Function of lepirudin in heparin-induced thrombocytopenia



Developed by the German company Hoechst Marion Roussel and derived from genetic modification of hirudin, lepirudin is the most important and most commonly used recombinant hirudin. Hirudin is a drug with both antiplatelet aggregation and anticoagulation effect. Compared with hirudin, recombinant hirudin has more effective pharmacological effects and fewer adverse reactions. Lepirudin has almost the same chemical structure as hirudin extracted from Hirudo medicinalis, which differs by the substitution of leucine for isoleucine at the N-terminal end of the molecule and the absence of a sulfate group on the tyrosine at position 63. Lepirudin has been developed for the treatment of heparin-induced thrombocytopenia (HIT).

Pharmacologic action

HIT is the development of thrombocytopenia and the therapy of this disease requires further anticoagulation. Thrombin is the most powerful substance to promote the activation of platelets. Lepirudin, when combined with thrombin, can weaken the action of thrombin activating platelets. Therefore lepirudin has a clear inhibitory effect on platelet aggregation by inhibiting the activation of platelets induced by thrombin. Lepirudin can also inhibit the binding site of coagulation factor I on thrombin, resulting in the inability of coagulation factor I to bind to thrombin, which directly inhibits the coagulation process. The whole anticoagulation process does not require the assistance of antithrombin III or other cofactors.


As a drug with both antiplatelet aggregation and anticoagulation effect, lepirudin has a wide range of clinical applications. Heparin is the most commonly used anticoagulant drug. But some patients will develop HIT in 5-10 days after the beginning of heparin therapy. For patients with a history of HIT, lepirudin can take the place of heparin when heparin is needed. Lepirudin can also be used in other diseases which need therapy of antiplatelet aggregation or anticoagulation effect, such as acute coronary syndrome, acute myocardial infarction, and deep venous thrombosis so on.

Pharmacokinetics and metabolism

Lepirudin is a peptide containing 65 amino acids with a molecular weight of about 6,980. Lepirudin can only be administered intravenously or subcutaneously, and can't be administered orally. A peak lepirudin concentration of about 0.7 mg·L-1 occurs in 3 to 4 hours after subcutaneous injection of 0.75 mg·kg-1. The terminal plasma elimination half-life (T1/2) is 0.8 to 1.7 hours after intravenous injection of 0.01 to 0.5 mg·kg-1 and 1.1 to 2.0 hours for continuous intravenous infusions over 6 hours. With intravenous or subcutaneous administration, bioavailability of lepirudin is nearly 100%. Since lepirudin is mainly metabolized in the kidney, lepirudin should be reduced appropriately with patients with mild renal insufficiency, and lepirudin should be forbidden or used with caution with patients with moderate or severe renal insufficiency.


1. Farner, B., Eichler, P., Kroll, H., Urban, G., & Greinacher, A. (2000, December). A first approach to compare efficacy and safety of lepirudin and danaparoid in patients with heparin‐induced thrombocytopenia (HIT). In Transfusion Medicine: Abstracts of papers presented at the 6th European Platelet, Granulocyte and Red Cell Immunobiology meeting, September 2000 (Vol. 10, No. 4, pp. 325-325). Oxford, UK: Blackwell Science Ltd.

2. Lubenow, N., Eichler, P., Lietz, T., Greinacher, A., & Hit Investigators Group. (2005). Lepirudin in patients with heparin‐induced thrombocytopenia–results of the third prospective study (HAT‐3) and a combined analysis of HAT‐1, HAT‐2, and HAT‐3. Journal of Thrombosis and Haemostasis, 3(11), 2428-2436.

3. Greinacher, A., & Lubenow, N. (2001). Recombinant hirudin in clinical practice: focus on lepirudin. Circulation, 103(10), 1479-1484.

4. Weitz, J. I., Leslie, B., & Hudoba, M. (1998). Thrombin binds to soluble fibrin degradation products where it is protected from inhibition by heparin-antithrombin but susceptible to inactivation by antithrombin-independent inhibitors. Circulation, 97(6), 544-552.

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