The Dynamic Interplay Between Bleeding Phenotype and Baseline Factor Level in Moderate and Mild Hemophilia A and B
The Dynamic Interplay Between Bleeding Phenotype and Baseline Factor Level in Moderate and Mild Hemophilia A and B
There are large inter-individual differences in the bleeding pattern of patients with
 moderate or mild hemophilia. The major determinant of bleeding phenotype is the level of
 coagulant factor VIII or IX. In hemophilia A, studies addressing the association between
 factor VIII level and the clinical bleeding pattern yield conflicting results. In hemophilia
 B such studies have not yet been performed.

 The primary aim of this project is to analyze the association between factor VIII and factor
 IX levels and the bleeding phenotype. The secondary aim is to analyze potential differences
 in phenotype between hemophilia A and B.

 The project is a multicentre observational cohort study. We will include 500 patients with
 moderate or mild hemophilia A (FVIII 0.02-0.35 IU/mL) and 500 patients with moderate or mild
 hemophilia B (FIX 0.02-0.35 IU/mL) who are 12 to 55 years old. The main cohort study consists
 of clinical data collection, one blood sample and an online questionnaire for patients. Data
 will be collected on the nature and duration of all bleeding episodes, disease and treatment
 characteristics, physical activity level and musculoskeletal status. One blood withdrawal
 will be performed for centralized laboratory assays for FVIII or FIX levels (both one-stage
 and chromogenic assays) and genetic analysis for the most prevalent prothrombotic mutations.
 The online questionnaire for patients focuses on bleeds experienced in the past.

 A subset of 200 patients aged 24 years or older (100 with moderate or mild hemophilia A and
 100 with moderate or mild hemophilia B) will be investigated in more detail by longitudinal
 data collection including analysis of physical joint status, MRI imaging of joints and
 biomarkers for joint damage. This longitudinal observation will consist of two time points
 that lie two years apart, allowing us to identify any changes that occur over the observed
 time period with respect to joint status.
Inclusion Criteria:

 -  Moderate or mild hemophilia A (FVIII:C 0.02-0.35 IU/mL) or hemophilia B (FIX:C
 0.02-0.35 IU/mL)

 -  Age from 12 up to and including 55 years

 Exclusion Criteria:

 -  Other clotting disorder

 -  Participation in another trial with an investigational product

 -  Comorbidity affecting the musculoskeletal status

 -  Clinically relevant inhibitor status at present or in the past

 -  Hemophilia B Leyden

 -  Use of anticoagulants