Clinical utility of subcutaneous hirudins

Abstract

The clinical utility of subcutaneous hirudins is discussed. The term "hirudins" refers to a class of antithrombotic agents structurally derived from the medicinal leech salivary protein hirudin. Breakthroughs in biotechnology over the past 20 years have resulted in the development of recombinant versions of hirudin (r-hirudin). Lepirudin is one such r-hirudin that is identical to natural hirudin except for the substitution of leucine for isoleucine at the N-terminus and the elimination of a sulfate group on the tyrosine at position 63. Another r-hirudin, desirudin, is identical to hirudin except for a valine-valine in the N-terminus and the absence of the sulfate group on tyrosine at position 63. Both r-hirudins are bivalent and tightly bind to both the catalytic site and the exposite of thrombin to exert their inhibitory effects on thrombin. Unfractionated heparin (UF) and low-molecular-weight heparins (LMWHs) are widely used in medical and surgical patients to prevent and treat arterial and venous thrombotic events. Besides bleeding, the major adverse effect of heparins is heparin-induced thrombocytopenia (HIT). HIT is associated with a paradoxical hypercoagulable state and marked risk of clinical thrombosis. Management of HIT requires the immediate cessation of all heparin exposure, and the initiation of an alternative anticoagulant. Because r-hirudins are effective agents and do not cross-react with HIT-associated antibodies, they are excellent anticoagulants in patients with past or current HIT. Clinical trials have also demonstrated the efficacy and safety of subcutaneous (s.c.) r-hirudins compared to heparins in non-HIT settings. Results of these trials support the use of r-hirudin therapy in patients with HIT or at risk of developing HIT. Additionally, case reports have described safe and effective use of s.c. r-hirudin therapy in the outpatient setting in both HIT and non-HIT patients.