Blood . Platelet activation and platelet-monocyte aggregates formation trigger tissue factor expression in severe COVID-19 patients

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Blood


. 2020 Jul 17;blood.2020007252.
doi: 10.1182/blood.2020007252. Online ahead of print.
Platelet activation and platelet-monocyte aggregates formation trigger tissue factor expression in severe COVID-19 patients


Eugenio Damaceno Hottz ¹ , Isaclaudia G Azevedo-Quintanilha ² , Lohanna Palhinha ² , L?via Teixeira ² , Ester A Barreto ² , Camila R R P?o ² , C?ssia Righy ³ , S?rgio Franco ⁴ , Thiago Moreno L Souza ⁵ , Pedro Kurtz ⁶ , Fernando Augusto Bozza ⁷ , Patricia T Bozza ²



Affiliations

• PMID: 32678428
• DOI: 10.1182/blood.2020007252

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is an emergent pathogen responsible for the coronavirus disease 2019 (COVID-19). Since its emergence, the novel coronavirus has rapidly achieved pandemic proportions causing remarkably increased morbidity and mortality around the world. A hypercoagulability state has been reported as a major pathologic event in COVID-19, and thromboembolic complications listed among life-threatening complications of the disease. Platelets are chief effector cells of hemostasis and pathological thrombosis. However, the participation of platelets in the pathogenesis of COVID-19 remains elusive. This report demonstrates that increased platelet activation and platelet-monocyte aggregates formation is observed in severe COVID-19 patients, but not in patients presenting mild COVID-19 syndrome. In addition, exposure to plasma from severe COVID-19 patients increased the activation of control platelets ex vivo. In our cohort of COVID-19 patients admitted to the ICU, platelet-monocyte interaction was strongly associated with TF expression by the monocytes. Platelet activation and monocyte TF expression were associated with markers of coagulation dysfunction as fibrinogen and D-dimers, and were increased in patients requiring invasive mechanical ventilation or patients that evolved with in-hospital mortality. Finally, platelets from severe COVID-19 patients were able to induce TF expression ex vivo in monocytes from healthy volunteers, a phenomenon that was inhibited by platelet P-selectin neutralization or integrin αIIb/β3 blocking with the aggregation inhibitor abciximab. Altogether, these data shed light on new pathological mechanisms involving platelet activation and platelet-dependent monocyte TF expression, which were associated with COVID-19 severity and mortality.