Inhibitor development and substitution therapy in a developing country: Turkey

Area of Science:

• Hematology
• Immunology
• Pediatrics

Background:

• Inhibitor development is a significant complication in hemophilia treatment.
• The prevalence of inhibitors in developing countries using fresh frozen plasma (FFP) is largely unknown.
• Turkey utilizes FFP due to the high cost of clotting factor concentrates.

Purpose of the Study:

• To determine the frequency of inhibitors in Turkish patients with hemophilia A and B.
• To investigate the association between different treatment modalities (concentrates vs. FFP) and inhibitor development.
• To evaluate a potential low-cost immune tolerance regimen.

Main Methods:

• A cohort of 53 hemophilia A and 12 hemophilia B patients (ages 1-20) were evaluated.
• Patients were categorized based on treatment: plasma-derived concentrates or FFP.
• Inhibitor screening and characterization were performed.

Main Results:

• No inhibitors were detected in hemophilia B patients.
• Seven of 53 hemophilia A patients (13%) developed inhibitors, all with severe disease and treated with concentrates (30%).
• Severe hemophilia A patients treated with FFP had a lower risk of inhibitor development (0/10, P=0.07).
• Intermediate-purity concentrates and pasteurization were associated with higher inhibitor risk compared to high-purity, solvent-detergent treated concentrates.
• A low-dose concentrate regimen (25 IU/kg twice weekly) led to inhibitor disappearance in four patients, suggesting potential for immune tolerance.

Conclusions:

• Concentrate use, particularly intermediate-purity products, is associated with a higher risk of inhibitor development in severe hemophilia A patients in Turkey.
• Fresh frozen plasma (FFP) may confer a lower risk of inhibitor development.
• A low-cost, low-dose concentrate regimen may be effective for immune tolerance in resource-limited settings.