Dextran 40 reduces heparin-mediated platelet aggregation

Using platelet aggregometry, we investigated the in vitro efficacy of dextran, mean MW 40,000, in reducing the heparin-mediated platelet aggregation seen with the syndrome of heparin-associated thrombocytopenia (HAT). Six patients with the clinical syndrome of HAT were studied who had a plasma factor which induced aggregation of normal platelets in the presence of heparin. At a final concentration of 2% (20 mg/ml) Dextran 40 reduced heparin-stimulated aggregation by 60.5 +/- 36% (SD) in mixtures of normal platelet-rich plasma/HAT patient plasma. In contrast, the same dextran concentration reduced ADP-stimulated aggregation of normal platelet-rich plasma by only 18.6 +/- 12%. This selective inhibition of heparin-mediated aggregation by dextran was highly significant (P less than 0.005, Wilcoxon rank sum). Whereas protamine abolished heparin's anticoagulant and platelet aggregating activity, dextran had no effect on heparin's anticoagulant properties. These data show that Dextran 40 selectively blocks heparin-mediated aggregation in vitro, perhaps by blocking heparin binding to the platelet membrane. This study suggests that dextran may be a clinically useful adjunct in the treatment of HAT, and describes a simple method for testing the efficacy of drugs in the treatment of HAT.