MacGregor I R, Ferguson J F, Dawes J, McLaughlin L, Prowse C V
Scottish National Blood Transfusion Service, Edinburgh, UK.
Blood Coagul Fibrinolysis. 1990 Mar-Apr;1(1):23-30. doi: 10.1097/00001721-199003000-00005.
Dose-ranging studies with a batch of factor IX concentrate have been performed in a canine non-stasis model of thrombogenicity. Doses between 50 and 200 IU/kg were infused over a 30 min period, and beagles were found to be more sensitive than greyhounds with regard to subsequent alterations in haemostatic parameters over a 150 min period. In beagles we detected significant increases in plasma fibrin(ogen) degradation products and reduction in fibrinogen concentrations in a dose-related manner after infusion of factor IX concentrate over the range 50-150 IU/kg. Plasma fibrinopeptide A was the most sensitive marker of activation of coagulation with significantly increased levels after factor IX at 50 IU/kg compared with control infusions of albumin. Recovery of infused factor IX was similar to values reported in man. In these experiments, measurement of urinary fibrinopeptide A did not prove to be a useful indicator of thrombogenicity. In conclusion, the beagle non-stasis model will provide a sensitive method to quantify the unwanted thrombogenic activities associated with the use of high doses of certain factor IX concentrates.
已在犬类非静态血栓形成模型中对一批凝血因子IX浓缩物进行了剂量范围研究。在30分钟内输注50至200 IU/kg的剂量，发现在150分钟内，比格犬在止血参数的后续变化方面比灵缇犬更敏感。在比格犬中，输注50 - 150 IU/kg范围内的凝血因子IX浓缩物后，我们检测到血浆纤维蛋白（原）降解产物显著增加，纤维蛋白原浓度呈剂量相关下降。血浆纤维肽A是凝血激活最敏感的标志物，与白蛋白对照输注相比，50 IU/kg的凝血因子IX后其水平显著升高。输注的凝血因子IX的回收率与人报道的值相似。在这些实验中，尿纤维肽A的测量并未证明是血栓形成的有用指标。总之，比格犬非静态模型将提供一种敏感的方法来量化与使用高剂量某些凝血因子IX浓缩物相关的不良血栓形成活性。
