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危重症患者新冠病毒疾病相关凝血病的管理及获得性血管性血友病综合征的风险

Management of COVID-19 associated coagulopathy in critically ill patients and the risk of acquired von willebrand syndrome.

作者信息

Ishikura Hiroyasu, Irie Yuhei, Nakashio Maiko, Maruyama Junichi, Nakamura Yoshihiko, Yamagaito Takahiro, Yoshida Maho, Hatomoto Hiroki, Yamasaki Shintaro, Hoshino Kota

机构信息

Emergency and Critical Care Center, Rakuwakai Otowa Hospital, 2 Otowachinji-cho, Yamashina-ku, Kyoto, 607-8062, Japan.

Department of Emergency and Critical Care Medicine, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.

出版信息

Sci Rep. 2025 Jun 2;15(1):19321. doi: 10.1038/s41598-025-99786-z.

DOI:10.1038/s41598-025-99786-z
PMID:40456934
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12130217/
Abstract

This study investigated the interplay between thrombosis and hemorrhage in critically ill COVID-19 patients, particularly those on extracorporeal membrane oxygenation (ECMO). Forty-three mechanically ventilated patients were divided into ECMO (n = 22) and non-ECMO (n = 21) groups. Thrombotic events occurred similarly in both groups (22.7% in ECMO, 28.6% in non-ECMO), both higher than the approximately 5% observed in patients hospitalized with viral respiratory illnesses other than COVID-19. However, bleeding events were significantly more frequent in the ECMO group (72.7%) compared to the non-ECMO group (14.3%) (P < 0.01). ECMO patients showed decreased platelet counts, fibrinogen, von Willebrand factor (VWF) activity using a ristocetin cofactor (VWF: RCo) assay, and developed acquired von Willebrand syndrome (AvWS) (VWF: RCo/VWF antigen (Ag) ratio < 0.7), along with increased D-dimer and lower high-molecular-weight VWF multimers. In contrast, the non-ECMO group showed no significant changes in platelet counts, fibrinogen, VWF: RCo, or D-dimer. Over time, both VWF: Ag and VWF: RCo increased significantly in both groups, but the VWF: RCo/VWF: Ag ratio remained above 0.7, and high-molecular-weight VWF multimers did not change significantly. These findings emphasize the need for vigilance regarding thrombotic and hemorrhagic complications, particularly in ECMO patients, where ECMO-induced shear stress may lead to AvWS, necessitating monitoring of VWF: Ag and VWF: RCo.

摘要

本研究调查了危重症新型冠状病毒肺炎(COVID-19)患者,尤其是接受体外膜肺氧合(ECMO)治疗的患者中血栓形成与出血之间的相互作用。43例机械通气患者被分为ECMO组(n = 22)和非ECMO组(n = 21)。两组血栓形成事件发生率相似(ECMO组为22.7%,非ECMO组为28.6%),均高于在非COVID-19病毒性呼吸道疾病住院患者中观察到的约5%。然而,与非ECMO组(14.3%)相比,ECMO组出血事件明显更频繁(72.7%)(P < 0.01)。ECMO患者血小板计数、纤维蛋白原、使用瑞斯托霉素辅因子(VWF:RCo)检测的血管性血友病因子(VWF)活性降低,并发生获得性血管性血友病综合征(AvWS)(VWF:RCo/VWF抗原(Ag)比值<0.7),同时D-二聚体升高,高分子量VWF多聚体降低。相比之下,非ECMO组血小板计数、纤维蛋白原、VWF:RCo或D-二聚体无显著变化。随着时间推移,两组VWF:Ag和VWF:RCo均显著升高,但VWF:RCo/VWF:Ag比值仍高于0.7,高分子量VWF多聚体无显著变化。这些发现强调了对血栓形成和出血并发症保持警惕的必要性,尤其是在ECMO患者中,ECMO诱导的剪切应力可能导致AvWS,因此需要监测VWF:Ag和VWF:RCo。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3858/12130217/50c3e9e2eb30/41598_2025_99786_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3858/12130217/470f595067fc/41598_2025_99786_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3858/12130217/a06932a7aabe/41598_2025_99786_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3858/12130217/73fdcf9fba28/41598_2025_99786_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3858/12130217/50c3e9e2eb30/41598_2025_99786_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3858/12130217/470f595067fc/41598_2025_99786_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3858/12130217/a06932a7aabe/41598_2025_99786_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3858/12130217/73fdcf9fba28/41598_2025_99786_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3858/12130217/50c3e9e2eb30/41598_2025_99786_Fig4_HTML.jpg

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