Factor VIII Deficiency (Hemophilia A)

Key Features

Essentials of Diagnosis

• Bruising, soft-tissue bleeding, hemarthrosis

• Prolonged activated partial thromboplastin time (aPTT)

• Reduced factor VIII activity

General Considerations

• Normal range for factor VIII activity is 0.50–1.50 units/mL (50–150%)

• Hemophilia A occurs predominantly in males as an X-linked disorder

• One-third of cases are due to a new mutation

• Incidence of factor VIII deficiency is 1:5000 male births

Clinical Findings

• Mild hemophilia A (5–40% factor VIII activity): patients mainly bleed at times of trauma or surgery

• Moderate hemophilia A (1% to < 5% factor VIII activity): patients typically have intermediate bleeding manifestations

• Severe hemophilia A (< 1% plasma factor VIII activity): patients have frequent spontaneous bleeding episodes involving skin, mucous membranes, joints, muscles, and viscera in the absence of factor VIII

• Tendency to develop recurrent hemarthroses that incite joint destruction is most crippling aspect of disease

Diagnosis

• Prolonged aPTT, except in some cases of mild deficiency

• Prothrombin time is normal

• Diagnosis is confirmed by finding decreased factor VIII activity with normal von Willebrand factor (vWF) activity

• In a male fetus or newborn with a family history of hemophilia A, cord blood sampling for factor VIII activity is accurate and important in subsequent care

Treatment

• General aim is to raise the factor VIII activity to prevent or stop bleeding

• Some patients with mild factor VIII deficiency

  • May respond to desmopressin via release of endothelial stores of factor VIII and vWF into plasma

  • However, most patients require administration of exogenous factor VIII to achieve hemostasis

• Non–life-threatening, non–limb-threatening hemorrhage is treated initially with 20–30 units/kg of factor VIII, to achieve a rise in plasma factor VIII activity to 40–60%

• Large joint hemarthrosis and life- or limb-threatening hemorrhage is treated initially with approximately 50 units/kg of factor VIII, targeting a rise to 100% factor VIII activity

• Prophylactic factor VIII infusions (eg, two or four times weekly)

  • May prevent the development of arthropathy in severe hemophiliacs

  • Standard of care in pediatric hemophilia

• Extended half-life factor VIII concentrates have been approved by the FDA with the hope of decreasing infusions and improving clinical outcomes caused by bleeding

• Immunization with hepatitis A and hepatitis B vaccines is recommended for all hemophilia patients

Outcome

Complications

• Intracranial hemorrhage is the leading disease-related cause of death among patients with hemophilia

• Hemarthroses begin early in childhood and, particularly when recurrent, can result in joint destruction (ie, hemophilic arthropathy).

• Large intramuscular hematomas can lead to a compartment syndrome with resultant neurologic compromise

Prognosis

• The development of safe and effective therapies has resulted in improved long-term survival

• In addition, more aggressive management and the coordination of comprehensive care through hemophilia centers have greatly improved quality of ...