Wuillemin W A, Hack C E, Bleeker W K, Biemond B J, Levi M, ten Cate H
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, The Netherlands.
Thromb Haemost. 1996 Oct;76(4):549-55.
C1-inhibitor (C1Inh), antithrombin III (ATIII), alpha 1-antitrypsin (a1AT), and alpha 2-antiplasmin (a2AP) are known inhibitors of factor XIa (FXIa). However, their precise contribution to FXIa inactivation in vivo is not known. We investigated FXIa inactivation in chimpanzees and assessed the contribution of these inhibitors to FXIa inactivation in patients with presumed FXI activation. Chimpanzees were infused with FXIa and the various FXIa-FXIa inhibitor complexes formed were measured. Most of FXIa was complexed to C1Inh (68%), followed by a2AP (13%), a1AT (10%), and ATIII (9%). Analysis of the plasma elimination kinetics revealed a half-life time of clearance (t1/2) for the FXIa-FXIa inhibitor complexes of 95 to 104 min, except for FXIa-a1AT, which had a t1/2 of 349 min. Due to this long t1/2, FXIa-a1AT complexes were predicted to show the highest levels in plasma samples from patients with activation of FXI. This was indeed shown in patients with disseminated intravascular coagulation, recent myocardial infarction or unstable angina pectoris. We conclude from this study that in vivo C1Inh is the predominant inhibitor of FXIa, but that FXIa-a1AT complexes due to their relatively long t 1/2 may be the best parameter to assess FXI activation in clinical samples.
C1抑制剂（C1Inh）、抗凝血酶III（ATIII）、α1-抗胰蛋白酶（a1AT）和α2-抗纤溶酶（a2AP）是已知的因子XIa（FXIa）抑制剂。然而，它们在体内对FXIa失活的确切作用尚不清楚。我们研究了黑猩猩体内FXIa的失活情况，并评估了这些抑制剂对疑似FXI激活患者FXIa失活的作用。给黑猩猩输注FXIa，并测量形成的各种FXIa-FXIa抑制剂复合物。大部分FXIa与C1Inh形成复合物（68%），其次是a2AP（13%）、a1AT（10%）和ATIII（9%）。血浆消除动力学分析显示，除FXIa-a1AT的清除半衰期（t1/2）为349分钟外，FXIa-FXIa抑制剂复合物的t1/2为95至104分钟。由于t1/2较长，预计FXIa-a1AT复合物在FXI激活患者的血浆样本中水平最高。这在弥散性血管内凝血、近期心肌梗死或不稳定型心绞痛患者中确实得到了证实。我们从这项研究得出结论，在体内C1Inh是FXIa的主要抑制剂，但由于FXIa-a1AT复合物的t1/2相对较长，它们可能是评估临床样本中FXI激活的最佳参数。
