Small-molecule complement inhibitors cannot prevent the development of the platelet storage lesion

Area of Science:

• Transfusion Medicine
• Immunology
• Hematology

Background:

• Platelet (PLT) storage lesion impacts PLT quality and limits storage duration.
• Complement system activation may contribute to the PLT storage lesion.
• Improving PLT storage is crucial for managing blood inventories and reducing waste.

Purpose of the Study:

• To investigate the effect of complement inhibition on the development of the PLT storage lesion.
• To evaluate the efficacy of NAAGA and compstatin in preserving PLT quality during storage.

Main Methods:

• Leukofiltered PLT concentrates (PCs) were treated with NAAGA, compstatin, a control peptide, or saline.
• Complement activation was measured by C3a generation.
• PLT quality was assessed using morphology, activation markers (CD62, CD63), fibrinogen binding, pH, mean PLT volume, annexin V binding, and viability.
• PLT apoptosis was measured by caspase-3 activity.

Main Results:

• NAAGA increased PLT activation and caspase-3 activity at concentrations achieving 50% complement inhibition.
• Compstatin showed variable complement inhibition but consistently reduced PLT caspase-3 activity by 37-55%.
• Compstatin treatment did not improve PLT quality or viability compared to controls over 11 days of storage.

Conclusions:

• Neither NAAGA nor compstatin achieved complete complement inhibition during the storage period.
• The tested complement inhibitors did not mitigate the PLT storage lesion.
• Despite partial inhibition of apoptosis, compstatin did not enhance PLT quality or viability.