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1. OVERVIEW OF HEMOPHILIA A


           1.1. PATHOPHYSIOLOGY
           Hemophilia A is an X linked recessive bleeding disorder (Figure 1) characterized by congenital

           underproduction or dysfunction of blood coagulation factor VIII (FVIII). FVIII, which is usually
           produced in liver sinusoidal cells and endothelial cells outside the liver throughout the body, is
           a component of the intrinsic pathway in the coagulation cascade and essential for promoting
           clot formation. It is a cofactor for activated factor IX (FIXa) that forms a complex activating

           factor X (FXa), which in turn cleaves prothrombin to generate thrombin. Hemophilia A results
           from mutations or defects in the gene that encodes FVIII. Due to the fact that hemophilia A is
           passed along by X linked recessive inheritance, the vast majority (approximately 90%) of
           identified patients are males (WFH. 2016).





                         Parents              Unaffected                       Carrier
                                               father (XY)                    mother(XX)
                                                                  +






                        Children


                                       Unaffected        Carrier       Affected      Unaffected
                                         son (XY)     daughter (XX)    son (XY)    daughter (XX)




                         Parents                Affected                       Unaffected
                                               father (XY)        +           mother (XX)






                        Children



                                       Unaffected        Carrier       Affected        Carrier
                                         son (XY)     daughter (XX)    son (XY)    daughter (XX)


                                Figure 1: Hemophilia A X-linked recessive inheritance




           Hemophilia A results in a lifelong bleeding tendency and is a serious chronic disease that can
           be fatal. Some patients who are born with normal FVIII develop autoantibodies directed
           against FVIII.





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