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prothrombin -> activated thrombin (factor IIa) + thrombin activation peptide (prothrombinase catalyst)

Stable Identifier
R-HSA-140664
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

The membrane-bound Va:Xa (prothrombinase) complex rapidly activates large amounts of thrombin.

Factor Xa (aka Factor X heavy chain), a cleavage product of coagulation factor X (F10), is a vitamin K-dependent glycoprotein able to convert prothrombin to thrombin during the blood clotting process. Factor Xa is a target for direct oral anticoagulant (DOAC) drugs that are direct factor Xa inhibitors (the so-called 'xabans') and used in the treatment and prevention of thromboembolic disorders (Galanis et al. 2014). Rivaroxaban (brand name Xarelto) was the first medically approved drug of this class (Abrams & Emerson 2009, Misselwitz et al. 2011). In patients with non-valvular atrial fibrillation, 'xabans' appears to be as effective as warfarin in preventing nonhemorrhagic strokes and embolic events (Patel et al. 2011, Gomez-Outes et al. 2013). The most serious side-effect of rivaroxaban is GI bleeding, and with there being no antidote for rivaroxaban, bleeding events can be difficult to manage (Siegal et al. 2014). Rivaroxaban binds to and inhibits both free factor Xa and factor Xa bound in the prothrombinase complex (Roehrig et al. 2005). Unlike warfarin, the 'xabans' exhibit a predictable dose response and do not require routine coagulation monitoring.

Literature References
PubMed ID Title Journal Year
3052293 Cofactor proteins in the assembly and expression of blood clotting enzyme complexes Annu Rev Biochem 1988
14982929 The factor V activation paradox J Biol Chem 2004
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
serine-type endopeptidase activity of Va:Xa complex (prothrombinase) [plasma membrane]
Physical Entity
Activity
This entity is regulated by
Orthologous Events