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

Fadel Muhammad Garishah; Dana Huskens; Setyo Gundi Pramudo; Dessy Andriani; Mila Astrilia; Rizky Akbar Sentosa; André J. A. M. van der Ven; Bas de Laat; Muhammad Hussein Gasem; Quirijn de Mast; Mark Roest

doi:10.1055/s-0042-1757163

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2022; 122(12): 2001-2010
DOI: 10.1055/s-0042-1757163

Cellular Haemostasis and Platelets

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

Autor*innen

Fadel Muhammad Garishah

¹Department of Internal Medicine and the Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands

²Center for Tropical and Infectious Diseases (CENTRID), Faculty of Medicine, Diponegoro University, Dr. Kariadi Hospital, Semarang, Indonesia
Dana Huskens

³Department of Platelet Pathophysiology, Synapse Research Institute, Maastricht, The Netherlands

⁴Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands
Setyo Gundi Pramudo

⁵Department of Internal Medicine, Diponegoro National University Hospital, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
Dessy Andriani

⁶Department of Internal Medicine, KRMT Wongsonegoro General Hospital, Semarang, Indonesia
Mila Astrilia

⁶Department of Internal Medicine, KRMT Wongsonegoro General Hospital, Semarang, Indonesia
Rizky Akbar Sentosa

⁵Department of Internal Medicine, Diponegoro National University Hospital, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
André J. A. M. van der Ven

¹Department of Internal Medicine and the Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
Bas de Laat

³Department of Platelet Pathophysiology, Synapse Research Institute, Maastricht, The Netherlands

⁴Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands
Muhammad Hussein Gasem

²Center for Tropical and Infectious Diseases (CENTRID), Faculty of Medicine, Diponegoro University, Dr. Kariadi Hospital, Semarang, Indonesia

⁵Department of Internal Medicine, Diponegoro National University Hospital, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
Quirijn de Mast^*

¹Department of Internal Medicine and the Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
Mark Roest^*

³Department of Platelet Pathophysiology, Synapse Research Institute, Maastricht, The Netherlands

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.

Keywords

ATP - COVID-19 - granule release capacity - platelets - platelet function

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Referenzen

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