Stuart Prower Factor

Factor Xa
	Ribbon / surface model of factor Xa (blue / red) with factor VIIa (dark green / gray) and thromboplastin (light green) according to PDB 1NL8 .
	Existing structural data: s. UniProt
Properties of human protein
Mass / length primary structure	447 = 139 + 306 amino acids
Cofactor	Factor Va, Ca 2+ , phospholipid
Identifier
Gene names	F10 ; FX; FXA
External IDs	OMIM : 227600 ; UniProt : P00742 ; MGI : 103107 ;
Enzyme classification
EC, category	3.4.21.6 , serine protease
MEROPS	S01.216
Substrate	Arg - + - Thr and Arg - + - Ile in prothrombin
Products	Thrombin
Occurrence
Homology family	Trypsin
Parent taxon	Creature
	Orthologue

Stuart Prower Factor (also known as thrombokinase or factor X ) is an enzyme involved in blood clotting . It is therefore included in the group of coagulation factors .

physiology

The Stuart Prower factor is a human coagulation factor . It is synthesized in the liver and vitamin K is required for this. It belongs to the group of α-globulins and consists of a heavy and a light chain. It has a molecular mass of 59 kDa and belongs to the serine proteases , with an EC number of 3.4.21.6. Its half-life in the blood is 40 to 45 hours and its plasma concentration is 7–10 mg / l. and

When the Stuart-Prower factor is activated, a peptide bond within the heavy chain carrying the active center is cleaved. This can be activated in two different ways. In the extrinsic pathway , which occurs when blood vessels are damaged, a complex of activated proconvertin (factor VIIa) and tissue factor (factor III) activates the Stuart-Prower factor (factor Xa). In contrast, in the intrinsic pathway , which occurs when parts of the coagulation cascade encounter negatively charged particles (such as collagen under the endothelium ), it is through a complex of activated Christmas factor (factor IXa) and antihemophilic globulin A (factor VIIIa) activated. It can also be activated by the digestive enzyme trypsin and the poison of the Russel viper .

Factor Xa is therefore the first step in the coagulation phase, everything before that is part of the activation phase. It cleaves prothrombin (factor II) in two places; between an Arg - Thr bond and between an Arg - Ile bond. This converts prothrombin to thrombin . For this process, the Stuart-Prower factor requires activated proaccelerin (factor Va) as a cofactor.

Factor Xa is inactivated by a protein Z- dependent serine proteinase. The affinity of this enzyme for Factor Xa is a thousand-fold by protein Z. Defective protein Z leads to an increased activity of the Stuart-Prower factor and a tendency to form thromboses .

Diseases

Factor X defects are associated with nosebleeds (epistaxis), joint bleeding ( hemarthrosis ) and blood loss in the digestive tract (gastrointestinal bleeding). Factor X defects can be congenital or acquired. The congenital defect is rare (1: 500,000). The Stuart-Prower factor gene is found in humans on chromosome 13 , gene locus q34.

A decreased incidence of Stuart-Prower factor can occur in various acquired diseases, such as: B. amyloidosis. A deficiency in vitamin K leads to the formation of inactive factor X. If vitamin K is inhibited by warfarin therapy or similar antagonists, this effect is desirable in order to avoid thrombosis .

use

Factor X is contained as a concentrate in frozen blood plasma and in the prothrombin complex . In 2012 the only approved Factor X concentrate is Factor XP Behring , manufactured by CSL Behring .

A high-purity, plasma-derived factor X concentrate (pdFX) is approved in the United States and the European Union as a replacement therapy for FXD. Data on the use of pdFX for the prophylaxis of bleeding in children under 12 years of age were published in 2018.

Andexanet alfa is a recombinant analogue of factor Xa.

Research history

Factor X deficiency was independently discovered by British (C. Hougie et al.), German ( M. Hörder ) and Swiss (K.-D. Bachmann et al.) Researchers and described in 1957 and 1958. Like other coagulation factors, factor X was named after those patients in whom a deficiency was first described. The nomenclature comes from the Swiss working group around K.-D. Bachmann.

Web links

Stuart Prower Factor. In: Online Mendelian Inheritance in Man . (English)
Factor X (Emedicine, Engl.)
Factor X deficiency

Individual evidence

^ Mark Brooker: Registry of Clotting Factor Concentrates. 9th edition, World Federation of Hemophilia, 2012.
↑ R. Liesner, C. Akanezi u. a .: Prophylactic treatment of bleeding episodes in children <12 years with moderate to severe hereditary factor X deficiency (FXD): Efficacy and safety of a high-purity plasma-derived factor X (pdFX) concentrate. In: Haemophilia. 24, 2018, p. 941, PMID 29707881 . doi : 10.1111 / hae.13500 .
↑ Ludwig Heilmeyer: Presentation on the habilitation thesis by MH Hörder "Experimental and clinical studies on the V. blood coagulation factor" . 1959.
↑ Max-Hermann Hörder: Experimental and clinical studies on the fifth blood coagulation factor , habilitation thesis, 1959, p. 69 DNB 480023476 .

[1] Mark Brooker: Registry of Clotting Factor Concentrates. 9th edition, World Federation of Hemophilia, 2012.

[2] R. Liesner, C. Akanezi u. a .: Prophylactic treatment of bleeding episodes in children <12 years with moderate to severe hereditary factor X deficiency (FXD): Efficacy and safety of a high-purity plasma-derived factor X (pdFX) concentrate. In: Haemophilia. 24, 2018, p. 941, PMID 29707881 . doi : 10.1111 / hae.13500 .

[3] Ludwig Heilmeyer: Presentation on the habilitation thesis by MH Hörder "Experimental and clinical studies on the V. blood coagulation factor" . 1959.

[4] Max-Hermann Hörder: Experimental and clinical studies on the fifth blood coagulation factor , habilitation thesis, 1959, p. 69 DNB 480023476 .