Evidence for a role in thrombus stabilization for thromboxane A2 in human platelet deposition on collagen.
The role of thromboxane A2 (TxA2) in platelet deposition onto collagen was studied in flowing whole heparinized human blood in vitro by using a cyclooxygenase inhibitor, aspirin, and a TxA2 receptor antagonist, GR32191B. Previous studies have demonstrated a role for TxA2 in platelet aggregation in citrated plasma, and for platelet deposition in flowing citrated human and rabbit blood, but not in flowing heparinized rabbit blood. In contrast with the literature regarding rabbit blood, aspirin was demonstrated to be effective in reducing platelet accumulation in heparinized human blood, as was GR32191B. The temporal pattern of the platelet deposition, which reached an asymptote with TxA2 inhibition at 2.0 minutes but did not do so without inhibition, suggested that TxA2 plays a role in thrombus stabilization. The reduction in platelet deposition (which included some aggregation) seen with aspirin and GR32191B in the first 1.5 minutes of perfusion indicated that some inhibition of platelet recruitment occurred. Scanning electron microscopy revealed that less fibrin was present in thrombi derived from GR32191B-treated heparinized blood than in thrombi derived from control heparinized blood. No fibrin formation was observed in citrated blood with or without TxA2 inhibition. It is proposed that, in addition to its role as a mediator of platelet recruitment, TxA2 is involved in the stabilization of platelet-platelet interactions in the thrombus, perhaps by enhancing local fibrin formation or binding.
Wagner
W R
WR
Department of Chemical Engineering, University of Texas, Austin 78712.
Hubbell
J A
JA
D001241:Aspirin / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D002951:Citrates / Q000494:pharmacology; D003094:Collagen; D006493:Heparin / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000502:physiology*; D017482:Receptors, Thromboxane; D013927:Thrombosis / Q000097:blood* / Q000473:pathology; D013928:Thromboxane A2 / Q000502:physiology*
D001713:Biphenyl Compounds; D002951:Citrates; D006538:Heptanoic Acids; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D006493:Heparin; D003094:Collagen; C060013:vapiprost; D001241:Aspirin