Hathaway W E, Wuepper K D, Weston W L, Humbert J R, Rivers R P, Genton E, August C S, Montgomery R R, Mass M F
Am J Med. 1976 May 10;60(5):654-64. doi: 10.1016/0002-9343(76)90500-3.
Two siblings with hereditary Fletcher factor (prekallikrein) deficiency were studied for alterations of fibrinolysis, platelet function, skin inflammatory responses, permeability factor (PF/dil) formation and leukocyte chemotaxis. In vivo stimulation of fibrinolytic activity was normal; the bleeding time and platelet functions (adhesivity, aggregation, release reaction) were also normal. Both immediate (wheal-flare reaction to histamine, bradykinin, prostaglandin E1, physical agents) and delayed sensitivity skin test reactions were within normal limits. Migration of subjects' leukocytes to attractants in skin windows and in Boyden-type chambers was the same as that of control leukocytes. Serum complement components were essentially normal. One subject's leukocytes showed normal tissue factor production on stimulation by endotoxin, although prekallikrein deficiency did impair the endotoxin-stimulated generation of serum procoagulant activity. PF/dil caused increased vessel permeability in human skin; in vitro generation of PF/dil required both the Hageman factor and prekallikrein. The Fletcher factor-deficient subjects responded in a normal manner to PF/dil. Based on the Fletcher factor-coagulation assay, the biologic half-disappearance time of prekallikrein (after the transfusion of normal plasma in one of the subjects) was estimated at 35 hours. Therefore, these studies suggest that severe prekallikrein (Fletcher factor) deficiency in man is not associated with any clinically significant impairment in hemostasis, fibrinolysis, inflammatory responses or leukocyte function.
对两名患有遗传性弗莱彻因子（前激肽释放酶）缺乏症的兄弟姐妹进行了纤溶、血小板功能、皮肤炎症反应、通透性因子（PF/dil）形成和白细胞趋化性改变的研究。体内纤溶活性刺激正常；出血时间和血小板功能（黏附性、聚集性、释放反应）也正常。即时（对组胺、缓激肽、前列腺素E1、物理因素的风团-潮红反应）和迟发性超敏皮肤试验反应均在正常范围内。受试者白细胞在皮肤窗和博伊登型小室中向趋化剂的迁移与对照白细胞相同。血清补体成分基本正常。一名受试者的白细胞在内毒素刺激下显示正常的组织因子产生，尽管前激肽释放酶缺乏确实损害了内毒素刺激的血清促凝活性的产生。PF/dil可导致人皮肤血管通透性增加；PF/dil的体外产生需要哈格曼因子和前激肽释放酶。弗莱彻因子缺乏的受试者对PF/dil的反应正常。根据弗莱彻因子凝血测定，估计前激肽释放酶的生物半衰期（在其中一名受试者输注正常血浆后）为35小时。因此，这些研究表明，人类严重的前激肽释放酶（弗莱彻因子）缺乏与止血、纤溶、炎症反应或白细胞功能的任何临床上显著损害无关。
