Hirudin in heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT), a serious side effect of heparin treatment, requires alternative anticoagulation in most affected patients. The recombinant hirudin (r-hirudin) lepirudin has been approved for this purpose after two prospective trials in laboratory-confirmed HIT patients. Other drugs available for this purpose are danaparoid sodium (a heparinoid) and argatroban, a synthetic direct thrombin inhibitor. In this article, recommendations for optimal use of r-hirudin in HIT are given, covering therapy in uncomplicated patients as well as in special situations such as heparin reexposure of HIT patients. Because lepirudin's half-life depends on renal function, it may vary between 1 and 200 hours, which requires individual dose adjustments. Lepirudin compares favorably with danaparoid, based on retrospective data. No direct comparisons of lepirudin with argatroban are available, but argatroban might offer advantages in patients with renal failure, because it is mainly eliminated hepatically. Major hemorrhage, the main risk of lepirudin treatment, occurring in about 15% of patients, makes close monitoring important. New monitoring tools, such as the ecarin clotting time (ECT), might further reduce bleeding risks. Antihirudin antibodies, which can alter the pharmacokinetics as well as the pharmacodynamics of hirudin, can also be countered by close monitoring and appropriate dose adjustments. Whereas hirudins have not yet managed to gain importance in non-HIT indications such as unstable coronary syndromes, they have a major role to play in the treatment of HIT. The choice between the available drugs for HIT, namely lepirudin, danaparoid, and argatroban, has to be made according to the clinical presentation of the patient.
Lubenow
Norbert
N
Ernst-Moritz-Arndt University, Greifswald, Germany.
Greinacher
Andreas
A
D000925:Anticoagulants / Q000494:pharmacology; D000991:Antithrombins / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives; D001777:Blood Coagulation; D002809:Chondroitin Sulfates / Q000494:pharmacology; D002986:Clinical Trials as Topic; D003871:Dermatan Sulfate / Q000494:pharmacology; D004338:Drug Combinations; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006493:Heparin / Q000009:adverse effects / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000494:pharmacology; D024764:Hirudin Therapy; D006629:Hirudins / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D010875:Pipecolic Acids / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000188:drug therapy*; D013927:Thrombosis / Q000188:drug therapy; D013997:Time Factors
D000925:Anticoagulants; D000991:Antithrombins; D001120:Arginine; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D004338:Drug Combinations; D005343:Fibrinolytic Agents; D006493:Heparin; D006497:Heparan Sulfate; D006629:Hirudins; D010875:Pipecolic Acids; D011994:Recombinant Proteins; D013449:Sulfonamides; C035838:danaparoid; C031942:argatroban; C083544:lepirudin