Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19

Blood. 2020 Sep 10;136(11):1330-1341. doi: 10.1182/blood.2020007252.


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 aggregate formation are 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 intensive care unit, platelet-monocyte interaction was strongly associated with tissue factor (TF) expression by the monocytes. Platelet activation and monocyte TF expression were associated with markers of coagulation exacerbation as fibrinogen and D-dimers, and were increased in patients requiring invasive mechanical ventilation or patients who 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Betacoronavirus / immunology*
  • Biomarkers / metabolism
  • Blood Coagulation Disorders / immunology
  • Blood Coagulation Disorders / metabolism
  • Blood Coagulation Disorders / pathology*
  • Blood Coagulation Disorders / virology
  • Blood Platelets / metabolism
  • Blood Platelets / pathology*
  • Blood Platelets / virology
  • COVID-19
  • Case-Control Studies
  • Coronavirus Infections / complications*
  • Coronavirus Infections / immunology
  • Coronavirus Infections / metabolism
  • Coronavirus Infections / virology
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Monocytes / pathology*
  • Monocytes / virology
  • P-Selectin / metabolism
  • Pandemics
  • Platelet Activation
  • Pneumonia, Viral / complications*
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / metabolism
  • Pneumonia, Viral / virology
  • Prognosis
  • Prospective Studies
  • SARS-CoV-2
  • Survival Rate
  • Thromboplastin / metabolism*


  • Biomarkers
  • P-Selectin
  • SELP protein, human
  • Thromboplastin