Dutton Richard P, McCunn Maureen, Hyder Mary, D'Angelo Matthew, O'Connor James, Hess John R, Scalea Thomas M
Program in Trauma, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
J Trauma. 2004 Oct;57(4):709-18; discussion 718-9. doi: 10.1097/01.ta.0000140646.66852.ab.
Activated factor VIIa (FVIIa) was developed to treat hemophiliacs with high-titer antibodies to factor VIII. FVIIa initiates thrombin formation by binding with exposed tissue factor. Anecdotal reports have described the utility of FVIIa in correcting coagulopathy from trauma, but no large series exists. We present our experience with 81 coagulopathic trauma patients treated using FVIIa in years 2001-2003, compared with "control" patients matched from the trauma registry from the same time period.
Use of FVIIa was restricted to active hemorrhage with clinical coagulopathy. We recorded the cause of coagulopathy, dose of FVIIa administered, effect on clinical coagulation, pertinent laboratory values, length of stay, number and type of blood products administered, and patient outcome. For the same time period we also examined outcomes in coagulopathic patients who did not receive FVIIa.
Causes of coagulopathy were diverse, and included acute traumatic hemorrhage (46 patients), traumatic brain injury (20), warfarin use (9), congenital Factor VII deficiency (2), and other acquired hematologic defects (4). Coagulopathy was reversed in 61/81 cases (75%), with an associated reduction in PT from 19.6 to 10.8 (p=0.000018). 34 patients (42%) survived to hospital discharge (20/46 traumatic hemorrhage, 5/20 TBI, 4/9 on warfarin, 2/2 factor deficient, 3/4 other). Patients died from irreversible shock, multiple organ system failure, or traumatic brain injury. FVIIa patients had a higher mortality than coagulopathic controls matched by specific anatomic injuries, admission lactate value, and predicted probability of survival. Only a group identified by all three characteristics had a similar mortality to the FVIIa cohort, but the number of patients that could be matched this way was too small to be meaningful.
FVIIa therapy lead to an immediate reduction in coagulopathic hemorrhage in most cases, accompanied by a significant improvement in laboratory measures. Application of FVIIa as a therapy of last resort makes the identification of equivalent control patients difficult. Use of FVIIa should be considered for any patient with coagulopathic hemorrhage in which surgically-accessible bleeding has been controlled. Prospective trials of FVIIa in patients with traumatic coagulopathy are strongly indicated, and should focus on appropriate patient selection and the dose and timing of therapy.
活化凝血因子VIIa（FVIIa）被开发用于治疗对凝血因子VIII有高滴度抗体的血友病患者。FVIIa通过与暴露的组织因子结合启动凝血酶形成。有轶事报道描述了FVIIa在纠正创伤性凝血病方面的效用，但尚无大型系列研究。我们介绍了2001年至2003年期间使用FVIIa治疗的81例凝血病创伤患者的经验，并与同期创伤登记处匹配的“对照”患者进行了比较。
FVIIa的使用仅限于伴有临床凝血病的活动性出血。我们记录了凝血病的病因、FVIIa的给药剂量、对临床凝血的影响、相关实验室值、住院时间、输注血液制品的数量和类型以及患者结局。在同一时期，我们还检查了未接受FVIIa的凝血病患者的结局。
凝血病的病因多种多样，包括急性创伤性出血（46例患者）、创伤性脑损伤（20例）、华法林使用（9例）、先天性凝血因子VII缺乏（2例）和其他获得性血液学缺陷（4例）。81例中有61例（75%）的凝血病得到逆转，凝血酶原时间（PT）从19.6降至10.8（p = 0.000018）。34例患者（42%）存活至出院（创伤性出血20/46例、创伤性脑损伤5/20例、服用华法林4/9例、凝血因子缺乏2/2例、其他3/4例）。患者死于不可逆性休克、多器官系统衰竭或创伤性脑损伤。与根据特定解剖损伤、入院时乳酸值和预测生存概率匹配的凝血病对照组相比，接受FVIIa治疗的患者死亡率更高。只有由所有这三个特征确定的一组患者的死亡率与FVIIa队列相似，但以这种方式匹配的患者数量太少，无实际意义。
在大多数情况下，FVIIa治疗可使凝血病性出血立即减少，同时实验室指标有显著改善。将FVIIa作为最后手段进行治疗使得确定等效的对照患者变得困难。对于任何手术可控制出血的凝血病性出血患者，都应考虑使用FVIIa。强烈建议对创伤性凝血病患者进行FVIIa的前瞻性试验，试验应侧重于合适的患者选择以及治疗的剂量和时机。
