Cmolik B L, Spero J A, Magovern G J, Clark R E
Department of Surgery, Allegheny General Hospital, Pittsburgh, Pa.
J Thorac Cardiovasc Surg. 1993 Feb;105(2):222-7; discussion 227-8.
Bovine thrombin-induced factor V deficiency was though to be a very rare acquired coagulopathy, with only three documented cases. We report a series of nine patients seen during a period of 32 months; these patients had normal preoperative coagulation profiles, and this unique coagulopathy developed 1 to 2 weeks after cardiovascular operations. The coagulopathy was characterized by a markedly elevated prothrombin time (40.9 +/- 5.8 seconds), an elevated activated partial thromboplastin time (96.3 +/- 12.2 seconds), a study positive for lupus anticoagulation (9/9), and markedly decreased levels of factor V (0.09 +/- 0.03 U/ml) and factor XI (0.04 +/- 0.02 U/ml), respectively. All patients had been exposed to commercially available bovine thrombin during prior cardiovascular or vascular operations and received a second bovine thrombin challenge during the latest procedure. Coagulopathic bleeding developed in four of the nine patients. Bleeding was unrelated to absolute fall in factor V level, but cessation of hemorrhage appeared to correlate with improvement in factor V level. Treatment with vitamin K, fresh frozen plasma, and platelet infusion were all unsuccessful in altering prothrombin time or factor V levels. Intravenous gamma globulin was used in three patients, two of whom were bleeding. All three patients showed a transient increase in factor V levels. Bleeding stopped in one of the two patients; the other continued to bleed and subsequently died. The third patient was treated prophylactically to increase factor V levels in preparation for flap reconstruction of his sternum. His factor V level increased from 0.26 to 0.49 U/ml, and he underwent the procedure without incident. Bovine thrombin-induced factor V deficiency may have been previously unrecognized. This deficiency should be suspected in patients who have undergone redo cardiovascular operations and in whom marked elevations in their prothrombin time occur 7 to 10 days after exposure to bovine thrombin. The resulting coagulopathy, although usually self-limited, has the potential to produce devastating bleeding complications. Intravenous gamma globulin (1 gm/kg during each of 2 days) has been used to increase factor V levels transiently but its role in therapy of this coagulopathy requires further investigation.
牛凝血酶诱导的因子V缺乏症曾被认为是一种非常罕见的获得性凝血病,仅有三例文献记载。我们报告了在32个月期间见到的一系列9例患者;这些患者术前凝血指标正常,这种独特的凝血病在心血管手术后1至2周出现。凝血病的特征为凝血酶原时间显著延长(40.9±5.8秒)、活化部分凝血活酶时间延长(96.3±12.2秒)、狼疮抗凝物检查阳性(9/9),以及因子V(0.09±0.03 U/ml)和因子XI(0.04±0.02 U/ml)水平显著降低。所有患者在先前的心血管或血管手术中均接触过市售牛凝血酶,并在最近的手术中再次接受了牛凝血酶挑战。9例患者中有4例发生了凝血病性出血。出血与因子V水平的绝对下降无关,但出血停止似乎与因子V水平的改善相关。维生素K、新鲜冰冻血浆和血小板输注治疗均未能改变凝血酶原时间或因子V水平。3例患者使用了静脉注射丙种球蛋白,其中2例有出血症状。所有3例患者的因子V水平均出现短暂升高。2例出血患者中有1例出血停止;另1例继续出血,随后死亡。第3例患者接受预防性治疗以提高因子V水平,为胸骨皮瓣重建做准备。他的因子V水平从0.26升至0.49 U/ml,手术顺利进行。牛凝血酶诱导的因子V缺乏症可能以前未被认识到。对于接受过再次心血管手术且在接触牛凝血酶7至10天后凝血酶原时间显著延长的患者,应怀疑存在这种缺乏症。由此导致的凝血病虽然通常为自限性,但有可能产生严重的出血并发症。静脉注射丙种球蛋白(连续2天,每天1 gm/kg)已被用于短暂提高因子V水平,但其在这种凝血病治疗中的作用还需要进一步研究。