In Vitro Correction of Thrombin Generation by Concizumab (Anti-TFPI) for Severe Hemophilia Patients

Tissue Factor Pathway Inhibitor (TFPI) and Haemorrhagic Manifestations in Haemophilia A and B Patients

Studies have shown, in haemophilia patients, the effectiveness of Anti TFPI antibody (aTFPIAb) to prevent joint and muscular bleeding (tissues poor in Tissue Factor (TF)). However, cases of cerebral thrombosis (tissues rich in TF) have been observed in some patients treated with this antibody. Because an inter-individual variation in thrombin generation correction by aTFPIAb, an aTFPIAb concentration effective at low TF concentration could be at the same time thrombogenic at high TF concentration.

The aim of this study is to determine, for each patient, the minimum concentration of aTFPIAb necessary to restore thrombin generation in the presence of low (1pM) TF concentration and to evaluate at this concentration of aTFPIAb a potential thrombogenic effect in the presence of a high (10pM) TF concentration.

Inclusion Criteria:

• Severe or moderate haemophilia A or B patient with FVIII or FIX <5% with or without prophylaxis
• Affiliated or beneficiary of a social security regimen
• Signature of consent

Exclusion Criteria:

• Haemophilia patients aged 12 years or less with a weight less than 30 kg (taking into account the volume of blood collection).
• Patients who received factor VIII concentrates less than 48 hours or factor IX concentrates less than 96 hours prior to the routine blood draw at the Hemophilia Clinic. 96 hours prior to the routine blood draw at the Hemophilia Centre