Inter Individual Variability in Initiation Pathway Activation and Regulation and Phenotypic Heterogeneity in Patients With Haemophilia A and B

Inter Individual Variability in Initiation Pathway Activation and Regulation and Phenotypic Heterogeneity in Patients With Haemophilia A and B

Severe haemophilia A and B (SHA, SHB) are X - linked inherited bleeding disorders, characterised by factor VIII and IX levels of <1 IU/dL respectively. The mainstay of treatment in SHA and SHB is replacement therapy with intravenous infusions of factor VIII and IX. However, there is significant variability in the bleeding phenotype within severe haemophiliacs with some presenting with minimal bleeding episodes even on less intensive treatment regimens. A significant contributor to inter-individual variability in the bleeding phenotype is the coagulation phenotype, but there are no established assays in routine clinical practice that can be used to quantify this. This study aims to study novel assays and characterise the observed phenotypic heterogeneity.

Patients

Inclusion Criteria:

1. Patients with haemophilia A or B (baseline FVIII/FIX level <30%)
2. Age ≥ 18 years
3. Written informed consent in accordance with local and institutional guidelines.

Exclusion Criteria:

1. Patients currently enrolled into a clinical trial of investigational medicinal product for haemophilia.

Healthy Volunteers

Inclusion Criteria:

1. Currently not receiving any antiplatelet or anticoagulant therapy or other drugs that can affect the coagulation system.
2. Age ≥ 18 years
3. Written informed consent in accordance with local and institutional guidelines.