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Biochemistry

The vitamin K-dependent factor X is a central enzyme of the coagulation cascade. It can be activated by the intrinsic pathway through the tenase complex consisting of factor IXa, factor VIIIa, phospholipids and calcium ions or by the complex of tissue factor and factor VIIa of the extrinsic pathway. Factor Xa is a serine protease and forms together with factor Va, phospholipids and calcium ions the prothrombinase complex, by which prothrombin (factor II) is activated to thrombin (factor IIa). Factor Va acts as a cofactor, which amplifies this activation step a thousandfold.

Clinical Significance

The rare hereditary form of factor X deficiency is autosomal recessively inherited. As with all vitamin K-dependent factors an acquired deficiency results from vitamin K-deficiency or coumarin therapy. Hepatic disorders, L-asparaginase therapy and DIC  lead to reduced FX levels. The symptoms of a factor X deficiency extend from articular and mucosal bleedings to postoperative and cerebral bleedings. Increased factor X activities are observed during vitamin K-administration and in hyperlipidaemia.

Indication

• of anticoagulant diagnosis of a to date unknown hereditary bleeding disorder
• Reason for pathological INR values
• Adjustment of INR in patients with pathological Quick values due to inhibitors
• Monitoring of plasma levels during anticoagulant therapy with heparin or coumarin derivatives (during the transition phase) and during a fibrinolytic therapy
• Monitoring of plasma levels during anticoagulant therapy with thrombin inhibitors
• Differential diagnosis between synthesis disorder and increased consumption
• Monitoring therapy in patients with phospholipid antibody syndrome

Literature

1. Girolami A. The discovery of factor X. J Thromb Haemost 2, 187-188, 2004.
2. Arpino PA et al. Use of the chromogenic factor X assay to predict the international normalized ratio in patients transitioning from argatroban to warfarin. Pharmacotherapy 25, 157-164, 2005.
3. Lindhout MJ et al. Activation of decarboxyfactor X by protein from Russell´s Viper Venom. Purification and partial characterization of activated decarboxyfactor X. Biochem Biophys Acta 533, 327-341, 1978.
4. Bergström K, Egberg N. Determination of vitamin K sensitive coagulation factors in plasma. Studies on three methods using synthetic chromogenic substrates. Thromb Res 12, 531-547, 1978.
5. Van Wijk EM et al. A rapid manual chromogenic factor X assay. Thromb Res 22, 681-686, 1981.
6. Egberg N, Heedman PA. Simplified performance of amidolytic factor X assay. Thromb Res 25, 437-440, 1982.
7. Moll S, Ortel TL. Monitoring warfarin therapy in patients with Lupus anticoagulants. Ann Intern Med. 127, 177-185, 1997.
8. Girolami A, Cosi E, Sambado L, Girolami B, Randi ML. Complex history of the discovery and characterization of congenital factor X deficiency. Semin Thromb Hemost. Jun 41(4), 359-65, 2015.
9. Matsui H, Sakurai F, Katayama K, Yamaguchi T, Okamoto S, Takahira K, Tachibana M, Nakagawa S, Mizuguchi H. A hexon-specific PEGylated adenovirus vector utilizing blood coagulation factor X. Biomaterials. May 33(14), 3743-55, 2012.