Abstract Number: PB0198
Meeting: ISTH 2021 Congress
Background: The SARS-COV-2 direct interaction with Angiotensin-Converting-Enzyme-2 (ACE2) membrane receptor on pulmonary epithelial and endothelial cells, impairs angiotensin 1-7 production and its vasculoprotective role, promoting an upregulation of the ACE/angiotensinII/angiotensinII receptor type-1 pathway. The consequent endothelial activation and increasing secretion of VWF and FVIII levels contributes to complement activation and leukocyte extravasation, leading to local microcirculation damage.
Aims: Our case-control study is aimed to investigate the characteristics of thrombotic microangiopathies (TMA)-like syndromes in COVID-19 evaluating VWF, FVIII and ADAMTS-13 levels, because the complement-mediated TMA and multiorgan microvascular lesions, observed in COVID-19 patients, seem not attributable to typical TMA.
Methods: Ten COVID-19 cases presenting fever, cough and sore throat, admitted to the Fondazione Policlinico Gemelli IRCCS, Rome, and diagnosed by RT-PCR, were compared to ten control patients with non-SARS-CoV-2 interstitial pneumonia, diagnosed by chest Xray/computerized tomography; notably no patient needed mechanical ventilation.
ADAMTS-13 activity was measured by a FRET-based assay; FVIII levels by a two-stage clotting assay, while VWF:antigen and VWF:activity were evaluated by chemiluminescence assays. Platelet count, schistocytes, D-dimer, C-reactive protein were centrally measured.
Results: COVID-19 pneumonia patients compared with controls showed a marked elevation of both VWF:Ag (median values: 324.1 Vs 139.5%, p<0.0001) and VWF:act levels (median values: 341.5 Vs 133%, p<0.001), as well as FVIII levels (median values: 202.5 Vs 123%, p<0.0001), consistent with the presence of a thrombophilic condition; without significant differences in ADAMTS-13 activity (median values: 69 Vs 76%, p=0.473). In both groups, D-dimer and C-reactive protein levels were elevated, but not statistically different, platelet counts were normal, and schistocytes, a typical TMAs hallmark, were not observed
Conclusions: The increased VWF/FVIII levels in COVID-19 pneumonia cases compared with non-COVID-19 controls cannot be fully explained by the inflammatory state alone and was likely caused by SARS-CoV-2-mediated downregulation of the ACE2 axis, resulting in damage to the local microcirculation and increased leukocyte extravasation.
To cite this abstract in AMA style:Sacco M, De Cristofaro R, Liuzzo G, Lancellotti S, Pedicino D, Andreotti F. Increased von Willebrand Factor (VWF) and Factor VIII (FVIII) Levels in Severe Acute Respiratory Syndrome Sars-Cov2-positive Pneumonia Compared with Severe Acute Respiratory Syndrome Sars-Cov2-negative: A Case-control Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/increased-von-willebrand-factor-vwf-and-factor-viii-fviii-levels-in-severe-acute-respiratory-syndrome-sars-cov2-positive-pneumonia-compared-with-severe-acute-respiratory-syndrome-sars-cov2-negativ/. Accessed September 24, 2023.
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