Heparin-induced thrombocytopoenia — argatroban
Blood clots are generally treated with heparin, a very effective anticoagulant drug, which is generally well tolerated and relatively simple to administer. However, it can lead to the potentially serious side effect of heparin-induced thrombocytopoenia (HIT), where the blood contains insufficient platelets for effective clotting.1
Two forms of the condition exist. Type I is caused by a direct interaction between platelets and heparin, and is not serious. Type II, however, can be life-threatening, and is an immune-mediated condition that can result in the formation of venous or arterial thromboses or even pulmonary embolism. It is estimated to occur in between 1 and 5% of patients being treated with heparin.
A new treatment for HIT is the drug argatroban. It is a reversible thrombin inhibitor, binding directly to thrombin and inhibits fibrin formation, as well as preventing the activation of coagulation factors V, VIII and XIII and the natural anticoagulant protein C.2 Unlike heparin, it has been found to bind to thrombin that is bound in clots as well as thrombin free in solution.3
A non-randomised Phase III trial of argotroban's efficacy in 304 patients with HIT has been carried out, just under half of which had thrombosis as well as HIT.4 The drug was administered intravenously, with a starting dose of 2µg/kg/min, for six days on average.
Compared to a historical control, the incidence of death, amputation or new thrombosis was significantly lower in argotroban-treated patients, and risk of bleeding did not increase.
No serious side-effects were observed, the most common problems being dizziness, headache and pain at the administration site.
The drug has been found to be an effective inhibitor of thrombin, both free and bound, and is currently undergoing multinational Phase II and III trials to establish its clinical effectiveness as an anticoagulant drug.