DANAPAROID - A REVIEW OF ITS PHARMACOLOGY AND CLINICAL USE IN THE MANAGEMENT OF HEPARIN-INDUCED THROMBOCYTOPENIA

Danaparoid, a low molecular weight heparinoid consisting of a mixture of heparan, dermatan and chondroitin sulfates, has well established an tithrombotic activity. The drug has a high antifactor Xa to antifactor IIa (thrombin) activity ratio, a low tendency to cause bleeding and m inimal effects on the fibrinolytic system. Danaparoid has a low cross- reactivity rate with heparin-associated antiplatelet antibodies (0 to 20%: mean approximate to 10%). This represents a significant advantage over low molecular weight heparins (LMWHs) as a potential replacement agent for unfractionated heparin (UFH) in patients with immune-mediat ed (type II) heparin-induced thrombocytopenia (HIT). In a worldwide co mpassionate-use programme involving a total of 667 patients with HIT t o date, 93% of danaparoid treatment courses were considered to be succ essful. Thrombocytopenia resolved in 91% of episodes. In a multicentre randomised comparative trial of danaparoid and dextran in patients wi th HIT plus thrombosis (HITT), significantly more danaparoid than dext ran recipients had resolution of thromboses, and an effective clinical response was achieved in significantly more danaparoid recipients. Re sults of a retrospective case-controlled study of danaparoid and ancro d in patients with HITT showed significantly fewer new or progressive thromboses with danaparoid. In the compassionate-use programme, danapa roid was associated with a mortality rate of 10.4% during treatment (u p to 3.5 years) and 7.8% during the follow-up period (3 months). 14 of 114 deaths during the follow-up period were considered to be related to danaparoid therapy. A mortality rate of 23.5% was reported in patie nts accepted for, but not treated with, danaparoid. Mortality rates wi th danaparoid, ancrod and dextran in the comparative studies were simi lar (7, 11 and 12% respectively). Severe bleeding was reported in 3.1% of patients in the compassionate-use programme, persistent or recurre nt thrombocytopenia in 2.6% and new thromboembolic events/extension of existing thrombosis in 1.7%. The incidence of bleeding was similar wi th danaparoid and dextran in a comparative trial. Although in vitro cr oss-reactivity does not always translate into clinical cross-reactivit y, testing is currently recommended, when possible, before initiation of danaparoid therapy. Thus, danaparoid appears to be an effective and well tolerated replacement agent for UFH in many patients with HIT wh o require further anticoagulation. The drug has low cross-reactivity w ith HIT-associated antibodies. Further comparative trials are needed t o confirm these promising findings.