Thrombotic events in COVID-19 are associated with a lower use of prophylactic anticoagulation before hospitalizationand followed by decreases in platelet reactivity

Background : Coronavirus disease of 2019 (COVID-19) is associated with a prothrombotic state and high incidence of thrombotic events (TE). Platelet hyperreactivity has been reported in COVID-19 patients and might contribute to TE development. Aims : To study platelet reactivity in hospitalized COVID-19 patients and to determine a possible association with the clinical outcomes thrombosis and all-cause mortality. Methods : 79 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 (median age of 55 versus 70 years;adjusted odds ratio (AOR), 0.96 per 1 year of age [95% CI, 0.92-1.00];P = 0.042). Furthermore, patients using preexisting thromboprophylaxis were less likely to develop a TE than patients that were not (18% versus 54%;adjusted odds ratio, 0.18 [95% CI, 0.04-0.82];P = 0.026). Conversely, having asthma strongly increased the risk on TE development (adjusted odds ratio, 6.4 [95% CI, 1.17-35.4];P = 0.032). 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 = 24), nor between COVID-19 survivors or non-survivors. However, patients showed decreased platelet reactivity in response TRAP-6 following TE development compared to patients without TE. Conclusions : 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.