FIBRINOGEN PHILADELPHIA - HEREDITARY HYPODYSFIBRINOGENEMIA CHARACTERIZED BY FIBRINOGEN HYPERCATABOLISM
FIBRINOGEN PHILADELPHIA - HEREDITARY HYPODYSFIBRINOGENEMIA CHARACTERIZED BY FIBRINOGEN HYPERCATABOLISM
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DOI：
10.1172/jci107595
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发表时间：
1974-01-01
影响因子：
15.9
通讯作者：
ERSLEV, AJ
中科院分区：
文献类型：
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作者：
MARTINEZ, J;HOLBURN, RR;ERSLEV, AJ
一个新的，常遗传异常纤维蛋白原与低纤维蛋白原血症已被描述在几个家庭成员。血浆纤维蛋白原以可凝血蛋白法或免疫扩散法测定，其水平在60 ~ 90mg / 100ml之间。血浆或纯化纤维蛋白原的凝血酶时间延长，且只能通过钙的加入部分纠正。纯化纤维蛋白原可延长正常血浆凝血酶时间。凝血酶释放纤维蛋白肽的速率和数量正常，但纤维蛋白单体聚集受到严重干扰，特别是在高离子强度介质中。我们将这种纤维蛋白原命名为“费城纤维蛋白原”[121I]正常和[125I]异常纤维蛋白原混合物的丙烯酰胺凝胶电泳显示，费城纤维蛋白原的阳极迁移率略有增加。同样，deae -纤维素层析显示费城纤维蛋白原的结合比正常情况稍强。为了阐明低血浆纤维蛋白原浓度的机制，在两名受影响的受试者中同时进行了分别标记为125I和121I的自体（患者）和同源（正常）纤维蛋白原的代谢研究。两家族成员的自体纤维蛋白原半衰期短，部分分解代谢率明显增加。相比之下，同源纤维蛋白原半衰期和分数分解代谢率正常。这些代谢研究表明，费城纤维蛋白原的快速降解是血浆纤维蛋白原水平降低的主要原因。这是血浆蛋白突变的第一个例子，其中分子缺陷与改变的分解代谢有关。
A new, autosomally inherited abnormal fibrinogen associated with hypofibrinogenemia has been described in several members of a family. Plasma fibrinogen measured either as thrombin-clottable protein or by immunodiffusion revealed a fibrinogen level ranging between 60 and 90 mg/100 ml. The thrombin time of plasma or purified fibrinogen was prolonged and only partially corrected by the addition of calcium. Purified fibrinogen prolonged the thrombin time of normal plasma. Fibrinopeptide release by thrombin was normal in rate and amount, but fibrin monomer aggregation was grossly disturbed, especially in a high ionic strength medium. We have designated this fibrinogen "fibrinogen Philadelphia." Acrylamide gel electrophoresis of mixtures of [121I]normal and [125I]abnormal fibrinogens revealed a slight increase in the anodal mobility of fibrinogen Philadelphia. Similarly, DEAE-cellulose chromatography showed slightly stronger binding of fibrinogen Philadelphia than normal. To elucidate the mechanism responsible for the low plasma fibrinogen concentration, simultaneous metabolic studies of autologous (patient) and homologous (normal) fibrinogen, labeled with 125I and 121I, respectively, were performed in two affected subjects. Autologous fibrinogen half-life was short and the fractional catabolic rate was markedly increased in both family members. In contrast, homologous fibrinogen half-life and fractional catabolic rate were normal. These metabolic studies demonstrate that rapid degradation of fibrinogen Philadelphia is largely responsible for the depressed levels of a plasma fibrinogen. This represents the first example of a mutant plasma protein in which the molecular defect is associated with an altered catabolism.