Microfluidic hemophilia models using blood from healthy donors

Area of Science:

• Biomedical Engineering
• Hematology
• Pharmacology

Background:

• Microfluidic clotting assays are crucial for studying hemophilia therapeutics under flow conditions.
• Limited patient samples and inter-donor variability hinder current assay applications, particularly for patients on prophylaxis.

Purpose of the Study:

• To create novel approaches for phenocopying hemophilia (A and B) in microfluidic assays using modified healthy blood.
• To establish reliable and sensitive models for evaluating hemophilia drug efficacy.

Main Methods:

• Healthy blood was treated with corn trypsin inhibitor and then dosed with anti-factor VIII (FVIII) for hemophilia A or a factor IX (FIX) missense variant for hemophilia B.
• Blood was perfused over collagen/tissue factor (TF) or collagen/factor XIa (FXIa) surfaces at a wall shear rate of 100 s⁻¹.

Main Results:

• Anti-FVIII treatment blocked fibrin production on collagen/FXIa, a phenotype reversed by emicizumab, mimicking hemophilia A drug action.
• A patient-derived FVIII-neutralizing antibody also reduced fibrin production in the modified healthy blood model.
• A FIX missense variant fully blocked platelet and fibrin deposition, reversed by anti-TFPI, modeling hemophilia B.

Conclusions:

• Developed two new microfluidic models for hemophilia A and B using modified healthy blood.
• These models demonstrate the effectiveness of emicizumab and patient-derived antibodies.
• Collagen/FXIa-coated surfaces provide sensitive and reliable hemophilia models.