纤维蛋白原休斯顿：一种表现出纤维蛋白单体聚集缺陷和α链交联缺陷的异常纤维蛋白原。

Weinger R S, Rudy C, Moake J L, Conlon C L, Cimo P L

Am J Hematol. 1980;9(3):237-48. doi: 10.1002/ajh.2830090302.

A 38-year-old male patient with a life-long history of easy bruising and mild bleeding had a prolonged activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Reptilase (Bathrops atrox) clotting time was normal. His undiluted and diluted plasma prolonged the APTT, PT, and TT of normal plasma. Fibrin produced from patient plasma was insoluble in 5 M urea. Plasma fibrinogen level was increased when measured as clottable protein and by Laurell electroimmunoassay. Specific assays of plasma factors II, V, VII, X, VIII, IX, XI, and XII were normal. A circulating antithrombin in patient plasma was excluded by demonstrating normal thrombin-induced platelet aggregation of gel-separated platelets in the presence of patient plasma. Purified patient fibrinogen reproduced the anticoagulant effect of patient plasma. Patient fibrinogen antigen was similar to normal fibrinogen antigen by immunodiffusion, immunoelectrophoresis (pH 5.2 and 8.6), and crossed immunoelectrophoresis. His unreduced purified fibrinogen had normal migration on polyacrylamide slab gels. Also, the migration in gel slabs of A alpha, B beta and gamma-polypeptide chains, produced by mercaptoethanol reduction of purified patient fibrinogen, was similar to reduced normal fibrinogen. Thrombin-induced total fibrinopeptide release was normal. However, fibrin monomers produced from patient fibrinogen by thrombin (devoid of fibrinopeptides A and B) reaggregated abnormally; fibrin monomers produced by reptilase (devoid of only fibrinopeptides A) reaggregated normally. Fibrin generated from patient plasma in the presence of factor XIII and calcium, was defective in the formation of covalently bonded alpha-alpha polymers and demonstrated an increased susceptibility to the lytic effects of plasmin (generated in vitro by the addition of streptokinase).

一名有终生易瘀伤和轻度出血病史的38岁男性患者，其活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）和凝血酶时间（TT）延长。蛇毒凝血酶（矛头蝮蛇）凝血时间正常。其未稀释和稀释后的血浆延长了正常血浆的APTT、PT和TT。患者血浆产生的纤维蛋白不溶于5M尿素。以可凝蛋白测定和Laurell电免疫分析法测定时，血浆纤维蛋白原水平升高。血浆因子II、V VII、X、VIII、IX、XI和XII的特异性检测均正常。通过证明在患者血浆存在的情况下，凝胶分离血小板的凝血酶诱导血小板聚集正常，排除了患者血浆中存在循环抗凝血酶。纯化的患者纤维蛋白原再现了患者血浆的抗凝作用。通过免疫扩散、免疫电泳（pH 5.2和8.6）和交叉免疫电泳，患者纤维蛋白原抗原与正常纤维蛋白原抗原相似。其未还原的纯化纤维蛋白原在聚丙烯酰胺平板凝胶上迁移正常。此外，通过巯基乙醇还原纯化的患者纤维蛋白原产生的Aα、Bβ和γ多肽链在凝胶板上的迁移与还原的正常纤维蛋白原相似。凝血酶诱导的总纤维蛋白肽释放正常。然而，凝血酶（不含纤维蛋白肽A和B）作用于患者纤维蛋白原产生的纤维蛋白单体异常重新聚集；蛇毒凝血酶（仅不含纤维蛋白肽A）作用产生的纤维蛋白单体正常重新聚集。在因子XIII和钙存在的情况下，患者血浆产生的纤维蛋白在共价结合的α-α聚合物形成方面存在缺陷，并且对纤溶酶（通过添加链激酶在体外产生）的溶解作用敏感性增加。