Thrombotic Events in COVID-19 Are Associated With a Lower Use of Prophylactic Anticoagulation Before Hospitalization and Followed by Decreases in Platelet Reactivity

Chantal C Clark; Bernard N Jukema; Arjan D Barendrecht; Judith S Spanjaard; Nikita K N Jorritsma; Simone Smits; Steven de Maat; Cor W Seinen; Sandra Verhoef; Naomi M J Parr; Silvie A E Sebastian; Arnold C Koekman; Annet C W van Wesel; Harriet M R van Goor; Roy Spijkerman; Suzanne H Bongers; Erhard van der Vries; Stefan Nierkens; Marianne Boes; Leo Koenderman; Karin A H Kaasjager; Coen Maas

doi:10.3389/fmed.2021.650129

Thrombotic Events in COVID-19 Are Associated With a Lower Use of Prophylactic Anticoagulation Before Hospitalization and Followed by Decreases in Platelet Reactivity

Front Med (Lausanne). 2021 Apr 22:8:650129. doi: 10.3389/fmed.2021.650129. eCollection 2021.

Authors

Chantal C Clark¹, Bernard N Jukema¹, Arjan D Barendrecht¹, Judith S Spanjaard², Nikita K N Jorritsma², Simone Smits¹, Steven de Maat¹, Cor W Seinen¹, Sandra Verhoef¹, Naomi M J Parr¹, Silvie A E Sebastian¹, Arnold C Koekman¹, Annet C W van Wesel¹, Harriet M R van Goor³, Roy Spijkerman^{2

4}, Suzanne H Bongers^{2

5}, Erhard van der Vries¹, Stefan Nierkens², Marianne Boes², Leo Koenderman^{2

4}, Karin A H Kaasjager³, Coen Maas¹

Affiliations

¹ Department of Central Diagnostic Laboratory Research, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
² Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
³ Department of Internal Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
⁴ Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
⁵ Department of Trauma Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.

Abstract

Background: Coronavirus disease of 2019 (COVID-19) is associated with a prothrombotic state and a high incidence of thrombotic event(s) (TE). Objectives: To study platelet reactivity in hospitalized COVID-19 patients and determine a possible association with the clinical outcomes thrombosis and all-cause mortality. Methods: Seventy nine hospitalized COVID-19 patients were enrolled in this retrospective cohort study and provided blood samples in which platelet reactivity in response to stimulation with ADP and TRAP-6 was determined using flow cytometry. Clinical outcomes included thrombotic events, and all-cause mortality. Results: The incidence of TE in this study was 28% and all-cause mortality 16%. Patients that developed a TE were younger than patients that did not develop a TE [median age of 55 vs. 70 years; adjusted odds ratio (AOR) = 0.96 per 1 year of age, 95% confidence interval (CI) 0.92-1.00; p = 0.041]. Furthermore, patients using preexisting thromboprophylaxis were less likely to develop a thrombotic complication than patients that were not (18 vs. 54%; AOR = 0.19, 95% CI 0.04-0.84; p = 0.029). Conversely, having asthma strongly increased the risk on TE development (AOR = 6.2, 95% CI 1.15-33.7; p = 0.034). No significant differences in baseline P-selectin expression or platelet reactivity were observed between the COVID-19 positive patients (n = 79) and COVID-19 negative hospitalized control patients (n = 21), nor between COVID-19 positive survivors or non-survivors. However, patients showed decreased platelet reactivity in response to TRAP-6 following TE development. Conclusion: We observed an association between the use of preexisting thromboprophylaxis and a decreased risk of TE during COVID-19. This suggests that these therapies are beneficial for coping with COVID-19 associated hypercoagulability. This highlights the importance of patient therapy adherence. We observed lowered platelet reactivity after the development of TE, which might be attributed to platelet desensitization during thromboinflammation.

Keywords: COVID-19; SARS-CoV-2; platelets; pulmonary thrombosis; thromboinflammation; thrombosis; thrombotic event.

Copyright © 2021 Clark, Jukema, Barendrecht, Spanjaard, Jorritsma, Smits, de Maat, Seinen, Verhoef, Parr, Sebastian, Koekman, van Wesel, van Goor, Spijkerman, Bongers, van der Vries, Nierkens, Boes, Koenderman, Kaasjager and Maas.