Antithrombotic and Platelet Activating Effects of Heparin in Prevention of Microarterial Thrombosis

It has been proposed that the limited effectiveness of heparin in preventing arterial thrombosis may be caused by heparin-mediated platelet activation. The effect of heparin on platelets and thrombus formation in vivo was investigated using a microarterial model of thrombosis involving registration of labeled platelets. Three groups of six rabbits each were treated with either saline, standard heparin, or heparin with low affinity for antithrombin III (LA-heparin), which exhibits a low anticoagulant potential but has a molecular weight distribution similar to standard heparin. (Fifty to 70 percent of standard heparin consists of low-affinity material). The heparins were infused intravenously at doses of 1 mg/kg body weight, followed by maintenance injections. Platelet accumulation was significantly increased in the LA-heparin group compared with the saline group, demonstrating heparin-induced platelet activation in vivo. In contrast to a powerful anticoagulant response observed in rabbit plasma, the antithrombotic effect of standard heparin was expressed incompletely. (Only two of three of the treated vessels remained patent). This study demonstrates heparin-induced platelet activation in vivo in conditions of platelet-mediated thrombus formation. The observations are consistent with the concept of heparin-induced platelet activation as one of the mechanisms explaining the limited effects of heparin in preventing arterial thrombosis.