On the Mechanism of Platelet Aggregation Induced by Heparin, Protamine and Polybrene

Heparin and the two heparin‐neutralizing agents protamine and polybrene aggregated washed human platelets by different mechanisms. The aggregation by heparin was preceded by a lag phase and was inhibited by EDTA, adenosine, apyrase, acetylsalicylic acid and inhibitors of platelet metabolism. It is concluded that heparin aggregates platelets by inducing release of platelet ADP. In contrast, the aggregation by protamine and polybrene occurred immediately and was not influenced by the above mentioned inhibitors. It is concluded that protamine and polybrene aggregate platelets by a direct effect on the platelet membrane. Polybrene was, weight for weight, approximately twice as potent as protamine, in accordance with their antiheparin effect. Some possible reasons for the conflicting reports concerning the aggregating effect of heparin on platelets are discussed.