COMPLEMENT-MEDIATED FRAGMENTATION AND LYSIS OF OPSONIZED PLATELETS - GENDER DIFFERENCES IN SENSITIVITY

It was reported that elevated levels of platelet microparticles (PMPs) in patients with immune thrombocytopenic purpura (ITP) were associate d with decreased bleeding, and in some cases with small vessel thrombo ses (J LAB CLIN MED 1992;119:334). To investigate the possible role of complement in PMP production in ITP, an in vitro assay was developed to simulate ITP: platelets were opsonized with well-defined monoclonal antibodies against glycoprotein IIb/IIIa, of immunoglobulin G (alpha- CD41), and of immunoglobulin M (alpha-Plt-1) class, then exposed to se rum as a source of complement. PMP generation and lysis were monitored by flow cytometer, by release of lactic dehydrogenase, and by generat ion of procoagulant activity. These effects were largely abolished by heating the serum (30 minutes, 65 degrees) or by incubation with alpha -C1q, confirming the role of complement. At low concentrations of seru m, both monoclonal antibodies promoted PMP shedding in a concentration -dependent manner without loss of platelet population; at higher conce ntrations, extensive lysis occurred, but marked variations in resistan ce to lysis were observed in platelets from different individuals. The PMPs produced were associated with increased procoagulant activity, a s measured by the Russell's viper venom test. The immunoglobulin M ant ibody was more potent than the immunoglobulin G antibody in promoting lysis, and the resulting PMPs had greater procoagulant activity. To cl arify the variation seen in platelets from different donors, data was sorted on the basis of gender, with the finding that women's platelets are significantly more sensitive to complement-mediated damage than m en's. This may explain in part why ITP is three to four times more pre valent in women than in men. We conclude that complement activation is the most likely explanation for the elevated level of PMPs often seen in patients with ITP and sometimes associated with thrombosis and tha t the determining factors are the concentration and nature of antibody as well as individual differences in sensitivity to complement-mediat ed damage. Because complement activation can occur without participati on of antibody, complement activation may also be the cause of elevate d PMP levels seen in other thrombotic disorders not involving platelet -specific antibodies.