Severe anaphylactic reaction after repeated intermittent exposure to lepirudin.

Lepirudin, a recombinant DNA derivative of hirudin, is used to prevent thromboembolic complications caused by heparin-induced thrombocytopenia type II. Anaphylactic and anaphylactoid reactions have been reported with its use in patients both with and without known previous exposure to lepirudin. We describe the case of a 57-year-old woman who received five uneventful courses of lepirudin therapy before having a severe anaphylactic reaction during administration of the intravenous bolus dose that began her sixth course. The patient experienced cardiorespiratory arrest but recovered from the reaction. The decision to administer lepirudin to a patient who has previously received it should be reached with due consideration of the risk:benefit ratio and strategies to manage risk resulting from readministration. Risk factors for an anaphylactic reaction to lepirudin may include use of an initial bolus dose, intravenous rather than subcutaneous administration, length of any single course of therapy beyond 3 days, and repeat administration of lepirudin within 100 days.

Pharmacokinetics, effect on clotting tests and assessment of the immunogenic potential of hirudin after a single subcutaneous or intravenous bolus administration in man.

The pharmacokinetics and the anticoagulant effects of hirudin were investigated in 12 healthy volunteers after single subcutaneous or intravenous bolus administrations. Hirudin concentrations in citrated plasma and urine were determined with a radioimmunobioassay, which detects the inhibitor by its thrombin-binding capacity. Plasma profiles could be adequately described by the equation for an open two-compartment model (intravenous route) and by the Bateman equation (subcutaneous route), respectively. Within 24 h half of the administered hirudin dose was recovered in the urine in biologically active form. The prolongation of clotting times (activated partial thromboplastin and thrombin time) was dependent on the hirudin plasma concentration. All test subjects tolerated the hirudin injection without visible or measurable side effects. No hirudin-specific antibodies were found after single parenteral administrations.