Ryder Trauma Center, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.
JAMA Surg. 2018 Feb 1;153(2):144-149. doi: 10.1001/jamasurg.2017.3787.
The efficacy of anti-factor Xa (anti-Xa)-guided dosing of thromboprophylaxis after trauma remains controversial.
To assess whether dosing of enoxaparin sodium based on peak anti-Xa levels is associated with the venous thromboembolism (VTE) rate after trauma.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of 950 consecutive adults admitted to a single level I trauma intensive care unit for more than 48 hours from December 1, 2014, through March 31, 2017. Within 24 hours of admission, these trauma patients were screened with the Greenfield Risk Assessment Profile (RAP) (possible score range, 0-46). Patients younger than 18 years and those with VTE on admission were excluded, resulting in a study population of 792 patients.
The control group received fixed doses of either heparin sodium, 5000 U 3 times a day, or enoxaparin sodium, 30 mg twice a day. The adjustment cohort initially received enoxaparin sodium, 30 mg twice a day. A peak anti-Xa level was drawn 4 hours after the third dose. If the anti-Xa level was 0.2 IU/mL or higher, no adjustment was made. If the anti-Xa level was less than 0.2 IU/mL, each dose was increased by 10 mg. The process was repeated up to a maximum dose of 60 mg twice a day.
Rates of VTE were measured. Venous duplex ultrasonography and computed tomographic angiography were used for diagnosis.
The study population comprised 792 patients with a mean (SD) age of 46 (19) years and was composed of 598 men (75.5%). The control group comprised 570 patients, was older, and had a longer time to thromboprophylaxis initiation. The adjustment group consisted of 222 patients, was more severely injured, and had a longer hospital length of stay. The mean (SD) RAP scores were 9 (4) for the control group and 9 (5) for the adjustment group (P = .28). The VTE rates were similar for both groups (34 patients [6.0%] vs 15 [6.8%]; P = .68). Prophylactic anti-Xa levels were reached in 119 patients (53.6%) in the adjustment group. No difference in VTE rates was observed between those who became prophylactic and those who did not (7 patients [5.9%] vs 8 [7.8%]; P = .58). To control for confounders, 132 patients receiving standard fixed-dose enoxaparin were propensity matched to 84 patients receiving dose-adjusted enoxaparin. The VTE rates remained similar between the control and adjustment groups (3 patients [2.3%] vs 3 [3.6%]; P = .57).
Rates of VTE were not reduced with anti-Xa-guided dosing, and almost half of the patients never reached prophylactic anti-Xa levels; achieving those levels did not decrease VTE rates. Thus, other targets, such as platelets, may be necessary to optimize thromboprophylaxis after trauma.
抗因子 Xa（anti-Xa）指导的创伤后血栓预防剂量的疗效仍存在争议。
评估依诺肝素钠的剂量基于峰值抗 Xa 水平是否与创伤后静脉血栓栓塞（VTE）的发生率相关。
设计、设置和参与者：回顾性分析了 2014 年 12 月 1 日至 2017 年 3 月 31 日期间，950 例连续入住单一 1 级创伤重症监护病房超过 48 小时的成年患者。在入院后 24 小时内，这些创伤患者通过 Greenfield 风险评估量表（RAP）进行筛查（可能得分范围为 0-46）。排除年龄小于 18 岁和入院时已有 VTE 的患者，最终纳入了 792 例患者。
对照组接受肝素钠 5000 U 每日 3 次或依诺肝素钠 30 mg 每日 2 次的固定剂量。调整组最初接受依诺肝素钠 30 mg 每日 2 次。第三次剂量后 4 小时抽取峰值抗 Xa 水平。如果抗 Xa 水平为 0.2 IU/mL 或更高，则无需调整。如果抗 Xa 水平低于 0.2 IU/mL，则每次剂量增加 10 mg。最多可重复至每日 60 mg 2 次。
测量 VTE 的发生率。静脉双功超声和计算机断层血管造影用于诊断。
研究人群包括 792 例平均（标准差）年龄为 46（19）岁的患者，其中 598 例为男性（75.5%）。对照组有 570 例患者，年龄较大，血栓预防开始时间较长。调整组包括 222 例患者，损伤更严重，住院时间更长。对照组的平均（标准差）RAP 评分分别为 9（4），调整组为 9（5）（P=0.28）。两组的 VTE 发生率相似（34 例[6.0%]与 15 例[6.8%]；P=0.68）。调整组中有 119 例（53.6%）达到预防性抗 Xa 水平。达到预防性抗 Xa 水平与未达到的患者之间的 VTE 发生率无差异（7 例[5.9%]与 8 例[7.8%]；P=0.58）。为了控制混杂因素，对 132 例接受标准固定剂量依诺肝素的患者进行倾向匹配，以匹配 84 例接受剂量调整依诺肝素的患者。对照组和调整组的 VTE 发生率仍相似（3 例[2.3%]与 3 例[3.6%]；P=0.57）。
抗 Xa 指导的剂量并未降低 VTE 的发生率，几乎一半的患者从未达到预防性抗 Xa 水平；达到这些水平并不能降低 VTE 的发生率。因此，其他目标，如血小板，可能需要优化创伤后的血栓预防。
