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Hirudin in heparin-induced thrombocytopenia.

Abstract
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.
AuthorsNorbert Lubenow, Andreas Greinacher
JournalSeminars in thrombosis and hemostasis (Semin Thromb Hemost) Vol. 28 Issue 5 Pg. 431-8 (Oct 2002) ISSN: 0094-6176 [Print] United States
PMID12420238 (Publication Type: Journal Article, Review)
Chemical References
  • Anticoagulants
  • Antithrombins
  • Drug Combinations
  • Fibrinolytic Agents
  • Hirudins
  • Pipecolic Acids
  • Recombinant Proteins
  • Sulfonamides
  • Dermatan Sulfate
  • Heparin
  • Chondroitin Sulfates
  • Heparitin Sulfate
  • Arginine
  • danaparoid
  • argatroban
  • lepirudin
Topics
  • Anticoagulants (pharmacology)
  • Antithrombins (pharmacology)
  • Arginine (analogs & derivatives)
  • Blood Coagulation
  • Chondroitin Sulfates (pharmacology)
  • Clinical Trials as Topic
  • Dermatan Sulfate (pharmacology)
  • Drug Combinations
  • Fibrinolytic Agents (pharmacology)
  • Heparin (adverse effects, pharmacology)
  • Heparitin Sulfate (pharmacology)
  • Hirudin Therapy
  • Hirudins (analogs & derivatives, pharmacology)
  • Humans
  • Pipecolic Acids (pharmacology)
  • Recombinant Proteins (pharmacology)
  • Sulfonamides
  • Thrombocytopenia (drug therapy)
  • Thrombosis (drug therapy)
  • Time Factors

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