Factor VIII Antigen, Activity, and Mutations in Hemophilia A

Factor VIII (FVIII) activity, antigen, and its gene mutation in patients may give us some insight into structure–activity relationship and probable reason for its low level in a particular patient. A total of 53 cases with hemophilia A and 17 normal individuals were analyzed for FVIII:C and FVIII:Ag levels along with their blood groups to determine their cross-reacting material (CRM) status. In all, 37 cases (18 moderate and 19 mild) were found to have discordant CRM status. Missense mutations (Ala723Thr and Lys439Ser) and protein truncating changes (Trp1854* and Arg2326*) were observed in 2 each of these cases. Although 37 (70%) of the 53 had discordant antigen–activity ratio, majority of those mutations produced FVIII with low FVIII-specific activity. However, 4 (7.5%) of the 53 mutations produced higher specific activity of FVIII. It is possible that these mutations either produce a secretory defect or an increased metabolic turnover to account for the low levels of FVIII with these mutations.
Source: Clinical and Applied Thrombosis/Hemostasis - Category: Hematology Authors: Tags: Original Articles Source Type: research