title: Joint health scores in a haemophilia A cohort from Pakistan with minimal or no access to factor VIII concentrate: correlation with thrombin generation and underlying mutation.
abstract: Haemophilia A is associated with recurrent joint bleeding which leads to synovitis and debilitating arthropathy. Coagulation factor VIII level is an important determinant of bleed number and development of arthropathy . The aim of this study was to compare the haemophilia joint health score (HJHS) and Gilbert score with severity, age, thrombin generation (TG) and underlying mutation in a haemophilia A cohort which had minimal access to haemostatic replacement therapy. Ninety-two haemophilia A individuals were recruited from Pakistan. Age, age at first bleed, target joints, haemophilic arthropathy joints, HJHS and Gilbert score were recorded. A strong correlation was found between HJHS and Gilbert score (r = 0.98), both were significantly higher in severe (n = 59) compared with non-severe (n = 29) individuals before the age of 12 years (P ≤ 0.01) but not thereafter. When individuals were divided according to developmental age (<12 years, 12-16 years and >16 years), both HJHS and Gilbert score were significantly lower in the youngest group (P ≤ 0.001), there was no difference between 12-16 years and >16 years. In severe individuals there was no correlation between in vitro TG and joint score, whereas in non-severe individuals there was a weak negative correlation. In the severe group, no significant difference was observed for either joint score according to the underlying mutation type (inversion, missense, nonsense, frameshift). In this cohort of haemophilia A individuals with minimal access to haemostatic treatment, haemophilic arthropathy correlated with severity and age; among severe individuals, joint health scores did not relate to either the underlying mutation or in vitro TG.
authors.affiliation: Department of Haematology, Cardiff University, School of Medicine, Cardiff, UK.
authors.forename: F
authors.initials: F
authors.lastname: Khanum
authors.forename: D J
authors.initials: DJ
authors.lastname: Bowen
authors.forename: B C
authors.initials: BC
authors.lastname: Kerr
authors.forename: P W
authors.initials: PW
authors.lastname: Collins
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D005169:Factor VIII / Q000008:administration & dosage / Q000600:supply & distribution*; D005260:Female; D006395:Hemarthrosis / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D006467:Hemophilia A / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010154:Pakistan; D013917:Thrombin / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D005169:Factor VIII; D013917:Thrombin
keywords: Gilbert score; Pakistan; haemophilia A; haemophilia joint health score; thrombin generation