Abstract
Platelets are the blood cells in charge of maintaining the body hemostasis, recognising
the damaged vessel wall, and providing the appropriate cellular surface for the coagulation
cascade to act locally. Additionally, platelets are active immunomodulators. At the
crossroads of hemostasis and inflammation, platelets may exert either beneficial actions
or participate in pathological manifestations, and have been associated with the prothrombotic
nature of multi-organ failure in systemic inflammation. Platelet number alterations
have been reported in septis, and platelet transfusions are given to thrombocytopenic
patients. However, the risk to develop transfusion related acute lung injury (TRALI)
is higher in sepsis patients. In this manuscript we show that platelets produced during
inflammation in preclinical mouse models of sterile inflammation display lower aggregation
capacity when stimulating certain receptors, while responses through other receptors
remain intact, and we name them “inflammation-conditioned” platelets. In a cohort
of sepsis patients, we observed, as previously reported, alterations in the number
of platelets and platelet hyperreactivity. Furthermore, we identified a receptor-wise
platelet aggregation response disbalance in these patients, although not similar to
platelets from preclinical models of sterile inflammation. Interestingly, we generated
evidence supporting the notion that platelet aggregation capacity disbalance was partially
triggered by plasma components from sepsis patients. Our findings have implications
in the indication of platelet transfusions in sepsis patients: Are fully functional
platelets suitable for transfusion in sepsis patients? Current Clinical Trials (RESCUE)
will answer whether platelet production stimulation with thrombopoietin receptor agonists
(TPO-RAs) could be a substitute of platelet transfusions.
Keywords
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Article info
Publication history
Published online: March 11, 2022
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