Department of Pharmacy, NYU Langone Health, New York, NY, USA.
Department of Pharmacy Services, Memorial Hermann-Texas Medical Center, Houston, TX, USA.
J Intensive Care Med. 2019 Nov-Dec;34(11-12):877-888. doi: 10.1177/0885066618796486. Epub 2018 Aug 30.
Venous thromboembolism (VTE) is a major health concern associated with significant morbidity and mortality. Critically ill patients are at an increased risk of VTE compared to general medical patients due to unique risk factors: prolonged immobilization, invasive lines and devices, certain medications, and acquired thrombophilia. Furthermore, VTE in the critically ill is associated with increased duration of mechanical ventilation, increased length of intensive care unit and hospital stay, and a trend toward increased mortality. Clinical practice guidelines therefore recommend VTE prophylaxis with either subcutaneous heparin or low-molecular-weight heparin for all critically ill patients without contraindication. Yet, many patients will develop VTE despite appropriate pharmacologic prophylaxis, which has led to interest in risk-stratifying critically ill patients for more aggressive prophylaxis strategies. Recent research identified patients at highest risk of failure of thromboprophylaxis and provided insight into the pathophysiologic mechanisms. Obesity and the receipt of vasopressors are 2 risk factors consistently identified in observational studies; further clinical data support decreased absorption of anticoagulant administered via the subcutaneous route as the likely mechanism behind thromboprophylaxis failure in these patient populations. Several studies have investigated novel thromboprophylaxis strategies to circumvent pharmacokinetic limitations in patients who are obese or on vasopressors: increased fixed-dose, weight-based subcutaneous, or continuous intravenous infusion of a prophylactic dose of anticoagulant has shown promise in limited studies; however, the results have yet to demonstrate superiority compared to current standard-of-care. This review discusses observational studies identifying patients at risk of thromboprophylaxis failure and critiques clinical studies evaluating novel thromboprophylaxis strategies in high-risk, critically ill patients with a focus on their limitations. Future studies are currently being conducted that will provide further guidance into the appropriate use of individualized thromboprophylaxis.
静脉血栓栓塞症（VTE）是一个严重的健康问题，与高发病率和死亡率密切相关。与一般内科患者相比，重症患者由于存在一些独特的危险因素，如长时间卧床不动、有创性的管路和设备、某些药物以及获得性血栓形成倾向等，VTE 的风险更高。此外，重症患者的 VTE 与机械通气时间延长、重症监护病房和住院时间延长以及死亡率增加有关。因此，临床实践指南建议对所有无禁忌证的重症患者进行 VTE 预防，可选择皮下肝素或低分子肝素。然而，尽管进行了适当的药物预防，许多患者仍会发生 VTE，这导致人们对高危重症患者进行更积极的预防策略产生了兴趣。最近的研究确定了最易发生血栓预防失败的患者，并深入了解了病理生理学机制。肥胖和使用血管加压药是观察性研究中始终确定的两个危险因素；进一步的临床数据支持，由于肥胖或使用血管加压药患者的抗凝剂经皮下途径吸收减少，这可能是这些患者群体中血栓预防失败的机制。一些研究已经探讨了新的血栓预防策略，以克服肥胖或使用血管加压药患者的药代动力学限制：增加固定剂量、基于体重的皮下或连续静脉输注预防性剂量的抗凝剂在有限的研究中显示出了前景；然而，这些结果尚未证明与目前的标准治疗相比具有优越性。本文综述了确定血栓预防失败风险患者的观察性研究，并对评估高危重症患者新的血栓预防策略的临床研究进行了评价，重点讨论了这些研究的局限性。目前正在进行的未来研究将为个体化血栓预防的合理应用提供进一步的指导。
