A relative ADAMTS13 deficiency supports the presence of a secondary microangiopathy in COVID 19

Martinelli, Nicola; Montagnana, Martina; Pizzolo, Francesca; Friso, Simonetta; Salvagno, Gian Luca; Forni, Gian Luca; Gianesin, Barbara; Morandi, Matteo; Lunardi, Claudio; Lippi, Giuseppe; Polati, Enrico; Olivieri, Oliviero; Franceschi, Lucia De

doi:10.1016/j.thromres.2020.07.034

Cited by 65 publications

(89 citation statements)

References 11 publications

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“…In line with this finding, ADAMTS13 antigen correlated inversely with glycocalyx damage and SOFA score and predicted ARDS and 60-day mortality in our study [33]. Evidence of reduced ADAMTS13 activity in the presence of schistocytes (~ 2-4%) appeared compatible with thrombotic microangiopathy (TMA) secondary to COVID-19 [34].…”

Section: Discussionsupporting

confidence: 88%

Microvascular dysfunction in COVID-19: the MYSTIC study

et al. 2020

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Rationale Pre-clinical and autopsy studies have fueled the hypothesis that a dysregulated vascular endothelium might play a central role in the pathogenesis of ARDS and multi-organ failure in COVID-19. Objectives To comprehensively characterize and quantify microvascular alterations in patients with COVID-19. Methods Hospitalized adult patients with moderate-to-severe or critical COVID-19 (n = 23) were enrolled non-consecutively in this prospective, observational, cross-sectional, multi-center study. Fifteen healthy volunteers served as controls. All participants underwent intravital microscopy by sidestream dark field imaging to quantify vascular density, red blood cell velocity (VRBC), and glycocalyx dimensions (perfused boundary region, PBR) in sublingual microvessels. Circulating levels of endothelial and glycocalyx-associated markers were measured by multiplex proximity extension assay and enzyme-linked immunosorbent assay. Measurements and main results COVID-19 patients showed an up to 90% reduction in vascular density, almost exclusively limited to small capillaries (diameter 4–6 µm), and also significant reductions of VRBC. Especially, patients on mechanical ventilation showed severe glycocalyx damage as indicated by higher PBR values (i.e., thinner glycocalyx) and increased blood levels of shed glycocalyx constituents. Several markers of endothelial dysfunction were increased and correlated with disease severity in COVID-19. PBR (AUC 0.75, p = 0.01), ADAMTS13 (von Willebrand factor-cleaving protease; AUC 0.74, p = 0.02), and vascular endothelial growth factor A (VEGF-A; AUC 0.73, p = 0.04) showed the best discriminatory ability to predict 60-day in-hospital mortality. Conclusions Our data clearly show severe alterations of the microcirculation and the endothelial glycocalyx in patients with COVID-19. Future therapeutic approaches should consider the importance of systemic vascular involvement in COVID-19.

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Section: Discussionsupporting

confidence: 88%

Microvascular dysfunction in COVID-19: the MYSTIC study

et al. 2020

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“…Intravascular coagulopathy, either localized to the lung parenchyma or disseminated, is also common in COVID-19 patients developing severe or critical illness [ 23 ]. The development of micro- and macro-thrombi in many blood vessels is a well-known cause of erythrocyte injury, which would contribute to the presence of RBCs with many morphological abnormalities (e.g., especially schistocytes) and large size heterogeneity within the circulation [ 24 ]. Moreover, it is possible that such microthrombi could perpetuate AKI, which could lead to disrupted production of erythropoietin, thus exacerbating anisocytosis and/or anemia in patients with COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Red Blood Cell Distribution Width (RDW) Predicts COVID-19 Severity: A Prospective, Observational Study from the Cincinnati SARS-CoV-2 Emergency Department Cohort

Henry

Benoit

et al. 2020

Diagnostics

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Since previous evidence has demonstrated that red blood cell distribution width (RDW) may be a useful prognostic parameter in many critical illnesses and infectious diseases, we investigated the utility of RDW for monitoring patients with coronavirus disease 2019 (COVID-19). The study population consisted of 49 COVID-19 patients, including 16 (32.6%) with severe illness, 12 (24.5%) with severe acute kidney injury (AKI), and 8 (16.3%) requiring renal replacement therapy (RRT). The predictive value of blood tests, performed during emergency department evaluation, was then addressed. A progressive increase of RDW was observed with advancing COVID-19 severity. The area under the curve (AUC) of RDW was 0.73 for predicting severe illness, 0.80 for severe AKI, and 0.83 for RRT, respectively. In multivariate analysis, elevated RDW was associated with 9-fold and 16-fold increased odds of severe COVID-19 and AKI, respectively. The results of this study suggest that RDW should be part of routine laboratory assessment and monitoring of COVID-19.

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“…Escher et al [ 66 , 68 ] reported elevated vWF antigen and function, together with increased FVIII clotting activity in COVID-19 patients, likely reflecting the combined effect of the greater release of Weibel-Palade bodies from endothelial cells and the acute-phase reaction that raises the FVIII level. ADAMTS13 activity is mild-to-moderately reduced in COVID-19 patients [ 68 , 69 , 70 ].…”

Section: Endothelium Von Willebrand Factor and Abo Blood Groupmentioning

confidence: 99%

The Impact of COVID-19 Disease on Platelets and Coagulation

2020

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Coronavirus disease 2019 (COVID-19) causes a spectrum of disease; some patients develop a severe proinflammatory state which can be associated with a unique coagulopathy and procoagulant endothelial phenotype. Initially, COVID-19 infection produces a prominent elevation of fibrinogen and D-dimer/fibrin(ogen) degradation products. This is associated with systemic hypercoagulability and frequent venous thromboembolic events. The degree of D-dimer elevation positively correlates with mortality in COVID-19 patients. COVID-19 also leads to arterial thrombotic events (including strokes and ischemic limbs) as well as microvascular thrombotic disorders (as frequently documented at autopsy in the pulmonary vascular beds). COVID-19 patients often have mild thrombocytopenia and appear to have increased platelet consumption, together with a corresponding increase in platelet production. Disseminated intravascular coagulopathy (DIC) and severe bleeding events are uncommon in COVID-19 patients. Here, we review the current state of knowledge of COVID-19 and hemostasis.

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A relative ADAMTS13 deficiency supports the presence of a secondary microangiopathy in COVID 19

Cited by 65 publications

References 11 publications

Microvascular dysfunction in COVID-19: the MYSTIC study

Microvascular dysfunction in COVID-19: the MYSTIC study

Red Blood Cell Distribution Width (RDW) Predicts COVID-19 Severity: A Prospective, Observational Study from the Cincinnati SARS-CoV-2 Emergency Department Cohort

The Impact of COVID-19 Disease on Platelets and Coagulation

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