Reduction of ADAMTS13 Levels Predicts Mortality in SARS-CoV-2 Patients

Tiscia, Giovanni Luca; Favuzzi, Giovanni; Laurenzo, Antonio De; Cappucci, Filomena; Fischetti, Lucia; Mauro, Lazzaro Di; Miscio, Giuseppe; Mirijello, Antonio; Chinni, Elena

doi:10.1055/s-0040-1716379

Cited by 35 publications

(48 citation statements)

References 23 publications

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“…We confirm and extend published findings on hemostatic alterations in COVID‐19 and compare hemostatic profiles between patients stratified according to level of care and according to level of respiratory support. Previous studies were either small or assessed a limited number of hemostatic tests, but in aggregate these studies are in line with our findings on changes in the VWF/ADAMTS13 axis, 18,30‐33 in vivo and ex vivo activation of coagulation, 18,19,25,34‐36 and in vivo and ex vivo fibrinolytic status 18‐20,26 …”

Section: Discussionsupporting

confidence: 90%

Prothrombotic changes in patients with COVID‐19 are associated with disease severity and mortality

Meijenfeldt

Havervall

Adelmeijer

et al. 2021

Research and Practice in Thrombosis and Haemostasis

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Background and Aims Patients with severe coronavirus disease 2019 (COVID‐19) are at significant risk of thrombotic complications. However, their prothrombotic state is incompletely understood. Therefore, we measured in vivo activation markers of hemostasis, plasma levels of hemostatic proteins, and functional assays of coagulation and fibrinolysis in plasma from patients with COVID‐19 and determined their association with disease severity and 30‐day mortality. Methods We included 102 patients with COVID‐19 receiving various levels of respiratory support admitted to general wards, intermediate units, or intensive care units and collected plasma samples shortly after hospital admission. Results Patients with COVID‐19 with higher respiratory support had increased in vivo activation of coagulation and fibrinolysis, as reflected by higher plasma levels of d ‐dimer, thrombin‐antithrombin, and plasmin‐antiplasmin complexes as compared to patients with no to minimal respiratory support and healthy controls. Moreover, the patients with COVID‐19 with higher respiratory support exhibited substantial ex vivo thrombin generation and lower ex vivo fibrinolytic capacity, despite higher doses of anticoagulant therapy compared to less severely ill patients. Fibrinogen, factor VIII, and von Willebrand factor levels increased, and ADAMTS13 levels decreased with increasing respiratory support in patients with COVID‐19. Low platelet count; low levels of prothrombin, antithrombin, and ADAMTS13; and high levels of von Willebrand factor were associated with short‐term mortality. Conclusions Severe COVID‐19 is associated with prothrombotic changes with increased in vivo activation of coagulation and fibrinolysis, despite anticoagulant therapy.

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Section: Discussionsupporting

confidence: 90%

Prothrombotic changes in patients with COVID‐19 are associated with disease severity and mortality

Meijenfeldt

Havervall

Adelmeijer

et al. 2021

Research and Practice in Thrombosis and Haemostasis

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“…At variance with the aforementioned studies and ours, Escher et al reported markedly elevated VWF but normal levels of ADAMTS13 activity in COVID‐19 patients, but their sample size was limited (only three patients, two of whom requiring high‐intensity care and intubation) 40 . Finally, Tiscia and colleagues reported a normal median level of ADAMTS13 activity of 70 IU/dL in another Italian cohort of 77 COVID‐19 patients, with patients with ADAMTS13 activity below 70 IU/dL showing a significantly lower survival at Kaplan‐Meier analysis 41 . The type of patient populations and the severity of disease could play an important role in the different results across studies.…”

Section: Discussionmentioning

confidence: 99%

“…To further investigate the central role of the endothelium in the progression into severe COVID‐19, we also measured the VWF propeptide that, not being consumed by platelet aggregation or influenced by blood group, 42 represents a more accurate marker of endothelial activation. Furthermore, because of the equimolar secretion but differential half‐lives of the two polypeptides, 43 the VWF propeptide to VWF antigen ratio has been used as a tool to distinguish between acute or chronic vascular perturbation (ie, increase of both markers as seen in acute thrombotic microangiopathy or sepsis vs increase in VWF antigen alone as seen in diabetes) 24 and to evaluate VWF clearance 41 . We found increased levels of the VWF propeptide across all patient groups (overall mean 199 IU/dL vs 103 IU/dL in historical controls) 44 .…”

Section: Discussionmentioning

confidence: 99%

The ADAMTS13‐von Willebrand factor axis in COVID‐19 patients

Mancini

Baronciani

Artoni

et al. 2021

Journal of Thrombosis and Haemostasis

197

233

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Background Severe coronavirus disease 2019 (COVID‐19) is characterized by an increased risk of thromboembolic events, with evidence of microthrombosis in the lungs of deceased patients. Objectives To investigate the mechanism of microthrombosis in COVID‐19 progression. Patients/Methods We assessed von Willebrand factor (VWF) antigen (VWF:Ag), VWF ristocetin‐cofactor (VWF:RCo), VWF multimers, VWF propeptide (VWFpp), and ADAMTS13 activity in a cross‐sectional study of 50 patients stratified according to their admission to three different intensity of care units: low (requiring high‐flow nasal cannula oxygenation, n = 14), intermediate (requiring continuous positive airway pressure devices, n = 17), and high (requiring mechanical ventilation, n = 19). Results Median VWF:Ag, VWF:RCo, and VWFpp levels were markedly elevated in COVID‐19 patients and increased with intensity of care, with VWF:Ag being 268, 386, and 476 IU/dL; VWF:RCo 216, 334, and 388 IU/dL; and VWFpp 156, 172, and 192 IU/dL in patients at low, intermediate, and high intensity of care, respectively. Conversely, the high‐to‐low molecular‐weight VWF multimers ratios progressively decreased with increasing intensity of care, as well as median ADAMTS13 activity levels, which ranged from 82 IU/dL for patients at low intensity of care to 62 and 55 IU/dL for those at intermediate and high intensity of care. Conclusions We found a significant alteration of the VWF‐ADAMTS13 axis in COVID‐19 patients, with an elevated VWF:Ag to ADAMTS13 activity ratio that was strongly associated with disease severity. Such an imbalance enhances the hypercoagulable state of COVID‐19 patients and their risk of microthrombosis.

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“…Indeed, COVID-19 can present with a variety of clinical manifestations (from nil, to pauci-symptomatic, to dramatic disease), leading to mortality especially those subjects with one or more comorbidities [ 3 ]. The mortality rate is particularly high in patients admitted to the intensive care unit (ICU) [ 4 , 5 ], with older patients showing a higher fatality rate [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Mortality and Transfusion Requirements in COVID-19 Hospitalized Italian Patients According to Severity of the Disease

Pesavento

Tiscia

Laurenzo

et al. 2021

JCM

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There is paucity of data on the transfusion need and its impact on the overall mortality in patients with COVID-19. We explored mortality in hospitalized patients with COVID-19 who required transfusions. Information on clinical variables and in-hospital mortality were obtained from medical records of 422 patients admitted to medical wards or the Intensive Care Unit (ICU). In-hospital mortality occurred in 147 (34.8%) patients, 94 (63.9%) of whom were admitted to the ICU. The median fatalities age was 77 years (IQR 14). Overall, 100 patients (60 males) received transfusion during hospitalization. The overall mortality was significantly and independently associated with age, ICU admission, Chronic Kidney Disease (CKD), and the number of transfused Red Blood Cell (RBC) units. Specifically, CKD was associated with mortality in patients admitted to medical wards, whereas the number of transfused RBC units predicted mortality in those admitted to the ICU. Transfusion strongly interacted with the admission to ICU (OR: 9.9; 95% CI: 2.5–40.0). In patients with COVID-19, age is one of the strongest risk factors in predicting mortality independently of the disease’s severity. CKD confers a higher risk of mortality in patients admitted to medical wards. In those admitted to the ICU, the more RBC units are transfused, the more mortality increases.

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Reduction of ADAMTS13 Levels Predicts Mortality in SARS-CoV-2 Patients

Cited by 35 publications

References 23 publications

Prothrombotic changes in patients with COVID‐19 are associated with disease severity and mortality

Prothrombotic changes in patients with COVID‐19 are associated with disease severity and mortality

The ADAMTS13‐von Willebrand factor axis in COVID‐19 patients

Mortality and Transfusion Requirements in COVID-19 Hospitalized Italian Patients According to Severity of the Disease

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