Factor XII: Difference between revisions

'''Coagulation factor XII''', also known as '''Hageman factor''', is a [[plasma protein]] involved in [[proteincoagulation]]. It is the [[zymogen]] form of factor XIIa, an [[enzyme]] ({{EC number|3.4.21.38}}), an [[enzyme]] of the [[serine protease]] (or serine endopeptidase) class. In humans, factor XII is encoded by the ''F12'' [[gene]].<ref name="pmid2888762">{{cite journal | vauthors = Cool DE, MacGillivray RT | title = Characterization of the human blood coagulation factor XII gene. Intron/exon gene organization and analysis of the 5'-flanking region | journal = The Journal of Biological Chemistry | volume = 262 | issue = 28 | pages = 13662–7313662–13673 | date = October 1987 | pmid = 2888762 | urldoi = http://www10.jbc.org1016/cgi/reprint/262/28/13662S0021-9258(19)76478-3 | doi-access = free }}</ref>

Human Factor XII is 596 [[amino acids]] long and consists of two chains, the heavy chain (353 [[Amino acid|residues]]) and light chain (243 residues) held together by a [[disulfide bond]]. It is 80,000 daltons in molecular weight. ItsThe heavy chain contains two [[fibronectin]]-type domains (type I and II), two [[epidermal growth factor]]-like domains, a kringle domain, and a proline-rich region, andwhile itsthe light chain contains the protease domain. TheFXII structurecan ofbe thecleaved FnI-EGF-likesequentially tandemat [[Proteintwo domain|domain]]sites, ofArg353 coagulation factor XII has been solved by [[X-ray crystallography]].<ref>{{cite journal | vauthors = Stavrouand EArg334, Schmaierwith AHthe |second titlecleavage =liberating Factorthe XII:light what does it contribute to our understanding of the physiologychain and pathophysiologyforming of hemostasis & thrombosis | journal = Thrombosis Research | volume = 125 | issue = 3 | pages = 210–5 | date = March 2010 | pmid = 20022081 | pmc = 2851158 | doi = 10β-FXIIa.1016/j.thromres.2009.11.028 }}</ref><ref>{{cite journal | vauthors = BeringerIvanov DXI, Kroon-BatenburgMatafonov LMA, Gailani D | title = TheSingle-chain structurefactor ofXII: thea FnI-EGF-likenew tandem domainform of coagulationactivated factor XII solved using SIRAS | journal = ActaCurrent CrystallographicaOpinion Sectionin FHematology | volume = 6924 | issue = Pt 25 | pages = 94–102411–418 | date = FebruarySeptember 20132017 | pmid = 2338574528604413 | pmcdoi = 356460610.1097/MOH.0000000000000363 | doipmc = 10.1107/S17443091130002865762122 }}</ref>

The structure of the FnI-EGF-like tandem [[Protein domain|domain]] of coagulation factor XII has been solved by [[X-ray crystallography]].<ref>{{cite journal | vauthors = Stavrou E, Schmaier AH | title = Factor XII: what does it contribute to our understanding of the physiology and pathophysiology of hemostasis & thrombosis | journal = Thrombosis Research | volume = 125 | issue = 3 | pages = 210–215 | date = March 2010 | pmid = 20022081 | pmc = 2851158 | doi = 10.1016/j.thromres.2009.11.028 }}</ref><ref>{{cite journal | vauthors = Beringer DX, Kroon-Batenburg LM | title = The structure of the FnI-EGF-like tandem domain of coagulation factor XII solved using SIRAS | journal = Acta Crystallographica Section F | volume = 69 | issue = Pt 2 | pages = 94–102 | date = February 2013 | pmid = 23385745 | pmc = 3564606 | doi = 10.1107/S1744309113000286 }}</ref> Crystal structures of the FXII light chain hashave also been determined, both unbound (β-FXII) and bound (β-FXIIa) to [[Enzyme inhibitor|inhibitors]].<ref>{{cite journal | vauthors = Dementiev A, Silva A, Yee C, Li Z, Flavin MT, Sham H, Partridge JR | title = Structures of human plasma β-factor XIIa cocrystallized with potent inhibitors | journal = Blood Advances | volume = 2 | issue = 5 | pages = 549–558 | date = March 2018 | pmid = 29519898 | pmc = 5851424 | doi = 10.1182/bloodadvances.2018016337 }}</ref><ref>{{cite journal | vauthors = Pathak M, Wilmann P, Awford J, Li C, Hamad BK, Fischer PM, Dreveny I, Dekker LV, Emsley J | display-authors = 6 | title = Coagulation factor XII protease domain crystal structure | journal = Journal of Thrombosis and Haemostasis | volume = 13 | issue = 4 | pages = 580–91580–591 | date = April 2015 | pmid = 25604127 | pmc = 4418343 | doi = 10.1111/jth.12849 }}</ref><ref>{{cite journal | vauthors = Pathak M, Manna R, Li C, Kaira BG, Hamad BK, Belviso BD, Bonturi CR, Dreveny I, Fischer PM, Dekker LV, Oliva ML, Emsley J | display-authors = 6 | title = Crystal structures of the recombinant β-factor XIIa protease with bound Thr-Arg and Pro-Arg substrate mimetics | journal = Acta Crystallographica Section D | volume = 75 | issue = Pt 6 | pages = 578–591 | date = June 2019 | pmid = 31205020 | doi = 10.1107/S2059798319006910 | s2cid = 189944782 | url = https://nottingham-repository.worktribe.com/output/2390798 }}</ref>

Factor XII (FXII, Hageman factor) is a plasma glycoprotein of approximately 90 kDa and is part of the [[coagulation]] cascade. andIt activates [[factor XI]] and [[prekallikrein]] in vitro. Factor XII itselfFXII is activated to factor XIIaFXIIa by negatively charged surfaces, such as glass., This is the starting point ofinitiating the intrinsic pathway.<ref>{{cite book | url = https://www.moscmm.org/pdf/Guyton%20physiology.pdf | title = Textbook of Medical Physiology | edition = 11th | vauthors = Guyton AC, Hall JE | pages = 462–463 | isbn = 0-7216-0240-1 | access-date = 2021-01-25 | archive-date = 2020-07-14 | archive-url = https://web.archive.org/web/20200714104902/https://www.moscmm.org/pdf/Guyton%20physiology.pdf | url-status = dead }}</ref> Factor XII canFXII also beplays useda torole startin diagnostic coagulation cascadesassays incalled activated partial thromboplastin laboratorytimes studies(aPTT).<ref name="pmid22993391">{{cite journal | vauthors = Renné T, Schmaier AH, Nickel KF, Blombäck M, Maas C | title = In vivo roles of factor XII | journal = Blood | volume = 120 | issue = 22 | pages = 4296–3034296–4303 | date = November 2012 | pmid = 22993391 | pmc = 3507141 | doi = 10.1182/blood-2012-07-292094 }}</ref>

== RoleClinical in diseasesignificance ==

Factor XII deficiency is a rare disorder that is inherited in an [[autosomal recessive]] manner.<ref name=Wagenman>{{cite journal | vauthors = Wagenman BL, Townsend KT, Mathew P, Crookston KP | title = The laboratory approach to inherited and acquired coagulation factor deficiencies | journal = Clinics in Laboratory Medicine | volume = 29 | issue = 2 | pages = 229–52229–252 | date = June 2009 | pmid = 19665676 | doi = 10.1016/j.cll.2009.04.002 | url = https://zenodo.org/record/894920 }}</ref> Unlike other clotting factor deficiencies, factor XII deficiency is totally asymptomatic and does not cause excess bleeding.<ref name=Wagenman /> Mice lacking the gene for factor XII, however, are less susceptible to [[thrombosis]]. The protein seems to be involved in the later stages of clot formation rather than the first occlusion of damages in the blood vessel wall.<ref name="pmid16009717">{{cite journal | vauthors = Renné T, Pozgajová M, Grüner S, Schuh K, Pauer HU, Burfeind P, Gailani D, Nieswandt B | display-authors = 6 | title = Defective thrombus formation in mice lacking coagulation factor XII | journal = The Journal of Experimental Medicine | volume = 202 | issue = 2 | pages = 271–81271–281 | date = July 2005 | pmid = 16009717 | pmc = 2213000 | doi = 10.1084/jem.20050664 }}</ref>

Excess levels of factor XII can predispose individuals towards greater risk of [[venous thrombosis]] due to factor XII's role as one of the catalysts for conversion of plasminogen to its active fibrinolytic form of [[plasmin]].<ref name=isbn0-86542-446-2>{{cite book |title= Manual of Coagulation Disorders|last vauthors = Kroll|first= MichaelMH H.|year= 2001|publisher= Blackwell Science|isbn= 0-86542-446-2|pages= 3–4, 206–207}}</ref>

Hageman factor was first discovered in 1955 when a routine preoperative [[Sampling (medicine)|blood sample]] of the 37-year-old railroad brakeman John Hageman (1918) was found to have prolonged clotting time in test tubes, even though he had no [[Bleeding|hemorrhagic symptoms]]. Hageman was then examined by hematologist [[Oscar Ratnoff]], who found that Hageman lacked a previously unidentified clotting factor.<ref name="pmid13299324">{{cite journal | vauthors = Ratnoff OD, Margolius A | title = Hageman trait: an asymptomatic disorder of blood coagulation | journal = Transactions of the Association of American Physicians | volume = 68 | pages = 149–54149–154 | year = 1955 | pmid = 13299324 }}</ref> Ratnoff later found that the Hageman factor deficiency is an [[autosomal recessive]] disorder, after examining several related people who had the deficiency. Paradoxically, [[pulmonary embolism]] contributed to Hageman's death after an occupational accident in 1968. Since then, case studies and clinical studies identified an association between [[thrombosis]] and Factor XII deficiency. [[Hepatocytes]] express blood coagulation factor XII.<ref name="pmid2324612">{{cite journal | vauthors = Gordon EM, Gallagher CA, Johnson TR, Blossey BK, Ilan J | title = Hepatocytes express blood coagulation factor XII (Hageman factor) | journal = The Journal of Laboratory and Clinical Medicine | volume = 115 | issue = 4 | pages = 463–9463–469 | date = April 1990 | pmid = 2324612 }}</ref>

Currently produced [[QuikClot]] products, produced and marketed primarily for use in [[Battlefieldbattlefield Medicinemedicine]] to treat penetrating trauma (such as [[gunshot wounds]] and [[stab wounds]]), and other injuries that are known to commonly cause [[exsanguination]] (such as [[blast injury]]), are used with the overarching goal of increasing the time between the blood loss occurring, and the patient succumbing to the blood loss. The purpose of increasing this time is so that the patient may reaching a higher level of medical care before succumbing from their injuries. These products use a [[Kaolinite]]-based coating, applied to the bandages by the manufacturer before packaging and sale. This coating, when applied to an open wound via the application of the bandages, directly promotes blood clotting by activating Factor XII in the coagulation cascade. <ref>{{cite book | vauthors = Dee KC, Puleo DA, Bizios R., Madhavan G | title = Tissue-Biomaterialbiomaterial Interactionsinteractions. | location = Hoboken: | publisher = Wiley & Sons, | date = 2002. | isbn = 978-0-471-46112-8 }}</ref> Also, due to the [[Activeactive Ingredient]]ingredient nature of [[Kaolinite]], the activation of the Factor XII occurs in both an earlier amount of time than it otherwise would, and at an increased, more rapid rate than it otherwise would.<ref name="pmid21476127">{{cite journal | vauthors = Trabattoni D, Montorsi P, Fabbiocchi F, Lualdi A, Gatto P, Bartorelli A.AL | title = "A new kaolin-based haemostatic bandage compared with manual compression for bleeding control after percutaneous coronary procedures". Eur| Radiol.journal = European Radiology | volume = 2011;21:1687-1691 | issue = 8 | pages = 1687–1691 | date = August 2011 | pmid = 21476127 | doi = 10.1007/s00330-011-2117-3 | s2cid = 11755594 }}</ref><ref name="pmid20807305">{{cite journal | vauthors = Politi L, Aprile A, Paganelli C, etAmato al.A, Zoccai GB, Sgura F, Monopoli D, Rossi R, Modena MG, Sangiorgi GM | title = "Randomized clinical trial on short-time compression with kaolinKaolin-filled pad: a new strategy to avoid early bleeding and subacute radial artery occlusion after percutaneous coronary intervention". J| Intervenjournal Cardiol.= Journal of Interventional Cardiology | volume = 2011;24:65 | issue = 1 | pages = 65–72 | date = February 2011 | pmid = 20807305 | doi = 10.1111/j.1540-728183.2010.00584.x | hdl = 11380/649198 | hdl-access = free }}</ref> This coating is widely considered amongst [[combat medics]] to be vastly superior to the older [[QuikClot]] powder formulation, which was poured into wounds, due to the fact that the older formulation used bead-form [[Zeolite]], a mineral which promotes the coagulation cascade, due to the fact that the reaction between the Zeolite powder and the blood inside the wound site was an [[Exothermic]] one, sometimes so intensely that it caused cases of [[burn|second degree burns]] on the inside surface of the wound. This, obviously, caused extreme pain to the patient, often more-so than the initial injury was causing them at the time (assuming the patient was still [[conscious]] at the time of the application of the powder).<ref name="pmid15345965">{{cite journal | vauthors = Wright J.KJK, Kalns J, Wolf E.AEA, Traweek F, Schwarz S, Loeffler C.KCK, ...Snyder &W, Yantis LD, Eggers J (2004).| title = Thermal injury (see: [[Burns]]) resulting from application of a granular mineral hemostatic agent. | journal = The Journal of Trauma and| Acutevolume Care Surgery,= 57( | issue = 2), 224-230| pages = 224–230 | date = August 2004 | pmid = 15345965 | doi = 10.1097/01.ta.0000105916.30158.06 }}</ref> This effect is often seen in movies and TV programs, with the QuikClot powder being poured into wounds, and the patient screaming out in pain as their wounds were violently burned on the inside surface of the wounds. This created a common misconception, which persists to this day, that commonly used QuikClot products still use this method of clot promotion ([[Zeolite]] powder) to this day. However, Zeolite-based clotting products are no longer widely used by militaries and police departments throughout the western world, as they have been widely supplanted by the Kaolinite-based bandage products, which do not cause any exothermic reaction whatsoever, nor do they have the absolute-requirement of the application of the product exclusively to the inside-surface of the wound.

* {{cite journal | vauthors = Girolami A, Randi ML, Gavasso S, Lombardi AM, Spiezia F | title = The occasional venous thromboses seen in patients with severe (homozygous) FXII deficiency are probably due to associated risk factors: a study of prevalence in 21 patients and review of the literature | journal = Journal of Thrombosis and Thrombolysis | volume = 17 | issue = 2 | pages = 139–43139–143 | date = April 2004 | pmid = 15306750 | doi = 10.1023/B:THRO.0000037670.42776.cd | s2cid = 19336633 }}

* {{cite journal | vauthors = Renné T, Gailani D | title = Role of Factor XII in hemostasis and thrombosis: clinical implications | journal = Expert Review of Cardiovascular Therapy | volume = 5 | issue = 4 | pages = 733–41733–741 | date = July 2007 | pmid = 17605651 | doi = 10.1586/14779072.5.4.733 | s2cid = 41250936 }}

* {{cite journal | vauthors = Harris RJ, Ling VT, Spellman MW | title = O-linked fucose is present in the first epidermal growth factor domain of factor XII but not protein C | journal = The Journal of Biological Chemistry | volume = 267 | issue = 8 | pages = 5102–75102–5107 | date = March 1992 | pmid = 1544894 | doi = 10.1016/S0021-9258(18)42736-6 | doi-access = free }}

* {{cite journal | vauthors = McMullen BA, Fujikawa K, Davie EW | title = Location of the disulfide bonds in human plasma prekallikrein: the presence of four novel apple domains in the amino-terminal portion of the molecule | journal = Biochemistry | volume = 30 | issue = 8 | pages = 2050–62050–2056 | date = February 1991 | pmid = 1998666 | doi = 10.1021/bi00222a007 }}

* {{cite journal | vauthors = Miyata T, Kawabata S, Iwanaga S, Takahashi I, Alving B, Saito H | title = Coagulation factor XII (Hageman factor) Washington D.C.: inactive factor XIIa results from Cys-571----Ser substitution | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 86 | issue = 21 | pages = 8319–228319–8322 | date = November 1989 | pmid = 2510163 | pmc = 298272 | doi = 10.1073/pnas.86.21.8319 | doi-access = free | bibcode = 1989PNAS...86.8319M }}

* {{cite journal | vauthors = Bernardi F, Marchetti G, Patracchini P, del Senno L, Tripodi M, Fantoni A, Bartolai S, Vannini F, Felloni L, Rossi L | display-authors = 6 | title = Factor XII gene alteration in Hageman trait detected by TaqI restriction enzyme | journal = Blood | volume = 69 | issue = 5 | pages = 1421–41421–1424 | date = May 1987 | pmid = 2882793 | doi = 10.1182/blood.V69.5.1421.1421 | doi-access = free }}

* {{cite journal | vauthors = Cool DE, MacGillivray RT | title = Characterization of the human blood coagulation factor XII gene. Intron/exon gene organization and analysis of the 5'-flanking region | journal = The Journal of Biological Chemistry | volume = 262 | issue = 28 | pages = 13662–7313662–13673 | date = October 1987 | pmid = 2888762 | doi = 10.1016/S0021-9258(19)76478-3 | doi-access = free }}

* {{cite journal | vauthors = Que BG, Davie EW | title = Characterization of a cDNA coding for human factor XII (Hageman factor) | journal = Biochemistry | volume = 25 | issue = 7 | pages = 1525–81525–1528 | date = April 1986 | pmid = 3011063 | doi = 10.1021/bi00355a009 }}

* {{cite journal | vauthors = Royle NJ, Nigli M, Cool D, MacGillivray RT, Hamerton JL | title = Structural gene encoding human factor XII is located at 5q33-qter | journal = Somatic Cell and Molecular Genetics | volume = 14 | issue = 2 | pages = 217–21217–221 | date = March 1988 | pmid = 3162339 | doi = 10.1007/BF01534407 | s2cid = 7868690 }}

* {{cite journal | vauthors = Citarella F, Tripodi M, Fantoni A, Bernardi F, Romeo G, Rocchi M | title = Assignment of human coagulation factor XII (fXII) to chromosome 5 by cDNA hybridization to DNA from somatic cell hybrids | journal = Human Genetics | volume = 80 | issue = 4 | pages = 397–8397–398 | date = December 1988 | pmid = 3198120 | doi = 10.1007/BF00273661 | s2cid = 13428786 }}

* {{cite journal | vauthors = Henry ML, Everson B, Ratnoff OD | title = Inhibition of the activation of Hageman factor (factor XII) by beta 2-glycoprotein I | journal = The Journal of Laboratory and Clinical Medicine | volume = 111 | issue = 5 | pages = 519–23519–523 | date = May 1988 | pmid = 3361230 }}

* {{cite journal | vauthors = Chung DW, Fujikawa K, McMullen BA, Davie EW | title = Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeats | journal = Biochemistry | volume = 25 | issue = 9 | pages = 2410–72410–2417 | date = May 1986 | pmid = 3521732 | doi = 10.1021/bi00357a017 }}

* {{cite journal | vauthors = Cool DE, Edgell CJ, Louie GV, Zoller MJ, Brayer GD, MacGillivray RT | title = Characterization of human blood coagulation factor XII cDNA. Prediction of the primary structure of factor XII and the tertiary structure of beta-factor XIIa | journal = The Journal of Biological Chemistry | volume = 260 | issue = 25 | pages = 13666–7613666–13676 | date = November 1985 | pmid = 3877053 | doi = 10.1016/S0021-9258(17)38776-8 | doi-access = free }}

* {{cite journal | vauthors = McMullen BA, Fujikawa K | title = Amino acid sequence of the heavy chain of human alpha-factor XIIa (activated Hageman factor) | journal = The Journal of Biological Chemistry | volume = 260 | issue = 9 | pages = 5328–415328–5341 | date = May 1985 | pmid = 3886654 | doi = 10.1016/S0021-9258(18)89026-3 | doi-access = free }}

* {{cite journal | vauthors = Fujikawa K, McMullen BA | title = Amino acid sequence of human beta-factor XIIa | journal = The Journal of Biological Chemistry | volume = 258 | issue = 18 | pages = 10924–3310924–10933 | date = September 1983 | pmid = 6604055 | doi = 10.1016/S0021-9258(17)44364-X | doi-access = free }}

* {{cite journal | vauthors = Hovinga JK, Schaller J, Stricker H, Wuillemin WA, Furlan M, Lämmle B | title = Coagulation factor XII Locarno: the functional defect is caused by the amino acid substitution Arg 353-->Pro leading to loss of a kallikrein cleavage site | journal = Blood | volume = 84 | issue = 4 | pages = 1173–811173–1181 | date = August 1994 | pmid = 8049433 | doi = 10.1182/blood.V84.4.1173.1173 | doi-access = free }}

* {{cite journal | vauthors = Schloesser M, Hofferbert S, Bartz U, Lutze G, Lämmle B, Engel W | title = The novel acceptor splice site mutation 11396(G-->A) in the factor XII gene causes a truncated transcript in cross-reacting material negative patients | journal = Human Molecular Genetics | volume = 4 | issue = 7 | pages = 1235–71235–1237 | date = July 1995 | pmid = 8528215 | doi = 10.1093/hmg/4.7.1235 | url = https://boris.unibe.ch/115714/1/4-7-1235.pdf }}

* {{cite journal | vauthors = Hofferbert S, Müller J, Köstering H, von Ohlen WD, Schloesser M | title = A novel 5'-upstream mutation in the factor XII gene is associated with a TaqI restriction site in an Alu repeat in factor XII-deficient patients | journal = Human Genetics | volume = 97 | issue = 6 | pages = 838–41838–841 | date = June 1996 | pmid = 8641707 | doi = 10.1007/BF02346200 | s2cid = 9589165 }}

* {{cite web | title = Summary for peptidase S01.211: coagulation factor XIIa | work = The [[MEROPS]] online database for peptidases and their inhibitors: [http| url = https://meropswww.sangerebi.ac.uk/merops/cgi-bin/merops.cgipepsum?id=S01.211 | url-status = live | archive-url = https://web.archive.org/web/20211012174247/https://www.ebi.ac.uk/merops/cgi-bin/pepsum?id=S01.211] | archive-date=12 October 2021 }}