Rev. bras. ortop. vol.52 número4

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SOCIEDADE BRASILEIRA DE ORTOPEDIA E TRAUMATOLOGIA

w w w . r b o . o r g . b r

Review

Article

Hand

and

wrist

surgery

without

suspending

warfarin

or

oral

antiplatelet

–

systematic

review

夽

Trajano

Sardenberg

∗

_,

_Francisco

_Simões

_Deienno,

_Raffaello

_de

_Freitas

_Miranda,

Denis

Varanda,

Andréa

Christina

Cortopassi,

Paulo

Roberto

de

Almeida

Silvares

UniversidadeEstadualPaulista(Unesp),FaculdadedeMedicinadeBotucatu,Botucatu,SP,Brazil

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Articlehistory: Received10May2016 Accepted19May2016 Availableonline14July2017

Keywords: Hand/surgery Anticoagulants Warfarin

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Toassess,throughasystematicliteraturereview,whetherornotitisnecessarytosuspend antithromboticmedications(warfarin,aspirin,andclopidogrel)toperformelectivewrist andhandsurgeries.Thesearchforarticleswasperformedusingacombinationofkeywords inthedatabasesavailable,withoutscientificdesignconstraints,beingselectedserieswith fiveormoresurgeries;theselectedarticleswereanalyzedregardingserious(needfor surgi-caltreatment)andmildcomplications(withoutsurgery).Sevenarticleswereretrievedand analyzed;410wristandhandsurgerieswereperformedinpatientsonwarfarinoraspirin andclopidogrel,withthreeseriouscomplications(0.7%)and38mild(9.2%);2023surgeries wereperformedinpatientswithoutuseofantithrombotics,withzeroseriousand18(0.8%) minorcomplications.Patientsusingwarfarinororalantiplatelet(aspirin,clopidogrel,and aspirinassociatedwithclopidogrel)neednotsuspendthemedicationtoundergowristand handsurgery.

Cirurgia

da

mão

e

do

punho

sem

suspender

varfarina

ou

antiplaquetários

orais

–

Revisão

sistemática

Palavras-chave: Mão/cirurgia Anticoagulantes Varfarina

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e

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u

m

o

Avaliar,pormeioderevisãosistemáticadaliteratura,seháounãonecessidadedesuspender medicamentosantitrombóticos(varfarina,AASeclopidogrel)paraarealizaçãode proced-imentoseletivosdecirurgiadopunhoedamão.Abuscadeartigosfoifeitapormeioda combinaçãodepalavras-chavenasbasesdedadosdisponíveis,semrestriçõesdedesenho científico,sendoselecionadassériescomcincooumaiscirurgias;osartigosselecionados foramanalisadosemrelaçãoàscomplicaçõesgraves(necessidadedetratamentocirúrgico)

夽

StudyconductedatUniversidadeEstadualPaulista(Unesp),FaculdadedeMedicinadeBotucatu,Botucatu,SP,Brazil.

∗ _{Corresponding}_author_.

E-mail:tsarden@fmb.unesp.br(T.Sardenberg).

http://dx.doi.org/10.1016/j.rboe.2017.07.001

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rev bras ortop.2017;52(4):390–395

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eleves(semnecessidadedetratamentocirúrgico).Seteartigosforamencontradose anal-isados;410cirurgiasdopunhoedamãoforamfeitasempacientesemusodevarfarinaou AASeclopidogreleobservoutrêscomplicaçõesgraves(0,7%)e38leves(9,2%);2.023cirurgias foramfeitasempacientessemusodosantitrombóticos,apresentaramzerocomplicações gravese18leves(0,8%).Pacientesemusodevarfarinaouantiplaquetáriosorais(AAS, clo-pidogreleAASassociadoaclopidogrel)nãonecessitamsuspenderamedicaçãoparaser submetidosacirurgiasdopunhoedamão.

Introduction

The indication of continuous use of oral antithrombotic drugsforthetreatmentorpreventionofcardiovascularand cerebrovasculardiseaseshasincreasedinrecentdecades.1,2 Antithromboticdrugsaredistributedintwogroups: anticoag-ulants,warfarinbeingthemostused,andantiplatelets,with acetylsalicylicacid(ASA)andclopidogrelaloneorin combina-tion,commonlyusedinthepreventionofthromboticdiseases. Theadjustment ofwarfarin dosageto keep the patient in an anticoagulated state, prevent thrombotic diseases, and avoidcausingserious bleedingisacomplextreatmentthat requires control through regular International Normalized Ratio(INR)testing;warfarin suspensionandreintroduction areevenmoredifficult,andmayleadtothedevelopmentof newthromboticeventsorhyperanticoagulationwithbleeding risk.Suspensionandreintroductionoforalantiplateletagents (ASAandclopidogrel)alsopresentahighriskofthrombotic diseases,aswellasofthrombosisorbleeding.3–6

Patients takingantithrombotic medications that require surgeryputphysiciansinadilemma:stoppingantithrombotic medicationtoavoidexcessivebleeding,butincreasingtherisk ofthromboembolic disease, or maintaining the antithrom-boticmedicationtopreventthromboembolism,butincreasing theriskofbleeding.Clinicalexperiencesand meta-analysis studiesindicatetwogroupsofsituations:surgeriesand inva-siveprocedureswithalowriskofbleeding(e.g.,endoscopy, cataractsurgery,arthrocentesis,and dermatological surger-ies)donotrequirediscontinuationofantithrombotictherapy, andsurgerieswithincreasedriskofbleedingrequirethe sus-pensionoforalantithromboticmedicationand,dependingon theriskofthrombosis,atransitionperiodwithheparin.4,7,8 Thepresentstudyaimedtoassesswhetheritisnecessaryto suspendantithromboticdrugs(warfarin,aspirin,and clopid-ogrel)forelectivesurgicalproceduresofthewristandhand, throughasystematicreview.

Material

and

methods

The search strategy for the databases used the terms hand surgery and anticoagulant or anticoagulants or indi-rectthrombininhibitorsorplateletaggregationinhibitorsor blood platelet antiaggregants or platelet antiaggregants or bloodplateletaggregationinhibitorsorplateletinhibitorsor antiplateletagentsorantiplateletdrugsorplateletantagonists

or blood platelet antagonists or warfarin or clopidogrel or ticlopidineoraspirinoracetylsalicylicacid.Thestrategywas adapted to search in MEDLINE (PubMed), Embase, Scopus, LILACS, SciELO, and Cochrane Library (Reviews and Trials) databases.

Therewasnoperiodlimitationforthestudy;thesearches werecarriedoutuntilDecember2015.

Articlesthatdirectlyaddressedthestudytopic,i.e.,wrist andhandsurgeryandtheuseorsuspensionofanticoagulants orantiplateletagents,wereselectedthroughtheanalysisof theirtitlesand,whennecessary,abstractsretrievedthrough thesearchstrategiesindatabases.

Therewere norestrictionsregardingstudy design. How-ever, only articles with samplesize (patients or surgeries) equaltoorgreaterthanfivepatientsoperatedonusing war-farinorantiplateletdrugs(ASAandclopidogrel)wereselected. Thebibliographicreferencesoftheselectedarticleswere analyzedinsearchofotherstudiesthatmaynothavebeen previouslyretrieved.

The articles were analyzed and the following charac-teristics were recorded: sample size (number of surgeries or patients); type of surgery; use of tourniquet; type of antithromboticmedication(warfarin,antiplateletassociated withwarfarin,ASA,clopidogrel,orASAassociatedwith clo-pidogrel);andnumberandseverityofcomplications.

Thecomplicationsassessedwerethosedirectlyrelatedto theeffectsofwarfarinandantiplateletagents(clopidogreland ASA)onbloodcoagulationduringsurgeryanduptotwoweeks postoperatively:excessive bleedingandbruising. Complica-tionsthatweretreatedonlywithconservativemethodswere consideredasmild;thosethatrequiredreoperationwere con-sideredassevere.

Results

A total of 387 articles were selected. After analyzing the titlesandabstractsandexcludingduplicatestudies,nine arti-cles were selected. Afterreading their full texts, twowere excluded,asthesamplesizewaslessthanfivesurgeriesor patients. Theanalysisofthereferencesofthe ninearticles didnotretrieveanynewpapers.Thefinalnumberofarticles includedforanalysiswasseven(Fig.1).

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articles 78

Medline (Via PubMed)

articles 143

Embase (excluding PubMed)

articles 147

Scopus

Lilacs 0 articles

Scielo 0 articles

Cochrane library (Reviews) articles

articles 2

17 Cochrane library (Clinical Trials)

Total number of articles – 3 87

Selection after exclusion of duplicate articles and after reading of titles and abstracts – 9 articles

Selection after reading the complete articles and application of the inclusion criteria (number of surgery or patients ≥ 5) – 7 articles

Fig.1–Studiesretrievedonhandandwristsurgeryinpatientsusingantithromboticdrugs(warfarin,aspirin,and

clopidogrel).

tunnelsyndrome[CTS]and 527forDupuytrencontracture); 22inuseofwarfarininpatientswithINR<3(nineforCTSand 13forDupuytrencontracture);andoneinuseofclopidogrel (Dupuytren contracture). The patient in use of clopidogrel whounderwentsurgeryforDupuytrencontracturepresented excessivebleedingtreatedconservatively,thuscharacterized asamildcomplication.Allotherpatientsoperatedon(1370 withoutantithromboticmedicationand22withwarfarin)did notpresentexcessivebleedingorbruisingcomplications.

Wallaceetal.10_conducted_a_{non-controlled}_clinical retro-spectiveseries.Allsurgerieswereperformedwiththeuseof atourniquet.Thesample(surgeries)included:55patientsin useofwarfarin(INRbetween1.3and2.9;17forCTS,12for Dupuytren contracture,five fortriggerfinger,and 21 other surgeries).Twopatients(oneoperatedforCTSandonewho underwentatrapeziectomy)developedhematoma,whichwas conservativelytreated,thusindicatingamildcomplication.

Jivanetal.11_conducted_a_{retrospective}_case-control_study. Thepatientswereoperatedwiththeuseofatourniquet.All patientsunderwent surgeryforCTS, 48 withoutthe use of antithromboticmedicationand48usingASA.Nobleedingor bruisingcomplicationswereobservedinbothgroups.

Edmunds and Avakian12 _conducted _a _{non-controlled,} prospectiveclinicalseries.Thepatientswereoperatedwith

the use of a tourniquet. The sample (surgeries) consisted of57 patientsusingwarfarin (INRbetween1.4and 3.2),40 using clopidogrel, and 24 using clopidogrel and ASA. The surgeries performed were: 59 for CTS, 12 for Dupuytren contracture, five for trigger finger, and 45 other surgeries. Six patients (five using clopidogreland oneusing clopido-grel and ASA) presented excessive bleeding conservatively treated,thuscharacterizingamildcomplication;onepatient onclopidogrelwithadiagnosisofVaughan-Jacksonsyndrome, who underwent resection of the distal ulna, tenosynovec-tomy, and tendon transfer, presented a hematoma that required surgical treatment, thus characterizing a severe complication.

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Bogunovicet al.5 _conducted _a_prospective _cohort _study. The patients were operated with the use of a tourniquet. Thesample(surgeries)included107patientswhodidnotuse antithromboticmedication(39forCTS,23fortriggerfinger, and45forothersurgeries)and107operatedonwhileusing antiplateletmedication(48forCTS,21fortriggerfingerand 38forothersurgeries).Amongthepatientsusingantiplatelet agents,76usedASA,fiveusedclopidogrel,and11used clo-pidogreland ASA.Noserious complicationswere observed inpatientswhodidnotuseantiplateletmedication.Oneof thepatientsusingantiplateletmedication presentedsevere bleedingrequiringreoperation(thepatienthadrheumatoid arthritisandwasusingahighdoseofASA,andunderwent arthrodesis of the wrist and tenosynovectomy). The rates of conservatively treated bruisings (which did not require surgeryandwerecharacterizedasmildcomplications)were 14% for patients who did not use medication and 17% in thosewhousedantiplateletagents;this differencewasnot statistically significant. No infection or dehiscence of sur-gical wound was observed in the group of patients using antiplateletagents.Theecchymosis size,digitalsensitivity, andQuick-Dashpresentedstatisticallysimilarresultsin oper-atedpatientsusingantiplateletagentsvs.thosewhowerenot. Bogunovicet al.6 _conducted _another _prospective_cohort studyonthisissue,thistimeaddressingwarfarin.Thesample included50surgeriesinpatientsusingwarfarinalone(32)or associatedwithASA(18;27forCTS,twofortriggerfinger,five formassorsynovialcystsresection,fourfortendonsurgeries, and12forbonesurgeries)and50surgeriesinpatientswhodid notuseantithromboticmedication(21forCTS,eightfortrigger finger,threetendonsurgeries,threefordeQuervain tenosyn-ovitis,onewristarthroscopy,threesofttissuesurgeries,and11 bonesurgeries).ThemeanINRinpatientsusingwarfarinwas 2.3.Allsurgeriesweremadewiththeuseofatourniquetand localanestheticwasinjectedwithoutepinephrineatthe sur-gicalsite.Noseriouscomplicationswereobservedinpatients whodidnotuseantithromboticmedication.Inpatientsusing warfarin,oneseriouscomplicationrequiringanewsurgical interventionwasobserved(patientsubmittedtocarpectomy ofthefirstrowwhodevelopedhematomaandcompression ofthemediannervefourdaysaftersurgery).Regardingmild complicationsthatdidnotrequirehospitalizationor reope-ration, patients using warfarin had a higher incidence of bruisingsonlyattwoweekspostoperatively,whichpairedwith thegroupthatdidnotuseantithromboticmedicationatfour weeks.Therewerenorelevantclinicaldifferencesbetweenthe groupsregardingpain,edema,andupperlimbdysfunction.

Tables1and2presentsummariesoftheresultsfromthe sevenarticlesincluded.

The indicationfor the use ofwarfarin and antiplatelet agents in the seven studies analyzed were atrial fib-rillation, cardiomyopathy, mitral valve prosthesis, coarc-tation of the aorta, venous thromboembolism, valvular prosthesis, atrioventricular communication, primary pre-vention of coronary disease, secondary prevention of coronary disease,combined secondary prevention of coro-naryand cerebrovascular diseases, pulmonary thrombosis, deepvenousthrombosis,thromboticdisorders, cardiovascu-lardisease,peripheral vascular disease,and neurovascular disease.

Discussion

The analysis of the results of the seven selected studies addressed handand wrist surgeries inpatients using war-farinororalantiplateletagents(ASAandclopidogrel)indicates thatthefrequencyofseverecomplications,definedas bleed-ing orbruisingrequiringsurgicaltreatment, wasextremely low – three in410 (0.7%). Thethree serious complications occurredinpatientsundergoingcomplexsurgicalwrist pro-cedures(wristarthrodesisassociatedwithtenosynovectomy; resectionofthedistalulnaassociatedwithtenosynovectomy andtendontransfer;andfirst-rowcarpectomy);onepatient used high-dose ASA, one used clopidogrel, and one used warfarin.5,6,12_Bogunovic_et_al.5_emphasize_the_similarity_of_the situationofpatientsusingantiplateletagents,inwhich seri-ouscomplicationswereobservedinthosewithrheumatoid arthritisundergoingboneprocedures.Inthe184surgeries per-formedonpatientsusingwarfarin,oneseriouscomplication wasobserved.6

Mild complications,definedas bleedingorbruising that did not require surgical treatment, occurred in 35 out of 410 surgeries (8.5%). Theprospective studies byBogunovic etal.5,6 _including_a_control_group_(patients_who_did_not_use antiplateletagentsorwarfarin)presentedthelargestamount ofmildcomplications,buttheauthorsadoptedabroad def-inition ofthe term hematoma (“any bulging withpalpable fluidcollection,regardlessofsize”)EdmundsandAvakian12 reportedsixminorcomplicationsinpatientsusing clopido-grelandASA,subjectivelydefinedas“excessiveintraoperative bleeding.”Stoneet al.14_analyzed_the _results_of_over_10,000 patientsundergoingmajorarterialsurgeryinuseof clopid-ogrel alone or in combination with ASA, and did not find evidenceofexcessiveintraoperativebleeding.

The four studies reporting surgery in patients using warfarin6,9,10,12_adopted_INR_equal_to_or_less_than_three_as_a parametertoperformthesurgerywithoutsuspending anti-coagulant; apparently, the selection of the INR value was determined subjectively. The four studies showed an INR variationfrom1.3to3.2.Wallaceetal.10_reported_two_mild complications,andtheINRrangedfrom1.3to2.9.Thestudy byBogunovietal.6_presented_a_case_with_serious_complication inwhichtheINRwas2.1preoperativelyand5.4onthefourth dayaftertheoperation,whenthecomplicationwasdetected. AlthoughtheINRparameteroflessthanorequalto3or3.5is subjective,theobservedresultssuggestthatthislimitissafe. Thesevenstudiesanalyzedhadlowlevelsofevidence,as onlythreewereprospectivestudiespresentingbetter detail-ingandcareindesignandexecution;thesestudiesreported morecasesofmildandseverecomplications,probablydueto thefactthatthedefinitionsofthecomplicationsweremore precise.5,6,12

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Table1–Characteristicsandsummaryofresultsofthesevenarticles.

Authors Typeofstudy Tourniquetuse AT Numberofsurgeries Mildcomplications Severecomplications Totalcomplications

WithAT WithoutAT WithAT WithoutAT WithAT WithoutAT

Smitand Hooper9

(2004)

Cohortstudy (retrospec-tive)

Yes Warfarin

(INR≤3)and

clopidogrel

23(22with warfarinand 1with clopidogrel)

1.370 1 (Bleed-ing/clopidogrel)

Zero Zero Zero 1(4.3%)(WithAT)

Wallace etal.10₍₂₀₀₄₎

Non-controlled clinicalseries (retrospec-tive)

Yes Warfarin(INR 1.3–2.9)

55 Doesnot

refer

2(hematoma) Doesnot refer

Zero Zero 2(3.6%)(WithAT)

Jivanetal.11

(2008)

Case-control studies (ret-rospective)

Yes ASA 48 48 Zero Zero Zero Zero Zero(withand

withoutAT)

Edmundsand Avakian12

(2010)

Non-controlled clinicalseries (prospective)

Yes Warfarin(INR 1.4–3.2) clopidogrel and

ASA+clopidogrel 121(57 warfarin,40 with clopidogrel, and24with clopido-grel+ASA)

Doesnot refer

6(bleeding;5 clopidogrel and1with ASA+clopidogrel)

Doesnot refer

1(hematoma/ clopidogrel)

Zero 7(5.8%)(WithAT)

Boogaarts etal.13₍₂₀₁₀₎

Cohortstudy (retrospec-tive)

No(local anesthesia with epinephrine)

ASA 6 448 Zero Zero Zero Zero Zero(withand

withoutAT)

Bogunovic etal.5₍₂₀₁₃₎

Cohortstudy (prospective)

Yes clopidogrel, ASA,and ASA+clopidogrel

107 107 15

(hematoma) 13

(hematoma)

1 (bleed-ing/highdose ofASA)

Zero 16(15%)withAT 13(12.1%) withoutAT Bogunovic

etal.6₍₂₀₁₅₎

Cohortstudy (prospective)

Yes Warfarin

(meanINR 2.3);18 war-farin+ASA

50(32 warfarinand 18with war-farin+ASA)

50 14

(hematoma)

5(hematoma) 1

(hematoma+ mediannerve compression)

Zero 15(30%)withAT 5(10%)without AT

Total 410 2023 38(9.2%) 18(0.8%) 3(0.7%) Zero 41(10%)withAT

18(0.8%)without AT

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Table2–Summaryandaggregationoftheresultsofthe

sevenarticles.

Surgeriesusingwarfarin,warfarin+ASA,orantiplateletagents (AAS;clopidogrel;AAS+clopidogrel):410

Mildcomplications:38(9.2%) Severecomplications:three(0.7%)

Surgeriesusingwarfarin:184 Mildcomplications:16(8.6%) Severecomplications:one(0.5%)

Surgeriesusingantiplateletagents(AAS;clopidogrel; AAS+clopidogrel):226

Mildcomplications:22(9.7%) Severecomplications:two(0.9%)

Surgerieswithouttheuseofantithrombotics(warfarin, warfarin+ASA,ASA,clopidogrel,ASA+clopidogrel):2023 Mildcomplications:18(0.8%)

Severecomplications:zero

physiciansshouldbeextremelycautiousbeforesuspending

theuseofthesemedications.2–4,7

Theidealstudy,whichwasnotretrievedintheliterature, would prospectively compare the results ofpatients using antithromboticdrugswiththoseofpatientswhohadtheuse ofthesedrugssuspended.

Thelimitationsof thepresent study,due inpart tothe methodological restrictions ofthe articles selected, hinder moreemphaticconclusionsregardingthe needtosuspend antithromboticdrugsforwristandhandsurgeries.However, thestudiesanalyzedsuggestthatwristand handsurgeries withlowriskofbleeding,involvingsoftparts,fingerjoints,and tubularbones,canbeperformedwithoutsuspendingwarfarin orantiplateletagents(ASAandclopidogrel).Furthermore,the studiessuggestthefollowingpracticesinthesurgical man-agement of patients taking antithrombotic drugs: in order nottodiscontinue warfarin,patients should haveINR less thanorequaltothreeontheeveofsurgery,andpatientson antiplateletagents(ASAandclopidogrel)maypresentgreater intraoperativebleedingandrequiregreaterhemostasiscare.

Morerandomizedandcontrolledstudies,especiallywith groupswithandwithoutantithromboticsuspension,are nec-essarytoelucidatethistheme.Moreover,theintroductionof antithrombotictreatmentwithanticoagulantandantiplatelet association,aswellastheadventofnewanticoagulants,also requiresnewstudiesonwristandhandsurgerywithoutthe suspensionofthesedrugs.16,17

Final

considerations

Patientstakingwarfarinororalantiplateletagents(ASA, clo-pidogrel,andASAassociatedwithclopidogrel)donotneedto discontinuethemedicationtoundergohandandwrist surger-ies.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgments

TothelibrarianEnilzedeSouzaNogueiraVolpatoforthehelp onthearticlessearchandreferencescitation.

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