Moderate haemophilia A and B in the Nordic countries – The MoHem study

Recurrent joint bleeds lead to progressive arthropathy, which is the main long-term complication for patients with haemophilia. Prophylactic replacement therapy from early age has improved joint health in severe haemophilia (factor VIII/factor IX activity (FVIII/FIX:C) < 1 IU/dL) and is now the standard of care. Patients with moderate haemophilia (1-5 IU/dL) have mainly received episodic treatment, and the prevalence of arthropathy in the group is not well characterised. The aims of the thesis were to describe current joint health in Nordic patients with moderate haemophilia A (MHA) and B (MHB) in relation to treatment modality, and to explore and compare ultrasound and physical examination to detect early arthropathy. We also explored the role of global coagulation assays to unravel the patients’ bleeding phenotype. The MoHem study was a cross-sectional, multicentre study covering 145 patients with MHA and MHB in Sweden, Finland, and Norway. Median age was 28 years and 38% were on prophylaxis, started at median 10 years of age. Patients with FVIII/FIX:C ≤ 3 IU/dL and those with MHA had experienced their first joint bleed at a younger age, implying more severe bleeding phenotype. Overall, current joint health was good, but 15% had undergone orthopaedic surgery because of haemophilic arthropathy. FVIII/FIX:C ≤ 3 IU/dL was associated with impaired joint health. Ultrasound clarified the origin of subtle clinical findings and detected subclinical pathology. In a study subgroup, thrombin generation and thromboelastometry distinguished between mild or more severe bleeding phenotypes. In conclusion, we suggested primary prophylaxis to all patients with FVIII/FIX:C ≤ 3 IU/dL according to similar guidelines as for severe haemophilia. Ultrasound improved joint assessment and should be used regularly in clinical practice to detect early arthropathy. Global coagulation assays were able to discriminate between bleeding phenotypes, which may contribute to personalised treatment