COVID-19 Infection is Associated with Antibody-mediated Procoagulant Platelets: Data from an Observational Study

K. Althaus^1,2, I. Marini¹, J. Zlamal¹, H. Häberle³, M. Mehrländer³, L. Pelzl¹, A. Singh¹, S. Hammer², M. Bitzer⁴, N. Malek⁴, D. Rath⁵, H. Bösmüller⁶, M. Gawaz⁵, P. Rosenberger³, T. Bakchoul^1,2

¹Transfusion Medicine, Medical Faculty of Tuebingen, University Hospital of Tuebingen, Tuebingen, Germany, ²Centre for Clinical Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany, ³Department of Anesthesiology and Intensive Care Medicine, University Hospital of Tuebingen, Tuebingen, Germany, ⁴Department of Internal Medicine I, University Hospital of Tuebingen, Tuebingen, Germany, ⁵Department of Medicine III, University Hospital of Tuebingen, Tuebingen, Germany, ⁶Institute for Pathology, University Hospital of Tuebingen, Tuebingen, Germany

Abstract Number: PB0179

Meeting: ISTH 2021 Congress

Theme: COVID and Coagulation » COVID and Coagulation, Clinical

Background: The pathophysiology of COVID-19-associated coagulopathy is to be complex and multifactorial. In this study, we hypothesized that the coagulopathy in COVID-19 is accompanied by immune mediated procoagulant platelets with subsequent alteration of the coagulation system.

Aims: We aimed to further analyze the role of platelets (PLTs) leading to increased thromboembolic events in patients with severe COVID-19.

Methods: Blood samples from COVID-19 intensive care unit (ICU) patients were analyzed for procoagulant markers. Flow cytometry was used to investigate depolarization of mitochondrial inner transmembrane potential (ΔΨm), intracellular Ca2+ concentration, and phosphatidylserine (PS) externalization.

Results: PLTs from COVID-19 patients (n=21) showed significantly higher ΔΨm depolarization (1.39±0.07 vs. 0.99±0.06, p=0.0005), Ca2+ concentration (2.73±0.31 vs. 1.00±0.05, p<0.0001) and PS externalization (2.05±0.48 vs. 0.86±0.11, p=0.0236), compared to healthy control (HC), respectively. Most importantly, PS exposure was associated with SOFA score (sequential organ failure assessment, r=0.5635, p=0.0078) and plasma levels of D-Dimer (r=0.4473, p=0.0420). Finally, patients with thromboembolic events had higher PS externalization compared to those without thrombosis (2.85±0.75 vs. 0.99±0.20, p=0.0340). Sera from COVID-19 patients also induced significant increase in procoagulant markers (ΔΨm depolarization (1.52 ±0.117 vs. 0.958 ±0.082, p=0.0086), Ca2+ concentration (1.372 ±0.074 vs. 0.984 ±0.055, p=0.0036) and PS externalization (1.624 ± 0.126 vs. 0.969 ±0.100, p=0.0051)) compared to sera from HC. Interestingly, immunoglobulin G (IgG) fractions from COVID-19 patients induced an Fc gamma receptor IIA dependent platelet apoptosis (ΔΨm depolarization (2.23 ±0.25 vs. 1.22 ±0.12, p=0.0216), Ca2+ concentration (1.80 ±0.15 vs. 0.58 ±0.04) and PS externalization (9.59 ±1.52 vs. 2.12 ±0.20, p=0.0371)).

Conclusions: Our study shows that COVID-19 patients had increased IgG-mediated procoagulant platelets. The strong correlations between procoagulant PLTs and increased D-Dimer levels as well as the incidence of thromboembolic complications may indicate that procoagulant platelets potentially contribute to sustained increased thromboembolic risk in COVID-19 ICU patients.

To cite this abstract in AMA style:

Althaus K, Marini I, Zlamal J, Häberle H, Mehrländer M, Pelzl L, Singh A, Hammer S, Bitzer M, Malek N, Rath D, Bösmüller H, Gawaz M, Rosenberger P, Bakchoul T. COVID-19 Infection is Associated with Antibody-mediated Procoagulant Platelets: Data from an Observational Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/covid-19-infection-is-associated-with-antibody-mediated-procoagulant-platelets-data-from-an-observational-study/. Accessed December 6, 2023.

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