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

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Thromb Haemost


. 2022 Oct 11.
doi: 10.1055/s-0042-1757163. Online ahead of print.
Hyperresponsive Platelets and a Reduced Platelet Granule Release Capacity Are Associated with Severity and Mortality in COVID-19 Patients


Fadel Muhammad Garishah ^{1 2} , Dana Huskens ^{3 4} , Setyo Gundi Pramudo ⁵ , Dessy Andriani ⁶ , Mila Astrilia ⁶ , Rizki Akbar Sentosa ^{2 3 4 5} , André J A M van der Ven ¹ , Bas de Laat ^{3 4} , Muhammad Hussein Gasem ^{2 5} , Quirijn de Mast ¹ , Mark Roest ³



Affiliations

• PMID: 36220126
• DOI: 10.1055/s-0042-1757163

Abstract

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 r [r _s] = -0.51, p < 0.0001 and r _s = -0.23, p < 0.05), C-reactive protein (CRP) (r _s = -0.59, p < 0.0001 and r _s = -0.41, p < 0.01), and neutrophil-to-lymphocyte ratio (NLR) (r _s = -0.42, p < 0.0001 and r _s = -0.26, p < 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, p < 0.0001 and OR: 4.0; 95% CI: 1.6-10.4, p < 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.