Clinical meaning
Hemophilia is an X-linked recessive bleeding disorder caused by deficiency or dysfunction of specific coagulation factors in the intrinsic pathway of the coagulation cascade. Hemophilia A (classic hemophilia, ~80% of cases) results from deficiency of factor VIII, while hemophilia B (Christmas disease, ~20% of cases) results from deficiency of factor IX. Because the genes for both factors VIII and IX are located on the X chromosome, hemophilia predominantly affects males (who have only one X chromosome), while females are typically carriers who may have mildly reduced factor levels but are usually asymptomatic. Severity is classified by factor activity level: severe (<1% factor activity) presents with spontaneous bleeding into joints (hemarthrosis) and muscles, often beginning in infancy when the child starts crawling or walking; moderate (1-5%) causes bleeding with minor trauma or surgery; mild (5-40%) may only bleed with significant trauma or surgery and may not be diagnosed until adulthood. The coagulation cascade involves two converging pathways (intrinsic and extrinsic) that culminate in the common pathway activation of factor X, leading to thrombin generation and fibrin clot formation. Factors VIII and...