Heparin-induced thrombocytopenia: effect of heparin platelet antibody on platelets.
The plasma of two patients with heparin-induced thrombocytopenia has been shown to cause platelet aggregation in the presence of heparin. The platelet aggregating factor was isolated in the IgG reaction of the patients' sera suggesting that it was an antibody. This heparin anti-platelet antibody (HAP-Ab) induced platelet aggregation and release but did not cause platelet lysis, although it fixed complement. Platelet aggregation was inhibited by EDTA and by inactivation of complement. There was a significant production of malondialdehyde (MDA) and thromboxane B2 (TXB2) implying a role of the prostaglandin synthesis pathway in HAP-Ab induced aggregation. ADP-release also appeared to be involved as apyrase blocked aggregation while hirudin, a thrombin inhibitor, had no effect. The thrombotic complications that have recently been reported in patients with heparin-induced thrombocytopenia may be explained by some effects of HAP-Ab on platelets, namely: the antibody mediated platelet factor 3 release, prostaglandin endoperoxides and thromboxane A2 (TXA2) production and platelet aggregation in vivo. These HAP-Ab mediated effects could be inhibited by anti-platelet drugs such as aspirin, indomethacin and dipyridamole and thus may have therapeutic implications.
D000244:Adenosine Diphosphate / Q000097:blood; D000328:Adult; D000906:Antibodies / Q000276:immunology*; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000276:immunology*; D003168:Complement Fixation Tests; D004176:Dipyridamole / Q000494:pharmacology; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010977:Platelet Factor 3 / Q000378:metabolism; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D013929:Thromboxane B2 / Q000097:blood
D000906:Antibodies; D010977:Platelet Factor 3; D008315:Malondialdehyde; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D004176:Dipyridamole; D006493:Heparin; D001241:Aspirin; D007213:Indomethacin