Batch selection

Carmen Escuriola Ettingshausen will investigate the neutralisation activity of FVIII antibodies in the plasma of inhibitor patients against FVIII concentrates and different batches of the same FVIII concentrate.

Hypothesis 1:

Concentrates manifesting a low level of reactivity with the inhibitor have better haemostatic effect in vivo.

Hypothesis 2:

Haemophilia A patients with relatively high amounts of FVIII light-chain antibodies in plasma might benefit from FVIII concentrates containing VWF(VWF:RCo / FVIII:C > 0.3), since VWF appears to have some protective effect on FVIII.

Method:

A modified New Oxford inhibitor assay is being used. Dilutions of test plasma will be incubated with standardised amount of FVIII concentrate and the residual FVIII:C will be measured. FVIII inhibitors will be quantitated in Oxford Units, which are derived from neutralising-mixing studies of patient test plasma with diluted FVIII concentrate.

Literature overview:

• Berntop E et al. Variation in factor VIII inhibitor reactivity with different commercial factor VIII preparations. Haemophilia 1996; 2(2): 95-99.
• Suzuki T et al. Factor VIII inhibitor antibodies with C2 domain specificity are less inhibitory to factor VIII complexed with the von Willebrand factor. Thromb Haemost 1996; 76(5): 749-754.
• Kallas A and Talpsep T. VWF in FVIII concentrates protects against neutralisation by FVIII antibodies of heamophilia A patients. Haemophilia 2000; 7(4): 372-80.
• Sukhu K et al. Variation in inhibitor reactivity in aquired haemophilia A with different concentrates. Clin Lab Haematol 2000; 22(5): 287-90.
• Tagariello GL et al. In vitro reactivity of FVIII inhibitors with VWF in different commercial FVIII concentrates. Am J Hematol 2007; 82(6): 460-262.