VWF/ADAMTS13 Ratios Are Potential Markers of Immunothrombotic Complications in Patients with COVID-19: A Cross-Sectional Study
Bibliographic record
Abstract
BACKGROUND. COVID-19 is a prothrombotic disease, characterized by both arterial and venous thrombosis. The pathogenesis of coagulopathy in COVID-19 is multifactorial, with activation of endothelial cells, platelets, neutrophils, and other immune system effectors playing crucial roles. High levels of von Willebrand factor (VWF) and reduced levels of ADAMTS13 have been observed in COVID-19, sepsis, and immunothrombotic states, and an elevated VWF/ADAMTS13 ratio has been previously described in ischemic stroke1. In this study, we sought to evaluate potential associations of VWF activity and antigen ratios to ADAMTS13 with clinical outcomes in hospitalized patients with COVID-19 and to compare these ratios with other cytokines and markers of inflammation in critical illness. METHODS. Institutional Review Board approval was obtained for this study. Blood was collected from 49 hospitalized patients with a confirmed diagnosis of COVID-19 between April 13 and April 24, 2020, which included 40 patients in an intensive care unit and 9 on a non-ICU unit. Medical records were reviewed, and patient characteristics including age, sex, comorbidities, pertinent medications, imaging studies, history of arterial or venous thrombosis, and other pertinent patient information were compiled. Blood was collected in sodium citrate tubes and centrifuged at 4000 rpm for 20 minutes, with the resulting plasma supernatant used for further testing. Measurements of VWF antigen and VWF activity were performed on an ACL TOP machine using our institution's standard clinical laboratory protocol. Biomarker profiling analyses were performed at Eve Technologies (Calgary, Alberta, Canada). Statistical analysis was performed using GraphPad Prism (v8.4.3, GraphPad Software, San Diego, CA) and R (v4, R Core Team, 2020). P values <0.05 were considered statistically significant. RESULTS. The median age was 64 years; 36 (73%) were male, 11 (22.4%), 29 (59.2%), and 9 (18.4%) had BMI<25, between 25 and 40, and >40 kg/m2, respectively. The ratio of VWF activity/ADAMTS13 was significantly higher in patients with higher BMI (median [interquartile range, IQR] VWF activity/ADAMTS13 ratios: 0.66 [0.39-0.88] for BMI<25 kg/m2, 0.865 [0.769-1.102] for BMI 25-40 kg/m2, and 1.041 [0.747-2.032] for BMI>40 kg/m2; p = 0.0408, Kruskal-Wallis test). In patients who required mechanical ventilation, median [IQR] VWF activity/ADAMTS13 was 0.876 [0.75-1.769] vs 0.792 [0.566-0.932] for those who did not (p = 0.0497, Mann-Whitney U-test). The difference for the VWF antigen/ADAMTS13 ratio was more pronounced, 1.32 [0.991-2.456] vs 0.981 [0.628-1.162] (p = 0.0045, Mann-Whitney U-test). There was also a significant correlation between both VWF activity/ADAMTS13 and VWF antigen/ADAMTS13 ratios and neutrophil indices such as absolute neutrophil count (R = 0.57, p <0.0001 and R = 0.54, p = 0.0001, respectively) and neutrophil to lymphocyte count (R = 0.6, p <0.0001 and R = 0.57, p <0.0001, respectively). We also found significant correlations of these ratios with markers of neutrophils activation (HGF, resistin, and lipocalin-2; Figure 1). CONCLUSIONS. Ratios VWF activity/ADAMTS13 and VWF antigen/ADAMTS13 are elevated in patients with more severe COVID-19 disease and correlate with markers of neutrophils activation. These findings and that azurophillic granules in neutrophils contain α-defensins implicated in thrombosis2 suggest possible mechanistic links among VWF, ADAMTS13, contact pathway, and neutrophil function in mediating immunothrombotic complications in COVID-19, which might highlight potential therapeutic targets to attenuate the severity of coagulopathy and merit further investigation with a larger cohort of patients. REFERENCES 1. Taylor A, et al. Blood Adv. 2020;4(2):398-407 2. Abu-Fanne R, et al. Blood. 2019;133(5):481-493 Disclosures No relevant conflicts of interest to declare.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".