In a prospective cohort study, we assessed the incidence of spontaneous and risk period-related venous thromboembolism (VTE) in asymptomatic family members of patients who experienced VTE and had the factor V Leiden mutation. In all, 561 family members of 131 probands were included, 313 of whom were carriers (299 heterozygous and 14 homozygous) and 248 of whom were noncarriers of the factor V Leiden mutation. Average follow-up was 4 years (range, 4 months-6 years). There were 1255 and 984 observation-years of follow-up in carriers and noncarriers, respectively. Eight episodes of VTE occurred in heterozygous carriers, resulting in an annual incidence of 0.67% (95% confidence interval [CI], 0.29-1.33). Two events occurred in the absence of associated risk factors, determining an annual incidence of spontaneous VTE of 0.17% (95% CI, 0.02-0.6). Only one VTE (risk period-related) occurred in noncarriers, with an annual incidence of 0.1% (95% CI, 0.003-0.56). Relative risk for VTE in heterozygous carriers compared with noncarriers of the factor V Leiden mutation was 6.6 (95% CI, 1.1-39.8). Risk periodrelated VTE occurred with an incidence of 18% and 5% per risk period in heterozygous carriers and in noncarriers, respectively. Thus, the low rate of VTE in asymptomatic family members carrying the mutation did not justify continuous anticoagulant prophylaxis. Screening families of symptomatic probands with the factor V Leiden mutation has the potential to identify those asymptomatic carriers who might benefit from thromboprophylaxis during risk periods. (Blood. 2002;99: 1938-1942 © 2002 by The American Society of Hematology IntroductionFactor V Leiden mutation (factor V Arg5063Gln) is the most common genetic defect associated with an increased risk for venous thromboembolism (VTE). [1][2][3] Its prevalence in the white population is approximately 5% and is as high as 20% to 40% in patients with documented VTE, depending on selection criteria. Case-control studies have shown that heterozygous carriers of this mutation exhibit a 3-to 7-fold increased risk for VTE than healthy controls. 1,[4][5][6] The association of factor V Leiden with other coagulation abnormalities predisposing to thrombosis, including deficiencies of antithrombin, protein C, protein S, hyperhomocystinemia, and the prothrombin variant G20210A may further increase such risk. [7][8][9][10] Most persons identified as carriers of the factor V Leiden mutation as a result of family studies, however, do not exhibit other associated coagulation defects.Benefits from an early identification of carriership status among asymptomatic subjects in terms of appropriate prophylactic measures should be balanced against the disadvantage of potential bleeding complications secondary to preventive treatment and the inconvenience of labeling otherwise healthy people as having a disease. Thus, valid estimates of the absolute risk for spontaneous and risk period-related VTE in asymptomatic family members who are carriers of the factor V Leiden mutation are crucial for clinic...

MI is less common in patients with ET younger than 40 years than in older patients. Association of MI and cardiovascular risk factors is frequent in patients with ET and PV. A low dose of ASA could be able to reduce the number of coronary thrombosis without increasing bleeding complications in patients with elevated platelet count and common atherosclerotic risk factors. However, a larger population must be evaluated to confirm our hypothesis.

Summary.  Introduction:  Cirrhotic patients may present thrombotic complications that warrant anticoagulant therapy. However, the efficacy of low-molecular-weight heparin (LMWH) in this clinical setting is still unclear. Aims/methods:  To evaluate the in vitro effect of LMWH on thrombin generation (TG) in cirrhotic patients at different stages of liver disease. Thirty cirrhotics (10 Child Pugh A, 10 Child Pugh B and 10 Child Pugh C), 10 subjects with inherited type 1 antithrombin (AT) defect and 10 healthy controls were studied. TG was determined at baseline and with anti-Xa levels after the addition of enoxaparin at 0.35 and 0.7 U anti-Xa mL. The endogenous thrombin potential (ETP) ratio at 0.35 and 0.7 U anti-Xa mL was obtained by dividing ETP with LMWH by ETP at baseline. Results:  Mean AT levels in all cirrhotic subgroups and in patients with AT deficiency were significantly lower than in controls. The 0.35 ETP ratio was significantly lower in cirrhotic patients than in controls (0.26 ± 0.1 vs. 0.48 ± 0.1, P < 0.001) and the reduction paralleled the severity of liver disease, in spite of the concomitant decrease in AT and anti-Xa activity. AT-deficient subjects showed a significantly increased 0.35 ETP ratio compared with both cirrhotic patients and controls (0.69 ± 1 vs. 0.26 ± 0.1, P < 0.001, and vs. 0.48 ± 0.1, P = 0.04 respectively). LMWH at 0.7 U anti-Xa mL completely inhibited TG in 9/30 cirrhosis patients with more advanced liver disease (Child Pugh B and C), whereas complete TG abolition was seen in only 1/10 controls. Conclusions:  Cirrhotic patients show an increased response to LMWH, which correlates with the severity of liver disease, in spite of reduced AT and anti-Xa activity levels. Thrombin generation may be a useful tool to monitor the response to LMWH in cirrhotic patient

The occurrence of antibodies (Abs) capable of inhibiting factor VIII (FVIII) coagulant activity is a severe complication in haemophilia A, leading to the inhibition of transfused FVIII activity. It is not known whether, or to what extent, post-transfusion antibodies may also arise against non-coagulant epitopes. Therefore we set up a system capable, in theory, to detect all the FVIII-induced antibodies by use of an enzyme-linked immunoassorbent assay (ELISA) based on coating human recombinant FVIII onto polystyrene microtitre plates. Serum samples from 23 patients affected by haemophilia A of different gravity (22 referred to our Centre and one to the Bari Centre) were analysed. Although only one patient was positive at Bethesda assay, the presence of antibodies in ELISA was detected in 39% of patients in variable degrees; transfusion with FVIII was found to induce a raise in antibody titre, arguing in favour of the specificity of the phenomenon. The clinical relevance of these non-inhibitory antibodies was evaluated in three patients; although half-life did not show any change in the patients without or with low amount of antibodies, FVIII clearance was found enhanced in the patient displaying high titre antibodies. We propose detection of anti-FVIII antibodies by ELISA when routinely assessing haemophilia A patients.

Early diagnosis and early treatment are key factors for the successful management of PVT in cirrhosis, so that screening of PVT and prompt start of anticoagulant treatment should be mandatory.