Use of Fibrin Glue in Maxillofacial Surgery

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,
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