Recombinant ADAMTS13 reduces abnormally up-regulated von Willebrand factor in plasma from patients with severe COVID-19.
Recombinant ADAMTS13 reduces abnormally up-regulated von Willebrand factor in plasma from patients with severe COVID-19.
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DOI：
10.1016/j.thromres.2021.02.012
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发表时间：
2021-05
影响因子：
7.5
通讯作者：
Mumford AD
中科院分区：
文献类型：
--
作者：
Turecek PL;Peck RC;Rangarajan S;Reilly-Stitt C;Laffan MA;Kazmi R;James I;Dushianthan A;Schrenk G;Gritsch H;Ewenstein BM;Mellgard B;Erdlenbruch W;Jain N;Binder NB;Mumford AD
影响肺和全身血管系统的血栓形成在严重的COVID-19期间很常见，并导致不良后果。虽然血栓形成可能是由血管细胞的炎症激活引起的，但血栓形成的介质仍未得到证实。在36例严重COVID-19患者的横断面队列中，我们发现血浆血管性血友病因子（VWF）水平显著升高，伴有VWF调节蛋白酶ADAMTS 13的部分降低。在所有患者中，我们发现这种VWF/ADAMTS 13失衡与超高分子量（UHMW）VWF多聚体的持续存在有关，这些多聚体在某些疾病中具有高度血栓形成性。来自严重COVID-19患者的血浆样品与重组ADAMTS 13（rADAMTS 13）的孵育以时间和浓度依赖性方式显著降低了异常高的VWF活性，减少了总体多聚体大小并耗尽了UHMW VWF多聚体。我们的数据表明，在严重COVID-19的发病机制中，正常VWF/ADAMTS 13稳态的破坏，并表明这可以通过纠正低血浆ADAMTS 13水平来体外逆转。这些发现表明rADAMTS 13在帮助COVID-19患者恢复止血平衡方面具有潜在的治疗作用。
Thrombosis affecting the pulmonary and systemic vasculature is common during severe COVID-19 and causes adverse outcomes. Although thrombosis likely results from inflammatory activation of vascular cells, the mediators of thrombosis remain unconfirmed. In a cross-sectional cohort of 36 severe COVID-19 patients, we show that markedly increased plasma von Willebrand factor (VWF) levels were accompanied by a partial reduction in the VWF regulatory protease ADAMTS13. In all patients we find this VWF/ADAMTS13 imbalance to be associated with persistence of ultra-high-molecular-weight (UHMW) VWF multimers that are highly thrombogenic in some disease settings. Incubation of plasma samples from patients with severe COVID-19 with recombinant ADAMTS13 (rADAMTS13) substantially reduced the abnormally high VWF activity, reduced overall multimer size and depleted UHMW VWF multimers in a time and concentration dependent manner. Our data implicate disruption of normal VWF/ADAMTS13 homeostasis in the pathogenesis of severe COVID-19 and indicate that this can be reversed ex vivo by correction of low plasma ADAMTS13 levels. These findings suggest a potential therapeutic role for rADAMTS13 in helping restore haemostatic balance in COVID-19 patients.
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影响因子：
82.9
作者：
Amanat F;Stadlbauer D;Strohmeier S;Nguyen THO;Chromikova V;McMahon M;Jiang K;Arunkumar GA;Jurczyszak D;Polanco J;Bermudez-Gonzalez M;Kleiner G;Aydillo T;Miorin L;Fierer DS;Lugo LA;Kojic EM;Stoever J;Liu STH;Cunningham-Rundles C;Felgner PL;Moran T;García-Sastre A;Caplivski D;Cheng AC;Kedzierska K;Vapalahti O;Hepojoki JM;Simon V;Krammer F
通讯作者：
Krammer F
影响因子：
6.7
作者：
Crescente, Marilena;Thomas, Grace M.;Wagner, Denisa D.
通讯作者：
Wagner, Denisa D.
影响因子：
2.9
作者：
Dyer, Mitchell R.;Plautz, William E.;Neal, Matthew D.
通讯作者：
Neal, Matthew D.
ADAMTS-13与von Willebrand因子的多步结合。
DOI：
10.1111/j.1538-7836.2009.03620.x
发表时间：
2009-12
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Feys HB;Anderson PJ;Vanhoorelbeke K;Majerus EM;Sadler JE
通讯作者：
Sadler JE
影响因子：
10.4
作者：
Cui, Songping;Chen, Shuo;Wang, Feng
通讯作者：
Wang, Feng