Explaining variation in bleeding pattern of severe haemophilia

Abstract

Patients with severe haemophilia have a plasma activity level of factor VIII or IX below 1%. Although the laboratory diagnosis of severe haemophilia is distinct, marked variation in bleeding pattern among patients has been observed. Knowledge of indicators and determinants of this variation may enhance the quality of patient care in terms of individualized prophylactic treatment. Individual tailoring of treatment may increase cost-effectiveness of treatment. Karin van Dijk examined bleeding patterns of 285 patients with severe haemophilia at the Van Creveldkliniek. She studied the age at first joint bleed, annual joint bleed frequency, annual clotting factor consumption and arthropathy. In total 4737 patient-years were collected - which is approximately 17 per patient. The median age at first joint bleed was 1.8 years and varied from 2.5 months to 5.8 years. The age at first joint bleed was associated with the use of clotting factor concentrate later in life. Patients who experienced their first joint bleed at an early age had consistently higher annual clotting factor consumption than patients who had their first joint bleed later in life. The age at first joint bleed may therefore be used as an indicator of bleeding pattern.

The determinants of variation in bleeding pattern are largely unknown. To study determinants of this variation, Van Dijk selected 21 people with a more severe bleeding pattern and 21 with a less severe bleeding pattern. In these, pharmacokinetics, proteins involved in clot formation and -lysis and thrombingeneration were analysed. Furthermore, the effect of the underlying defect in the gene encoding for factor VIII was studied in 241 patients with severe haemophilia. These factors were not, or only to a limited extent, associated with bleeding pattern.