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Title: Genetic, phenotypic and clinical evaluation of haemophilia A in Pakistan
Author: Khanum, Fatima
ISNI:       0000 0004 5351 9201
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2014
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Hereditary haemophilia A (HA), an X-linked bleeding disorder, is caused by mutations in the coagulation factor VIII gene (FVIII abbreviates protein, gene symbol F8). The aim of this study was (1) to characterise F8 mutations in HA cohort from Pakistan, (2) to investigate whether in vitro thrombin generation (TG) differs according to mutation type, and (3) to compare haemophilia joint health score (HJHS) and Gilbert score with severity, age, TG and underlying mutation in HA cohort which had minimal access to haemostatic replacement therapy. Methods: One hundred HA individuals and 100 healthy controls were recruited; clinical details were recorded. Results: Phenotypic measurements were re-evaulated in Cardiff; the essential regions of F8 were screened. Ninty two individuals were diagnosed with HA, 7 with haemophilia B and 1 was normal. The F8 defects were characterised and comprised point mutations, inversions and frameshifts. Thirty novel variants were identified. No significant difference was observed in vitro TG between severes with null mutation and those with a missense change. HJHS was strongly correlated with Gilbert score (r =0.98), both were siginificantly higher in severe compared with nonsevere before the age of 12 years (P≤0.01) but not thereafter. According to developmental age (<12 years, 12-16 years and > 16 years), both scores were significantly lower in the youngest group (P≤0.001). In severes there was no correlation between in vitro TG and joint score, no significant difference was observed for either joint score according to the underlying mutation type. Whereas in nonseveres, negative correlation between in vitro TG and joint score was observed. Conclusions: F8 defects in Pakistan is heterogenous; in severe HA in in vitro TG are not influenced by underlying mutation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: R Medicine (General)