From the Department of Anesthesiology, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma.
Department of Anesthesiology, University of Virginia School of Medicine, Charlottesville, Virginia.
Anesth Analg. 2023 May 1;136(5):894-904. doi: 10.1213/ANE.0000000000006356. Epub 2023 Apr 14.
A trace amount of thrombin cleaves factor VIII (FVIII) into an active form (FVIIIa), which catalyzes FIXa-mediated activation of FX on the activated platelet surface. FVIII rapidly binds to von Willebrand factor (VWF) after secretion and becomes highly concentrated via VWF-platelet interaction at a site of endothelial inflammation or injury. Circulating levels of FVIII and VWF are influenced by age, blood type (nontype O > type O), and metabolic syndromes. In the latter, hypercoagulability is associated with chronic inflammation (known as thrombo-inflammation). In acute stress including trauma, releasable pools of FVIII/VWF are secreted from the Weibel-Palade bodies in the endothelium and then augment local platelet accumulation, thrombin generation, and leukocyte recruitment. Early systemic increases of FVIII/VWF (>200% of normal) levels in trauma result in a lower sensitivity of contact-activated clotting time (activated partial thromboplastin time [aPTT] or viscoelastic coagulation test [VCT]). However, in severely injured patients, multiple serine proteases (FXa plasmin and activated protein C [APC]) are locally activated and may be systemically released. Severity of traumatic injury correlates with prolonged aPTT and elevated activation markers of FXa, plasmin, and APC, culminating in a poor prognosis. In a subset of acute trauma patients, cryoprecipitate that contains fibrinogen, FVIII/VWF, and FXIII is theoretically advantageous over purified fibrinogen concentrate to promote stable clot formation, but comparative efficacy data are lacking. In chronic inflammation or subacute phase of trauma, elevated FVIII/VWF contributes to the pathogenesis of venous thrombosis by enhancing not only thrombin generation but also augmenting inflammatory functions. Future developments in coagulation monitoring specific to trauma patients, and targeted to enhancement or inhibition of FVIII/VWF, are likely to help clinicians gain better control of hemostasis and thromboprophylaxis. The main goal of this narrative is to review the physiological functions and regulations of FVIII and implications of FVIII in coagulation monitoring and thromboembolic complications in major trauma patients.
微量的凝血酶将因子 VIII（FVIII）切割成活性形式（FVIIIa），后者催化 FIXa 在活化血小板表面介导 FX 的活化。FVIII 在分泌后迅速与血管性血友病因子（VWF）结合，并通过 VWF-血小板相互作用在血管内皮炎症或损伤部位高度浓缩。FVIII 和 VWF 的循环水平受年龄、血型（非 O 型>O 型）和代谢综合征的影响。在后一种情况下，高凝状态与慢性炎症（称为血栓炎症）有关。在包括创伤在内的急性应激中，FVIII/VWF 的可释放池从内皮的 Weibel-Palade 体中分泌出来，然后增加局部血小板聚集、凝血酶生成和白细胞募集。创伤后早期系统中 FVIII/VWF（高于正常水平的 200%）水平的增加导致接触激活凝血时间（活化部分凝血活酶时间[aPTT]或黏弹性凝血试验[VCT]）的敏感性降低。然而，在严重受伤的患者中，多种丝氨酸蛋白酶（FXa、纤溶酶和活化蛋白 C [APC]）被局部激活并可能被系统释放。创伤的严重程度与 aPTT 延长和 FXa、纤溶酶和 APC 的活化标志物升高相关，最终导致预后不良。在一部分急性创伤患者中，含有纤维蛋白原、FVIII/VWF 和 FXIII 的冷沉淀理论上比纯化的纤维蛋白原浓缩物更有利于促进稳定的血栓形成，但缺乏比较疗效数据。在慢性炎症或创伤的亚急性期，FVIII/VWF 的升高通过增强凝血酶生成和增强炎症功能，促进静脉血栓形成的发病机制。针对创伤患者的凝血监测的特定发展，以及针对 FVIII/VWF 的增强或抑制，可能有助于临床医生更好地控制止血和血栓预防。本叙述的主要目的是回顾 FVIII 的生理功能和调节及其在凝血监测和重大创伤患者血栓栓塞并发症中的意义。
