Lane D A, Cuddigan B, VanRoss M, Kakkar V V
Br J Haematol. 1980 Mar;44(3):483-94. doi: 10.1111/j.1365-2141.1980.tb05918.x.
Routine testing on plasma from a patient due to undergo a coronary artery bypass graft operation revealed a prolonged thrombin clotting time associated with a normal plasma fibrinogen level when this was determined by a method not dependent upon the rate of fibrin formation. Fibrinogen purified from the patient's plasma by precipitation with beta-alanine also gave a prolonged thrombin time and this confirmed the presence of a dysfibrinogenaemia. Increasing calcium chloride concentration, addition of protamine sulphate and decreasing ionic strength all produced a partial correction of the clotting defect. Addition of normal plasma to patient's plasma failed to correct the prolonged thrombin clotting time and a pH dependence of the defect was also observed. Kinetic studies of fibrinopeptide release, using a specific radioimmunoassay, demonstrated no delay in the release of patient fibrinopeptide A. The functional defect was localized as an abnormality in the polymerization of fibrin monomers by studying fibrin monomers prepared and isolated from plasma and from purified fibrinogen solution. An electrophoretic examination of the patient's fibrinogen using both agarose and polyacrylamide gels failed to demonstrate any alteration in mobility or any structural defect associated with the polypeptide chains A alpha, B beta and gamma. All seven of the living siblings of the propositus and also his daughter showed no abnormality in any clotting assay. However, because the propositus did not suffer from liver disease it has been assumed that the abnormality is genetic in origin.
对一名即将接受冠状动脉搭桥手术患者的血浆进行常规检测时发现，当采用不依赖纤维蛋白形成速率的方法测定时，凝血酶凝血时间延长，而血浆纤维蛋白原水平正常。通过用β-丙氨酸沉淀从患者血浆中纯化的纤维蛋白原，其凝血酶时间也延长，这证实了异常纤维蛋白原血症的存在。增加氯化钙浓度、添加硫酸鱼精蛋白以及降低离子强度均能部分纠正凝血缺陷。向患者血浆中添加正常血浆未能纠正延长的凝血酶凝血时间，并且还观察到该缺陷存在pH依赖性。使用特异性放射免疫测定法对纤维蛋白肽释放进行动力学研究表明，患者纤维蛋白肽A的释放没有延迟。通过研究从血浆和纯化的纤维蛋白原溶液中制备和分离的纤维蛋白单体，将功能缺陷定位为纤维蛋白单体聚合异常。使用琼脂糖和聚丙烯酰胺凝胶对患者纤维蛋白原进行电泳检查，未显示迁移率有任何改变，也未显示与Aα、Bβ和γ多肽链相关的任何结构缺陷。先证者的所有七个在世兄弟姐妹及其女儿在任何凝血试验中均未显示异常。然而，由于先证者没有肝病，因此推测该异常起源于遗传。
