Editing Coagulation (section)

===Cofactors===
Various substances are required for the proper functioning of the coagulation cascade:

====Calcium and phospholipids====
[[Calcium]] and [[phospholipid]]s (constituents of [[platelet]] membrane) are required for the [[tenase]] and prothrombinase complexes to function.<ref>{{Cite journal |last=Palta |first=A. |last2=Palta |first2=S. |last3=Saroa |first3=R. |date=2014 |title=Overview of the coagulation system |journal=Indian Journal of Anaesthesia |volume=58 |issue=5 |pages=515–23 |doi=10.4103/0019-5049.144643 |issn=0019-5049 |pmc=4260295 |pmid=25535411 |doi-access=free}}</ref> Calcium mediates the binding of the complexes via the terminal gamma-carboxy residues on Factor Xa and Factor IXa to the phospholipid surfaces expressed by platelets, as well as procoagulant microparticles or [[microvesicles]] shed from them.<ref>{{Cite journal |last=Signorelli |first=Salvatore Santo |last2=Oliveri Conti |first2=Gea |last3=Fiore |first3=Maria |last4=Cangiano |first4=Federica |last5=Zuccarello |first5=Pietro |last6=Gaudio |first6=Agostino |last7=Ferrante |first7=Margherita |date=2020-11-26 |title=Platelet-Derived Microparticles (MPs) and Thrombin Generation Velocity in Deep Vein Thrombosis (DVT): Results of a Case–Control Study |journal=Vascular Health and Risk Management |volume=16 |pages=489–95 |doi=10.2147/VHRM.S236286 |issn=1176-6344 |pmc=7705281 |pmid=33273818 |doi-access=free}}</ref> Calcium is also required at other points in the coagulation cascade. Calcium ions play a major role in the regulation of coagulation cascade that is paramount in the maintenance of hemostasis. Other than platelet activation, calcium ions are responsible for complete activation of several coagulation factors, including coagulation Factor XIII.<ref>{{Cite journal |last=Singh |first=S. |last2=Dodt |first2=J |last3=Volkers |first3=P. |last4=Hethershaw |first4=E. |last5=Philippou |first5=H. |last6=Ivaskevicius |first6=V. |last7=Imhof |first7=D. |last8=Oldenburg |first8=J. |last9=Biswas |first9=A. |date=5 August 2019 |title=Structure functional insights into calcium binding during the activation of coagulation factor XIII A |journal=Scientific Reports |volume=9 |issue=1 |page=11324 |bibcode=2019NatSR...911324S |doi=10.1038/s41598-019-47815-z |issn=2045-2322 |pmc=6683118 |pmid=31383913}}</ref>

====Vitamin K====
[[Vitamin K]] is an essential factor to the hepatic [[gamma-glutamyl carboxylase]] that adds a [[carboxyl]] group to [[glutamic acid]] residues on factors II, VII, IX and X, as well as [[Protein S]], [[Protein C]] and [[Protein Z]]. In adding the gamma-carboxyl group to glutamate residues on the immature clotting factors, Vitamin K is itself oxidized. Another enzyme, ''[[Vitamin K epoxide reductase]]'' (VKORC), reduces vitamin K back to its active form. Vitamin K epoxide reductase is pharmacologically important as a target of anticoagulant drugs [[warfarin]] and related [[coumarin]]s such as [[acenocoumarol]], [[phenprocoumon]], and [[dicumarol]]. These drugs create a deficiency of reduced vitamin K by blocking VKORC, thereby inhibiting maturation of clotting factors. Vitamin K deficiency from other causes (e.g., in [[malabsorption]]) or impaired vitamin K metabolism in disease (e.g., in [[liver failure]]) lead to the formation of PIVKAs (proteins formed in vitamin K absence), which are partially or totally non-gamma carboxylated, affecting the coagulation factors' ability to bind to phospholipid.<ref name="Paulus">{{Cite journal |last=Paulus |first=MC |last2=Drent |first2=M |last3=Kouw |first3=IWK |last4=Balvers |first4=MGJ |last5=Bast |first5=A |last6=van Zanten |first6=ARH |date=1 July 2024 |title=Vitamin K: a potential missing link in critical illness-a scoping review. |journal=Critical Care |volume=28 |issue=1 |page=212 |doi=10.1186/s13054-024-05001-2 |pmc=11218309 |pmid=38956732 |doi-access=free}}</ref>