Division of Trauma, Critical Care, and Acute Care Surgery, Department of Surgery, Oregon Health and Science University, Portland.
Department of Surgery, Oregon Health and Science University, Portland.
JAMA Surg. 2016 Oct 19;151(10):e162069. doi: 10.1001/jamasurg.2016.2069.
Prophylactic enoxaparin is used to prevent venous thromboembolism (VTE) in surgical and trauma patients. However, VTE remains an important source of morbidity and mortality, potentially exacerbated by antithrombin III or anti-Factor Xa deficiencies and missed enoxaparin doses. Recent data suggest that a difference in reaction time (time to initial fibrin formation) greater than 1 minute between heparinase and standard thrombelastogram (TEG) is associated with a decreased risk of VTE.
To evaluate the effectiveness of TEG-adjusted prophylactic enoxaparin dosing among trauma and surgical patients.
DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial, conducted from October 2012 to May 2015, compared standard dosing (30 mg twice daily) with TEG-adjusted enoxaparin dosing (35 mg twice daily) for 185 surgical and trauma patients screened for VTE at 3 level I trauma centers in the United States.
The incidence of VTE, bleeding complications, anti-Factor Xa deficiency, and antithrombin III deficiency.
Of the 185 trial participants, 89 were randomized to the control group (median age, 44.0 years; 55.1% male) and 96 to the intervention group (median age, 48.5 years; 74.0% male). Patients in the intervention group received a higher median enoxaparin dose than control patients (35 mg vs 30 mg twice daily; P < .001). Anti-Factor Xa levels in intervention patients were not higher than levels in control patients until day 6 (0.4 U/mL vs 0.21 U/mL; P < .001). Only 22 patients (11.9%) achieved a difference in reaction time greater than 1 minute, which was similar between the control and intervention groups (10.4% vs 13.5%; P = .68). The time to enoxaparin initiation was similar between the control and intervention groups (median [range] days, 1.0 [0.0-2.0] vs 1.0 [1.0-2.0]; P = .39), and the number of patients who missed at least 1 dose was also similar (43 [48.3%] vs 54 [56.3%]; P = .30). Rates of VTE (6 [6.7%] vs 6 [6.3%]; P > .99) were similar, but the difference in bleeding complications (5 [5.6%] vs 13 [13.5%]; P = .08) was not statistically significant. Antithrombin III and anti-Factor Xa deficiencies and hypercoagulable TEG parameters, including elevated coagulation index (>3), maximum amplitude (>74 mm), and G value (>12.4 dynes/cm2), were prevalent in both groups. Identified risk factors for VTE included older age (61.0 years vs 46.0 years; P = .04), higher body mass index (calculated as weight in kilograms divided by height in meters squared; 30.6 vs 27.1; P = .03), increased Acute Physiology and Chronic Health Evaluation II score (8.5 vs 7.0; P = .03), and increased percentage of missed doses per patient (14.8% vs 2.5%; P = .05).
The incidence of VTE was low and similar between groups; however, few patients achieved a difference in reaction time greater than 1 minute. Antithrombin III deficiencies and hypercoagulable TEG parameters were prevalent among patients with VTE. Low VTE incidence may be due to an early time to enoxaparin initiation and an overall healthier and less severely injured study population than previously reported.
clinicaltrials.gov Identifier: NCT00990236.
预防性依诺肝素用于预防手术和创伤患者的静脉血栓栓塞症 (VTE)。然而，VTE 仍然是发病率和死亡率的一个重要来源，潜在地因抗凝血酶 III 或抗因子 Xa 缺乏和漏用依诺肝素剂量而加剧。最近的数据表明，肝素酶和标准血栓弹力图 (TEG) 之间的反应时间 (初始纤维蛋白形成时间) 差异大于 1 分钟与 VTE 风险降低相关。
评估在创伤和手术患者中调整 TEG 的依诺肝素预防性剂量的效果。
设计、地点和参与者：这是一项随机临床试验，于 2012 年 10 月至 2015 年 5 月期间在美国 3 家一级创伤中心对筛查 VTE 的 185 例手术和创伤患者进行，比较了标准剂量 (每天两次 30 毫克) 和 TEG 调整的依诺肝素剂量 (每天两次 35 毫克)。
VTE、出血并发症、抗因子 Xa 缺乏和抗凝血酶 III 缺乏的发生率。
在 185 名试验参与者中，89 名被随机分配到对照组 (中位年龄 44.0 岁；55.1%男性)，96 名分配到干预组 (中位年龄 48.5 岁；74.0%男性)。干预组患者接受的依诺肝素中位剂量高于对照组患者 (35 毫克 vs 30 毫克，每天两次；P<0.001)。直到第 6 天，干预组患者的抗因子 Xa 水平才高于对照组患者 (0.4 U/mL vs 0.21 U/mL；P<0.001)。只有 22 名患者 (11.9%) 的反应时间差异大于 1 分钟，这与对照组和干预组相似 (10.4% vs 13.5%；P=0.68)。依诺肝素起始时间在对照组和干预组之间相似 (中位数[范围]，天 1.0[0.0-2.0] vs 1.0[1.0-2.0]；P=0.39)，错过至少 1 剂的患者人数也相似 (43 [48.3%] vs 54 [56.3%]；P=0.30)。VTE 发生率相似 (6 [6.7%] vs 6 [6.3%]；P>0.99)，但出血并发症的差异无统计学意义 (5 [5.6%] vs 13 [13.5%]；P=0.08)。抗凝血酶 III 和抗因子 Xa 缺乏以及包括凝血指数升高 (>3)、最大振幅升高 (>74 毫米)和 G 值升高 (>12.4 达因/平方厘米)在内的高凝 TEG 参数在两组中都很常见。VTE 的确定危险因素包括年龄较大 (61.0 岁 vs 46.0 岁；P=0.04)、体重指数较高 (计算为体重公斤数除以身高米数的平方；30.6 比 27.1；P=0.03)、急性生理学和慢性健康评估 II 评分较高 (8.5 比 7.0；P=0.03)，以及每位患者漏用剂量的百分比较高 (14.8% vs 2.5%；P=0.05)。
VTE 的发生率较低，两组之间相似；然而，很少有患者的反应时间差异大于 1 分钟。抗凝血酶 III 缺乏和高凝 TEG 参数在 VTE 患者中很常见。低 VTE 发生率可能是由于依诺肝素起始时间较早，以及与之前报道的相比，研究人群整体更健康且受伤程度较轻。
clinicaltrials.gov 标识符：NCT00990236。
