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CD40L is selectively expressed on platelets from thrombocytopenic septic patients
Critical Care volume 14, Article number: P19 (2010)
It has been recently hypothesized that septic microangiopathy is caused or at least promoted by the interaction between endothelial surface receptor CD40 and its ligand CD40L, expressed by activated platelets. This interaction produces procoagulative changes in endothelial cells, endothelial apoptosis, subendothelial matrix exposition and microthrombi formation. Since virtually all septic patients show a certain degree of coagulation abnormalities, we hypothesized that low platelet count is associated with a different degree of CD40L expression and that this could correlate with the severity of disease.
To determine the influence of sepsis on levels of platelet-derived CD40L expression, we performed a prospective observational study in a polyvalent university hospital ICU. Eighteen consecutively septic patients were enrolled in the study, independently of the platelet count and the severity of disease (SOFA score). Flow cytometry of fresh blood from septic patients (n = 18) and age-matched controls (n = 8) was performed for membrane-bound CD40L and CD62P on circulating platelets.
Flow cytometry demonstrated low levels of CD62P in controls while the levels in patients were high. CD40L+ platelets were selectively found from patients with thrombocytopenia (platelet count ≤60,000/mm3). Furthermore a direct correlation between CD40L expression and the SOFA score was found in patients with sepsis and thrombocytopenia compared to patients with sepsis without thrombocytopenia.
These results suggest that CD40L expression on platelets is somehow related to the degree of thrombocytopenia and possibly can be a marker of the severity of sepsis. Although the role of endothelial-derived CD40/platelet-derived CD40L interaction is not fully understood during sepsis, the expression of CD40L on platelets could be related to the severity of organ disease due to the possible bursting of endothelial damage through this pathway. Further investigation is needed to determine whether platelets CD40L contributes to endothelial and subsequent organ damage, its role in thrombocytopenia and its correlation with the outcome of sepsis. The microvascular injury seems to be a central event in sepsis, so understanding the mechanisms underlying its development is crucial for the individuation of new and specific therapeutic strategies.
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Montalbano, A., Turani, F., Ciotti, E. et al. CD40L is selectively expressed on platelets from thrombocytopenic septic patients. Crit Care 14, P19 (2010). https://doi.org/10.1186/cc8251
- Septic Patient
- Sofa Score
- Microvascular Injury
- Endothelial Apoptosis