Zivelin A, Rao L V, Rapaport S I
Department of Medicine, University of California, San Diego 92093.
J Clin Invest. 1993 Nov;92(5):2131-40. doi: 10.1172/JCI116814.
We have evaluated the contribution of depression of individual procoagulant vitamin K-dependent clotting factors to the ability of warfarin to protect rabbits against tissue factor-induced coagulation. Mean activities of individual procoagulant factors were determined, in assays with rabbit substrates, for a group of rabbits achieving a protective degree of anticoagulation with warfarin. Values were: factor VII, 12%; factor IX, 7%; factor X, 14%, and prothrombin, 13%. The effect upon tissue factor-induced coagulation of selective immunodepletion of each factor to a comparable level was then evaluated. Immunodepletion of plasma factor X or prothrombin, but not of factor VII or factor IX, protected otherwise normal rabbits against tissue factor-induced coagulation. Next, we determined the effect upon the protection in warfarin-treated rabbits of selectively restoring factor X or prothrombin before infusing tissue factor. When either factor was selectively restored, warfarin's protective effect was abolished. Moreover, selective restoration of prothrombin sensitized warfarin-treated rabbits to coagulation more severe than observed in nontreated control rabbits. One may extrapolate from these data that depression of both factor X and prothrombin are required for warfarin's clinical antithrombotic efficacy and that depression of plasma prothrombin is particularly important.
我们评估了华法林对兔体内单个促凝血维生素K依赖性凝血因子的抑制作用，以及这种抑制作用对兔抵抗组织因子诱导的凝血的能力的影响。在兔底物检测中，测定了一组用华法林达到保护程度的抗凝兔体内单个促凝血因子的平均活性。结果如下：因子VII为12%；因子IX为7%；因子X为14%；凝血酶原为13%。然后评估了将每个因子选择性免疫耗竭至可比水平对组织因子诱导的凝血的影响。血浆因子X或凝血酶原的免疫耗竭（而非因子VII或因子IX的免疫耗竭）可保护原本正常的兔抵抗组织因子诱导的凝血。接下来，我们测定了在输注组织因子之前选择性恢复因子X或凝血酶原对华法林治疗兔的保护作用的影响。当选择性恢复任一因子时，华法林的保护作用即被消除。此外，凝血酶原的选择性恢复使华法林治疗的兔对凝血更敏感，比未治疗的对照兔表现出更严重的凝血。从这些数据可以推断，华法林的临床抗血栓疗效需要因子X和凝血酶原均受到抑制，并且血浆凝血酶原的抑制尤为重要。
