Menache D, Behre H E, Orthner C L, Nunez H, Anderson H D, Triantaphyllopoulos D C, Kosow D P
Blood. 1984 Dec;64(6):1220-7.
Thrombosis and/or disseminated intravascular coagulation (DIC) are complications specifically associated with the use of factor IX complex in some patients. Assuming that these complications might result from zymogen overload, we have produced, using diethylaminoethyl (DEAE)-Sephadex (Pharmacia, Piscataway, NJ) and sulfated dextran chromatography, a factor IX concentrate (coagulation factor IX) that is essentially free of prothrombin, factor VII, and factor X. Factor IX specific activity is at least 5 U/mg protein, a 250-fold purification compared to plasma. Amounts of factors II, VII, and X are less than 5 units each per 100 units of factor IX. The concentrate is essentially free of activated clotting factors and contains no added heparin. In the rabbit stasis model, a dose of 200 factor IX U/kg was less thrombogenic than 100 factor IX U/kg of the DEAE-Sephadex eluate from which the concentrate was derived. Infusion of 200 factor IX U/kg did not induce DIC in the nonstasis rabbit model, whereas 100 factor IX U/kg of the DEAE-Sephadex eluate resulted in DIC in this model. Several factor IX lots were found to have shortened nonactivated partial thromboplastin times (PTTs), but were nonthrombogenic in both animal models. These data indicate that coagulation factor IX concentrate is less thrombogenic than factor IX complex.
血栓形成和/或弥散性血管内凝血（DIC）是某些患者使用凝血因子IX复合物时特有的并发症。假设这些并发症可能是由于酶原过载引起的，我们使用二乙氨基乙基（DEAE）-葡聚糖凝胶（Pharmacia，皮斯卡塔韦，新泽西州）和硫酸葡聚糖色谱法制备了一种凝血因子IX浓缩物（凝血因子IX），该浓缩物基本不含凝血酶原、因子VII和因子X。凝血因子IX的比活性至少为5 U/mg蛋白，与血浆相比纯化了250倍。每100单位凝血因子IX中，因子II、VII和X的含量均低于5单位。该浓缩物基本不含活化的凝血因子，且未添加肝素。在兔血瘀模型中，200凝血因子IX U/kg的剂量比从中提取浓缩物的DEAE-葡聚糖凝胶洗脱液的100凝血因子IX U/kg血栓形成性更低。在非血瘀兔模型中，输注200凝血因子IX U/kg不会诱发DIC，而100凝血因子IX U/kg的DEAE-葡聚糖凝胶洗脱液在该模型中会导致DIC。发现几个凝血因子IX批次的非活化部分凝血活酶时间（PTT）缩短，但在两种动物模型中均无血栓形成性。这些数据表明，凝血因子IX浓缩物的血栓形成性低于凝血因子IX复合物。
