Osterud B, Harper E, Rapaport S I, Lavine K K
Scand J Haematol. 1979 Mar;22(3):205-13. doi: 10.1111/j.1600-0609.1979.tb02798.x.
Collagen activation of platelet-associated Factor XI has been proposed as a mechanism for initiating intrinsic clotting independent of Factor XII. Since this could explain the lack of bleeding in patients with hereditary Factor XII deficiency, prekallikrein deficiency and high molecular weight kininogen deficiency, we subjected the hypothesis to rigorous testing. Incubation of isolated platelets with collagen and calcium ions failed to generate activity shortening the clotting time of an activated Factor XI (XIa) assay that had been modified to eliminate effects due to platelet-associated activated Factor V. Nor could generation of traces of Factor XIa in such mixtures be detected by incubation with purified Factor IX and testing for the generation of activated Factor IX (IXa) in clotting and amidolytic assays. Moreover, when blood or platelet-rich plasma containing added 125I-Factor IX was incubated with calcium ions and collagen and then subjected to reduced sodium dodecyl sulfate polyacrylamide gel electrophoresis, the radioactivity profiles revealed only native 125I-Factor IX without evidence of the polypeptide chains of Factor IXa. The negative results of this study mitigate against the hypothesis that collagen activation of platelet-associated Factor XI represents a physiologically significant mechanism for initiating clotting independent of Factor XII.
血小板相关因子XI的胶原激活已被提出作为一种独立于因子XII启动内源性凝血的机制。由于这可以解释遗传性因子XII缺乏、前激肽释放酶缺乏和高分子量激肽原缺乏患者无出血现象的原因，我们对这一假设进行了严格的检验。将分离的血小板与胶原和钙离子一起孵育，未能产生能缩短已改良以消除血小板相关活化因子V影响的活化因子XI（XIa）检测的凝血时间的活性。通过与纯化的因子IX孵育并在凝血和酰胺水解检测中检测活化因子IX（IXa）的产生，也无法检测到此类混合物中痕量XIa的产生。此外，当含有添加的125I-因子IX的血液或富含血小板的血浆与钙离子和胶原一起孵育，然后进行还原十二烷基硫酸钠聚丙烯酰胺凝胶电泳时，放射性图谱仅显示天然的125I-因子IX，而没有因子IXa多肽链的证据。这项研究的阴性结果不利于血小板相关因子XI的胶原激活代表一种独立于因子XII启动凝血的生理重要机制这一假设。
