mellitus.

The effects of isolated estrogen therapy on the hemostatic system and arterial distensibility were determined in postmenopausal females with type 2 diabetes mellitus. This was a prospective nonrandomized study of 19 subjects (age, 56.2 +/- 4.7 years; body mass index, 27.8 +/- 2.4 kg/m(2) [mean +/- SD]). Inclusion was done after 2 months of glycemic and blood pressure control. The study consisted of 4 months of placebo treatment immediately followed by an equal period of oral conjugated equine estrogens (CEE) 0.625 mg/d. Measures included anthropometrics, a metabolic profile (oral glucose tolerance test and fasting glycated hemoglobin, total cholesterol and fractions, and triglyceride levels), and coagulation and fibrinolytic factors at the end of the placebo period and after 4 months of oral CEE. Conjugated equine estrogen therapy decreased plasminogen activator inhibitor 1 (placebo x CEE: 16.33 +/- 9.11 x 13.08 +/- 8.87 UI/mL, P < .03) and increased factor VIII activity (134.11% +/- 46.18% x 145.33% +/- 42.04%, P < .04). An increase in high-density lipoprotein cholesterol levels (placebo x CEE: 42.47 +/- 6.80 x 53.32 +/- 11.89 mg/dL, P < .01), and a decrease in glycated hemoglobin (8.45% +/- 1.30% vs 7.58% +/- 1.06%, P < .02) and in fasting glucose levels (121.51 +/- 21.05 x 111.21 +/- 20.74 mg/dL, P = .02) followed CEE therapy. Pulse wave velocity and augmentation index were performed by applanation tonometry and were obtained at the end of the placebo period (placebo), again after an intravenous load of 1.25 mg of CEE (short-term), and after 4 months of oral CEE (long-term). A significant decrease in central (carotid-femoral) pulse wave velocity was seen both after short- and long-term CEE (placebo vs short-term vs long-term: 9.36 +/- 2.58 vs 8.26 +/- 2.20 vs 7.98 +/- 1.90 m/s, respectively [analysis of variance, P < .03]; placebo vs short-term, P < .05; placebo vs long-term, P < .01), whereas augmentation index decreased only after long-term CEE (placebo vs short-term vs long-term: 39.14% +/- 6.94% vs 37.48% +/- 8.67% vs 34.3.3% +/- 8.11% [analysis of variance, P < .05], respectively; placebo vs long-term, P < .05). Long-term administration of CEE leads to an improvement in fibrinolysis and arterial distensibility, associated with an increase of the intrinsic coagulation pathway in postmenopausal women with type 2 diabetes mellitus.

Branch retinal vein thrombosis and visual loss probably associated with pegylated interferon therapy of chronic hepatitis C.

Ophthalmological complications with interferon therapy are usually mild and reversible, not requiring the withdrawal of the treatment. We report a case of a patient who had visual loss probably associated with interferon therapy. Chronic hepatitis C virus infection (genotype 1a) was diagnosed in a 33-year old asymptomatic man. His past medical history was unremarkable and previous routine ophthalmologic check-up was normal. Pegylated interferon alpha and ribavirin were started. Three weeks later he reported painless reduction of vision. Ophthalmologic examination showed extensive intraretinal hemorrhages and cotton-wool spots, associated with inferior branch retinal vein thrombosis. Antiviral therapy was immediately discontinued, but one year later he persists with severely decreased visual acuity. This case illustrates the possibility of unpredictable and severe complications during pegylated interferon therapy.

Drug Interaction Between Clopidogrel and Ranitidine or Omeprazole in Stable Coronary Artery Disease: A Double-Blind, Double Dummy, Randomized Study.

BACKGROUND: Proton-pump inhibitors (PPIs) are often prescribed to patients receiving dual antiplatelet therapy (DAPT). However, this class of medication, especially omeprazole, has been associated with a reduction in clopidogrel efficacy, leading many clinicians to substitute omeprazole with ranitidine. OBJECTIVES: Our objective was to compare the antiplatelet effect of clopidogrel before and after the addition of omeprazole or ranitidine. METHODS: We measured platelet aggregability at baseline and after 1 week of clopidogrel 75 mg daily. Subjects were then randomized in a double-blinded, double-dummy fashion to omeprazole 20 mg twice daily (bid) or ranitidine 150 mg bid. We repeated aggregability tests after 1 additional week, using VerifyNow P2Y12™ (Accumetrics; San Diego, CA, USA), depicting aggregability as percent inhibition of platelet aggregation (IPA). RESULTS: We enrolled 41 patients in the omeprazole group and 44 in the ranitidine group. IPA was significantly decreased after the addition of omeprazole to clopidogrel (from 26.3 ± 32.9 to 17.4 ± 33.1 %; p = 0.025), with no statistical significant changes observed in the ranitidine group (from 32.6 ± 28.9 to 30.1 ± 31.3 %; p = 0.310). The comparison of IPA in both groups at the end of the follow-up showed a trend toward significance (p = 0.07, 95 % confidence interval [CI] -1.19 to 26.59); after excluding homozygous patients for 2C19*2 genotype, the comparison of IPA between the groups reached statistical significance (32.7 ± 30.8 vs. 17.7 ± 33.4 %, respectively, for ranitidine and omeprazole groups; p = 0.04). CONCLUSIONS: Unlike omeprazole, ranitidine did not influence platelet aggregability response to clopidogrel. CLINICAL TRIAL REGISTRATION: NCT01896557.

Postmenopausal hormone replacement therapy increases plasmatic thromboxane beta 2.

OBJECTIVE: This study shows the effect of hormone replacement therapy (HRT), using oral estrogen exclusively or in combination with progestin, on platelet activation in healthy menopaused women. BACKGROUND: Recent evidence from studies of postmenopausal HRT in healthy women demonstrated a short-time increased risk of coronary heart disease. Platelet activation, which generates vasoconstrictory thromboxane A(2) (TxA(2)), has been related to the risk of cardiovascular diseases. METHODS: By means of a placebo-controlled study twenty-seven postmenopausal patients were continuously orally administered estrogen in combination with progestin or estrogen exclusively for an 8-week period. Platelet activation was evaluated by flow cytometric P-selectin expression and by enzyme immunoassay plasmatic TxA(2) (TxB(2)) concentrations. RESULTS: P-selectin binding index changed from 6.3+/-3.6 to 7.0+/-3 in the placebo group (n=10); from 5.9+2.2 to 7.9+/-3.3 in the E+P group (n=8) and from 6.4+2.7 to 7.1+/-1.9 in the E group (n=9). Plasma concentrations of TxB(2) before and after intervention, changed from 1.2+1.2 to 1.5+1.4 (pg/well) in the placebo group; significantly (p=0.005) in the E+P group (n=8), from 0.9+0.3 to 6.1+6.5 (pg/well), and from 1.3+1.5 to 0.8+0.4 (pg/well) in the E group (n=8; mean+standard deviation, basal x therapy, p<0.05). CONCLUSIONS: Healthy menopaused women who were administered estradiol in association with norethisterone continuously had an increase of plasmatic thromboxane, possibly determined by platelet activation, which indicates a higher short-term thrombotic risk. P-selectin expression analyses failed to demonstrate the impact of HRT on platelets.

Long-term Clinical Outcomes of Splanchnic Vein Thrombosis: Results of an International Registry.

IMPORTANCE: Little information is available on the long-term clinical outcome of patients with splanchnic vein thrombosis (SVT). OBJECTIVE: To assess the incidence rates of bleeding, thrombotic events, and mortality in a large international cohort of patients with SVT. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted beginning May 2, 2008, and completed January 30, 2014, at hospital-based centers specialized in the management of thromboembolic disorders; a 2-year follow-up period was completed January 30, 2014, and data analysis was conducted from July 1, 2014, to February 28, 2015. Participants included 604 consecutive patients with objectively diagnosed SVT; there were no exclusion critieria. Information was gathered on baseline characteristics, risk factors, and antithrombotic treatment. Clinical outcomes during the follow-up period were documented and reviewed by a central adjudication committee. MAIN OUTCOMES AND MEASURES: Major bleeding, defined according to the International Society on Thrombosis and Hemostasis; bleeding requiring hospitalization; thrombotic events, including venous and arterial thrombosis; and all-cause mortality. RESULTS: Of the 604 patients (median age, 54 years; 62.6% males), 21 (3.5%) did not complete follow-up. The most common risk factors for SVT were liver cirrhosis (167 of 600 patients [27.8%]) and solid cancer (136 of 600 [22.7%]); the most common sites of thrombosis were the portal vein (465 of 604 [77.0%]) and the mesenteric veins (266 of 604 [44.0%]). Anticoagulation was administered to 465 patients in the entire cohort (77.0%) with a mean duration of 13.9 months; 175 of the anticoagulant group (37.6%) received parenteral treatment only, and 290 patients (62.4%) were receiving vitamin K antagonists. The incidence rates (reported with 95% CIs) were 3.8 per 100 patient-years (2.7-5.2) for major bleeding, 7.3 per 100 patient-years (5.8-9.3) for thrombotic events, and 10.3 per 100 patient-years (8.5-12.5) for all-cause mortality. During anticoagulant treatment, these rates were 3.9 per 100 patient-years (2.6-6.0) for major bleeding and 5.6 per 100 patient-years (3.9-8.0) for thrombotic events. After treatment discontinuation, rates were 1.0 per 100 patient-years (0.3-4.2) and 10.5 per 100 patient-years (6.8-16.3), respectively. The highest rates of major bleeding and thrombotic events during the whole study period were observed in patients with cirrhosis (10.0 per 100 patient-years [6.6-15.1] and 11.3 per 100 patient-years [7.7-16.8], respectively); the lowest rates were in patients with SVT secondary to transient risk factors (0.5 per 100 patient-years [0.1-3.7] and 3.2 per 100 patient-years [1.4-7.0], respectively). CONCLUSIONS AND RELEVANCE: Most patients with SVT have a substantial long-term risk of thrombotic events. In patients with cirrhosis, this risk must be balanced against a similarly high risk of major bleeding. Anticoagulant treatment appears to be safe and effective in most patients with SVT.

Hypopituitarism, deficiency of factors V and VIII and von Willebrand factor: an uncommon association.

A 9 year-old boy with hypopituitarism and blood coagulation abnormalities is presented and discussed. The association between acquired von Willebrand disease and hypothyroidism has been reported but the combination of hypopituitarism and coagulopathy is unusual. Combined multiple clotting deficiencies are rare and, when present, factors V and VIII is the commonest association. Although it is known that hypothyroid patients may have a decrease in von Willebrand's factor (vWf) and factor VIII, there are no reports of hypopituitarism associated with combined deficiency of factors V, VIII, and vWf.

New prevalence estimate of TT virus (TTV) infection in low- and high-risk population from São Paulo, Brazil.

The prevalence of TT virus (TTV) infection was investigated by Polymerase Chain Reaction (PCR) in low- (blood donors and healthy children/adolescents) and high-risk (hemophiliacs) groups from São Paulo, Brazil. Primers based on the untranslated region (UTR) of the viral genome proved to be much more ubiquitous, leading to much higher frequencies for both groups (>or= 81%) than the earlier N22-PCR directed to the open reading frame 1 (blood donors, 5.5%, and hemophiliacs, 42.3%). The UTR-PCR also revealed an interesting profile for healthy children/adolescents: very high prevalence at the early years and significant decrease in male teenagers. The N22-PCR, in turn, demonstrated higher frequency in hemophiliacs treated with fresh blood products (58%), than in those treated with virus-inactivated clotting factors (9.4%) and blood donors (5.5%).

Successful management of neonatal alloimmune thrombocytopenia in the second pregnancy: a case report.

Neonatal alloimmune thrombocytopenia is a serious disease, in which the mother produces antibodies against fetal platelet antigens inherited from the father; it is still an underdiagnosed disease. This disease is considered the platelet counterpart of the RhD hemolytic disease of the fetus and newborn, yet in neonatal alloimmune thrombocytopenia the first child is affected with fetal and/or neonatal thrombocytopenia. There is a significant risk of intracranial hemorrhage and severe neurological impairment, with a tendency for earlier and more severe thrombocytopenia in subsequent pregnancies. This article reports a case of neonatal alloimmune thrombocytopenia in the second pregnancy affected and discusses diagnosis, management and the clinical importance of this disease.