THE INFLUENCE OF HEPARIN AND PROTAMINE SULFATE ON PLATELET ADP AND PLATELET FACTOR-4 RELEASE AND THE EXPRESSION OF GLYCOPROTEIN-IIB IIIA/

We present results concerning the pathogenic mechanism of heparin-indu ced thrombocytopenia type I. An ELISA was developed for directly measu ring the expression of glycoprotein IIb/IIIa (GPIIb/IIIa) on platelets in the presence and absence of ADP and under the influence of various heparins. In addition, the release of ADP and platelet factor 4 (PF4) was measured in platelet-rich plasma. Heparin also induced the expres sion of GPIIb/IIIa without prior stimulation with ADP. On the other ha nd we could demonstrate that the addition of heparins and protamine su lfate to platelets resulted in a significant release of intracellularl y stored ADP and PF4. These results suggested that heparin(oid)s modul ate the expression of GPIIb/IIIa with ADP as a mediator, and that prot amine sulfate is contraindicated as an antidote in heparin-induced thr ombocytopenia.