OBJECTIVES: 

Although COVID-19 is associated with high von Willebrand factor (vWF) parameters promoting thrombosis, venovenous extracorporeal membrane oxygenation (vvECMO) is associated with the development of acquired von Willebrand syndrome (AVWS) promoting bleeding. This study was designed to assess both the incidence and severity of AVWS in COVID-19 patients undergoing vvECMO, and the benefit of comprehensive vWF analyses.

DESIGN: 

Prospective observational study.

SETTING: 

ICU at a tertiary-care center.

PATIENTS: 

Twenty-seven consecutive COVID-19 patients with acute respiratory distress syndrome (ARDS) requiring vvECMO.

MEASUREMENTS AND MAIN RESULTS: 

Comprehensive vWF analyses (including sodium dodecyl-sulfate polyacrylamide gel electrophoresis) were performed before, during, and after vvECMO. In a subgroup of 12 patients with AVWS, effectiveness of treatment with desmopressin was assessed. The patients’ mean age was 53 years (range, 23–73), 70% were male, and all had various comorbidities. Following markedly elevated vwf antigen (vWF: Ag; mean, 546% (sd, 282]), vWF collagen binding capacity (mean, 469% [sd, 271]), vWF activity (vWF:A; mean, 383% [sd, 132]), and factor VIII activity (mean, 302% [sd, 106]), and only borderline decreases in high-molecular-weight (HMW) vWF multimers before vvECMO, all of these variables decreased and HMW vWF multimers became undetectable within hours following initiation of vvECMO. All variables fully recovered within 3–38 hours after discontinuation of vvECMO. During vvECMO, decreases in the vWF:A/vWF:Ag ratio correlated with absent HMW vWF multimers. Desmopressin did not affect vWF parameters.

CONCLUSIONS: 

In patients with COVID-19-associated ARDS, AVWS developed soon after initiation of vvECMO. The vWF:A/vWF:Ag ratio was a suitable screening test for AVWS. As desmopressin was ineffective, bleeding during vvECMO-associated AVWS should preferably be treated with concentrates containing vWF.

中文翻译：

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COVID-19 患者静脉体外膜氧合期间获得性冯维勒布兰德综合征和去氨加压素耐药：一项前瞻性观察研究

目标： 

尽管 COVID-19 与促进血栓形成的高血管性血友病因子 (vWF) 参数相关，但静脉静脉体外膜氧合 (vvECMO) 与促进出血的获得性血管性血友病综合征(AVWS)的发生有关。本研究旨在评估接受 vvECMO 的 COVID-19 患者 AVWS 的发生率和严重程度，以及全面 vWF 分析的益处。

设计： 

前瞻性观察研究。

环境： 

三级护理中心的 ICU。

患者： 

连续 27 名患有急性呼吸窘迫综合征 (ARDS) 的 COVID-19 患者需要 vvECMO。

测量和主要结果： 

在 vvECMO 之前、期间和之后进行了全面的 vWF 分析（包括十二烷基硫酸钠聚丙烯酰胺凝胶电泳）。在 12 名 AVWS 患者组成的亚组中，评估了去氨加压素治疗的有效性。患者的平均年龄为 53 岁（范围为 23-73 岁），70% 为男性，并且均患有各种合并症。vWF 抗原显着升高（vWF：Ag；平均值，546% ( sd，282]）、vWF 胶原结合能力（平均值，469% [ sd，271]）、vWF 活性（vWF：A；平均值，383% [ sd]，132]）和因子 VIII 活性（平均值，302% [ sd，106]），并且在 vvECMO 之前高分子量 (HMW) vWF 多聚体仅出现边缘性下降，所有这些变量均下降，并且 HMW vWF 多聚体变得不可检测vvECMO 启动后数小时内。停止 vvECMO 后 3-38 小时内所有变量完全恢复。在 vvECMO 期间，vWF:A/vWF:Ag 比率的降低与 HMW vWF 多聚体缺失相关。去氨加压素不影响 vWF 参数。

结论： 

在患有 COVID-19 相关 ARDS 的患者中，在 vvECMO 启动后不久就出现了 AVWS。vWF:A/vWF:Ag 比率是 AVWS 的合适筛查测试。由于去氨加压素无效，因此 vvECMO 相关 AVWS 期间的出血应优选使用含有 vWF 的浓缩物进行治疗。