Complement factor D is linked to platelet activation in human and rodent sepsis

Area of Science:

• Immunology
• Hematology
• Critical Care Medicine

Background:

• Complement factor D (CFD) has a known regulatory role in infection.
• Its specific physiological functions in coagulopathy and impact on sepsis progression are not fully understood.

Purpose of the Study:

• To investigate the role of CFD in sepsis-induced coagulopathy and its association with host immune response and clinical outcomes.
• To explore the relationship between CFD levels, platelet activation, and mortality in sepsis patients.

Main Methods:

• Sepsis was induced in wild-type and CFD-deficient mice using cecal ligation and puncture.
• Coagulation markers and host-immune responses were assessed in mice.
• CFD levels were measured in patients with sepsis or SIRS and correlated with clinical data and outcomes.

Main Results:

• Septic CFD-deficient mice showed higher thrombin-antithrombin complexes and impaired clot firmness.
• Wild-type mice exhibited increased platelet activation markers, including GPIIb/IIIa surface expression.
• Elevated CFD levels in human sepsis patients correlated with organ failure (SOFA score) and increased mortality.

Conclusions:

• CFD is implicated in platelet activation during sepsis, particularly in wild-type mice.
• High plasma CFD concentrations in sepsis patients are associated with adverse outcomes, including organ failure and mortality.
• These findings highlight CFD as a potential biomarker and therapeutic target in sepsis management.