Gray E, Tubbs J, Thomas S, Oates A, Boisclair M, Kemball-Cook G, Barrowcliffe T W
Division of Haematology, NIBSC, South Mimms, Potters Bar, Hertfordshire, UK.
Thromb Haemost. 1995 Apr;73(4):675-9.
Current in vitro tests for thrombogenicity of FIX concentrates used for prothrombin complex concentrates (PCCs), are of little value when applied to high purity FIX (HP FIXs). In the present study, we have developed a chromogenic assay for activated FIX (FIXa) and evaluated its ability to predict in vivo thrombogenic potential of HP FIXs in a modified Wessler stasis model. Among the HP FIXs, only 1 out of 7 products had no detectable FIXa; this product also showed no in vivo thrombogenicity. In the other 6 products, FIXa content ranged from 0.15-1.2 U/1000 in FIX, and all showed some evidence of in vivo thrombogenicity, with mean thrombus scores ranging from 0.25-4. There was a significant positive correlation (r = 0.55, p < 0.02) between FIXa levels and in vivo thrombogenicity of HP FIXs. NAPTT data were not significantly correlated with the in vivo results and the TFCT also showed no direct correlation with the mean thrombus score. These results indicate that HP FIXs may still carry a small residual thrombotic risk and measurement of FIXa content of these products may be a better predictor of thrombogenicity than the current in vitro tests.
目前用于凝血酶原复合物浓缩剂（PCCs）的FIX浓缩剂血栓形成性的体外试验，应用于高纯度FIX（HP FIXs）时价值不大。在本研究中，我们开发了一种针对活化FIX（FIXa）的显色测定法，并在改良的韦氏停滞模型中评估了其预测HP FIXs体内血栓形成潜力的能力。在HP FIXs中，7种产品中只有1种未检测到FIXa；该产品在体内也未表现出血栓形成性。在其他6种产品中，FIX中的FIXa含量为0.15 - 1.2 U/1000，并且均显示出一些体内血栓形成性的证据，平均血栓评分范围为0.25 - 4。HP FIXs的FIXa水平与体内血栓形成性之间存在显著正相关（r = 0.55，p < 0.02）。NAPTT数据与体内结果无显著相关性，TFCT也与平均血栓评分无直接相关性。这些结果表明，HP FIXs可能仍具有较小的残余血栓形成风险，并且测量这些产品的FIXa含量可能比当前的体外试验更能预测血栓形成性。
