Pharmacological Properties of Hirudin and its Derivatives

Abstract

Hirudin and its derivatives represent the first parenteral anticoagulants introduced since the discovery of heparin in the early 1900s. Hirudin, the naturally occurring anticoagulant of the leech, is a single peptide chain of 65 amino acids with a molecular weight of about 7000. Recombinant technology has developed methods to produce recombinant forms of hirudin (r-hirudin) in sufficient quantities for therapeutic use. Hirudin is a potent thrombin-specific inhibitor that forms equimolar complexes with thrombin. It represents a new anticoagulant agent in a field in which heparin has been the only available drug for many years. In contrast to heparin, hirudin does not require antithrombin III as a cofactor, is not inactivated by antiheparin proteins, has no direct effects on platelets and may also inactivate thrombin bound to clot or the subendothelium. In humans, experience with r-hirudin in preventing or treating venous thromboembolism is very preliminary. However, r-hirudin achieved promising results in patients with unstable angina, or following coronary angioplasty. In patients with acute myocardial infarction, 3 important clinical trials were stopped because of an excess of bleeding complications. At present, the discovery of a r-hirudin regimen that is more efficacious than heparin and at least as safe needs a reappraisal of the drug in further trials.

Treatment of Heparin-Induced Thrombocytopenia: Is There a Role for Bivalirudin?

“…2 Many pharmacologic differences exist among the direct thrombin inhibitors (Table 1). 2,4,[6][7][8][9][10] Lepirudin Lepirudin is indicated for anticoagulation in patients with HIT and associated thromboembolic disease in order to prevent thromboembolic complications. 6 Lepirudin is a recombinant form of hirudin, isolated from the leech, and it differs from the natural product by the substitution of leucine for isoleucine at the N-terminal and the deletion of a sulfate group on tyrosine 63.…”

Pharmacotherapy of heparin-induced thrombocytopenia

“…When given as a subcutaneous injection or as an intravenous bolus with infusion, there is a direct dose-response relationship between desirudin and both the aPTT and the thrombin time [60]. Excretion is primarily by the kidneys (40 -60% removed unchanged) and the half-life is 2 -3 h [61].…”

The Management of Suspected Heparin-Induced Thrombocytopenia in US Hospitals

“…4,5 However, heparins have several limitations, including patient-to-patient variability in anticoagulation response, an inability to inhibit clot-bound thrombin, and risk of associated thrombocytopenia. [6][7][8][9] Thrombocytopenia is common, occurring in up to 36% of hospitalized patients receiving heparin. 10 It is associated with poor short-term outcomes, including the risk of thrombosis and death.…”