title: Determinants of factor VIII plasma levels in carriers of haemophilia A and in control women.
abstract: Factor VIII (FVIII) levels show a considerable variability in female carriers of haemophilia A. Presently, the reasons for this are poorly understood. The aim of the study was to elucidate the influence of genetic and non-genetic parameters on FVIII plasma levels in carriers (n = 42). Results were compared with age-matched healthy women without carriership of haemophilia A (n = 42). Each carrier was tested for the family-specific mutation, ABO blood group, FVIII level, von Willebrand factor (VWF) antigen and activity and C-reactive protein (CRP). FVIII levels were lower in carriers compared to non-carriers [74% (51-103) vs. 142% (109-169), P < 0.001]. No statistically significant differences were observed between the two groups with respect to VWF activity, prothrombin-time, hs-CRP, fibrinogen, body mass index (BMI), age and smoking status as well as the distribution of ABO blood groups. In non-carriers, FVIII was statistically significantly correlated with BMI, activated partial thromboplastin time (APTT), VWF antigen, hs-CRP and fibrinogen. In carriers, significant correlations between FVIII and APTT, VWF antigen and activity were found, whereas BMI, hs-CRP or fibrinogen did not correlate with FVIII. In non-carriers, the association of FVIII with ABO blood groups was statistically significant (P = 0.006), but not in carriers of haemophilia A (P = 0.234). The type of FVIII gene mutation did not influence FVIII levels. Carrier status is the major determinant of a carrier;s FVIII plasma level. Factors known to influence FVIII levels in the general population do not significantly affect FVIII activity in carriers, neither does the type of mutation influence FVIII levels.
authors.affiliation: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Ay
authors.forename: K
authors.initials: K
authors.lastname: Thom
authors.forename: F
authors.initials: F
authors.lastname: Abu-Hamdeh
authors.forename: B
authors.initials: B
authors.lastname: Horvath
authors.forename: P
authors.initials: P
authors.lastname: Quehenberger
authors.forename: C
authors.initials: C
authors.lastname: Male
authors.forename: C
authors.initials: C
authors.lastname: Mannhalter
authors.forename: I
authors.initials: I
authors.lastname: Pabinger
mesh_terms: D000017:ABO Blood-Group System; D000328:Adult; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D004252:DNA Mutational Analysis; D005169:Factor VIII / Q000032:analysis* / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006467:Hemophilia A / Q000097:blood* / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008875:Middle Aged; D057345:Sequence Inversion; D055815:Young Adult; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D000017:ABO Blood-Group System; D014841:von Willebrand Factor; D005169:Factor VIII; D005340:Fibrinogen; D002097:C-Reactive Protein