title: Modulation of intrinsic prothrombin activation by fibrinogen and fibrin I.
abstract: Recent observations raise the possibility that by binding thrombin, fibrin(ogen) could modulate prothrombin activation, perhaps by modulating thrombin-mediated activation of factors VIII and V. Factors VIIIa and Va are the cofactors of intrinsic tenase and prothrombinase, respectively. This study compared the profile of prothrombin activation in pooled normal plasma, defibrinated pooled normal plasma, and pooled normal plasma containing fibrin I. Prothrombin activation was initiated with three stimuli, as follows: (1) addition of a suspension of thrombin, CaCl2, and coagulant phospholipids to plasma; (2) contact activation followed by recalcification of plasma; and (3) addition of a suspension of crude rabbit brain tissue factor and CaCl2 to plasma. Each plasma sample contained 2 mmol/L gly-pro-arg-pro, which prevents the polymerization of fibrin. Prothrombin activation, indexed as the concentration of prothrombin activation fragment 1 + 2 produced, was quantitated by enzyme-linked immunosorbent assay. Fibrinogen significantly delayed the onset of prothrombin activation initiated by thrombin or by contact activation but not that initiated with tissue factor. In contrast, fibrin I in solution accelerated prothrombin activation initiated with thrombin or by contact activation. Although fibrinogen had no effect on intrinsic activation of factor IX or factor IX activation initiated by adding thrombin to plasma, it inhibited factor X activation initiated with either stimuli. We therefore conclude that fibrinogen can inhibit the activation of factor X and prothrombin. Second, fibrin I accelerates prothrombin activation. Fibrinogen and fibrin, therefore, have the potential to bioregulate blood coagulation.
authors.affiliation: Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: J I
authors.initials: JI
authors.lastname: Okwusidi
authors.forename: N
authors.initials: N
authors.lastname: Anvari
authors.forename: F A
authors.initials: FA
authors.lastname: Ofosu
mesh_terms: D005164:Factor IX / Q000502:physiology; D005170:Factor X / Q000502:physiology; D005337:Fibrin / Q000494:pharmacology*; D005340:Fibrinogen / Q000494:pharmacology*; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D011516:Prothrombin / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology
chemical_list: D009842:Oligopeptides; C034585:glycyl-prolyl-arginyl-proline; D011516:Prothrombin; D005164:Factor IX; D005170:Factor X; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin