Clinical practice guideline of the spanish society of oral surgery for oral surgery in patients with coagulation disorders

e58 Med O al Pa ol O al Ci Bucal. 2024 Jan 1;29 (1):e58-66. O al su ge y and coagulopa hies Jou nal sec ion: O al Su ge y Publica ion Types: Resea ch Clinical p ac ice guideline o he spanish socie y o o al su ge y o o al su ge y in pa ien s wi h coagula ion diso de s Ja ie Valenzuela-Mencia 1, Ma ía Ángeles Se e a-Figallo 2, Daniel To es-Laga es 3, Guille mo Machuca- Po illo 4, Elena Sánchez-Fe nández 5, Edua d Valmaseda-Cas ellón 6, Ma ía Peña ocha-Diago 7, Nu ia Fe nández-Mos ei ín 8, José Manuel Somoza-Ma in 9, Alba Pé ez-Ja dón 10, Cin ia Micaela Chamo o- Pe onacci 11, Abel Ga cía-Ga cía 12 1 O al Su ge y eaching eam. Uni e si y o Se ille 2 Full P o esso in In eg a ed Den is y in Special Pa ien s, O al Medicine and O al Su ge y. Uni e si y o Se ille 3 Tenu ed P o esso o O al Su ge y. Uni e si y o Se ille 4 Tenu ed P o esso o Den is y in Special Pa ien s. Depa men o S oma ology. Facul y o Den is y. Uni e si y o Se ille 5 Full P o esso o O al Su ge y. Depa men o S oma ology. Facul y o Den is y. Uni e si y o G anada. 6 Tenu ed P o esso o Odon os oma ology. Facul y o Medicine and Heal h Sciences. Uni e si y o Ba celona. Resea che o he g oup “Den al and Maxillo acial Pa hology and The apeu ics” o he Biomedical Resea ch Ins i u e o Bell i ge (IDIBELL) 7 Full P o esso o O al Su ge y. Depa men o S oma ology. Facul y o Medicine and Den is y. Uni e si y o Valencia 8 Medical A ea Specialis in Haema ology and Haemo he apy. Haemos asis Depa men . Haema ology and Haemo he apy Se - ice. Miguel Se e Uni e si y Hospi al. Za agoza 9 Associa e P o esso . Depa men o Su ge y and Medical-Su gical Speciali ies. Facul y o Medicine and Den is y. Uni e si y o San iago 10 Heal h Resea ch Ins i u e o San iago de Compos ela (IDIS) 11 Heal h Resea ch Ins i u e o San iago de Compos ela; Uni e si y o San iago de Compos ela 12 Tenu ed P o esso o S oma ology. Facul y o Medicine and Den is y. Uni e si y o San iago de Compos ela. Heal h Resea ch Ins i u e o San iago de Compos ela. Head o he Maxillo acial Su ge y Se ice o he Uni e si y Hospi al Clinic o San iago de Compos ela o he Galician Heal h Se ice (SERGAS) Co espondence: c/ En e ios S/N, 15706 San iago de Compos ela. Spain cin ia.chamo [email protected] Recei ed: 04/04/2023 Accep ed: 08/05/2023 Abs ac Backg ound: The numbe o pa ien s ea ed wi h coagula ion diso de s, and mo e speci ically wi h an icoagulan he apy, has inc eased wo ldwide in ecen yea s due o inc eased li e expec ancy in de eloped coun ies. The p o ocols o managing his ype o pa ien in o al su ge y has a ied o e ecen yea s, especially a e he appea - ance o new di ec -ac ing o al an icoagulan s (DOACs). The assessmen o isk o bleeding in his ype o pa ien when unde going a su gical p ocedu e con inues o be a con o e sial issue o pa ien s, den is s and gene al p ac- i ione s. The objec i e o his documen is o o e ecommenda ions, based on e idence, o decision making o pa ien s wi h coagulopa hies who equi e den al su gical in e en ion. doi:10.4317/medo al.26063 Valenzuela-Mencia J, Se e a-Figallo MÁ, To es-Laga es D, Machu- ca-Po illo G, Sánchez-Fe nández E, Valmaseda-Cas ellón E, e al. Clinical p ac ice guideline o he spanish socie y o o al su ge y o o al su ge y in pa ien s wi h coagula ion diso de s. Med O al Pa ol O al Ci Bucal. 2024 Jan 1;29 (1):e58-66. A icle Numbe :26063 h p://www.medicinao al.com/ © Medicina O al S. L. C.I.F. B 96689336 - pISSN 1698-4447 - eISSN: 1698-6946 eMail: [email p o ec ed] Indexed in: Science Ci a ion Index Expanded Jou nal Ci a ion Repo s Index Medicus, MEDLINE, PubMed Scopus, Embase and Emca e Indice Médico Español e59 Med O al Pa ol O al Ci Bucal. 2024 Jan 1;29 (1):e58-66. O al su ge y and coagulopa hies In oduc ion The numbe o pa ien s wi h coagula ion diso de s, and wi h an icoagulan he apy, has inc eased wo ld- wide in ecen yea s due o inc eased li e expec ancy in de eloped coun ies. (1). In ac , couma in de i a i es and i amin K an agonis s (VKAs) such as Wa a in (Aldocuma ®) and acenocouma ol (Sin om®) a e wo o he 100 medica ions mos p esc ibed in de el- oped coun ies (2). Al hough VKAs ha e been he gold s anda d an icoagulan ea men o o e 60 yea s, in ecen decades, new di ec -ac ing o al an icoagulan s (DOACs) ha e p og essi ely been in oduced, whose e ec s a e mo e p edic able as hey ha e a b oade he apeu ic ange (3). Managemen o pa ien s wi h coagula ion diso de s, whe he acqui ed o congeni al, con inues o be an issue ha conce ns pa ien s, den is s and gene al p ac i io- ne s (4,5). P o essionals who mus decide he guidelines o managing hese pa ien s, abo e all wi h ega d o con inua ion o an icoagulan /an iagg egan ea men when hey will unde go a su gical p ocedu e (6), ha e doub s due o he p o ocols ha ing unde gone a ia ions in a ela i ely sho pe iod o ime (7-9). Den al ex ac ion is a common p ocedu e, and in he case o an icoagula ed pa ien s, den is s usually consul he need o al e he medica ion guidelines due o he pe cei ed isk o po en ial uncon olled bleeding a e he den al ea men (10). Shi e al. (2017) ca ied ou a me a-analysis which included s udies wi h an icoagula - ed pa ien s wi h VKAs and DOACs and asce ained ha he isk o pos ope a i e bleeding in an icoagula ed pa- ien s was g ea e (RR: 2,7) in compa ison wi h heal hy indi iduals. Ne e heless, he ela i e isk was signi i- can ly g ea e o pa ien s ea ed wi h VKAs (RR=3) han o hose ea ed wi h DOACs (RR=1.6) (11). I mus be aken in o accoun ha cu en clinical p ac- ice guidelines o pa ien s wi h coagula ion diso de s a e based on s udies ca ied ou in di e en geog aphic a eas o he wo ld, whose idiosync asies equi e a c i i- cal iew o allow ex apola ion o he esul s globally o ou daily p ac ice. The majo i y o he li e a u e a ail- able on he haemo hagic isk o an icoagula ed pa ien s who equi e a den al ex ac ion and a e ea ed wi h a couma in d ug e ol e a ound Wa a in (12-15), how- e e , in Spain he couma in d ug used mos is aceno- couma ol (16). Ano he signi ican aspec is he de e mina ion o he ideal INR (In e na ional No malized Ra io) alue o ea ing pa ien s. Some clinical guidelines o man- aging an icoagula ed pa ien s, such as he Sco ish Den al Clinical E ec i eness P og amme (SDCEP) a ailable on h ps://www.sdcep.o g.uk/media/ypnl- 2cpz/sdcep-managemen -o -den al-pa ien s- aking- an icoagulan s-o -an ipla ele -d ugs-2nd-edi ion.pd , ecommend no al e ing he an icoagulan ea men guidelines in pa ien s who ha e an INR lowe han 4, i being ecommended ha his INR is de e mined in he 24 hou s p io o he den al ea men o wi h alidi y o up o 72 hou s i i s alue is usually s able o e ime. Howe e , almos hal o an icoagula ed pa ien s p esen di icul ies achie ing adequa e con ol o INR (Spanish Fede a ion o An icoagula ed Pa ien Associa ions). In o he Spanish guidelines, such as ha published by he Spanish Socie y o Ca diology and he Spanish Soci- e y o Epidemiology and Public Heal h, his alue is educed o an INR o 3, ecommending no o ea he pa ien wi hou consul ing he doc o and adjus ing he dose o he an icoagulan in case o p esen ing a g ea e INR. In line wi h he main guidelines on ca diology a a global le el, i is conside ed ha he desi ed INR in pa ien s unde an icoagulan ea men mus be be- ween 2 and 3 (17). Due o e e y hing desc ibed abo e, his Clinical P ac- ice Guideline (CPG) has been p epa ed by he Span- ish Socie y o O al Su ge y (SECIB) wi h he in en ion o p esen ing an e alua ion o he cu en e idence on pa ien s wi h coagula ion diso de s and helping p o es- sionals o heal h sciences o make clinical decisions. Ma e ial and Me hods: Based on he indica ions o he “P epa a ion o Clinical P ac ice guidelines in he Na ional Heal h Sys em. Me hodological manual”, we ga he ed a g oup o expe s who ag eed on 15 PICO ques ions based on managing pa ien s wi h coagula ion diso de s in den al su gical p ocedu es, such as i ing o implan s o den al ex ac ions. Resul s: The 15 PICO ques ions we e answe ed based on he a ailable e idence, being limi ed in mos cases due o he lack o a con ol g oup. Two o he PICO ques ions we e answe ed by he expe s wi h a g ade C ecommenda ion, while he es we e answe ed wi h g ade D. Conclusions: The esul s o his e iew highligh he need o unde ake well designed clinical ials wi h con ol g oups and wi h a ep esen a i e sample size. Key wo ds: O al su ge y, coagulopa hies, den al ex ac ion, den al implan , o al an icoagulan s, hepa in, wa a in, acenocouma ol. e60 Med O al Pa ol O al Ci Bucal. 2024 Jan 1;29 (1):e58-66. O al su ge y and coagulopa hies and conc e e me hodology o he bibliog aphic sea ch based on: a) sea ches in da abases such as MEDLINE/ PubMed, EMBASE, Coch ane Lib a y; b) he subjec heading wi h he sea ch e ms and o he Boolean ope a- o s (AND, OR, NOT), as well as he use o keywo ds, Em ee and MeSH; and c) he sea ch esul s indexing all bibliog aphic e e ences. 6) E alua ion and syn he- sis o he e idence: He e he esul o he e alua ion o each one o he s udies e e enced in he p e ious sec- ion is lis ed. The analysis discussed de e mines he quali y o he scien i ic e idence on which we will base he ecommenda ions made and which i will subse- quen ly be necessa y o know o de ine he “s eng h” o he ecommenda ion. To ca y ou he analysis, we use e i ica ion empla es o checklis s o he Sco ish In e collegia e Guidelines Ne wo k (SIGN) a ailable on h ps://www.sign.ac.uk/media/2038/sign50_2019.pd , o e alua e he andomised clinical ials (RCT), sys- ema ic e iews and me a-analysis, coho s udies, case- con ol s udies, s udies o diagnos ic es s and economic e alua ions; OSTEBA da ashee s o e alua ing case se ies and he AGREE ools o e alua ing he CPGs. 7) P epa a ion o conclusions: This inal poin includes he ecommenda ions ha he g oup o mula es on he ini ial PICO clinical ques ion, as well as he g ade o his ecommenda ion. The ools ha he au ho s ha e used o ca y ou his ecommenda ion (e alua ing he quali y o he e idence and g ading he s eng h o he ecommenda ion) a e called SIGN, om he Ox o d Cen e o E idence-Based Medicine (CEBM), he wo ha ha e been used being speci ically: he Modi- ied SIGN o issues on diagnosis, and he SIGN o he es o he issues ( ea men , p ognosis, ae iology, e c.). A e ca aloguing each piece o e idence ound which esponds o a PICO ques ion, we gi e hem a deg ee o ecommenda ion, classi ied by he le e A, B, C o D and whose meaning can be obse ed in Table 1. Ma e ial and Me hods The g oup o au ho s o his CPG has ollowed a ig- o ous me hodological p ocess o i s p epa a ion, based on he indica ions o he documen “P epa a- ion o Clinical P ac ice Guidelines in he Na ional Heal h Sys em. Me hodological manual” o he wo k- ing g oup o upda ing he Manual o he P epa a ion o Clinical P ac ice Guidelines in he Spanish Na ional Heal h Sys em, and he ecommenda ions a ailable on GuíaSalud (h ps://po al.guiasalud.es/wp-con en / uploads/2019/01/manual_gpc_comple o.pd ). and he ecommenda ions a ailable on GuíaSalud. Likewise, he scien i ic bibliog aphy a ailable om Decembe 2011 o Decembe 2021 has been e iewed, ollowing he sea ch s a egies included in he CPG (h ps://po - al.guiasalud.es/wp-con en /uploads/2023/03/gpc_622_ ci ugia_bucal_ as o nos_coagulacion_secib_compl. pd ). Addi ionally, o each clinical issue aised, a wo k shee was c ea ed (own c ea ion) in which he ollow- ing aspec s we e de ailed: 1) Clinical doub : Issue on which he au ho s o mula e he clinical ques ion, and which a ises om expe knowledge on he subjec ma - e and he p o essional expe ience o each o hem. 2) PICO ques ion: Ques ion which aises he clinical is- sue, and which is s uc u ed so as o inco po a e he Pa ien (o a ge popula ion o whom he in e en ion is in ended), he In e en ion/Compa ison (in e en ion measu ed as a compa ison o no wi h ano he ca ied ou ) and Ou come (expec ed esul upon applying he indica ed in e en ion). 3) In oduc ion: Con ex ualisa- ion o he scien i ic knowledge ha exis s in ela ion wi h he speci ic pa hology on he clinical doub aised, accompanied by he PICO ques ion and he ecommen- da ion. 4) Type o ques ion: Classi ica ion o he ype o ques ion om he ollowing possibili ies: epidemiologi- cal/e iological, diagnos ic, he apeu ic o p ognos ic. 5) Me hodology used: This sec ion desc ibes he speci ic G ade o ecommenda ion ABased on a leas a me a-analysis, a sys ema ic e iew, a 1++ clinical ial, o on a olume o scien i ic e idence made up o s udies classi ied as 1+ and o high consis ency wi h each o he . BVolume o scien i ic e idence made up o s udies classi ied as 2++, di ec ly applicable o he a ge popula ion o he guideline and demons a ing high consis ency wi h each o he ; o scien i ic e idence ex apola ed om s udies classi ied as 1++ o 1+. CVolume o scien i ic e idence made up o s udies classi ied as 2+ di ec ly applicable o he a ge popula ion o he guideline and demons a ing high consis ency wi h each o he ; o scien i ic e idence ex apola ed om s udies clas- si ied as 2++. DLe el 3 o 4 scien i ic e idence o scien i ic e idence ex apola ed om s udies classi ied as 2+. Table 1: Summa y o e idence and ecommenda ions on clinical p ac ice acco ding o GRADE (G ading o Recommenda ions, Assessmen , De elopmen , and E alua ions). e61 Med O al Pa ol O al Ci Bucal. 2024 Jan 1;29 (1):e58-66. O al su ge y and coagulopa hies 8) Recommenda ions o u u e esea ch: In he p ocess o p epa ing a CPG, knowledge gaps a e iden i ied o which he au ho s may conside i necessa y o ecom- mend u u e lines o esea ch, i hey conside hem pe - inen o pa ien s and p o essionals. In ou case, hese p oposals a e in ended o be as speci ic as possible so ha hey a e use ul and unde s andable o u u e e- sea ch p ojec s. - De elopmen g oup o he guideline The SECIB is a scien i ic associa ion c ea ed o o e adequa e suppo o all p o essionals who call o an up- o-da e scien i ic space o O al Su ge y. To ul il i s objec i es, he Associa ion has commissioned a g oup o expe s wi h de eloping a CPG on managing pa ien s wi h coagula ion diso de s in den al su gical p oce- du es, such as i ing o implan s o den al ex ac ions. This Guideline has been c ea ed add essing di e en cases o co e he wides ange o possible scena ios ha o al heal h p o essionals ace wi h his ype o pa- ien . The g oup ha has p epa ed his CPG is made up o clinical and uni e si y expe s o he heal h sciences depa men : specialis s in o al su ge y wi h ex ensi e ca ee s in eaching and esea ch, specialis s in he ield o haema ology and haemo he apy, p o essionals wi h ex ensi e expe ience in managing pa ien s wi h coagu- la ion diso de s in o al su gical p ocedu es, expe s in o al su ge y, o al medicine and enowned esea che s. This CPG has been p epa ed and e alua ed based on he scien i ic e idence a ailable and is in ended o be use- ul o pa ien s and p o essionals om di e en ields: den is s, s oma ologis s, o al su geons, maxillo acial su geons, doc o s and clinical specialis s o he heal h sciences depa men . - Exhaus i e sea ch o scien i ic e idence The i s app oach o he bibliog aphy h ough he MEDLINE/PubMed da abase con ibu ed o de ining he scope and objec i es o he guideline. A i s p e- limina y sea ch o he bibliog aphy was ca ied ou be ween Sep embe and Oc obe 2021. The e e ences we e downloaded on he Mendeley manage , and hanks o he e iew by he panel o expe s i was possible o de ec he impo an e e ences ha had been omi ed. The second phase o he sea ch began in Oc obe 2021, once he ini ial app oach had been e alua ed and i was conside ed necessa y o ede ine bo h he sea ch c i e ia and he scope o he guidelines hemsel es. The c i e- ia o de eloping he ques ions in PICO o ma we e de eloped, a ask ca ied ou om No embe 2019 o Sep embe 2021, bu which con inued being comple ed un il Decembe 2021 hanks o weekly ale s, o upda e he ma e ial. The comple e ex s o hese e e ences we e sha ed wi h he panel o expe s h ough Mende- ley. F om he exhaus i e sea ch o he bibliog aphy, he ques ions we e cons uc ed gene a ing lis s o speci ic issues which could be conside ed. C i e ia o inclusion and exclusion we e also de ined: in gene al, any e e - ence which was no w i en in English, F ench o Span- ish was excluded, and he publica ion da e was limi ed o he las 10 yea s. Finally, a selec ion was ca ied ou on he i les and abs ac s o he a icles iden i ied in he sea ches o elimina e hose which did no ul il he sea ch c i e ia. Wi h ega d o sou ces o in o ma ion, MEDLINE ( h ough i s PubMed in e ace) and he EMBASE da abase we e used. Sea ch s a egies we e de eloped o bo h wi h he pu pose o es ic ing o b oadening he scope: combina ion o con olled lan- guage ocabula y ( he MeSH and Em ee hesau uses) and e ms in ee language o ph ases which appea ed in i les o abs ac s. The e e ences we e s o ed in a p i a e g oup on Mendeley, h ough which he e was access o he ull ex , wi h a display o ma king and making anno a ions on he e e ences. The a icles we e pas ed in o he ull ex di ec ly on he Mendeley e - e ence manage . Using he Mendeley social module, e iewe s we e also able o check whe he any o he a icle had been published and add hei commen s. Addi ionally, o each one o he e e ences, Mendeley di ec ly loaded he associa ed ags, bu added a gene al ag o iden i ying o which PICO ques ion o ques- ions ha e e ence co esponded, as well as he ype o s udy (clinical ial, sys ema ic e iew, me a-analysis, e c.). Finally, a inal documen was p epa ed wi h all he e e ences co esponding o each PICO ques ion o he CPG. The sea ch s a egies we e e iewed ollowing he documen by Sampson e al. “An e idence- based p ac- ice guideline o he pee e iew o elec onic sea ch s a egies” (18). Resul s 1. In an icoagula ed pa ien s wi h a couma in d ug (acenocouma ol o wa a in) who equi e a den al ex- ac ion, is he e an inc eased haemo hagic isk in compa ison wi h non-an icoagula ed pa ien s? And wha i hey a e also aking an iagg egan medica ion? Den al ex ac ion in an icoagula ed pa ien s wi h di- couma inics appea s p edic able i he INR anges a e con olled, ex ac ing a single oo h and applying local haemos a ic measu es o con ol he haemo hage. The isk o pos ope a i e bleeding o hese pa ien s appea s simila o he isk o heal hy indi iduals when he INR alue does no exceed 2.2. I we ake in o accoun o he condi ions such as INR g ea e han 3 o se e al ex ac- ions, he e idence a ailable is limi ed o answe ing his ques ion, he e o e in hese cases i is ecommended o con ac he pa ien ’s doc o o decide a ea men plan (G ade C ecommenda ion). Wi hou doub , in his e- iew we ha e lacked mo e s udies on acenocouma ol, as he majo i y included pa ien s ea ed wi h wa a in o did no speci y he i amin K an agonis medica ion adminis e ed. The s udies designed o assess he isk o e62 Med O al Pa ol O al Ci Bucal. 2024 Jan 1;29 (1):e58-66. O al su ge y and coagulopa hies bleeding mus e y clea ly de ine aspec s such as: he moni o ing ime o he pa ien , which we ecommend being a leas 7 days; he main isk a iable, which we ecommend being den al ex ac ion, as he medical con- di ion o he pa ien may a y a di e en imes; he INR ange ha will be es ablished o include an icoagula ed pa ien s; he a ge popula ion (as he polymo phism o isoenzyme CYP2C9 p e alen in he Asian popula ion a ec s he clea ance o wa a in); as well as also egis- e ing whe he he pa ien has p e iously been ea ed wi h an ibio ics and concomi an ea men wi h pla ele an iagg egan s. 2. In an icoagula ed pa ien s wi h hepa in who equi e a den al ex ac ion, wha inc ease in haemo hagic isk exis s in compa ison wi h non-an icoagula ed pa ien s? And wha i hey a e also aking an iagg egan medica- ion? E idence on den al ex ac ions in pa ien s ea ed wi h hepa in mos ly e e s o an icoagula ed pa ien s wi h acenocouma ol who ha e been ea ed wi h b idge he apy wi h hepa in o a den al ex ac ion. Publica- ions appea o e lec an inc eased isk o bleeding in compa ison wi h he guideline o con inue wi h he an i- coagulan ea men . Ne e heless, i appea s ha local haemos a ic measu es should be su icien o manag- ing o con ain he pos -ex ac ion haemo hage in any case (G ade D ecommenda ion). I mus be aken in o accoun ha he e idence o hese esul s is limi ed, and i should be expec ed ha in ligh o e iewed publi- ca ions, his li e a u e will dec ease, as he guideline o no eplacing he an icoagulan ea men wi h subcu a- neous hepa in appea s o ha e mo e p edic able esul s. 3. In an icoagula ed pa ien s wi h DOACs who equi e a den al ex ac ion, wha inc ease in haemo hagic isk exis s in compa ison wi h non-an icoagula ed pa ien s? And wha i hey a e also aking an iagg egan medica- ion? The e idence on isk o pos ope a i e bleeding a e den al ex ac ions in pa ien s ea ed wi h DOACs ap- pea s o demons a e an inc eased isk o bleeding in compa ison wi h heal hy indi iduals (G ade D ecom- menda ion). Ne e heless, he e idence o hese esul s is limi ed and he e ogeneous. In he majo i y o he a - icles included he e is no a signi ican ep esen a ion o pa ien s ea ed wi h DOACs o o all ypes comme - cialised in Spain. The majo i y o s udies a e e ospec- i e and apply di e en p o ocols in hese pa ien s, such as he con inua ion o he ea men , he in e up ion o he dose on he day o su ge y o suspension up o 5 days be o e he ex ac ion. This makes con olled clini- cal ials wi h a ep esen a i e sample size o all ypes o DOACs and heal hy indi iduals necessa y. 4. In an icoagula ed pa ien s wi h a couma in d ug (acenocouma ol o wa a in) who equi e i ing o den- al implan s, is he e an inc eased haemo hagic isk in compa ison wi h non-an icoagula ed pa ien s? And wha i hey a e also aking an iagg egan medica ion? The con inua ion o he an icoagulan ea men in pa- ien s unde going simple p ocedu es in i ing implan s does no en ail a signi ican inc ease in he isk o haem- o hages compa ed wi h s opping o educing he ea - men , he e o e i s suspension is no jus i ied (G ade D ecommenda ion). Fu u e lines o esea ch should s udy he po en ial e ec o o al an icoagulan s on he isk o haemo hages h ough andomised clinical ials wi h an adequa e sample size, e alua ing he e ec o his ype o medica ion on pa ien s unde going i ing o im- plan s o allow alid conclusions o be ob ained. These ials should be ca ied ou wi h pa ien s unde going only implan su ge y, as i he pa ien s a e unde going di e en su gical echniques hese esul s a e no con- clusi e o any o hem. Addi ionally, i should be e alu- a ed whe he he join use o o al an icoagulan s and an iagg egan medica ion al e s he haemo hagic isk, o he eby be able o c ea e p o ocols which guide clini- cal p ac ice. Likewise, i should be compa ed be ween pa ien s who con inue hei an icoagulan ea men and hose who s op i , o he eby be able o ob ain esul s wi h su icien scien i ic e idence o con ibu e o guid- ing clinical p ac ice. 5. In an icoagula ed pa ien s wi h hepa in who equi e i ing o den al implan s, wha inc ease in haemo - hagic isk exis s in compa ison wi h non-an icoagula - ed pa ien s? And wha i hey a e also aking an iagg e- gan medica ion? T ea men wi h hepa in in pa ien s unde going simple p ocedu es in he i ing o implan s does no en ail a signi ican inc ease in he isk o haemo hages, he e- o e hei con inua ion du ing his ype o su ge y is ecommended (G ade D ecommenda ion). The subs i- u ion o he o al an icoagulan wi h hepa in in pa ien s unde going simple p ocedu es in he i ing o implan s does no o e bene i s wi h ega d o he isk o haem- o hages, he e o e his ac ion is no jus i ied. (G ade D ecommenda ion). Fu u e lines o esea ch should s udy he po en ial e ec o hepa in on he isk o haemo - hages h ough andomised clinical ials, e alua ing he e ec o his ype o medica ion on pa ien s unde - going i ing o implan s o allow alid conclusions o be ob ained. These ials should include a la ge sample o pa ien s, as well as g oups whe e he e is a compa ison be ween he con inua ion o he ea men wi h hepa- in, s opping his ype o he apy and a con ol g oup, o be able o analyse whe he hese si ua ions al e he isk o haemo hages. Addi ionally, i should be e alu- a ed whe he he join use o hepa in and an iagg egan medica ion al e s he isk o haemo hages, o he eby be able o c ea e p o ocols which guide clinical p ac ice. 6. In an icoagula ed pa ien s wi h a di ec -ac ing o al an icoagulan (DOAC) who equi e i ing o den al im- e63 Med O al Pa ol O al Ci Bucal. 2024 Jan 1;29 (1):e58-66. O al su ge y and coagulopa hies plan s, is he e an inc eased haemo hagic isk in com- pa ison wi h non-an icoagula ed pa ien s? And wha i hey a e also aking an iagg egan medica ion? Pa ien s being ea ed wi h di ec -ac ing o al an icoag- ulan s may be ea ed sa ely wi h osseoin eg a ed im- plan s. In aope a i e bleeding may be sligh ly g ea e , al hough pos ope a i e bleeding appea s o be simila o ha o pa ien s who do no ake an icoagulan s (G ade D ecommenda ion). The e is no clinical in o ma ion o de e mining he e ec ha he addi ional admin- is a ion o a pla ele an iagg egan may ha e on hese pa ien s. Fu he s udies should be ca ied ou includ- ing la ge samples, as he cu en samples only ha e a limi ed numbe o cases. I would also be necessa y o inc ease he me hodological quali y o he s udies, as he e a e nume ous biases which limi he s eng h o he ecommenda ions. 7. In pa ien s wi h he edi a y coagulopa hies who e- qui e a den al ex ac ion, wha inc ease in haemo hagic isk exis s in compa ison wi h heal hy indi iduals? And wha abou in pa ien s who equi e den al implan s? The e is no su icien in o ma ion on he inc eased isk o in aope a i e o pos ope a i e bleeding in pa- ien s wi h he edi a y coagulopa hies in compa ison wi h heal hy indi iduals in den al ex ac ion o implan ea men s. Den al ex ac ions may be ca ied ou a - e e alua ing he se e i y o he coagulopa hy. In he mos se ious cases, i is necessa y o gua an ee a mini- mum ac o be o e he den al ex ac ion. Cases o hae- mophilia wi h inhibi o an ibodies mus be conside ed se ious and may equi e g ea e p epa a ion o he pa- ien . The e o e, he e is no su icien da a on he ea - men wi h den al implan s in pa ien s wi h he edi a y/ congeni al coagulopa hies, such as haemophilia o Von Willeb and disease. Ne e heless, den al implan s may be i ed, as he isk o bleeding appea s lowe han o den al ex ac ions (G ade D ecommenda ion). The e- o e, i mus be conside ed whe he i is necessa y o ca y ou gene al anaes hesia o seda ion, a oid unk anaes hesia echniques, ca y ou a h ee-dimensional diagnosis wi h compu ed omog aphy, and ake mea- su es o p e en bleeding (local haemos a ic measu es and e alua ing sys emic measu es such as coagula ion ac o s) be o e, du ing and a e he in e en ion (G ade D ecommenda ion). In any case, an indi idual e alua- ion o he case should be ca ied ou wi h he haema ol- ogy uni o haemophilia cen e. S udies wi h a la ge amoun o e idence should be ca ied ou , because o da e only case se ies, isola ed clinical cases, documen s by expe s and a clinical p ac ice guideline a e a ail- able, and he e o e he e a e no s udies wi h g ade 2 e idence. Speci ic s udies should be ca ied ou o se- lec la ge samples o pa ien s wi h each coagulopa hy, especially he mos equen , such as haemophilia A and Von Willeb and disease, in o de o p epa e p o ocols o speci ic guidelines o each one. The me hodological quali y o he s udies should also be inc eased, design- ing obse a ional s udies ha may o e a minimum o g ade 2 e idence. 8. In an icoagula ed pa ien s wi h a couma in d ug (acenocouma ol o wa a in) who equi e a den al ex- ac ion, wha educ ion o haemo hagic isk is p o- duced by local haemos a ic measu es in compa ison wi h non-an icoagula ed pa ien s? And wha i hey a e also aking an iagg egan medica ion? In an icoagula ed pa ien s unde going simple ex ac- ions i is no ecommended o s op he an icoagulan ea men , ecommending he applica ion o local hae- mos a ic measu es (G ade C ecommenda ion). No lo- cal haemos a ic measu e has been demons a ed as supe io o he o he s, he e o e i is ecommended o use hose which ha e mo e e idence, such as su u es, collagen o cellulose sponges, as well as comp ession wi h gauze soaked in anexamic acid (G ade C ecom- menda ion). The appea ance o pos ope a i e haemo - hages is associa ed wi h he age o he pa ien , he e o e in olde pa ien s unde going simple ex ac ions he use o local haemos a ic measu es is ecommended (G ade C ecommenda ion). Fu u e lines o esea ch should s udy he e ec o di e en local haemos a ic measu es h ough andomised clinical ials e alua ing he e ec o hese measu es on an icoagula ed pa ien s unde - going ex ac ions o allow alid conclusions o be ob- ained. These ials mus be ca ied ou on la ge samples o pa ien s whe e he an icoagula ion is no s opped and wi h INR in he ange ecommended in he main guide- lines and p o ocols. Wi h ega d o he abo e, pa ien s wi h an INR o be ween 2 and 4 should be included, as i is common o ind pa ien s wi h INR le els o e 3, and o he eby be able o e alua e whe he hese haemos a ic measu es con inue o be e ec i e o such INR alues. Addi ionally, he e ec i eness o hese haemos a ic measu es should be s udied in pa ien s who combine an icoagulan and an iagg egan ea men , o he eby be able o c ea e p o ocols which guide clinical p ac ice in his ype o pa ien . 9. In an icoagula ed pa ien s wi h hepa in who equi e a den al ex ac ion, wha educ ion o haemo hagic isk is p oduced by local haemos a ic measu es in compa i- son wi h non-an icoagula ed pa ien s? And wha i hey a e also aking an iagg egan medica ion? Due o he cu en lack o e idence, u u e lines o e- sea ch should ocus on being able o answe his PICO ques ion h ough well designed clinical ials e alua - ing he e ec i eness o he di e en local haemos a ic measu es in pa ien s ea ed wi h hepa in unde going ex ac ions. In an icoagula ed pa ien s wi h hepa in and unde going ex ac ions, i is ecommended o ca y ou an exhaus i e anamnesis o he pa ien o asce ain he ime hey ha e been ea ed and o p ecisely know he e64 Med O al Pa ol O al Ci Bucal. 2024 Jan 1;29 (1):e58-66. O al su ge y and coagulopa hies hal -li e o he hepa in used. The su gical p ocedu e should be ca ied ou a he ime o maximum dec ease o he plasma concen a ions o he d ug, o hen con- inue wi h he an icoagulan ea men , simul aneously applying local haemos a ic measu es, such as comp es- sion wi h d y gauze o p e e ably soaked in anexamic acid, he su u e o he wound o he use o di e en ypes o haemos a ic sponges o d essings (G ade D ecommenda ion). 10. In an icoagula ed pa ien s wi h DOACs who equi e a den al ex ac ion, wha educ ion o haemo hagic isk is p oduced by he local measu es in compa ison wi h non-an icoagula ed pa ien s? And wha i hey a e also aking an iagg egan medica ion? Due o he lack o quali y scien i ic e idence in he li - e a u e on his issue, an expe opinion is p oposed. In an icoagula ed pa ien s wi h a di ec an icoagulan d ug and unde going ex ac ions, i is ecommended o p e- cisely know he hal -li e o he d ug used, he den al ex ac ion ha ing o be ca ied ou a he ime o maxi- mum dec ease o he plasma concen a ions o he spe- ci ic an icoagulan , delaying i s adminis a ion a leas 4 hou s a e he ex ac ion, simul aneously applying lo- cal haemos a ic measu es such as su u es, di e en hae- mos a ic sponges o d essings, o comp ession wi h d y gauze o p e e ably soaked in anexamic acid (G ade D Recommenda ion). Taking in o accoun he cu en limi ed e idence and i s me hodology, u u e lines o esea ch should ocus on being able o answe his PICO ques ion h ough well designed clinical ials e alua - ing he e ec i eness o he di e en local haemos a ic measu es in pa ien s ea ed wi h di ec an icoagulan s unde going ex ac ions compa ed wi h heal hy con ols and wi h an adequa e sample size. 11. In an icoagula ed pa ien s wi h a couma in d ug (acenocouma ol o wa a in) who equi e a den al ex- ac ion, wha educ ion o haemo hagic isk is p o- duced he PHARMACOLOGICAL TREATMENT in compa ison wi h non-an icoagula ed pa ien s? And wha i hey a e also aking an iagg egan medica ion? Due o he lack o quali y scien i ic e idence in he li - e a u e on his issue, an expe opinion is p oposed. In an icoagula ed pa ien s wi h a couma in d ug and un- de going ex ac ions he con inua ion o he o al an i- coagulan ea men is ecommended, wi h concomi an use o local haemos a ic measu es consis ing o su u es, comp ession wi h d y gauze o p e e ably soaked in anexamic acid, haemos a ic sponges o d essings, wi hou he need o use pha macological ea men o educe he haemo hagic isk (G ade D ecommenda- ion). Fu u e lines o esea ch should ocus on being able o answe his PICO ques ion h ough well de- signed clinical ials e alua ing he e ec i eness o he di e en pha macological ea men s aimed a p omo - ing haemos asis in an icoagula ed pa ien s wi h couma- in d ugs unde going ex ac ions. 12. In an icoagula ed pa ien s wi h hepa in who e- qui e a den al ex ac ion, wha educ ion o haemo - hagic isk is p oduced by he PHARMACOLOGICAL TREATMENT in compa ison wi h non-an icoagula ed pa ien s? And wha i hey a e also aking an iagg egan medica ion? In an icoagula ed pa ien s wi h hepa in and unde go- ing ex ac ions i is ecommended o use local hae- mos a ic measu es consis ing o su u es, comp ession wi h d y gauze o p e e ably soaked in anexamic acid, haemos a ic sponges o d essings, wi hou he need o use pha macological ea men o educe he haemo - hagic isk (G ade D ecommenda ion). Fu u e lines o esea ch should ocus on being able o answe his PICO ques ion h ough well designed clinical ials e alua - ing he e ec i eness o he di e en pha macological ea men s aimed a p omo ing haemos asis in pa ien s ea ed wi h hepa in unde going ex ac ions. 14. In pa ien s wi h he edi a y coagulopa hies who e- qui e a den al ex ac ion, wha educ ion in haemo - hagic isk is p oduced by local haemos a ic measu es in compa ison wi h heal hy indi iduals? And wha abou in pa ien s who equi e den al implan s? When making a ecommenda ion on his issue, he e is no a icle ha has ully add essed he PICO ques- ion ha we aise, as none ha e s udied he educ ion o haemo hagic isk in compa ison wi h heal hy indi- iduals. The le el o ecommenda ion o his sec ion is he opinion o he expe s signing he guideline (G ade D ecommenda ion). Wi h ega d o pu ely mechanical measu es, we ha e no ound bibliog aphy whe e hey a e applied only o he haemo hagic con ol, as oday hey a e usually used wi h obliga o y consul a ion o he haema ologis and combined wi h pha macological measu es. The e a e ha dly any s udies in his g oup o pa ien s o whom den al implan s a e i ed, he e o e he e idence is insu icien . Among he mos impo - an conside a ions a e: he p epa a ion o a ea men plan a e p epa ing he clinical his o y and consul ing he haema ologis , he ea men being ca ied ou i s hing in he mo ning and a he s a o he week, and unde aking he den al p ocedu es in a single session whene e possible. Fu u e lines o esea ch should o- cus on being able o answe his PICO ques ion h ough well designed clinical ials e alua ing he e ec i eness o local measu es aimed a p omo ing haemos asis in pa ien s wi h congeni al coagulopa hies unde going ex- ac ions. 15. In pa ien s wi h he edi a y coagulopa hies who e- qui e a den al ex ac ion, wha educ ion in haemo - hagic isk is p oduced by PHARMACOLOGICAL TREATMENT in compa ison wi h heal hy indi idu- als? And wha abou in pa ien s who equi e den al im- plan s? e65 Med O al Pa ol O al Ci Bucal. 2024 Jan 1;29 (1):e58-66. O al su ge y and coagulopa hies When making a ecommenda ion on his issue, no a - icle has ully s udied he PICO ques ion ha we aise. The e is no conclusi e e idence, and h ough he bib- liog aphy we canno answe his ques ion. The le el o ecommenda ion o his sec ion is he opinion o he expe s signing he guideline (G ade D ecommenda- ion). Based on ou clinical expe ience, he pha maco- logical ea men mus always be ca ied ou h ough consul a ion wi h he haema ologis . Al hough su i- cien , he e is mo e li e a u e on an i ib inoly ic ea - men in den al ex ac ions han in implan s. In case o doub , he su ge y mus be ca ied ou in a hospi al en i onmen . The au ho s o he a icles included in his e iew highligh ha u he esea ch is necessa y o imp o e he base o e idence in ea men o people wi h haemophilia and Von Willeb and disease, as well as o he a e congeni al diso de s. Ex e nal alida ion The me hodological suppo eam was made up o a echnical expe on me hodology and heal hca e based on e idence, and a lib a ian specialised in he ield o Heal h. Addi ionally, an ex e nal me hodological sup- po model was used (19), and o easons o e ec i e- ness and e iciency, an ex e nal consul an was inco po- a ed in he p epa a ion and de elopmen o p ojec s (20). Discussion The numbe o pa ien s ea ed wi h coagula ion diso - de s and, mo e speci ically, wi h an icoagulan he apy has inc eased h oughou he wo ld in ecen yea s due o he inc ease in li e expec ancy in de eloped coun ies. P o ocols o he ea men o his ype o pa ien s in o al su ge ies ha e changed in ecen yea s, especially a e he appea ance o he new di ec o al an icoagu- lan s (DOACs). E alua ion o he isk o bleeding in his ype o pa ien when unde going a su gical p ocedu e con inues o be a con o e sial issue o pa ien s, den- is s, and amily physicians. The p o essionals who mus decide he guidelines o he ea men o hese pa ien s, especially wi h ega d o he con inua ion o an icoagulan /an ipla ele ea men when hey a e going o unde go a su gical p ocedu e, ha e doub s because he p o ocols ha e unde gone a i- a ions o e a ela i ely sho pe iod o ime. This guide is aimed a p o essionals in Den is y and S oma ology, whe he hey a e gene alis s o specialis s, who p ac ise o al su ge y in uni e si y cen es, den al clinics, p ima y ca e cen es o hospi als, bo h in he public and p i a e sphe es. Consul a ion o hese ecom- menda ions, based on cu en scien i ic e idence, should help make he apeu ic decisions ha p omo e excellence in o al su ge y in pa ien s wi h coagula ion diso de s. This guide in e enes in di e en a eas o he su gical ca e p ocess in pa ien s wi h coagula ion diso de s. I allows he use o know he ele an aspec s o conside in pa ien s wi h coagulopa hies, as well as he a ailable e idence o p oceed wi h hem. I also makes p o es- sionals awa e o he impo ance o indi idualising he cases o an icoagula ed pa ien s and he alue o in e - consul a ions be ween heal h p o essionals. Re e ences 1. Chahine J, Khouda y MNMN, Nas S. An icoagula ion use p io o common den al p ocedu es: A sys ema ic e iew. Ca diol Res P ac . 2019;2019:1-13. 2. Bale i B. Should wa a in be discon inued be o e a den al ex ac- ion? A decision- ee analysis. O al Su g O al Med O al Pa hol O al Radiol Endod. 2010;110:691-7. 3. Johns on S. An e idence summa y o he managemen o pa ien s aking di ec o al an icoagulan s (DOACs) unde going den al su - ge y. In J O al Maxillo ac Su g. 2016;47:618-30. 4. Lanau N, Ma eque J, Gine L, Zabalza M. Di ec o al an icoagu- lan s and i s implica ions in den is y. A e iew o li e a u e. J Clin Exp Den . 2017;9:e1346-54. 5. Hewson ID, Daly J, Halle KB, Libe ali SA, Sco CLM, Spaile G, e al. Consensus s a emen by hospi al based den is s p o iding den al ea men o pa ien s wi h inhe i ed bleeding diso de s. Aus Den J. 2011;56:221-6. 6. Caliskan M, Tükel HC, Benlidayi ME, Deniz A. Is i necessa y o al e an icoagula ion he apy o oo h ex ac ion in pa ien s aking di ec o al an icoagulan s? Med O al Pa ol O al Ci Bucal. 2017;22:e767-73. 7. Bajkin BV, Popo ic SL, Selako ic SD. Randomized, p ospec i e ial compa ing b idging he apy using low-molecula -weigh hepa- in wi h main enance o o al an icoagula ion du ing ex ac ion o ee h. J O al Maxillo ac Su g. 2009;67:990-5 8. Se ano-Sánchez V, Ripollés-de-Ramón J, Collado-Yu i a L, Vaello-Checa I, Colmene o-Ruiz C, Helm A, e al. New ho izons in an icoagula ion: Di ec o al an icoagulan s and hei implica ions in o al su ge y. Med O al Pa ol O al Ci Bucal. 2017;22:e601-8 9. Se ano-Sánchez V, Ripollés-de-Ramón J, Collado-Yu i a L, Vaello-Checa I, Colmene o-Ruiz C, Helm A, e al. New ho izons in an icoagula ion: Di ec o al an icoagulan s and hei implica ions in o al su ge y. Med O al Pa ol O al Ci Bucal. 2017;22:e601-8 10. Hong C, Napenas JJJJ, B ennan M, Fu ney S, Lockha P, C. H, e al. Risk o pos ope a i e bleeding a e den al p ocedu es in pa ien s on wa a in: A e ospec i e s udy. O al Su g O al Med O al Pa hol O al Radiol. 2012;114:464-8. 11. Shi Q, Xu J, Zhang T, Zhang B, Liu H. Pos -ope a i e Bleeding Risk in Den al Su ge y o Pa ien s on O al An icoagulan The a- py: A Me a-analysis o Obse a ional S udies. F on Pha macol. 2017;8:58. 12. Febbo A, Cheng A, S ein B, Goss A, Samb ook P. Pos ope a i e Bleeding Following Den al Ex ac ions in Pa ien s An icoagula ed Wi h Wa a in. J O al Maxillo ac Su g. 2016;74:1518-23. 13. Kusa uka Y, Ku i a H, Saku ai S, Suzuki S, Nakanishi Y, Ka - suyama Y, e al. 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Funding This s udy was pa ly unded by a p e-doc o al g an (on a compe i- i e basis) om he Heal h Resea ch Ins i u e o San iago de Com- pos ela ha was awa ded o Alba Pé ez Ja dón. This wo k has no been inanced by any en i y. Con lic o in e es The au ho s ce i y ha he e is no con lic o in e es . E hics This wo k has no equi ed app o al by an e hics commi ee since i is a bibliog aphic e iew, so i has no been necessa y o ob ain any in o med consen . Au ho s con ibu ions Concep ualiza ion, design, me hodology bibliog aphic sea ch, da a collec ion and analysis o he esul s: Valenzuela-Mencia, Ja ie ; Se e a-Figallo, Ma ía Ángeles; To es-Laga es, Daniel; Machuca- Po illo, Guille mo; Sánchez-Fe nández, Elena; Valmaseda-Cas el- lón, Edua d; Peña ocha-Diago, Ma ía; Fe nández-Mos ei ín, Nu ia; Somoza-Ma in, José Manuel; Pé ez-Ja dón Alba; Chamo o-Pe o- nacci Cin ia Micaela; Ga cía-Ga cía, Abel. Valida ion: Daniel To es-Laga es and Ga cía-Ga cía Abel. W i ing—o iginal d a : Valenzuela-Mencía, Ja ie and Se e a- Figallo, Ma ía-Ángeles. W i ing— e iew: Valenzuela-Mencía, Ja ie and Daniel To es- Laga es. Edi ing: Daniel To es-Laga es. All au ho s ha e ead and ag eed o he published e sion o he manusc ip .