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- Deficiency of factor VIII (hemophilia A) or factor IX (hemophilia B) coagulation proteins leading to bleeding tendencies in affected individuals. The majority of cases are due to inherited genetic mutations in factor VIII or factor IX coagulation proteins. However, an estimated 30% of all hemophilia cases result from spontaneous mutations.
- Hemophilia A and B are clinically indistinguishable, but can be differentiated by assays that detect levels of factors VIII and IX, respectively.
- Disease severity correlates with the relative levels of coagulation factors present in serum analysis:
- Severe: frequent spontaneous bleeding (factor activity <1%)
- Moderate: bleeding with mild to moderate trauma (factor activity 1–5%)
- Mild: bleeding with major trauma, tooth extraction, or surgery (factor activity 5–40%)
- Frequency of bleeding is similar when levels of severity are comparable in hemophilia A and B.
- Worldwide, an estimated 400,000 people are affected with hemophilia; estimated frequency of 1 in 10,000 births (1)
- Hemophilia A represents 80–85% of the total hemophilia population; hemophilia B comprises the remaining 15–20%.
Etiology and Pathophysiology
- Damage to vascular endothelium leads to exposure of subendothelial tissue factors, which interact with platelets, plasma proteins, and coagulation factors to produce a localized platelet plug contributing to hemostasis. Complexes involving factors VIII and IX participate in the intrinsic coagulation pathway to activate factor X, FXa. Downstream interactions involving FXa culminate in the conversion of prothrombin to thrombin, mediating platelet activation, and fibrin deposition necessary for stabilization of the platelet plug.
- Deficiencies of factor VIII or factor IX result in decreased production of FXa, leading to an unstable platelet plug and impaired hemostasis.
- Exhibits an X-chromosome linked inheritance pattern. Males are almost exclusively affected; females are asymptomatic carriers, unless their factor activity is <40% of normal.
- Carriers with symptomatically low clotting factor levels are treated similarly to patients with the trait:
- May bleed at the time of surgery
- Males within the same family share similar deficiencies and level of severity owing to the same genetic defect.
- Patients should carry medical ID tags listing their bleeding disorder or factor deficiency, inhibitor status, type of treatment products used, and initial treatment doses for mild, moderate, or severe bleeding.
- Immediate family members of affected patients should have factor VIII and IX levels checked prior to invasive procedures, childbirth, and if bleeding tendencies occur.
- Genetic testing should be offered to at-risk female family members to facilitate genetic counseling.