Haemophilia
Conditions
Brief summary
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.
Interventions
DIAGNOSTIC_TESTThrombophilia screen
Thrombophilia screen (including antithrombin activity (AT:Ac), protein S antigen (PS:free), protein C activity (PC:Ac) , genetic analysis for FV Leiden and Prothrombin 3'UTR mutations and screening for lupus anticoagulant.
DIAGNOSTIC_TESTInitiation pathway analysis
Evaluation of inter-individual variability in regulation of TF.VIIa.Xa.TFPI complex (tissue factor, activated Factor VII, activated factor X, tissue factor pathway inhibitor)
Sponsors
Royal Free Hospital NHS Foundation Trust
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Initiation pathway correlation with clinical phenotype | Within 18 months of consent | Correlate lab assays that characterise initiation pathway with clinical phenotype. |
Secondary
| Measure | Time frame |
|---|---|
| Evaluation the sensitivity and specificity of global assays for disease severity and clinical phenotype. | Within 18 months of consent |
| Correlation analysis between FVIII:C/FIX:C levels and whole blood clotting time, thrombin generation in platelet poor plasma. | Within 18 months of consent |
| Correlation analysis between activation threshold of initiation pathway to thrombin generation and clinical phenotype | Within 18 months of consent |
Countries
United Kingdom
Contacts
Primary ContactThomas Roberts
Outcome results
None listed