Mechanism and characteristics of platelet activation by haematin.
The mechanism as well as some characteristics of haematin-induced human platelet aggregation were investigated. Haematin-induced platelet aggregation required the presence of devalent cations; Mg2+, and to a lesser extent, Co2+, were just as effective as Ca2+ in supporting the aggregation. Mono- and trivalent cations were ineffective. Verapamil inhibited the aggregation. The aggregation was accompanied by thromboxane formation which could be abolished by aspirin. The release of adenine nucleotides was only slightly inhibited by aspirin. The rate of aggregation and the ultrastructure of the aggregated platelets were comparable between control and aspirin-treated samples. It is concluded therefore that haematin-induced aggregation is not dependent on platelet prosta-glandin synthesis. Haematin induced binding of fibrinogen to platelets, and failed to aggregate thrombasthenic platelets. These findings indicate that haematin may induce platelet aggregation by promoting influx of divalent cations in association with increased fibrinogen binding and release of adenine nucleotides.
D000255:Adenosine Triphosphate / Q000097:blood; D001081:Apyrase / Q000494:pharmacology; D001791:Blood Platelet Disorders / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D002413:Cations, Divalent / Q000494:pharmacology; D002648:Child; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008854:Microscopy, Electron; D010974:Platelet Aggregation / Q000187:drug effects*; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D013931:Thromboxanes / Q000096:biosynthesis; D014700:Verapamil / Q000494:pharmacology
D002413:Cations, Divalent; D011457:Prostaglandins D; D011465:Prostaglandins, Synthetic; D013931:Thromboxanes; D006418:Heme; D006427:Hemin; D000255:Adenosine Triphosphate; D005340:Fibrinogen; D006493:Heparin; D014700:Verapamil; D011464:Epoprostenol; D001081:Apyrase; D015230:Prostaglandin D2