Stein Deborah M, Dutton Richard P, O'Connor James, Alexander Melvin, Scalea Thomas M
R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
J Trauma. 2005 Sep;59(3):609-15.
"Off-label" use of human coagulation factor VIIa (FVIIa) is presently restricted to patients in extremis at our institution. Although bleeding will diminish in most patients, some will still die early as a result of irreversible shock and/or rebleeding. Futile administration of FVIIa significantly increases the economic burden of this expensive therapy and therefore limits its availability. On the basis of both human and in vitro studies, profound acidosis may be expected to predict lack of response. In addition, the depth of hemorrhagic shock, as defined by the degree of hypoperfusion over a given period of time, may be predictive of failure of FVIIa administration. We hypothesized that retrospective review of FVIIa use would identify variables associated with clinical futility.
Characteristics of patients receiving FVIIa for acute traumatic hemorrhage were identified. Patients were retrospectively stratified into two groups; those who died as a result of acute hemorrhagic shock (nonresponders) and those in whom hemostasis was achieved and sustained (responders). Demographics, laboratory values, transfusion requirements, and outcomes were recorded for all patients. Data were analyzed using the Student's t test to identify the clinical characteristics of nonresponders and stepwise logistic regression was then used to identify independently predictive factors. A classification and regression tree analysis was conducted to develop a decision tree on the basis of our results.
Eighty-one patients received FVIIa therapy over a 3-year period. Among the 46 patients treated for acute hemorrhage, there were 26 with blunt and 20 with penetrating mechanisms of trauma. Average age was 35 +/- 15 years, 72% were male, and the average Injury Severity Score was 36 +/- 15. Revised Trauma Score (RTS), lactate, and preadministration prothrombin time (PT) each predicted lack of response (p < 0.05 for each). RTS and PT were independently predictive of failure of response. An RTS of less than 4.09 and a PT of greater than or equal to 17.6 seconds were significantly associated with futile administration of FVIIa. Age was a significant factor in patients with a PT greater than or equal to 17.6 seconds, whereas ISS was significant in patients with an RTS greater than or equal to 4.09.
Profound acidosis and coagulopathy may predict failure of FVIIa therapy. Depth of hemorrhagic shock, as described by the RTS, was also associated with futile administration. These variables should be considered as potential contraindications to the use of FVIIa. Earlier administration of FVIIa, before the development of massive blood loss and severe shock, may increase the rate of clinical response.
在我们机构，人凝血因子VIIa（FVIIa）的“超说明书”使用目前仅限于处于危急状态的患者。尽管大多数患者的出血会减少，但仍有一些患者会因不可逆休克和/或再次出血而早期死亡。无效使用FVIIa会显著增加这种昂贵治疗的经济负担，从而限制其可及性。基于人体和体外研究，严重酸中毒可能预示无反应。此外，出血性休克的深度，以给定时间段内的低灌注程度来定义，可能预示FVIIa治疗失败。我们假设对FVIIa使用情况进行回顾性分析可以确定与临床无效相关的变量。
确定接受FVIIa治疗急性创伤性出血的患者特征。患者被回顾性分为两组；因急性出血性休克死亡的患者（无反应者）和实现并维持止血的患者（有反应者）。记录所有患者的人口统计学资料、实验室值、输血需求和结局。使用学生t检验分析数据以确定无反应者的临床特征，然后使用逐步逻辑回归确定独立预测因素。基于我们的结果进行分类和回归树分析以构建决策树。
在3年期间，81例患者接受了FVIIa治疗。在46例治疗急性出血的患者中，26例为钝性创伤机制，20例为穿透性创伤机制。平均年龄为35±15岁，72%为男性，平均损伤严重度评分为36±15。修订创伤评分（RTS）、乳酸水平和给药前凝血酶原时间（PT）均预示无反应（每项p<0.05）。RTS和PT是反应失败的独立预测因素。RTS小于4.09且PT大于或等于17.6秒与FVIIa的无效使用显著相关。年龄在PT大于或等于17.6秒的患者中是一个显著因素，而损伤严重度评分在RTS大于或等于4.09的患者中是显著因素。
严重酸中毒和凝血病可能预示FVIIa治疗失败。如RTS所描述的出血性休克深度也与无效使用相关。这些变量应被视为使用FVIIa的潜在禁忌证。在发生大量失血和严重休克之前更早使用FVIIa可能会提高临床反应率。
