Thelournal of Otolaryngology,Volume27, Nutnber2, I ggg ReviewAr ticle Useof FibrinGluein Maxillofacial Surgery B e n i a minR. Dauis,BSc, DDS, and George K.B. Sdndor,MD, DDS, FRCSC,FRCDC, FACS Abstract Obiectiue:To describevariousapplicationsof homologousfibrin glue in maxillofacialsurgery.The clinicalourcomesof rhe rreatedcasesarediscussed. Methods:During the period.Januaryt993.to July 1995, 71 patientsunderwentmaxillofacialproceduresin which homologous fibrin 8l.ucw1s utilized. The rnaterialusedin eachcasl was Tisseel'',which is "otnpor"d of human fibrinogen and bovinethronrbin.The materialwas usedto providecloseand securere-approximationof soit tissuein 20 patientsriquiring coronalflaps,Boneot alloplastfixation was undertakenwith fibrin sealaniin 1.4patients.In 13 cleft lip and pul"t" po'ti"ntr, the materialwas usedin the repair.of residualfistulasor clefts.Twelve patientshad sinus lifr procedureswhere rhe materiai fixatedtlte bonegraft and lepaired the torn mucoperio-steal lining, Finally, 12 patienrswith coagulopathieshad fibrin glue placedfollowingexodontia.All patientswercfollowedfor a minimurnof ri monihspostoperatively. Resubs:Seventypatietltstreatedwith Tisseel"'had successful outcomesas determinedby preoperativecriteria.A singleoral antralfistularecurred3 weeksafter surgery.No adversereactionto the materialwas notid in any of the patients. Conclusions:, Homologousfibrin glue hasvariousapplicationsin the field of maxillofacialsurgeryand can be usedwifi safe and predictable resr.rlts. Sommalre Obiec.tif:D6crireles applicationsvari6esde la colle de fibrinehomologuedansla chirugir maxillo-faciale.L'6volutioncliniquedescastraitdsestdiscutie. Mdthodes:Au cours de la p6riodede janvier 19% ejuillEt 1995, 71 patientsorlt subi <lesinrerventionsmexillo-facialesau coursdesquelles_de la colle de fib.rineltomologuefut employ6e.Le matdrielemploy6dans chaquecas fut [e "Tisseel,'*',qur estcomposd de fibrinogine humain et de thrombinebovine.Le rnat6rielftrt employ€pou. rusutlr une r6-approximarionserr6e et sdcuritaire des tissus.nrous dans 20 patientsn6cessitant deslambeauxde type ioronal. La fixation d-'orou d'alloplast fut faiteavecla colle de fibrine chez_14 patients,Chez 13 patientsavecfissure-labiale et palatine, le mat6rielfut ernploy6 pour la riparation de fissuresou de fistulesr6siduelles. Douzepatientssubirentdesinterventionspour remonterle sinusau coursdesquelles le mnt6riela fix6 la greffeosseuse et r€parCle rev0tementmucop6riost6 d6chir6.Fiialement, L2 patientsavec coagulopathies eureltt une applicationde colle de fibrine i la suite d'une eiodontie. Tor.rsles patienti .ui.nt un suivi postop6ratoire de 6 r'noisau minimum. Rdsultats:Soixante-dixpatients trait6s avec le "Tisseel"eurenrune ivolution favorableselon les critEresd6termil6s en pr6op6ratoire. Seuleune fistule oro-antralea r6cidiv63 senraines aprBsla chirugie.Aucune r6action adverscau matdrielne frrt notiechezaucunclcspatients, Conclusiorts:La colle de fibrinc homologuea des applicationsvari6esdansle champde la chirugie maxillo-facialeet peut 6tre employ6e avecdesr6sultatss€curitaires et pr6visibles. I(cy words: fibrin glue,maxillofacialsurgery Received4128197, Receivcdrcvised9125197. Acccnrcdfor publicarion 10/03/97. B e n a m i nR . D a u i s : D e p a r r m e n t o f O r a l a n d M a x i l l o f a c i a l Surgery,QueenEliza[:cthFlcalth SciencesCcntre,Halifax, Nova Scotia;GeorgcK.B, Sdndor: Acting Head, Division of Oral and MaxillofacialSurgcry,The Toronto l-Iospital,The Hospital For Sick Childrcn, The Bloorvicw MacMillan Ccntre, ioronto, Ontario, Addressreprinr requeststo: Dr. George K,B. Sdndot, Department oI Dentistry,The Hospital for Sick Chilclren,SS.i Univer. sity Avenue,Toronto, ON MSG 1X8. Qurgeonshavelong soughta productthat could act r.Jas both a tissueadhesiveand a hemostaticagent. Unfortunately,the ideal characteristicsof an adhesive differ from thoseof a hemosraricagenr.Presently,fibrin glue demonstrates the best equilibrium between both properties. Fibrin was first used by Bergell in 1909 to esrablish hemostasis. In 19L5, Greyz usedtopical fibrin ro provide for hemostasiswhile performing cerebral surgery.In 1940 Young and Medawar3nored that fib- 107 108 TheJonrnalof Otolaryngology,Volumc27, Numbu 2, 1998 rinogencould act as a tissueadhesive.Cronkiteet al'a in 1943, mixed bovine thrombin with plasmafibrinogen to producethe first biologicadhesive.One year Lt.r, Tidrick and'uflarrenswere using fibrin to fixate skin grafts.In !972, Matras et al,6enhancedthe effectivenissof fibrin glue (FG) by increasingits fibrinogen concentration.Fearingpossibleviral transmission,the U,S, Food and DrurgAclministrationbannedthe saleof lronrologousfibrin glue in 1978, Virally inactivated homologousfibrin glue has beenavailablein Europe and Canaclafor numerousyears.Presently,only autologous FG products are availablein the United States, but phase-twoclinicaltrialsinvolvinghomologousfibrin gluearc now underway. SeveralhomologousFG preparationsexist. These includeTisseel"'',Beiiplast"',Biscol'u,and Hernacure'u. Theseproductsdiffer prirnarily in the concentrationof their components.The variouscomponentsof Tisseel"' are listedin Table1.7 of the FG involvesseveralstepsand can Preparation be performedin approxirnatelyL0 minutes,The vials aprotininsolutionareplaced containingtheTisseel'*'and heatingand mixing unit. The unit in the Fibrinotherm'*' heatsboth componentsto 37"C. The aprotininis then usinga suppliedsyringeinto theTisseel'"vial' transferecl This fonns componentI. The Tisseel"'vialcontainsa ciny mixing rod. IThen the vial is placedin the rnixing part of the Fibrinotherm"'unit, a uniform mixing and disolvingof the Product results'The clinicianmay choosethc desiredthrombin concentration,either 4 IU/mL or the faster setting 500 IU/mL. The calciurn chloricleis addeclto the heatedthrornbinvia a second I and II syringe,This forms comPonentII' Componenm are mixed togetherat deliveryusing the Duplojecr'^' systemallows syringesystem.This supplieddual-syringe ensurapplicationof both components' the simultaneous ing that they are quickly and thoroughly mixed. This systemhas rrumerousoptional attachments,inclucling sprayheadsand applicationcatheters. Concernexists over the possibilityof viral transm i s s i o nw h e n r r s i n ga p o o l e d h o m o l o g o u sb l o o d sonrce.Tisseel"'is preparedfrom selecteddonorswho unclergoextensivescreening.Virilogic testing and vapour hear treatmentof all donor productsis perforrned.To date,closeto 2.5-millionadministrations of the producthave occurredand not a singledocuhas beennoted.This mcntedcaseof viral tratrsmission article reports the resultsin 71 patientswho received Tisseel"'duringmaxillofacialprocedures. Material and Methods During the periodJanuary1993 to July 1995,hornologous fibrin glue was used in 71 patientswho under' went proceduresin the maxillofacialregion.The material usedin all caseswas Tisseel"'(Immuno,Ausrria). of Tisseel'^' Table 1 Components (human)r 1. Proteinconcentrate Total protein FactorXIII Fibrinogen Fibronectin Plasminogen 2. Aprotininsolution,bovine 3. Thrombin,freezedried,bovine 4. Calciumchloridesolution mlml 100-130 10-50UimL 70-110mg/ml 2-9 mglmL 40-120FglmL 3000KIU/mL .500or 4IU/mL 40 mmol/L The amount of material used and the Postoperative courseof eachpatient was noted. A breakdownof thesedatais notedin Table2. SprayedFG was usedto provide closeand secure reapproximationof soft tissuein 20 patientsrequirirtg coronal flaps.In those patientsundergoingesdretic thefrontalis, FG wasappliedafteraddressing procedures, and during procerus,and corrugatorsuperciliimuscles, the final reapproximationof the overlyingflap to its new position, Bonegraftsor alloplastswerefixatedwith FG in 14 patients.Ten patientshad cancellousgrafts stabilized with FG.The graftswereplacedfor eitheraugmentation of of alveolarridges(Figs.1 and 2), the reconstruction of mandibulardiscontinuitydefects,or the stabilization osteotomysites(Fig.3). Threealloplasticimplantswcre stabilizedwith FG. In all cases,the alloplastusedwas Biocoral"'.Finally,in a singleinstance,an orbital-floor calvarialgrafcwas fixated widr FG (Fig' a). The grnft was usedto reconstructan orbital-floor defectin a fracture. patientwith a zygomaticomaxillary oro' palate lip and In 13 cleft Patients'persistent FG, local flaps and using repaired nasal fistulaewere prc' and at closure attempts All caseshad failedearlier senteclwith significantscarringof the palatalsofttissue.Fibrin gluewas usedin eachinstanceto helpwidr closureof thc nasallining. A combinationof snturcs and FG wasusedto provideoral closure, Twetvepatientsunderwentmaxillarysinuslift bone grafting.Potentialdifficultiesinhercntwith this techniqueincludestabilizingthe bonegraft in the nmx' when illary sinus.The seconclpotentialProblemoccLlrs lining is torn duringfie the thin mucoperiosteal-sinus Fibrin glue was usedto stabilizethe cancel' dissection. Tabte2 Amountof FibrinGlueUsedfor VariousIndications Amount(nLl lndication Range Coronalflaps Bonegrafts Oronasalfistula Maxillary sinuslifts Exodontiain coagulopathy patients a J-O 20 T4 13 1' ) 1) 4-t2 6-7 6-7 1-2 l Mean ^ a 6.7 6.5 6 1,8 Dauis and Sdndor, Fibrin Glue in Maxillofacial Surgery 1,09 remainedradiographicallyin place during tt, t""iing or incorporationphase.No fnrther bleeding in the coagulopathypatientswho underwentextractionswas noted,Twelveof the 13 oronasalfistulaeremainedsuccessfullyclosedat a minimum of 6 monrhs follow-up. A singlefistula recurred3 weeksafter surgery. Discussion Fibrin glue mimicks the final stageof the coagulation cascadein which thrombin cleavesfibrinopeptidesA and B from fibrinogen forming a fibrin monorner. Crosslinkingof rhe fibrin monomer by the action of Flgure1 Alveolarcrestcancellousbonegraft securedwith factor XIII in the presence of calciumresultsin a stable fibrin glue. fibrin clot. I{emostasisis thus possible,evenin the face of a coagulationdefect, Presently,lroth homologousand autologousforms ious bone in the dcsired position and to repair the thin of fibrin gluehavefound numerousapplicationsin var.sinus lining, thus ensuring that the graft was isolated ions surgical specialties. In rhe field of orrhopaedic fiom the lumenof the maxillary sinus(Fig,5). surgery, FG has been used for the repair of osteochonFinally, FG was used to achievehemostasisin 12 dral talar fractures and radial headfractures. p a t i e n t sw h o u n d e r w e n t d e n t a l e x t r a c r i o n s .T h e Cardiovascular surgeons have usedthe product for patientsin whom FG was used had either a congenital years numerous to seal both aortic and coronary artery factor deficiency(factor VIII or IX) or factor deficiency leaks during bypass surgery! and to sealimplantedvassecondaryto advanced liver disease,Following extracgrafts. cular General surgeons have controlled gastroin. tion of the involved teeth, the sockets were curreted testinal, hepatic, splenic, pancreatic and bleeding using and irrigated, and FG was applied to the socketsusing Thoracic FG. surgeons haye used FG seal to esophathe Duploject"',syringe (Fig. 6). No further hemosfatic gogastricanastomoses and to closepleuropulmonary measutes wereused. and bronchopleuralfistula.8Postoperative chylothorax also has been successfully treated using FG.e Results Neurosurgeons have controlledintracranialbleedAllpatientswerefollowedfor a minimumof 6 months. ing and repaireddural tearswith fibrin g1ue.10,11 Fibrin glue has also beensuccessfully Thc average amountof Tisseel"'usedper casewas5 mL usedto stop postopera(range,1-12 mL). Table2 liststhe meansand rangesof tive CSFleaks.12 In the field of orbital surgery,FG has rhearnountof Tisseel"'usedfor eachprocedure beenusedto reapproximate category. conjunctiva,repair corneal 3 Seventy patientstreatedwith Tisseel'u per successforations, and had treat retinaldetachments.l ful outcomes. No adversereactionto the materialwas Otolaryngologists haveusedFG to decreaseor elirninotedin any patient.There were no postoperative nate the needfor nasalpacking following funcrional hematoma or seromaformationsin the coronalflap endoscopic sinussurgery.la A decreased hospitalsraywas patients,Bonegrafts and alloplastsfixatedwith FG alsonotedwhen FG was usedduringrhyroidectomies.lt Flgure2 Tongueflap usedfor soft tissuecoverage of graft. Figure3 Bonegraft securedwith fibrin gluein LeFort I level osteotomy. 110 'llte 27' Number 2' 1998 Jottrnalof Otolatyngology,Voltnne folFibringluehasbeenusedto providehemostasis lowing dentalextractionin patientswith inheretedcoagulation defectsor advancedliver disease,or in thosctaktheusc Martinowitzet al.zsdescribed ing anticoagulants, patientsrequiringexodontia of FG in anticoagulated with INR valuesabove2.5. Conventionalhemostatic oxidized agentssuchas collagenmatrices(Gelfoam'*'), and topicalthrombinrtrc matrices(Surgicel'n'), cellulose usuallyineffectivein patientswith low plateletcoullts replacenrcnl or deficientcoagulationfactors.Expensive therapyis usually required in the factor-deficicr:t showed very good success ar patient.Rakocz et a1l'26 hemostasis with Tisseel"'in irll providingpostextraction Martinowitztrttl but the most seveteof hemophiliacs. Figure4 Splitcalvarialbonegraftto orbitalfloordcfectfix' claim that the use of FG insteadof factor SchulmanzT atedwith fibringlue. in exodontiaaud mitlor surgeryresultitt I concentrates maystill tcn-foldreductionin cost.Factorreplacernent An amounts. evaluatiott reduced of in br-rt group lrad neccessary be Compareclto diathermy,an FG-treated in underway. is clifference currently this no pain, with post-tonsillectomy decreased availaltlc Tisseel"'is one of the severalcommelcially primary oi secondarybleedingnoted betweenthe two per mL approxi' cost is glues. The fibrin tymto secure hornologous gro.rpr.ttFibrin glue has also beenused glue and applica' fibrin the including Cdn$100, reconstruction'l7 mately iuni, -embranelrafts andin ossicr'rlar quoted coststlf the with favourably and This compares tor. In the area of craniofacialsurgery,Marchac p/zs (US$103/mL for glue US$50 was fibrin autologous Renierlsmixed FG with a bone paste.The Paste Autologous p/as the applicator).28 for in a US$50 thrombin mixed with the fibrin/aprotinincomponentalone fibrin glueproductsalsodifferiu tcrttrs andhomologous L:1 ratio. The thiclcpastewas then molded into the of components. concentration was and content of the desiredshape,afterwhich the thrombincomponent is'usuallyconsidfibrinogen of be could concentration product The addeclcausingit to solidify.The final products compatcd FG in autologous the recipient lower erably furrhershapedand was easierto secureto the for thc is important Fibrinogen FG. Sandorle to homologous site than cancellousbone alone.Marchacarrd product. ct nl.le Saltz of the in strength shearadhesive a statisticallysignificantdecrease clemonstrated fih' increasing that by experimentally whcn FG was sprayed demonstrated major hematomadevelopment in betweenthe SMAS layer and the overlyingskin flap face-liftsurgery.Blepharoplastyincisionshave been fewer sutures' closedwith the aid of FG, necessitating Graftsfor the coverageof burns or difficult wounds securedin placewith FG alone have beensuccessfully or in combinationwith a minirnalnumberof sutures. Fibrin glue has numerousapplicationsin oral and usedFG to rnaxillofacialsurgery.Tayapongsaket a1.20 securecancellousbonegraftsto homologousmandibles In the rabbitmodel,FG allowed duringreconstruction. for easiersoft-tissnereapproximationfollowing osteo' Severalclinicians plastiesof the mandibularcondyle,2r have noted that hydroxyapatitegranulesare much rnore easilyhandledand are lesslikely to becomedisplacedwhenFG is usedto securethem.22 of the tongueand lip Cavernoushemangiomas have beeninitially treatedwith intralesionalinjection of Tisseel'"'.Halling and Merten23claim that heman' giomaslessthan 15 mm in diameterwill involutespontaneouslyafter L or 2 intralesionalinjectionsof FC performed over a 4-week period. The often-difficult excisionof ranulas has also beenfaciliratedby the rvith in 1>lacc intraluminalinjectionof FG, resultingin easierdissec- Figure5 Maxillary sinuslift bonegra(tsecured fibrin glue, tion oncethe materialhassolidified.2a ll Dauisard Sdndor, Fihrin Glue in Maxillofacial Surgery rinogenlevelsfrom 20 to 70 mg/ml, the shearadhesive strengthof fibrin glueis increased19-fold. The breakingstrengthof the clot is affectedby fibrin crosslinking;therefore,factor XIII levels are also important.Native factor XIII, looselybound to the fibrinogen,is presentin concentrationsof 10 U/mL and seems to be adequatefor efficacyof the fibrin glue.3O Tire working time of the fibrin glue can be altered by varyingthe concentrationof the thrombin. Vhen 4 IU/mLof thrombin is used,the working rime is 30 or moresecondsbefore a fibrin clot will fomr. $7hen J00 IUAIL of thrombin is used,the fibrin clot fornrs wirhin 5 seconds.This is fairly constant for thrombin between20 and 1.000IU/m.30 concentrations The adclitionof an antifibrinolyricto fibrin glue is and is one reasonthe FDA has not yet controversial approvedits salein the United States.The antifibrinolyticmostcommonlyuseclin homologousfibrin glue is bovineaprotinin.Tranexamicacid and aminocaproic acidhavealsobeenused.The n'ranufacturers of homologousglueclaim that the absorptionrate of the fibrin gluecan be slowedby the additionof an antifibrinolytic.This is of particularbenefitin areasof high-fibrinolyticactivity,such irs the oral cavity, but may nor beimportantin othertissues, suchas bone,ll Severalreactionsto the conrponentsof fib:ringlue havebeennoted. Nonfatal anaphylacticreactionsto aprotininhavebeendescribed. Wurhrich er a1.32 also denronstrated au IgE-mecliated anaphylacticreacriollto apr:otinin. Aprotinin is a polypeptidederivedfrom bovinelung and has potentialantigenicity.Berguerer a1.33 described two cases,one fatal, in which profound hypotension developedafter treatingdeep liver lacerationswith nonaprotinin-containing fibrin glue. Bovinethrombin trlsocontainsbovine factor V, whichcanbe antigenic. The inhibitorsof bovinefacror V cancrossreact with human factor V. This can result in a significantreductionin human factor V levels.Ileexposure to FG will also increasethe likelihoodof developing inhibitors.Tissucol'^' (lrnnruno,France)has overcorlethis problemby using htrman drrombin in theirhomologous FG preparations. This articledescribesseveralnew applicationsfor. homologous fibrin glue.The volurneof FG usedfor sorneof the proceduresis higherthan expectedas a resultof a learning-curve phenomenonand operator and assistant en'ors,particularlyduring the early part of thisseries. Broadconclusions on any of the proceclures perfor:med in our seriesare not possibledr.reto the limited sample sizeand the lack of controls.!7e believe,however,that the use of FG improved ollr outcones or facilitated theprocedurein severalways. Placement of osseointegrated implantsin the posrerior edentulous maxilla often requiresbone grafting of this area.The graft, usuallycancellousbone harvested Lll Figure6 Fibringluensedto obtainhemostasis in extractron siteof patient with coagulopathy. frorn the ilium, is placedbelow an inract mucoperiostealsinuslining. An inta* Iining stabilizesand isolatesthe graft from the rernainderof the sinus.Several cliniciansrecommendaborting rhe procedureif large tearsin the thin mucoperiosteal lining occur. Fibrin glue allowedus to stabilizethe grafreasilyand repair tearsin the lining, thus ensuringits isolationfrom the maxillarysinus. Persisrant oronasalfistulaeare oftenchallengingto repair.A double-layered closureis preferred,as it decreases tl'reincidenceof fistula recurrence. The nasal [aye.r,however,can be difficult to close,parricularlyin redocleftlip and palatecases.Fibringlueallowedeasier closureof drenasallayer. Patientswitir coagulopathies of mild-to-moderate severitywereableto undergosimpleexodontiawithout the nseof factor replacemenr. Fibrin glue,in this situation, appearedto be lltore cost effective,decreased the total treatmenttirne, and in all but the most severeof coagulopathies, elirninatedthe risks involvedwith factor replacement. Patientcomfort was improvedby sprayingFG nnctercoronalflapsduringreapproxinlation,thus eliminating the need for postoperativedrains. It would seemthat this techniqnedoesnot increase the risk of hcmatomaor seromadevelopment, In nonloadedareas,FG aloneprovidedsufficient supportfor bone grafts,This not only easedthe stabigraftsin particular,but alsoelimlizationof cancellous inatedthe potentialneedof havingto removethe fixation hardwareat a later dare,Thereis, however,no contraindicatiorr to usingFG in the presence of fixation hardware.This is often necessary in loacledareas requi.ringbone grafting of defects.Most recently,we have begunusing FG togetherwith bioresorbable plates(Lactosorb'u, Walter Lorenz,Jacksonville,FL) for recontructingcomplexmaxillofacialfractures.Fibrin glue has beenusedto stabilizenonloadedbone grafts,and the resorbableplateshavebeenusedto fix- 1.LZ 1998 Thc Jounul of Otolaryngology,Volume27' Number2' ate fractures,In our opinion, this is an idealcombinasystem' a completelybiodegradable tion as it represents the field applications-in numerous Fibrin lloe has and cost-effective, safe, a It is surgery. of maxilloflcial hemostasis, providing of method clinically proven s.crlringor glueinghard and soft tissue,and sealingfri' able o,ldifficult-to-reachtissues'It doesnot, however' good surgicaltechnique. replace ^ Futir. appltations of this product includeusing FG as o u.hicle for the deliveryof antibioticsand growth factors.Improvedmethodsof producingautol6gousfibrin glue and recombinantproductsare also Presently,homologousfibrin glue uider development. over its autologouscounteradvantages offers several cost,easeof procurement' lower iuclude part. These The only disadvanproperties. mechanicai and better To date, transmission' disease of possibility tageis the case clocumented single a been not has there ho-wrver, admin'2'5 million over well in transrnission of disease istrationsof the product. References DtschMedWochenschr desFibrins. S.Uberlil/irkungen 1. Bergel 1909;35:633. in cerebralsurgery'Surg 2. Grey EG. Fibrin as a ltemostatic 27452. 1915; Obstet Gynecol nerves' 3. YoungJZ, MedawarPB.Fibrinsutureof peripheral Lancet1940;275:126' 4. CronkiteEP,LoznerEL, DeaverJ, Useof thrombinand fi[:rinogenin skingrafting'JAMA 1944iL24976' 5. Tidrick RT,lVarrenDD,Fibrinfixationof skintransplants' S u r g e r1y9 4 4 ; 1 5 1 9 0 . inter' 6, MatrasH, DingcsHP, Manolil!, ct al. Zur nahtlosen Wien im ticrexperiment' nerventransplantation faszikularen chr t972; 722:5 77, Med !(/ochens (I-Iurnan), VaporFlcatecl Fibrin Sealant 7, Two-Componcnt LnmunoAG, insert' information Product VH. Kit TisscelrM 1993, Issued February Austria, Vienna, 8, GloverlV, ChavisTV, DanielTM, et al. FibringlueapplicaA closurc tion throughthc flexiblcfiberopticbronchoscope; Surg fistulas, of bronchopulnonary J ThoracCardiovasc 7987;931470. 9, AkaogiE, Mitsui K, SoharaY. Treatmentof postoperative chylothoraxwith inuapleuralfibrin glue.Ann ThoracSurg 1989;48:116. 1984; 10, FlaaseJ. Useof Tisseelin neurosurgery, J Neurosurg 5t r 8 0 1 . ME, JaneJA.NeurosurV/D, Shaffrey 11. ShaffreyCI, Spornirz of duralclo' gicalapplications of fibrin glue:augmentation 1990;26207. Neurosurgery surein 134patients. AJ,PerkinsRC,WelshJE Fibringluein 12. NissenAJ,Johnson otologyandneurotology.Am J Otol 1993;74:147. fibrinogen 13. BartleyGB, McCaffreyTV. Cryoprecipitated (fibrin gluc)in orbital surgery(letter).Am J Ophthalmol 1990;709:227, SM. 14. GleichLL, RebeizEE, PankratovMM, Shapshay A u t o l o g o u sf i b r i n t i s s u ea d h e s i vien e n d o s c o p si ci n u s HeadNeckSurg1995;712:238. 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Autologousfibrin adhesivein mandibtrlarrcconstruction with particulatecancellousbonc and marrow, J Oral Maxillofac Surg1994; 52tl6l' Z L , Kurita K, WestessonPL, ErikssonnL, Stelnby NFL Ostco' plasty of the mandibular condyle with preservationof thc articular soft tissuecover: comparisonof fibrin sealantand suturesfor fixation of thc articular soft tissuecover in rabbits.Oral SurgOral Med Oral Pathol1990; 69$61. 2 2 . Hotz G, Alveolar ridge augnrentationwith hydroxylapatite usingfibrin sealantfor fixation. Part II; Cl.inicalnpplicotion, L5, IntJ Oral Maxillofac Surg 1991; 2Q208, Halling F, Merten HA, Use of fibrin sealantin the tre.ltmcnt o f m a x i l l o f a c i a lh e m a n g i o n r a sI.n r S c h l a gG , B o s c hP , Matras H, eds. Fibrin sealing in surgical and norrsrtrgicrtl fields: orthopedicsurgery, maxillofacial surgcry. llerlin: Springer-Verlag, 1994rt 5 8-I 64' TakimotoT, IshikawaS' NishimuraT, et al. Fibringluc in thc surgicaltreatmentof ranulas.Clin Otolaryngolt989i 14:429. 2 5 . Martinowitz U, Mazar AL, Taicher S, et al. Dental cxtrnctions for patientson oral anticoagulationtherapy,Oral Surg Oral Med Oral Pathol 1990;70274' in 26, RakoczM, MazarA, VaronD, et al. Dentalextractions Theuseof fibringlue'Oral disorders. patients with blceding SurgOralMedOralPathol1993;75:280-282, S' Fibrinscalantin surgcryof 27, MartinowitzU, Schulnran ThrornbHacmost diathesis. patientswith a henrorrhagic t995i74/.86. fibringluc: 28. TaweRL, SydotakGR, DuVallTB. Autologous 168: 1994; Surg Am hemostasis. the laststepinoperative J LZl. andclini' 29. SaltzR, SierraD, FeldmanD, et al. Experimental Surg1991;88: of fibrin glue'PlastReconstr cal applications r005, RA, et al' Effectof fibringlueson 30, ByrneDJ,I-IardyJ, til(/ood propertiesof healingwounds.Br J Surg the rnechanical L997;78t841. 31. MatrasI{, Fibrinseal:thestateof theart.J OralMaxillolac Surg1985;43605-611, Tilruthrich B, SchmidP, SchmidER,TornicM. IgEmediated 32. Lancct reactionto aprotininduringanaesthesia' anaphylactic 1992;34Q2173. 33. $erguerR, Staerkellll, Moore EE, et al. Varningl Fatal reactionto the useof fibrin gluein deephepaticwounds' Casereports. J Traunra1991;31:408,