title: Platelet deposition inhibits tissue factor activity: in vitro clots are impermeable to factor Xa.
abstract: Upon plaque rupture or vascular injury, tissue factor (TF) protein in the vessel wall becomes exposed to flowing blood, initiating a cascade of reactions resulting in the deposition of fibrin and platelets on the injured site. Paradoxically, the growing thrombus may act as a barrier, restricting the convective and diffusive exchange of substrates and coagulation products between the blood and reactive vessel wall, thus limiting the role TF plays in thrombus growth. In this study, various in vitro, platelet-fibrin clots were prepared on TF:VIIa-coated surfaces and the rate at which factor (F) X in the well-mixed clot supernatant permeates the clot and is converted to X(a) was monitored over several hours. The apparent diffusion coefficients of FX((a)) in fibrin and platelet-fibrin clots at 37 degrees C was 2.3 x 10(-7) and 5.3 x 10(-10) cm(2)/second, respectively, indicating that the mean time required for FX((a)), and likely FIX((a)), to diffuse 1 mm in a fibrin clot is 4 hours, and in the presence of platelets, 3.6 months. As complete human thrombotic occlusion has been observed within 10 minutes, an alternative source of procoagulant activity that can localize to the outer surface of growing thrombi, such as platelet factor XI or blood-borne TF, appears essential for rapid thrombus growth.
authors.affiliation: Division of Thrombosis Research, Mt Sinai School of Medicine, New York, NY 10029, USA. james.hathcock@mssm.edu
authors.forename: James J
authors.initials: JJ
authors.lastname: Hathcock
authors.forename: Yale
authors.initials: Y
authors.lastname: Nemerson
mesh_terms: D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D004058:Diffusion; D015942:Factor VIIa / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D015951:Factor Xa / Q000378:metabolism* / Q000493:pharmacokinetics; D005337:Fibrin / Q000737:chemistry / Q000502:physiology; D006801:Humans; D018613:Microscopy, Confocal; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D005337:Fibrin; D013925:Thromboplastin; D015942:Factor VIIa; D015951:Factor Xa