Treatment options for heparin-induced thrombocytopenia.
Appropriate management, as well as efficacy and safety, of heparin-induced thrombocytopenia (HIT) and prevention of severe consequences with argatroban and lepirudin are discussed. Heparin-induced thrombocytopenia, a serious immune-mediated drug reaction, can occur as an isolated incident (isolated HIT) or with acute thrombosis sometimes referred to as HIT and associated thrombosis syndrome (HITTS). Due to the severe consequences associated with HIT, appropriate management is critical. Argatroban and lepirudin, two direct thrombin inhibitors (DTIs), are currently FDA approved for use in patients with HIT. The clinical experience with these agents is critically examined in this article. The safety and efficacy of argatroban in management of HIT were the subject of a single published clinical trial. The study was designed to reflect conventional clinical practice, whereby treatment of patients with HIT was initiated upon clinical suspicion. In several of these patients, HIT antibodies could not be demonstrated. Compared to historical controls, argatroban demonstrated efficacy in patients with isolated HIT; however, no differences were observed in HIT patients with acute thrombosis. Rates of bleeding episodes did not differ between argatroban and control. The clinical efficacy and safety of lepirudin have been the subject of three clinical trials and one large drug monitoring program. Lepirudin has demonstrated benefit in HIT patients with or without existing thromboembolism. Bleeding rates were higher than in the historical control. However, bleedings requiring transfusion did not differ. Although no direct head-to-head comparison trials of argatroban and lepirudin have been conducted, parallels can be drawn between the agents based on careful review of published clinical trials. Consistently, rates of new thrombosis, limb amputation, and death appear to be lower in patients treated with lepirudin as compared with those treated with argatroban, whereas the risk for major bleeding per patient day seems to be similar with both DTIs.
Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University Greifswald, Diagnostikzentrum Saverbruchstrasse, 17487 Greifswald, Germany. greinach@uni-greifswald.de
Andreas
A
Greinacher
D000991:Antithrombins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D006493:Heparin / Q000009:adverse effects*; D006629:Hirudins / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D010875:Pipecolic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*; D013927:Thrombosis / Q000517:prevention & control; D014481:United States
D000991:Antithrombins; D006629:Hirudins; D010875:Pipecolic Acids; D011994:Recombinant Proteins; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban; C083544:lepirudin