Heparin, Platelets and Blood Coagulation: Implications for Low‐Dose Heparin Prophylactic Regimens in Venous Thrombosis

Summary. Heparin has been shown to inhibit the second phase of aggregation and the platelet release reaction induced by ADP. These platelet responses to ADP are mediated by thrombin, generated through the coagulation pathways, on the platelet membrane (Ardlie & Han, 1974), and evidence was obtained that the inhibitory action of heparin is due to inactivation of coagulation factor Xa in the presence of XaI. In contrast, it has been shown that thrombin adsorbed to the platelet surface is protected from destruction by its natural inhibitor and heparin. Since trace amounts of heparin were able to augment the inhibitory action of XaI on factor Xa, this phenomenon has relevance to low‐dose heparin regimens for prophylaxis of venous thrombosis. It is proposed that postoperative thrombosis is due to abnormal platelet function caused by accelerated coagulation, and that heparin prevents thrombosis through its anticoagulant action on factor Xa. It is also suggested that trace amounts of heparin which may be present normally in the circulation may act as a natural anticoagulant. One of two commercial preparations of heparin caused washed platelets, prepared by some, but not all, of the methods used, to aggregate and release their constituents. However, it was shown that these effects of heparin on washed platelets are simply a consequence of storage of platelets at 4°C, emphasizing the need to keep platelets at 37°C for in vitro studies. Heparin failed to inhibit the release reaction of platelets in citrated‐plasma, and it is suggested that this may be due to interference by citrate. These observations with washed platelets and citrated plasma are considered to be artefacts and thus have no relevance to heparin action in vivo.