Thomas Kimberly A, Liu Alice, Bark David L, Spinella Philip C, Shea Susan M
Division of Critical Care, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
Division of Hematology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.
Blood Vessel Thromb Hemost. 2025 May 9;2(3):100076. doi: 10.1016/j.bvth.2025.100076. eCollection 2025 Aug.
Traumatic injury has the highest burden on morbidity and mortality in the United States. Early deaths from trauma are most frequently due to hemorrhage and could be prevented with more timely and efficacious treatments. A hallmark of trauma-induced coagulopathy (TIC) is hypofibrinogenemia, which is treated with fibrinogen concentrates (FibCon) or cryoprecipitate (Cryo). Pathogen reduction (PR) of Cryo (PR-CryoFC) enables extended storage after thaw at room temperature, permitting immediate availability for patients with bleeding. As Cryo contains additional concentrated plasma proteins involved in hemostasis compared with FibCon, we hypothesized that Cryo and PR-CryoFC would result in more rapid and effective clot formation. To evaluate the hemostatic capacity of these adjuncts, we simulated TIC (dilution, hyperfibrinolysis) in an ex vivo model and administered Cryo, PR-CryoFC, and FibCon, then performed hemostatic assessment to include viscoelastometry, thrombin generation, and a microfluidic model of vessel injury. Cryo and PR-CryoFC had similar resuscitation capacity in assays without flow (viscoelastometry, thrombin generation), whereas in the dynamic microfluidic model, Cryo had faster von Willebrand factor (VWF)-mediated platelet recruitment. There was no difference in intrinsic VWF function between adjuncts in static, nonflowing assays, yet in a flow-dependent vortexing assay, PR reduced VWF cleavage by ADAMTS13, despite equivalent ADAMTS13 activity, suggesting impaired biophysical elongation and extension of VWF in PR-CryoFC, resulting in reduced cleavage and platelet binding capacity. Herein, we show ex vivo simulation of coagulopathy and resuscitation differentiated hemostatic function under flow among Cryo, PR-CryoFC, and FibCon. Further exploration of effects of PR on plasma proteins is warranted as well as effects on clinical outcomes.
在美国，创伤性损伤导致的发病率和死亡率负担最高。创伤导致的早期死亡最常见的原因是出血，而更及时有效的治疗可以预防此类情况。创伤性凝血病（TIC）的一个标志是低纤维蛋白原血症，可使用纤维蛋白原浓缩物（FibCon）或冷沉淀（Cryo）进行治疗。冷沉淀的病原体灭活（PR-CryoFC）可使解冻后的产品在室温下延长储存时间，以便能立即为出血患者提供使用。由于与FibCon相比，冷沉淀还含有参与止血的其他浓缩血浆蛋白，我们推测冷沉淀和PR-CryoFC将导致更快、更有效的凝块形成。为了评估这些辅助剂的止血能力，我们在体外模型中模拟TIC（稀释、高纤维蛋白溶解），并给予冷沉淀、PR-CryoFC和FibCon，然后进行止血评估，包括粘弹性测定、凝血酶生成以及血管损伤的微流体模型。在无血流的检测中（粘弹性测定、凝血酶生成），冷沉淀和PR-CryoFC具有相似的复苏能力，而在动态微流体模型中，冷沉淀具有更快的血管性血友病因子（VWF）介导的血小板募集。在静态、无血流的检测中，各辅助剂之间的内在VWF功能没有差异，但在血流依赖性涡旋检测中，尽管ADAMTS13活性相当，但PR减少了ADAMTS13对VWF的裂解，这表明PR-CryoFC中VWF的生物物理伸长和伸展受损，导致裂解和血小板结合能力降低。在此，我们展示了在体外模拟凝血病和复苏过程中，冷沉淀、PR-CryoFC和FibCon在血流状态下的止血功能差异。有必要进一步探索PR对血浆蛋白的影响以及对临床结果的影响。
