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Subcutaneous Direct Thrombin Inhibitor (Desirudin) Approved for Prevention of Deep Vein Thrombosis in the United States and Shown to be Superior to Heparin and Enoxaparin
Victor F. Tapson, MD
Desirudin (brand name Iprivask) is the first direct thrombin inhibitor approved in the United States for the prevention of deep venous thrombosis (DVT). In studies published in 1997, desirudin was found to be superior to both heparin1 and the low molecular weight heparin (LMWH) enoxaparin2 in head-to-head clinical trials for prevention of proximal deep venous thrombosis and for major venous thromboembolic events after elective hip replacement surgery. In both studies, administration of drug was started prior to the surgery (the "European" regimen). Based on use during the clinical trials in 2,159 patients undergoing elective hip replacement surgery, a comparable incidence of hemorrhagic events was seen in patients using desirudin, heparin, and enoxaparin.
Although heparin-based anticoagulation is adequate for many patients, the CATCH registry3 revealed that approximately 30% of patients receiving subcutaneous heparin for VTE prophylaxis experienced thrombocytopenia, and these patients had an increase in short-term mortality. Furthermore, in clinical practice, the development of thrombocytopenia often results in suspension of venous thromboembolism prophylaxis with heparin-based anticoagulation leaving patients unprotected for a period of time due to the lack of adequate alternatives.
As a direct thrombin inhibitor, desirudin does not cause thrombocytopenia or heparin-induced thrombocytopenia, is relatively short-acting, and is easy to monitor. It is administered as a fixed subcutaneous dose making it much simpler to use than intravenous direct thrombin inhibitors. Desirudin is contraindicated in patients with known hypersensitivity to natural or recombinant hirudins, and in patients with active bleeding and/or irreversible coagulation disorders. Based on the package insert information, dosage reduction is warranted in patients with a creatinine clearance of 60 ml/min/1.73 m2. The combined use of desirudin and warfarin, according to the package insert, create a monitoring issue because each medication enhances the other medication's effect to further elevate the aPTT and/or the PT/INR.
- Eriksson BI, Ekman S, Lindbratt S, et al. Prevention of Thromboembolism with Use of Recombinant Hirudin. Results of a Double-Blind, Multicenter Trial Comparing the Efficacy of Desirudin (Revasc) with That of Unfractionated Heparin in Patients Having a Total Hip Replacement. Journal of Bone and Joint Surgery Am. 1997; 79:326-333.
- Eriksson BI, Wille-Jorgensen P, Kalebo P, et al. A Comparison of Recombinant Hirudin with a Low-Molecular-Weight Heparin to Prevent Thromboembolic Complications after Total Hip Replacement New England Journal of Medicine 1997; 337:1329-1335.
- Oliveira GBF, Crespo EM, Becker RC, et al. Incidence and Prognostic Significance of Thrombocytopenia in Patients Treated With Prolonged Heparin Therapy. Archives of Internal Medicine 2008; 168:94-102.
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