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-induced thrombocytopenia type I. An ELISA was developed for directly measuring 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 expression of GPIIb/IIIa without prior stimulation with ADP. On the other hand we could demonstrate that the addition of heparins and protamine sulfate to platelets resulted in a significant release of intracellularly stored ADP and PF4. These results suggested that heparin(oid)s modulate the expression of GPIIb/IIIa with ADP as a mediator, and that protamine sulfate is contraindicated as an antidote in heparin-induced thrombocytopenia.
Physiologisches Institut II, Westfälische Wilhelms-Universität, Münster, Deutschland.
J
J
Storck
N
N
Höllger
R E
RE
Zimmermann
D000244:Adenosine Diphosphate / Q000097:blood* / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010978:Platelet Factor 4 / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis*; D011479:Protamines / Q000494:pharmacology*
D010980:Platelet Membrane Glycoproteins; D011479:Protamines; D010978:Platelet Factor 4; D000244:Adenosine Diphosphate; D006493:Heparin