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Oxidative modification of fibrinogen inhibits thrombin-catalyzed clot formation

1995; Elsevier BV; Volume: 18; Issue: 4 Linguagem: Inglês

10.1016/0891-5849(95)93872-4

1873-4596

Emily Shacter, Joy Williams, Rodney L. Levine,

Trauma, Hemostasis, Coagulopathy, Resuscitation

Plasma fibrinogen plays a central role in controlling hemostasis. In an earlier report, we found that fibrinogen is oxidized when whole plasma is treated with a metal-catalyzed oxidation system. These studies show that oxidative modification of purified human fibrinogen leads to an exposure-dependent loss of thrombin-induced clot formation. Inhibition of clotting occurred when either metal-catalyzed oxidation or gamma-irradiation was employed to generate oxidizing radicals. Both systems caused covalent modification of fibrinogen, assessed by measuring incorporation of protein carbonyls. Thrombin-catalyzed fibrinopeptide release was normal in irradiated fibrinogen and was only slightly diminished in protein exposed to metal-catalyzed oxidation, indicating that the inhibition of clotting activity was due to impaired fibrin monomer polymerization. Thus, oxidative modification of normal fibrinogen causes dysfibrinogenemia and constitutes a novel mechanism for inhibition of thrombosis.