Optimization of enoxaparin prophylaxis using real-time anti-Factor Xa levels in major reconstructive surgery patients

 描述（由申请人提供）：四肢（深静脉血栓形成）和肺部（肺栓塞）形成的血块是重建手术的可怕并发症。十分之一有症状的肺栓塞患者将在60分钟内死亡。深静脉血栓形成患者可能会出现血栓后综合征，这是生活质量差的主要原因。这些现象被广泛称为静脉血栓栓塞（VTE），具有实质性的下游后果，美国外科医生和美国整形外科医生协会（ASPS）等强调了手术患者预防VTE的重要性。重建手术，最常用于修复癌症切除后的创伤性损伤或缺损，通常涉及从身体上的邻近或远处区域借用组织;重建手术患者通常会有涉及其总体表面积20%或更多的手术损伤。已知损伤和由此产生的炎症会增加某些药物的代谢，包括那些用于预防手术后VTE的药物。依诺肝素是一种血液稀释药物，可降低血栓形成的可能性。先前的研究表明，重建手术患者在手术后给予依诺肝素的可能性较小。然而，尽管接受了标准剂量的依诺肝素，许多患者仍然发生这种危及生命的并发症。我们认为，患者代谢依诺肝素的不同程度的手术损伤重建过程中创建的，并寻求严格检查依诺肝素代谢重建手术患者。拟议的研究将评估依诺肝素如何影响重建手术后的标准，ASPS推荐剂量的血液;我们还将检查手术损伤的程度是否也会改变代谢。将使用抗Xa因子（aFXa）水平跟踪依诺肝素的有效性。如果观察到亚治疗aFXa水平，研究还将设计、实施和测试临床依诺肝素剂量调整方案，以达到适当的术后aFXa水平。基于这些数据的进一步研究将检查使用aFXa驱动的依诺肝素给药时VTE风险的降低。我们研究的最终目的是更好地了解依诺肝素剂量、手术损伤程度和主要重建手术后血凝块之间的相互作用。最终，这项研究将扩大我们对术后VTE发生原因的理解，使我们能够根据患者的独特特征制定个性化的VTE预防策略，并进一步提高重建手术后患者的安全性。

 DESCRIPTION (provided by applicant): Blood clots that form in the extremities (deep venous thrombosis) and lungs (pulmonary embolus) are feared complications of reconstructive surgery. One in ten patients with symptomatic pulmonary embolus will be dead in 60 minutes. Patients with deep venous thrombosis can develop the post-thrombotic syndrome, known to be a major driver of poor quality of life. These phenomena, broadly known as venous thromboembolism (VTE), have substantial downstream ramifications, and the US Surgeon General and the American Society of Plastic Surgeons (ASPS), among others, have underscored the importance of VTE prevention in surgical patients. Reconstructive surgery, most commonly performed to fix traumatic injuries or defects after cancer excision, often involves borrowing tissue from adjacent or distant areas on the body; reconstructive surgery patients can routinely have surgical injury involving 20% or more of their total body surface area. Injury and resultant inflammation are known to increase metabolism of certain drugs, including those used to prevent VTE after surgery. Enoxaparin is a blood-thinning medication that decreases likelihood of blood clot formation. Previous research has shown that reconstructive surgery patients who are given enoxaparin after surgery are less likely to develop VTE. However, despite receiving of a standard dose of enoxaparin, many patients still develop this life-threatening complication. We believe that patients metabolize enoxaparin differently based on the degree of surgical injury created during reconstruction, and seek to critically examine enoxaparin metabolism in reconstructive surgery patients. The proposed research will evaluate how enoxaparin affects the blood based on standard, ASPS-recommended dosing after reconstructive surgeries; we will also examine whether the extent of surgical injury alters metabolism as well. Enoxaparin effectiveness will be tracked using anti-Factor Xa (aFXa) levels. If subtherapeutic aFXa levels are observed, the study will also design, implement and test a clinical enoxaparin dose-adjustment protocol to achieve appropriate post-operative aFXa levels. Further research based on these data will examine reduction in VTE risk when aFXa-driven enoxaparin dosing is used. The ultimate goal of our research is to better understand the interplay between enoxaparin dosing, degree of surgical injury, and blood clots after major reconstructive surgery. Ultimately, this research will expand our understanding of why post-operative VTE occurs, will allow us to individualize a patient's VTE prophylaxis strategy based on their unique characteristics, and will further improve patient safety after reconstructive surgery.