Mannucci P M, Bauer K A, Gringeri A, Barzegar S, Bottasso B, Simoni L, Rosenberg R D
A. Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Italy.
Blood. 1990 Dec 15;76(12):2540-5.
Prothrombin complex concentrates (PCC), licensed for the treatment of hemophilia B, are known to carry a significant risk of thromboembolic complications. Although the reasons for thrombogenicity are not completely understood, several manufacturers have developed purified factor IX concentrates that contain negligible amounts of the other vitamin K-dependent factors. To evaluate whether or not the infusion of such a factor IX concentrate is followed by lesser activation of the hemostatic system than by the infusion of a PCC, we performed a series of coagulation assays on 11 hemophilia B patients before and after the administration of these two types of concentrate using a randomized cross-over design. The levels of prothrombin fragment F1 + 2, a sensitive measure of the in vivo cleavage of prothrombin by factor Xa, was significantly increased in plasma after PCC, but not after factor IX concentrate. Plasma fibrinopeptide A, a sensitive index of the enzymatic activity of thrombin on fibrinogen, also increased significantly after PCC but not after factor IX concentrate. The fragment B beta 15-42, a sensitive index of the enzymatic action of plasmin on fibrin II, did not change after either concentrate. There were also no differences in less sensitive coagulation measurements, such as plasma fibrinogen, antithrombin III, and fibrin monomers, nor in indices of platelet activation, such as beta-thromboglobulin and platelet factor 4. These findings show that the infusion of a purified factor IX concentrate can result in substantially less activation of the coagulation cascade than may be seen with PCC.
凝血酶原复合物浓缩剂（PCC）已获许可用于治疗乙型血友病，已知其具有血栓栓塞并发症的重大风险。尽管血栓形成的原因尚未完全明确，但几家制造商已研发出纯化的凝血因子IX浓缩剂，其中其他维生素K依赖因子的含量可忽略不计。为评估输注此类凝血因子IX浓缩剂后，止血系统的激活程度是否低于输注PCC后的激活程度，我们采用随机交叉设计，对11例乙型血友病患者在输注这两种浓缩剂前后进行了一系列凝血试验。凝血酶原片段F1 + 2是体内凝血酶原被因子Xa裂解的敏感指标，PCC输注后血浆中该指标显著升高，但凝血因子IX浓缩剂输注后未升高。血浆纤维蛋白肽A是凝血酶对纤维蛋白原酶活性的敏感指标，PCC输注后也显著升高，但凝血因子IX浓缩剂输注后未升高。纤维蛋白降解产物Bβ15 - 42是纤溶酶对纤维蛋白II酶作用的敏感指标，两种浓缩剂输注后均未改变。在血浆纤维蛋白原、抗凝血酶III和纤维蛋白单体等敏感性较低的凝血指标方面，以及β-血小板球蛋白和血小板因子4等血小板激活指标方面，也均无差异。这些发现表明，与PCC相比，输注纯化的凝血因子IX浓缩剂引起的凝血级联激活程度要低得多。
