Test ID: F8A    
Coagulation Factor VIII Activity Assay, Plasma

Diagnosing hemophilia A

Diagnosing von Willebrand disease when measured with the von Willebrand factor (VWF) antigen and VWF activity

Diagnosing acquired deficiency states

Investigation of prolonged activated partial thromboplastin time

Monitoring infusions of factor VIII replacement during interventional procedures and prophylactic infusions

This test is not useful for inferring carrier status in suspected female carriers of hemophilia A, unless it is 50% of normal (<28% activity in adults).

See Hemophilia Testing Algorithm in Special Instructions.

Factor VIII is synthesized in the liver and, perhaps, in other tissues. It is a coagulation cofactor that circulates bound to von Willebrand factor and is part of the intrinsic coagulation pathway. The biological half-life is 9 to 18 hours (average is 12 hours).

Congenital factor VIII deficiency is the cause of hemophilia A, which has an incidence of 1 in 10,000 and is inherited in a recessive sex-linked manner on the X chromosome. Severe deficiency (<1%) characteristically demonstrates as hemarthrosis, deep-tissue bleeding, excessive bleeding with trauma, and ecchymoses.

Factor VIII may be decreased in von Willebrand disease. Acquired deficiency states also occur.

Antibodies specific for factor VIII are the most commonly occurring specific inhibitors of coagulation factors and can produce serious bleeding disorders (acquired hemophilia).

Spuriously decreased results may occur as factor VIII is highly susceptible to proteolytic inactivation.

Adults: 55-200%

Normal, full-term newborn infants or healthy premature infants typically have levels greater than or equal to 40%.*

*See Pediatric Hemostasis References in Coagulation Guidelines for Specimen Handling and Processing  in Special Instructions.

Mild hemophilia A: 5% to 50% activity

Moderate hemophilia A: 1% to 5% activity

Severe hemophilia A: <1% activity

Congenital deficiency may also occur in combined association with factor V deficiency.

Liver disease usually causes an increase of factor VIII activity.

Acquired deficiencies of factor VIII have been associated with myeloproliferative or lymphoproliferative disorders (acquired von Willebrand disease: VWD), inhibitors of factor VIII (autoantibodies, postpartum conditions, etc), and intravascular coagulation and fibrinolysis.

Levels may be decreased with von Willebrand factor in VWD.

Factor VIII is a labile protein. Improper handling of a specimen may give a false result.

Factor VIII is highly susceptible to proteolytic inactivation, with the potential for spuriously decreased assay results. Normal results can be regarded as reliable, but decreased results need to be correlated with other clinical and laboratory information. Repeat testing may be necessary.

Factor VIII activity in frozen-thawed plasma specimens may be 10% to 20% lower than if assayed in fresh specimens, even under optimum conditions of processing and transportation, and may be even lower if these conditions are suboptimal.

Factor VIII activity rises in response to a number of factors, including pregnancy, estrogen therapy, stress, disease, etc.

Once artefactual reduction in FVIII is excluded, it is important to measure von Willebrand factor (VWF) levels to ensure that the patient does not have von Willebrand disease.

1. Spreafico M, Peyvandi F: Combined FV and FVIII deficiency. Haemophilia. 2008 Nov;14(6):1201-1208

2. Barrowcliffe TW, Raut S, Sands D, Hubbard AR: Coagulation and chromogenic assays of factor VIII activity: general aspects, standardization, and recommendations. Semin Thromb Hemost. 2002 Jun;28(3):247-256

3. Franchini M, Lippi G, Favaloro EJ: Acquired inhibitors of coagulation factors: part II. Semin Thromb Hemost. 2012 Jul;38(5):447-453

4. Carcao MD: The diagnosis and management of congenital hemophilia. Semin Thromb Hemost. 2012 Oct;38(7):727-734

• Coagulation Guidelines for Specimen Handling and Processing
• Hemophilia Testing Algorithm