Abstract
Immunological mechanisms have been shown to be involved in heparin-induced thrombocytopenia (HIT), type II, but the mechanisms involved in HIT, type I seem to be still unknown. We previously showed that activation of platelets by mechanical stimulation such as stirring and binding of RGDS-containing proteins to the GPIIb-IIIa complex followed by their clustering are necessary for platelet aggregation in the presence of heparin in vitro. To see the effect of heparin structure on the platelet activation induced by mechanical stirring and exposure to the cold, we compared low-molecular weight heparin and two types of heparinoids: Hirudoid and danaparoid, with un-fractionated heparin. A low but significant degree of platelet aggregation was observed in the presence of low-molecular weight heparin by stirring, but not by exposure to the cold. A low but significant degree of platelet aggregation was noted in the presence of danaparoid solely under exposure of platelets to the cold. On the contrary, a significantly increased platelet aggregation was induced by Hirudoid as compared with un-fractionated heparin by both stirring and exposure to the cold. The platelet aggregation induced by Hirudoid was, however, efficiently blocked by the addition of a tetrapeptide, RGDS, as that induced by un-fractionated heparin. Thus the molecular weight and the sulfacted structure of heparin appear to play some important roles in the heparin-induced platelet aggregation.
