Fibrinogen Nijmegen : Congenital Dysfibrinogenemia Associated with Impaired t-PA Mediated Plasminogen Activation and Decreased Binding of t-PA
Fibrinogen Nijmegen : Congenital Dysfibrinogenemia Associated with Impaired t-PA Mediated Plasminogen Activation and Decreased Binding of t-PA
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DOI：
10.1055/s-0038-1647646
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发表时间：
1988-08
影响因子：
6.7
通讯作者：
L. Engesser;J. Koopman;Gé Munk;F. Haverkate;Irena Novéková;J. Verheijen;E. Briët;E. Brommer
中科院分区：
文献类型：
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作者：
L. Engesser;J. Koopman;Gé Munk;F. Haverkate;Irena Novéková;J. Verheijen;E. Briët;E. Brommer
摘要先天性异常纤维蛋白原血症被发现在静脉血栓形成的患者。血凝块溶解延长，提示纤维蛋白溶解受损。我们调查了这是否与纤维蛋白原异常有关。纤维蛋白肽释放正常，但纤维蛋白聚合缺陷的病人。患者的纤维蛋白对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低约16%。变体t-PA（G K1 K2 P）仅包含两个纤维蛋白结合位点中的一个，即Kringle-2结构域，其仅与正常的50%的异常纤维蛋白结合。我们的结论是，血凝块溶解的延长和受损的刺激t-PA介导的纤溶酶原激活相关的缺陷结合的kringle-2结构域的t-PA上的纤维蛋白部分的异常纤维蛋白原。纤溶功能受损可能是血栓形成的原因。
Summary 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 abormality. 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 throm-bosis in the patient.