title: Variability in clinical phenotype of severe haemophilia: the role of the first joint bleed.
abstract: To quantify variation in clinical phenotype of severe haemophilia we performed a single centre cohort study among 171 severe haemophilia patients. Age at first joint bleed, treatment requirement (i.e. annual clotting factor use), annual bleeding frequency and arthropathy were documented. Because treatment strategies intensified during follow-up, patients were stratified in two age groups: patients born 1968-1985 (n = 91), or 1985-2002 (n = 80). A total of 2166 patient-years of follow-up were available (median 12.0 years per patient). Age at first joint bleed ranged from 0.2 to 5.8 years. Patients who had their first joint bleed later needed less treatment and developed less arthropathy. In patients born 1968-1985 during both on-demand and prophylactic treatment, the 75th percentile of annual joint bleed frequency was consistently four times as high as the 25th percentile. In both age groups variation in annual clotting factor use between 25th and 75th percentiles was 1.4-1.5 times for prophylaxis and 3.8 times for on-demand treatment. To conclude, the onset of joint bleeding is inversely related with treatment requirement and arthropathy and may serve as an indicator of clinical phenotype. Thus, providing a starting point for aetiological research and individualization of treatment.
authors.affiliation: Van Creveldkliniek, UMC Utrecht, Utrecht, The Netherlands. k_van_dijk@wanadoo.nl
authors.forename: K
authors.initials: K
authors.lastname: van Dijk
authors.forename: K
authors.initials: K
authors.lastname: Fischer
authors.forename: J G
authors.initials: JG
authors.lastname: van der Bom
authors.forename: D E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: H M
authors.initials: HM
authors.lastname: van den Berg
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005164:Factor IX / Q000008:administration & dosage; D005169:Factor VIII / Q000008:administration & dosage; D005500:Follow-Up Studies; D006395:Hemarthrosis / Q000209:etiology*; D006467:Hemophilia A / Q000150:complications* / Q000188:drug therapy; D002836:Hemophilia B / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D007592:Joint Diseases / Q000209:etiology; D010641:Phenotype; D011379:Prognosis; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D005169:Factor VIII; D005164:Factor IX