Hyperresponsive Platelets and a Reduced Platelet Granule Release Capacity Are Associated with Severity and Mortality in COVID-19 Patients.

Background:  Coronavirus disease 2019 (COVID-19) is often associated with mild thrombocytopenia and increased platelet reactivity.

Objective:  The aim of the current study was to investigate the adenosine triphosphate (ATP) release kinetics of platelets in hospitalized SARS-CoV-2-infected patients.

Methods:  We studied time-dependent platelet activation in whole blood by monitoring the ATP release kinetics upon stimulation with a PAR1 receptor agonist in 41 hospitalized critically ill COVID-19 patients, 47 hospitalized noncritically ill COVID-19 patients, and 30 healthy controls.

Results:  Our study demonstrated that platelets of critically ill COVID-19 patients were hyper-responsive with a shorter platelet response time (PRT) and a reduced platelet granule release capacity (GRC), probably due to chronic activation. The median PRT of COVID-19 patients admitted to the critical care unit was 10 and 7 seconds shorter than the median PRT in healthy controls and noncritical COVID-19 patients, respectively. Both PRT and GRC were also associated with D-dimer (Spearman [ ] = -0.51,  < 0.0001 and  = -0.23,  0.05), C-reactive protein (CRP) (  = -0.59,  < 0.0001 and  = -0.41,  < 0.01), and neutrophil-to-lymphocyte ratio (NLR) (  = -0.42,  < 0.0001 and  = -0.26,  < 0.05). Moreover, an increased PRT and a reduced GRC were associated with an increased mortality (odds ratio [OR]: 18.8, 95% confidence interval [CI]: 6.5-62.8,  0.0001 and OR: 4.0; 95% CI: 1.6-10.4,  0.01). These relationships remained significant after adjustment for age, sex, D-dimer, CRP, and NLR.

Conclusion:  Using an accessible agonist-induced platelet granule ATP release assay, we show that platelet hyper-responsiveness and reduced platelet GRC in COVID-19 patients were associated with critical illness and mortality.