Hirudin in the treatment of arterial and venous thrombotic diseases: a new perspective.
The first description of the anticoagulant action of a water-soluble, heat-resistant substance derived from the salivary glands of leeches (Hirudo medicinales) dates back to 1884. This substance was later called hirudin in 1904. Almost no research was done with this compound until the 1960's. More recently, after hirudin or fractions of it have been produced by recombinant techniques as well as by synthetic methods, there has been a fast growing interest in the clinical potential of this specific thrombin inhibitor. Hirudin is in particular effective in the inhibition of the feedback action of the coagulation system by thrombin. In addition hirudin is a potent inhibitor of the thrombin mediated platelet aggregation. At present this compound is investigated both in the treatment and prevention of venous and arterial thromboembolic diseases in experimental models as well as in man. With respect to acute coronary events hirudin is evaluated in models and patients with unstable angina, or with acute myocardial infarction treated with thrombolytic therapy, and also in patients undergoing PTCA in order to prevent restenosis. The preliminary clinical experience indicate that hirudin is well tolerated after intravenous and subcutaneous administration and that sustained plasma inhibitory activity can be obtained. Small comparative trials with heparin suggest that hirudin is at least as effective with a comparable safety profile. In the prevention of venous thrombosis following hip surgery, a dose finding study showed an efficacy superior to that obtained in earlier low molecular weight heparin studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Büller
H R
HR
Centre for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Centre, Amsterdam, The Netherlands.
D000818:Animals; D024764:Hirudin Therapy; D006801:Humans; D015912:Thrombolytic Therapy; D013924:Thrombophlebitis / Q000188:drug therapy*; D013927:Thrombosis / Q000188:drug therapy*