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PubMed · 8145000

Complement-mediated fragmentation and lysis of opsonized platelets: ender differences in sensitivity.

L L Horstman·W Jy·D R Schultz·W W Mao·Y S Ahn
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Abstract

It was reported that elevated levels of platelet microparticles (PMPs) in patients with immune thrombocytopenic purpura (ITP) were associated with decreased bleeding, and in some cases with small vessel thromboses (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 serum as a source of complement. PMP generation and lysis were monitored by flow cytometer, by release of lactic dehydrogenase, and by generation 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 serum, both monoclonal antibodies promoted PMP shedding in a concentration-dependent manner without loss of platelet population; at higher concentrations, extensive lysis occurred, but marked variations in resistance to lysis were observed in platelets from different individuals. The PMPs produced were associated with increased procoagulant activity, as measured by the Russell's viper venom test. The immunoglobulin M antibody was more potent than the immunoglobulin G antibody in promoting lysis, and the resulting PMPs had greater procoagulant activity. To clarify 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 men's. This may explain in part why ITP is three to four times more prevalent 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 that the determining factors are the concentration and nature of antibody as well as individual differences in sensitivity to complement-mediated damage. Because complement activation can occur without participation of antibody, complement activation may also be the cause of elevated PMP levels seen in other thrombotic disorders not involving platelet-specific antibodies.

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AdultBlood PlateletsComplement System ProteinsFemaleFlow CytometryHumansMaleMiddle AgedOpsonin ProteinsPurpura, Thrombocytopenic, IdiopathicSex CharacteristicsJournal ArticleResearch Support, Non-U.S. Gov't

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L L Horstman, W Jy, D R Schultz, W W Mao, Y S Ahn. 1994. Complement-mediated fragmentation and lysis of opsonized platelets: ender differences in sensitivity.. https://pubmed.ncbi.nlm.nih.gov/8145000/

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