From the Department of Anesthesiology and Critical Care Medicine, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia.
Department of Surgery, Division of Cardiothoracic Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
Anesth Analg. 2022 Feb 1;134(2):312-321. doi: 10.1213/ANE.0000000000005831.
Coagulopathic bleeding is common during adult extracorporeal membrane oxygenation (ECMO), and acquired von Willebrand syndrome is a contributing factor. We compared ECMO patient blood samples that were treated in vitro with recombinant von Willebrand Factor concentrate and plasma-derived von Willebrand Factor concentrate. Our hypothesis was that recombinant von Willebrand Factor (vWF) would have greater efficacy in increasing vWF function. Secondarily, we hypothesized that recombinant vWF would have less impact on thrombin generation.
Thirty ECMO patients and 10 cardiac surgical controls were enrolled in the study. ECMO patient blood samples were treated in vitro with low- and high-dose recombinant vWFs and low- and high-dose plasma-derived vWFs. Whole blood ristocetin-induced platelet aggregation (RIPA), plasma ristocetin cofactor activity (RCo), and thrombin generation were compared between ECMO patient blood samples and control blood samples and between vWF-treated ECMO patient blood samples and nontreated samples.
ECMO patient blood samples had severely reduced median RIPA compared to control samples 2 ohms (1-12 [25th-75th percentile]) vs 20 ohms (11-42) (P < .001). Treatment of ECMO patient blood samples with high-dose recombinant vWF significantly increased median RIPA to 10 ohms (2-15) (P < .001), while low-dose recombinant vWF and low- and high-dose plasma-derived vWFs did not significantly increase RIPA; 6 ohms (3-14), 4 ohms (1-13), and 6 ohms (2-10), respectively (P = .25, >.99, and >.99). Treatment with high-dose recombinant vWF and low- and high-dose plasma-derived vWFs significantly increased median plasma RCo to 4.7 international units (IU)/mL (3.7-5.9), 3.3 IU/mL (2.7-4.8), and 3.9 IU/mL (3.4-5.3), respectively, compared to controls 1.8 IU/mL (1.5-2.3) (all P < .001). Treatment with low- and high-dose plasma-derived vWFs significantly increased mean endogenous thrombin potential (6270.2 ± 2038.7 and 6313.1 ± 1913.3) compared to nontreated samples (5856.7 ± 1924.6) (P = .04 and .006), whereas treatment with low- and high-dose recombinant vWFs had no significant effect on mean endogenous thrombin potential (5776.1 ± 2087.3 and 5856.2 ± 1946.4) (P > .99 for both comparisons).
In vitro treatment of ECMO patient blood samples with high-dose recombinant vWF was superior to low-dose recombinant vWF and plasma-derived vWF in terms of improving RIPA. In addition, recombinant vWF treatment did not increase endogenous thrombin potential, which may reduce overall thrombotic risk if it used to treat acquired von Willebrand syndrome in ECMO patients.
成人体外膜肺氧合（ECMO）期间常发生凝血功能障碍性出血，获得性血管性血友病（von Willebrand syndrome，vWD）是其发病因素之一。我们比较了经体外处理的 ECMO 患者血液样本与重组 vWF 浓缩物和血浆源性 vWF 浓缩物。我们的假设是重组 vWF 在增加 vWF 功能方面更有效。其次，我们假设重组 vWF 对凝血酶生成的影响较小。
30 例 ECMO 患者和 10 例心脏手术对照患者纳入研究。用低剂量和高剂量重组 vWF 和低剂量和高剂量血浆源性 vWF 体外处理 ECMO 患者的血液样本。比较 ECMO 患者血液样本与对照血液样本、vWF 处理的 ECMO 患者血液样本与未处理样本之间的全血瑞斯托菌素诱导的血小板聚集（ristocetin-induced platelet aggregation，RIPA）、血浆瑞斯托菌素辅因子活性（ristocetin cofactor activity，RCo）和凝血酶生成。
与对照样本相比，ECMO 患者的血液样本中位 RIPA 明显降低，中位数分别为 2 欧姆（25-75 分位：1-12）和 20 欧姆（11-42）（P<0.001）。用高剂量重组 vWF 处理 ECMO 患者的血液样本可显著增加中位 RIPA，至 10 欧姆（2-15）（P<0.001），而低剂量重组 vWF 和低剂量及高剂量血浆源性 vWF 未显著增加 RIPA，中位数分别为 6 欧姆（3-14）、4 欧姆（1-13）和 6 欧姆（2-10）（P=0.25、>.99 和>.99）。与对照相比，高剂量重组 vWF 和低剂量及高剂量血浆源性 vWF 处理后中位血浆 RCo 显著增加，分别为 4.7 国际单位/毫升（3.7-5.9）、3.3 IU/mL（2.7-4.8）和 3.9 IU/mL（3.4-5.3）（均 P<0.001）。与未处理样本相比，用低剂量和高剂量血浆源性 vWF 处理可显著增加平均内源性凝血酶潜能（6270.2±2038.7 和 6313.1±1913.3）（P=0.04 和 0.006），而用低剂量和高剂量重组 vWF 处理对平均内源性凝血酶潜能无显著影响（5776.1±2087.3 和 5856.2±1946.4）（P>.99，两种比较均如此）。
与低剂量重组 vWF 和血浆源性 vWF 相比，体外处理 ECMO 患者血液样本用高剂量重组 vWF 可更有效改善 RIPA。此外，重组 vWF 治疗不会增加内源性凝血酶潜能，如果用于治疗 ECMO 患者的获得性 vWD，可能会降低整体血栓形成风险。
