Prothrombin complex concentrates: potentially thrombogenic materials and clues to the mechanism of thrombosis in vivo.
Prothrombin complex concentrates: potentially thrombogenic materials and clues to the mechanism of thrombosis in vivo.
复制标题
凝血酶原复合物浓缩物：潜在的血栓形成物质和体内血栓形成机制的线索。
作者：
Gilbert C. White;H. Roberts;Henry S. Kingdon;R. Lundblad
本实验室建立了一种灵敏的体外凝血活性测定方法，对影响两种不同凝血酶原复合体凝血活性的因素进行了研究。其中一种浓缩物含有大量潜在的血栓形成物质，而另一种浓缩物在生产过程中故意添加了抗凝血酶III和肝素，被判断为相对不会导致血栓形成。凝血浓缩物的凝血活性已被部分鉴定，主要是由于凝血因子IXa和Xa的存在。两种浓缩物都不含有可检测到的凝血酶。然而，在与钙或各种多胺孵育后，出现了大量额外的凝血物质，包括凝血酶。肝素和抗凝血酶III不仅中和了血栓形成浓缩物中的血栓形成物质，而且在与钙孵育时还抑制了凝血酶的从头生成。这些研究对凝血酶原复合体浓缩物的制备和临床使用期间宿主对血栓形成的易感性的影响进行了讨论。
Factors affecting the coagulant activity of two different prothrombin complex concentrates have been investigated using a sensitive in vitro assay developed in this laboratory. One concentrate contained substantial amounts of potentially thrombogenic material, while the other, which was deliberately fortified with antithrombin III and heparin during production, was judged to be relatively nonthrombogenic. The coagulant activity of the thrombogenic concentrate has been partially identified and was due largely to the presence of coagulation factos IXa and Xa. Neither concentrate contained detectable thrombin. However, after incubation with calcium or various polyamines, large amounts of additional coagulant material, including thrombin, appeared. Heparin and antithrombin III not only neutralized the thrombogenic materials present in the thrombogenic concentrate, but also inhibited the de novo generation of coagulant enzymes during incubation with calcium. The implication of these studies on the preparation of prothrombin complex concentrates and on host susceptibility to thrombosis during the clinical use of these concentrates is discussed.