[Direct inhibitors of thrombin, hirudin, bivalirudin, and dabigatran etexilate].
Thrombin inhibition is an important objective in the prevention and treatment of thrombosis. A new molecule, dabigatran etexilate or Pradaxa(®), has been recently licensed for thromboprophylaxis in major orthopedic surgery in several countries but not in the USA. In contrast, the FDA has approved it for prevention in patients with non-valvular atrial fibrillation. This new orally active anticoagulant is being developed for the treatment of venous thromboembolism and acute coronary syndromes in patients with non-valvular atrial fibrillation. Dabigatran is a reversible inhibitor of free thrombin and clot-bound thrombin. An oral thrombin inhibitor melagatran is no longer available due to hepatic toxicity. Several other thrombin inhibitors are used via parenteral administration: lepirudine and desirudine, bivalirudine and argatroban. They are mostly given to patients with heparin-induced thrombocytopenia (HIT). Bivalirudine is used for acute coronary syndrome in patients undergoing percutaneous interventions. The main pharmacologic characteristics of thrombin inhibitor agents are presented focusing on dabigatran etexilate and including the main results of clinical trials.
Unité hémostase-thrombose, service d'hématologie biologique, hôpital Hôtel-Dieu, Paris cedex 04, France. meddahi@laposte.net
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D000925:Anticoagulants / Q000627:therapeutic use; D000991:Antithrombins / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000075202:Contraindications; D000069604:Dabigatran; D004347:Drug Interactions; D006493:Heparin / Q000009:adverse effects; D024764:Hirudin Therapy; D006629:Hirudins; D006801:Humans; D019637:Orthopedic Procedures / Q000009:adverse effects; D010446:Peptide Fragments / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000517:prevention & control; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000188:drug therapy
D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D006629:Hirudins; D010446:Peptide Fragments; D011725:Pyridines; D011994:Recombinant Proteins; D006493:Heparin; D000069604:Dabigatran; C074619:bivalirudin