Predictive factors for thrombosis and major bleeding in an observational study in 181 patients with heparin-induced thrombocytopenia treated with lepirudin.

The antithrombotic efficacy of lepirudin in patients with heparin-induced thrombocytopenia (HIT) is compromised by an increased risk for bleeding. A retrospective observational analysis in 181 patients (median age, 67 years) with confirmed HIT treated in routine practice with lepirudin was performed to identify predictive factors for thrombotic and bleeding complications. Lepirudin was administered at a mean (+/- SD) dose of 0.06 +/- 0.04 mg/kg/h (compared with a recommended initial dose of 0.15 mg/kg/h). Mean activated partial thromboplastin time was greater than 1.5 times baseline value in 99.4% of patients. Median treatment duration was 7.7 days. Until discharge from the hospital, 13.8% and 20.4% of patients experienced a thrombotic or a major bleeding event, respectively. On multivariate analysis, mean lepirudin dose was not a significant predictive factor for thrombosis. In contrast, mean lepirudin dose greater than 0.07 mg/kg/h, long duration of lepirudin treatment, and moderate to severe renal impairment were significant positive factors for major bleeding. Overall, these results suggest that the recommended dose of lepirudin in patients with HIT is too high; the use of reduced doses may be safer with regard to bleeding risk and does not compromise antithrombotic efficacy.

Early overanticoagulation with acenocoumarol due to a genetic polymorphism of cytochrome P450 CYP2C9.

We report the case of a young healthy woman who presented an early overanticoagulation when receiving acenocoumarol for a first thromboembolic episode. The patient had none of the risk factors known to influence the response to the coumarinic derivative except that she carried the rare *3 allelic variant of the cytochrome P450 CYP2C9 in a homozygous status. This case illustrates the role of the *3 polymorphism of the cytochrome P450 CYP2C9 as an independent risk factor modulating the sensitivity of patients to the anticoagulant effect of acenocoumarol. The usefulness of CYP2C9 genotyping before starting coumarinic treatments is discussed.

Activated protein C resistance acquired through liver transplantation and associated with recurrent venous thrombosis.

We report a new case of recurrent, extra-hepatic, deep vein thrombosis occurring after orthotopic liver transplantation for hepatocellular carcinoma complicating 'mixed' alcoholic and post-hepatitic C cirrhosis. Coagulation tests showed activated protein C resistance. The patient's genomic DNA was negative for the factor V Leiden mutation. Analysis of the grafted liver DNA showed that the donor was a heterozygous carrier of the factor V Leiden mutation and that the recipient's activated protein C resistance was acquired through the transplantation. Screening of candidate liver donors for a prothrombotic tendency is controversial. However, this case suggests that patients who develop venous thrombosis after liver transplantation should be screened for thrombophilic abnormalities, bearing in mind that genetic abnormalities which do not affect clotting test results, such as the G20210A mutation in the factor II gene, can only be diagnosed by testing the donor or graft.