BACKGROUND: 

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.

METHODS: 

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.

RESULTS: 

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).

CONCLUSIONS: 

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.

中文翻译：

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重组和血浆来源的血管性血友病因子浓缩物治疗成人体外膜氧合患者获得性血管性血友病综合征的体外比较

背景： 

成人体外膜肺氧合 (ECMO) 期间凝血障碍性出血很常见，获得性血管性血友病综合征是一个促成因素。我们比较了用重组血管性血友病因子浓缩物和血浆衍生的血管性血友病因子浓缩物进行体外治疗的 ECMO 患者血液样本。我们的假设是重组血管性血友病因子 (vWF) 在增加 vWF 功能方面具有更大的功效。其次，我们假设重组 vWF 对凝血酶生成的影响较小。

方法： 

该研究招募了 30 名 ECMO 患者和 10 名心脏手术对照。ECMO 患者血液样本在体外用低剂量和高剂量重组 vWF 以及低剂量和高剂量血浆衍生的 vWF 进行处理。比较了 ECMO 患者血液样本和对照血液样本以及 vWF 治疗的 ECMO 患者血液样本和未处理样本之间的全血瑞斯托菌素诱导的血小板聚集 (RIPA)、血浆瑞斯托菌素辅助因子活性 (RCo) 和凝血酶生成。

结果： 

与对照样本 2 欧姆（1-12 [第 25-75 个百分位数]）对比 20 欧姆（11-42）（P < .001）相比，ECMO 患者血液样本的 RIPA 中值严重降低。用高剂量重组 vWF 处理 ECMO 患者血液样本可显着增加 RIPA 中值至 10 ohms (2-15) ( P < .001)，而低剂量重组 vWF 和低剂量和高剂量血浆衍生 vWF 没有显着增加 RIPA；分别为 6 ohms (3–14)、4 ohms (1–13) 和 6 ohms (2–10) ( P= .25、>.99 和 >.99）。用高剂量重组 vWF 和低剂量和高剂量血浆衍生 vWF 治疗显着增加血浆 RCo 中位数至 4.7 国际单位 (IU)/mL (3.7-5.9)、3.3 IU/mL (2.7-4.8) 和 3.9 IU/mL (3.4–5.3) 分别与对照组 1.8 IU/mL (1.5–2.3) 相比（所有P < .001）。与未经处理的样本 (5856.7 ± 1924.6) 相比，用低剂量和高剂量血浆衍生的 vWF 治疗显着增加平均内源性凝血酶电位 (6270.2 ± 2038.7 和 6313.1 ± 1913.3) ( P = .04 和 .006)，而用低剂量- 和高剂量重组 vWF 对平均内源性凝血酶潜能没有显着影响（5776.1 ± 2087.3 和 5856.2 ± 1946.4）（两个比较的P > .99）。

结论： 

在改善 RIPA 方面，用高剂量重组 vWF 对 ECMO 患者血液样本进行体外治疗优于低剂量重组 vWF 和血浆衍生 vWF。此外，重组 vWF 治疗不会增加内源性凝血酶的潜力，如果它用于治疗 ECMO 患者的获得性血管性血友病综合征，这可能会降低总体血栓形成风险。