Engesser L, Koopman J, de Munk G, Haverkate F, Nováková I, Verheijen J H, Briët E, Brommer E J
Gaubius Institute TNO, Leiden, The Netherlands.
Thromb Haemost. 1988 Aug 30;60(1):113-20.
Congenital dysfibrinogenemia was found in a patient with venous thrombosis. Blood clot lysis was prolonged and suggested an impairment of fibrinolysis. We investigated whether this was related to the fibrinogen abnormality. Fibrinopeptide release was normal but fibrin polymerization was defective in the patient. The stimulating effect of the patient's fibrin on t-PA mediated plasminogen activation was impaired. This could not be attributed to defective binding of plasminogen. However, the binding of t-PA to the patient's fibrin was about 16% less than to normal fibrin. A variant t-PA (G K1 K2 P), which contained only one of the two fibrin binding sites, i.e. the kringle-2 domain, was bound to the abnormal fibrin for only 50% of normal. We conclude that the prolongation of blood clot lysis and the impaired stimulation of t-PA mediated plasminogen activation are related to the defective binding of the kringle-2 domain of t-PA onto the fibrin moiety of the abnormal fibrinogen. The impairment of fibrinolysis might explain the occurrence of thrombosis in the patient.
在一名静脉血栓形成患者中发现了先天性异常纤维蛋白原血症。血凝块溶解时间延长，提示纤溶功能受损。我们研究了这是否与纤维蛋白原异常有关。该患者的纤维蛋白肽释放正常，但纤维蛋白聚合存在缺陷。患者纤维蛋白对组织型纤溶酶原激活物（t-PA）介导的纤溶酶原激活的刺激作用受损。这不能归因于纤溶酶原结合缺陷。然而，t-PA与患者纤维蛋白的结合比与正常纤维蛋白的结合少约16%。一种仅含有两个纤维蛋白结合位点之一即kringle-2结构域的变异型t-PA（G K1 K2 P）与异常纤维蛋白的结合仅为正常情况的50%。我们得出结论，血凝块溶解时间延长以及t-PA介导的纤溶酶原激活刺激受损与t-PA的kringle-2结构域与异常纤维蛋白原的纤维蛋白部分结合缺陷有关。纤溶功能受损可能解释了该患者血栓形成的发生。
