The inhibition of the anticoagulant activity of heparin by platelets, brain phospholipids, and tissue factor.
Platelets and phospholipids have been shown to protect factor Xa from inhibition by the heparin--antithrombin III complex. The studies reported herein investigated the effects of gel filtered platelets, activated platelets, brain phospholipids (cephalin), and brain tissue factor on the inactivation of thrombin and factor Xa by the heparin--antithrombin III complex. In addition, the relative anticoagulant effects of heparin on the extrinsic and intrinsic coagulation pathways were investigated. Our results suggest that gel filtered platelets, activated platelets, cephalin and tissue factor protect thrombin, as well as factor Xa, from inactivation by the heparin--antithrombin III complex. Tissue factor had the greatest anti-heparin activity. Activated platelets, gel filtered platelets, cephalin and tissue factor did not alter the protease--antithrombin III reaction rates measured in the absence of heparin. These observations are consistent with the hypothesis that platelets, brain phospholipids, and tissue factor, in the presence of calcium, partition heparin from antithrombin III, and thus prevent full expression of the antithrombin III-dependent anticoagulant activity of heparin.
D000990:Antithrombin III / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000502:physiology*; D001921:Brain; D005170:Factor X / Q000037:antagonists & inhibitors; D015951:Factor Xa; D006494:Heparin Antagonists; D006801:Humans; D010314:Partial Thromboplastin Time; D010714:Phosphatidylethanolamines / Q000494:pharmacology*; D011517:Prothrombin Time; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013925:Thromboplastin / Q000494:pharmacology*
D006494:Heparin Antagonists; D010714:Phosphatidylethanolamines; D000990:Antithrombin III; D005170:Factor X; D013925:Thromboplastin; D013917:Thrombin; D015951:Factor Xa