Biochemistry
| Synonym | Antihaemophilic Globulin A, Factor VIII Clotting-Activity (Factor VIII:C) |
|---|---|
| Molecular Weight | 280.000 Da |
| Synthesis | Liver, placenta, kidneys, spleen, lymphatic nodes, muscle cells |
| Half-life | 8 - 12 hours in complex with vWF 2.4 hours free Factor VIII |
| Plasma-Concentration | 0.15 mg/l |
| Normal range | 0 - 150% (blood group dependent) |
Factor VIII is present in plasma in complex with von Willebrand-factor. The glycoprotein is related to factor V with respect to primary structure (40% identity) as well as cofactor-function in the plasmatic coagulation. After the activation by thrombin factor VIIIa forms together with factor IXa, phospholipids and calcium ions the tenase complex, which is responsible for the activation of factor X. As factor V, factor VIII is also inactivated by activated Protein C through proteolytic cleavage.
Clinical significance
Hereditary factor VIII-deficiency is the cause of Haemophilia A.
> 5-40%: mild haemophilia A
1-5%: moderate haemophilia A
< 1%: severe haemophilia A
Also in the case of the von Willebrand-Syndrome a hereditary factor VIII-deficiency may be observed. Acquired deficiencies (disorders in synthesis and turnover) are rare. The formation of factor VIII inhibitors is observed more frequently; especially after substitution therapy in patients with Haemophilia A. Formation of inhibitors may also be caused by autoimmune diseases, drug treatments (e.g. penicillin) and in monoclonal granulopathies and lymphoproliferative diseases. As acute-phase-protein, factor VIII may be increased postoperatively, in phase I of a DIC, in liver diseases, tumor diseases, inflammation, and vascular disease, as well as after physical and mental stress situations (blood sampling).
Indication
- Differential diagnosis and clarification of a congenital bleeding tendency
- Diagnosis of factor VIII-inhibitors
- Monitoring of a substitution therapy
- Thrombophilia diagnosis
- Factor VIII determination of factor VIII concentrates
Literature
- Rosen S et al. Clinical application of a chromogenic substrate method for determination of factor VIII activity. Thromb Haemost 54, 818-823, 1985.
- Barrowcliffe T. Recommendations for the Assay of High-Purity Factor VIII Concentrates. Thromb Haemost 70, 876-877, 1993.
- Lethagen S et al. Clinical application of the chromogenic assay of factor VIII in hemophilia A and variants of von Willebrands disease. Scand J Haematol 37, 448-453, 1986.
- Prowse C et al. Room temperature, microtray chromogenic assay of factor VIII:C. Vox Sang 50, 21-25, 1986.
- Mikaelsson M. Factor VIII Assays. IMH 8, 4, 2000.
- Mahdi AJ, Obaji SG, Collins PW. Role of enhanced half-life factor VIII and IX in the treatment of haemophilia. Br J Haematol. Jun 169(6), 768-76, 2015.