Köhler M, Hellstern P, Lechler E, Uberfuhr P, Müller-Berghaus G
Department of Transfusion Medicine, University of Göttingen, Germany.
Thromb Haemost. 1998 Sep;80(3):399-402.
In 1994, shortly after a heat-treated prothrombin complex concentrate (PCC) had been withdrawn from the German market due to transmission of hepatitis B, the license of another brand was withdrawn, due to 3 acute fatalities associated with the use of this product. We report on the clinical data of altogether 5 patients, who died during a 3 month period in Germany after having received this brand of PCC. All patients had surgery, acquired deficiencies of coagulation factors, and underlying diseases predisposing for thrombosis or disseminated intravascular coagulation. PCC was administered for the prevention of bleeding. In three patients, a drug interaction of PCC with aprotinin may also have played a role. Several points, however, are suspicious of a major causative effect of the respective product, (a) the close temporal correlation between administration of the drug and the subsequent clinical as well as laboratory deterioration, (b) the accumulation of these adverse events in a short period of time, when the use and market share of this brand increased due to the shortage of other products, and (c) laboratory abnormalities of this brand which have been consistently observed in several in vitro studies.
1994年，一种经过热处理的凝血酶原复合物浓缩剂（PCC）因乙肝传播问题被德国市场撤市后不久，另一个品牌的许可证也被吊销，原因是使用该产品导致了3例急性死亡事件。我们报告了在德国共5例患者的临床数据，这些患者在使用该品牌PCC后的3个月内死亡。所有患者均接受了手术，存在获得性凝血因子缺乏，并有易发生血栓形成或弥散性血管内凝血的基础疾病。使用PCC是为了预防出血。在3例患者中，PCC与抑肽酶之间的药物相互作用可能也起到了一定作用。然而，有几点令人怀疑该产品是主要致病因素：（a）用药与随后临床及实验室指标恶化之间存在密切的时间相关性；（b）当该品牌因其他产品短缺导致使用量和市场份额增加时，这些不良事件在短时间内积聚；（c）在多项体外研究中一直观察到该品牌存在实验室异常情况。
