An objective assessment of the interaction of heparin and its fractions with human platelets.
We have shown that heparin and heparin fractions cause in vitro platelet aggregation in a large portion of a normal population. Furthermore, this aggregation occurs in a concentration-dependent manner and is not related to the anti-Xa activity of heparin or its fractions. In addition, it appears that at least part of the mechanism by which heparin induces aggregation is through the production of thromboxane. However, this is not the sole mechanism, since approximately 20% aggregation still occurs when thromboxane production is totally inhibited or the thromboxane receptor is completely blocked. Furthermore, although protamine (at the concentrations used) completely neutralizes the anticoagulant activity of heparin, it does not always completely inhibit the platelet aggregating activity of heparin. Finally, we have shown that heparin alone promotes thromboxane production and PF4 release in a whole blood system. Additional studies are needed to characterize further the mechanisms of heparin-induced platelet aggregation.
D000255:Adenosine Triphosphate / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010978:Platelet Factor 4 / Q000097:blood; D011466:Prostanoic Acids / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood
D011466:Prostanoic Acids; D011479:Protamines; D010978:Platelet Factor 4; D013929:Thromboxane B2; C022574:13-azaprostanoic acid; D000255:Adenosine Triphosphate; D006493:Heparin; D007213:Indomethacin