UPOTREBA Novo Sevena® U TOKU EKSTRAKCIJE ZUBA KOD

UPOTREBA Novo Sevena® U TOKU EKSTRAKCIJE ZUBA KOD

®
Tijanić
i Tijanić
/ Ekstrakcija zuba kod pacijenta
sa poremećajem
koagulacije
uz primenu
Sevena
Acta
Stomatologica
Naissi
decembar/December
2005,
vol. 21, broj/number
52,Novo
str./p 547
– 554
PRIKAZ IZ KLINIČKE PRAKSE
CASE REPORT
UPOTREBA Novo Sevena®
U TOKU EKSTRAKCIJE ZUBA KOD PACIJENTA
SA KONGENITALNIM NEDOSTATKOM VII FAKTORA
KOAGULACIJE – PRIKAZ SLUČAJA
THE USE OF Novo Seven® DURING
DENTAL EXTRACTION IN A PATIENT WITH CONGENITAL
FACTOR VII COAGULATION DEFICIENCY – CASE REPORT
Miloš Tijanić*, Ivan Tijanić**
MEDICINSKI FAKULTET, KLINIKA ZA STOMATOLOGIJU, ODELJENJE ZA ORALNU HIRURGIJU*
UNIVERZITETSKI KLINIČKI CENTAR , KLINIKA ZA HEMATOLOGIJU,** NIŠ, SRBIJA, SRBIJA I CRNA GORA
FACULTY OF MEDICINE, CLINIC OF STOMATOLOGY, ORAL SURGERY DEPARTMENT*
UNIVERSITY CLINICAL CENTER , CLINIC OF HEMATOLOGY,** NIŠ, SERBIA, SERBIA AND MONTENEGRO
Kratak sadržaj
Abstract
Kongenitalna deficijencija VII faktora je redak poremećaj koagulacije. Kongenitalni nedostatak FVII se manifestuje blažim
hemoragičnim poremećajima , pre svega krvarenjima na mukozi i koži
(epistaksa, krvarenje iz desni, menoragija, pojava modrica i dr.), dok su
kod težih oblika moguće intrakranijalne hemoragije, hemartroze, krvarenja iz gastrointestinalnog trakta.
U ovom radu prikazan je uspešan tretman pacijenta sa kongenitalnom deficijencijom FVII, kod koga je bilo potrebno ekstrahirati zub,
primenom rekombinantnog aktivisanog faktora VII, i lokalnih metoda
hemostaze.
Congenital factor VII deficiency is a rare coagulation disorder.
The congenital FVII deficiency is manifested by mild hemorrhagic disturbances, primarily by mucous membrane or skin bleeding (epistaxis,
gingival bleeding, menorrhagia, easy bruising, etc.), while its heavier
forms may exhibit intracranial hemorrhages, hemarthroses, gastrointestinal bleeding.
This paper presents a successful treatment of a patient with congenital FVII deficiency, which had to have his tooth extracted, by the
application of the recombinant activated factor VII and local methods
of hemostasis.
Ključne reči: deficijencija FVII, faktor VIIa, ekstrakcija zuba,
Novo Seven®
Key words: FVII deficiency, factor VIIa, tooth extraction, Novo
Seven®
Uvod
Introduction
Kongenitalna deficijencija VII faktora je
redak poremećaj koagulacije, sa prevalencom
od približno 1: 500.000 u opštoj populaciji.1
Deficijencija VII faktora koagulacije je u li­
teraturi poznata i kao Alexanderova bolest, hypoproconvertinemia ili deficijencija serum protrombin konverzionog akceleratora (SPCA).
Ova kongenitalna koagulopatija se nasleđuje
autozomno recesivno, sa izraženim kliničkim
manifestacijama prevashodno kod homozigota,
dok su hemoragični simptomi kod heterozigota
sporadični.2 Kongenitalna blaga deficijencija
Congenital factor VII deficiency is a rare
disorder of coagulation, with the prevalence of
approximately 1:500.000 in the general population.1 The factor VII coagulation deficiency
is also known in literature as the Alexander’s
disease, hypoproconvertinemia or serum prothrombin conversion accelerator (SPCA) deficiency. The inheritance of this congenital
coagulopathy is autosomal recessive, with pronounced clinical manifestations primarily in
homozygotes, while hemorrhagic symptoms in
heterozygotes are sporadic.2 A minor congeni547
Acta Stomatologica Naissi, decembar/December 2005, vol. 21, broj/number 52
FVII ponekad može koegzistirati sa lakšim
oblicima drugih deficijencija faktora koagulacije: FVIII, FIX, FX, FXI, FV i von Willebrandovom bolesti.3 Osim kongenitalne, deficijencija FVII može biti i stečena, kao posledica
smanjene funkcije jetre i upotrebe vitamin K
antagonista.3
Kod najvećeg broja pacijenata, kongenitalna deficijencija FVII se manifestuje blažim
hemoragičnim poremećajima , pre svega krvarenjima na mukozi i koži (epistaksa, krvare­nje iz
desni, menoragija, pojava modrica i dr.), dok su
kod težih oblika moguće intrakranijalne hemoragije, hemartroze, krvarenja iz gastrointestinalnog trakta. Najteži oblici krvarenja jav­ljaju se
najčešće u prvih šest meseci života.4 Kao jedan od najčešćih simptoma deficijencije FVII
navodi se produženo krvarenje nakon hirurških
intervencija. Kod deficijencije FVII produženo
je protrombinsko vreme, dok su parcijalno protrombinsko vreme, trombinsko vreme, broj i
funkcija trombocita normalni.2
U ovom radu prikazana je uspešna ekstrakcija zuba kod pacijenta sa kongenitalnom deficijencijom FVII, primenom rekombinantnog
aktivisanog faktora VII, i lokalnih metoda hemostaze.
Prikaz slučaja
Pacijent S.A. star 25 godina javio se na
odeljenje Oralne hirurgije Klinike za stomatologiju u Nišu, sa bolovima u predelu molara
donje vilice sa desne strane. U anamnezi pacijent
navodi da od 1982. godine, kada je postavljena
dijagnoza, boluje od Hypoproconvertinaemiae
congenitae, i da je više puta do sada hospita­
lizovan na Klinici za hematologiju Kliničkog
centra u Nišu. Navodi da je alergičan na krvnu
plazmu. U terapiji pacijent koristi jedino tablete
Vitamin C 3x1 dnevno. Pacijent u ličnoj anamnezi negira postojanje drugih hroničnih i dege­
nerativnih oboljenja, kao i postojanje oboljenja
u porodici. Osim umerenih bolova u navedenoj
regiji, pacijent od tegoba navodi i povremeno
krvarenje iz nosa i desni. U trenutku pregleda
nisu konstatovane promene na desnima koje bi
ukazivale na krvarenje. Kliničkim pregledom i
nakon urađenog ortopantomografskog snimka
konstatovano je prisustvo hroničnih periapikalnih lezija na zubu 47, pa je na osnovu veličine
lezije, razorenosti krunice zuba, kao i prethodno
dobijenih anamnestičkih podataka predložena 548
tal FVII deficiency can sometimes coexist with
milder forms of other deficiencies of the coagulation factors: FVIII, FIX, FX, FXI, FV and von
Willebrand’s disease.3 Apart from its congenital
form, the FVII deficiency can also be acquired
as a consequence of decreased liver function
and application of vitamin K antagonists.3
In most of the patients, congenital FVII deficiency is manifested in milder hemorrhagic disorders, most of all in mucosal and skin bleeding (epistaxis, gingival bleeding, menorrhagia,
easy bruising, etc.), while its more severe forms
may lead to intracranial hemorrhages, hemarthroses or gastrointestinal bleeding. The worst
forms of bleeding appear most often during the
first six months of life.4 One of the most frequent FVII deficiency symptoms is a prolonged
bleeding after surgical interventions. In the
FVII deficiency, the prothrombin time is prolonged, while the partial prothrombin time, the
thrombin time and the thrombocyte number and
function are normal.2
This paper describes a successful tooth extraction in a patient with congenital FVII deficiency, by the application of the recombinant
activated factor VII and local methods of hemostasis.
Case report
The patient S.A., 25 years old, came to the
Oral Surgery Department of the Stomatological
Clinic in Niš, having complained of a pain in
the area of the lower jaw dextral molar. In the
anamnesis, the patient declared that since 1982,
when the diagnosis had been made, he had
been suffering from Hypoproconvertinaemiae
congenitae, and that he had been several times
hospitalized in the Clinic of Hematology of the
Clinical Center in Niš so far. He claimed that he
was allergic to blood plasma. In his therapy, the
patient had been using only Vitamin C tablets
3x1 a day. The patient in his personal anamnesis denied the existence of any other chronic
and degenerative diseases as well as any diseases in his family. Apart from moderate pains
in the mentioned area, the patient mentioned
occasional bleeding from nostrils and gums as
problems. Gingival changes that would indicate
bleeding were not observed at the moment of
medical examination. A clinical test and orthopantomographic radiograph showed the existence of chronic periapical lesions in the tooth
47 and, on the basis of lesion size, tooth crown
destruction level and previously acquired an-
Tijanić and Tijanić / Dental extraction in coagulation deficiency with Novo Seven®
ekstrakcija ovog zuba. Zbog osnovnog obolje­
nja pacijent je upućen hematologu radi prethodne pripreme.
U danu prijema na Kliniku za hematologiju
koncentracija VII faktora koagulacije je bila
3%. Sutradan, kada je planirana ekstrakcija
zuba, koncentracija VII faktora u 9 h iznosila je
2%, da bi neposredno posle datog rekombinantnog aktivisanog faktora VII (rFVIIa, NovoSeven®, Novo Nordisk, Denmark) u količini od 1,2
mg (60 Ki.j.) koncentracija FVII iznosila 41%.
Pacijent je odmah upućen oralnom hirurgu, gde
je zub 47 ekstrahiran standardnom tehnikom.
Kao lokalni anestetik korišćen je 2% lidokain
sa adrenalinom koncentracije 1: 80.000 (Lidokain 2% sa adrenalinom, Galenika, Beograd),
u količini od 2ml, koji je aplikovan direktnom
tehnikom za n.alveolaris inferior i n.lingualis,
uz dopunsku anesteziju za n.bucalis. Posle
ekstrakcije zuba urađena je kiretaža hroničnih
periapikalnih procesa, aplikovane 2 kockice
želatinskog preparata (Gelatamp®) u ekstrakcionu ranu i postavljene povratne suture u
vidu osmice korišćenjem resorptivnog konca
amnestic data, the extraction of this tooth was
suggested. Due to his basic disease, the patient
was referred to a hematologist for precursory
preparation.
On the date of his admission to the Clinic
of Hematology, the concentration of the coagulation factor VII was 3%. The next day, when
the tooth extraction was planned, the factor VII
concentration was 2% at 9:00 h, while immediately after the application of the recombinant
activated factor VII (rFVIIa, NovoSeven®,
Novo Nordisk, Denmark) in the quantity of 1.2
mg (60 Ki.j.) the FVII concentration amounted to 41%. The patient was immediately directed to the oral surgeon, where the tooth 47
was extracted by standard technique. For local
anesthetizing, Lidokain 2% with adrenalin was
used in the concentration of 1:80.000 (Lidokain
2% with adrenalin, Galenika, Belgrade), in the
quantity of 2 ml, applied by the direct technique
for n. alveolaris inferior and n. lingualis, alongside with the supplementary anesthesia for n.
bucalis. Upon the tooth extraction, curettage of
chronic periapical processes was performed, 2
foam gelatin sponges (Gelatamp®) were applied
into the extraction socket and closing sutures in
Tabela 1. Koncentracija FVII u toku lečenja
Dan pre
ekstrakcije
Na dan
ekstrakcije
Dan posle
ekstrakcije
Referentne
vrednosti
Fibrinogen g/L
4,24
4,79
4,67
2-4
Protrombinsko vreme
(Quick)
8%
9%
24 %
75-120 %
26,9 s
26,0 s
26,1 s
27-35 s
INR
7,17
6,44
2,70
0,8-1,2
VII faktor
3%
2 % / 41 % *
17 %
50-150 %
Parcijalno tromboplastinsko
vreme
*posle jedne doze rFVIIa
Table 1. Concentration of FVII during the treatment
Day before
extraction
Extraction date
Day after
extraction
Fibrinogen g/L
4,24
4,79
4,67
2-4
Prothrombin time (Quick)
8%
9%
24 %
75-120 %
26,9 s
26,0 s
26,1 s
27-35 s
INR
7,17
6,44
2,70
0,8-1,2
VII factor
3%
2 % / 41 % *
17 %
50-150 %
Partial thromboplastin time
Referential
values
*after one dose of rFVIIa
549
Acta Stomatologica Naissi, decembar/December 2005, vol. 21, broj/number 52
sa atraumatskom iglom (Marlin 4/0 HR17).
U profilaktičke svrhe propisana je peroralna
primena antibiotika (amoxicillini 500mg/8h,
Sinacilin®,Galenika, Beograd) i sedativa (diazepam 2mg/ ,Bensedin®, Galenika, Beograd).
Po okončanju stomatološke intervencije nije
primećeno produženo krvarenje iz ekstrakcione
rane, i pacijent je vraćen na Kliniku za hematologiju, gde je nastavljeno sa primenom rFVIIa
u istoj dozi (1,2mg), još dva puta u razmaku od
8h. Dan posle ekstrakcije i posle 3 date ampule
rFVIIa na 8h, koncentracija VII faktora je bila
17% (tabela 1).
S obzirom da u periodu od 24 h od ekstrakcije
zuba nije bilo znakova krvarenja iz ekstrakcione
rane, pacijent je otpušten na kućno lečenje uz
svakodnevnu kontrolu oralnog hirurga u periodu od narednih sedam dana, u kome takođe nije
bilo komplikacija u smislu krvarenja, postekstrakcionih bolova ili otežanog zarastanja rane.
Diskusija
Sinteza FVII se odvija u jetri i zavisna je od
vitamina K. U krvi cirkuliše približno 1% FVII
koji je u aktivnoj formi (FVIIa). Posle izlaganja
tkivnom faktoru (TF) iz oštećenih ćelija formira
se kompleks TF:FVIIa koji aktiviše X i IX fakor koagulacije3 što konačno vodi ka stvaranju
trombina (slika 1).
the form of figure eight were made of resorptive
catgut by atraumatic needle (Marlin 4/0 HR17).
For the prophylactic purpose, peroral application of antibiotics (amoxicillin 500mg/8h, Sinacilin®, Galenika, Belgrade) and sedatives (diazepam 2mg/, Bensedin®, Galenika, Belgrade)
was prescribed. After the stomatological intervention, no protracted bleeding from the extraction socket was observed and the patient was
sent back to the Clinic of Hematology, where
the application of rFVIIa was continued in the
same dose (1.2 mg) for two more times at intervals of 8 h. One day after the extraction and
upon 3 administered rFVIIa ampoules every
8 h, the concentration of factor VII was 17%
(table 1).
Since there had not been any signs of bleeding in the extraction socket during the period of
24 h from the extraction, the patient was discharged and directed to domiciliary treatment
and daily control by an oral surgeon for the
following period of seven days. In this period
as well, no complications like bleeding, postextractional pains or aggravated healing of the
wound had appeared.
Discussion
The FVII synthesis takes place in the liver
and depends on the Vitamin K. Approximately
1% of FVII in its active form (FVIIa) circulates
Slika 1. Koagulaciona kaskada
(preuzeto sa www.novonordisk.com)
Figure 1. Coagulation cascade (taken
from www.novonordisk.com)
550
Tijanić i Tijanić / Ekstrakcija zuba kod pacijenta sa poremećajem koagulacije uz primenu Novo Sevena®
Težina deficijencije određena je nivoom
FVII, ali je odnos između nivoa faktora i
sklonosti ka krvarenju promenljiv, mada se ozbiljniji simptomi krvarenja javljaju uglavnom
kod pacijenata kod kojih je nivo faktora VII <
1%. 5 Dok se kod obolelih od hemofilije A i
B na osnovu nivoa faktora VIII i IX, može sa
dosta sigurnosti predvideti da li krvarenje može
da nastupi spontano, kao posledica manje ili
veće traume, kod deficijencije FVII taj odnos je
mnogo manje jasan, te postoji opšta saglasnost
da nivo faktora ne određuje sklonost ka krvarenju.
Među najčešćim simptomima krvarenja
kod deficijencije FVII koji su zabeleženi u
Međunarodnom registru deficijencije VII faktora (International Registry of Factor VII Deficiency- IRF7), nalazi se produženo krvarenje
posle ekstrakcija zuba. Postoperativno krvare­
nje je u najvećem procentu zabeleženo upravo
kod ekstrakcije zuba (nezavisno od toga koja je
supstituciona terapija primenjena!) a u odnosu
na tonzilektomiju, histerektomiju, apendektomiju, carski rez, kraniotomiju i druge hirurške intervencije.4 Na osnovu ovih podataka Mariani i
sar.4 zaključuju da su tretman i planiranje prevencije krvarenja kod ove intervencije daleko
od optimuma.
Malo je publikovanih radova u vezi
oralnohirurških intervencija kod pacijenata
sa deficijencijom FVII. Među prvima, svoje
iskustvo su publikovali Perhavec i Goldberg6,
Sumi i sar.7 koji navode da su postekstrakciona krvarenja bila blagog intenziteta. Ovi autori kao supstitucionu terapiju kod pacijenta
sa multiplim ekstrakcijama koriste koncentrovani protrombinski kompleks u postekstrakcionom periodu. U više navrata do otkrivanja
deficijencije FVII je dolazilo upravo posle
produženih krvarenja nakon ekstrakcije zuba
ili oralnohirurških intervencija.8 Cheng i sar.2
navode slučaj produženog profuznog krvarenja nakon hirurške ekstrakcije impaktiranog
očnjaka, uz kontrolu krvarenja lokalnim merama hemostaze, ali je pacijent otpušten tek nakon 14 dana. Billio i sar.9 kao i Kubisz i sar.10
objavili su svoja pozitivna iskustva sa rFVIIa
kod pacijenata sa deficijencijom FVII kod kojih
su ekstrahirani zubi.
U terapiji deficijencije FVII do sada su
korišćeni sveža smrznuta plazma (FFP), koncentrat protrombinskog kompleksa (PCC)
through blood. After having been exposed to
the tissue factor (TF), the TF:FVIIa complex is
formed out of injured cells. It activates X and
IX coagulation factors3, leading to the final creation of thrombin (figure 1).
The deficiency severity is determined by
the level of FVII, but the ratio of the factor level
versus bleeding liability is inconstant, although
heavier bleeding symptoms appear mainly in
the patients with the level of factor VII < 1%.5
In patients with hemophilia A and B it may be
foreseen with quite high certainty, based on the
levels of factors VIII and IX, whether bleeding
may set in spontaneously, as a consequence of
smaller or greater trauma. However, this ratio is
much less confident in the FVII deficiency, so
there is a general consent that the factor level
does not determine liability to bleed.
Prolonged bleeding after dental extractions
is one of the top-frequent symptoms of bleeding
in the FVII deficiency, which have been registered in the International Registry of Factor VII
Deficiency (IRF7). The highest percentage of
postoperative bleeding is recorded precisely in
the dental extraction (regardless of the type of
substitutive therapy administered!), in comparison to tonsillectomy, hysterectomy, appendectomy, cesarean section, craniotomy and other
surgical interventions.4 On the basis of these
data, Mariani et al.4 conclude that the treatment
and planning of bleeding prevention in this intervention are far from being optimal.
Not many papers have been published about
oral surgical interventions in patients with FVII
deficiency. Among the first to publish their experience were Perhavec and Goldberg6 and Sumi
et al.7, who stated that postextractional bleedings had been of mild intensity. These authors
apply concentrated prothrombin complex as a
substitutive therapy for patients with multiple
extractions in the postextractional period. On
several occasions, FVII deficiency was actually
discovered after protracted bleedings following dental extractions or oral surgical interventions8. Cheng et al.2 present the case of protracted profusive bleeding after surgical extraction
of an impacted canine tooth, with the control of
bleeding by local methods of hemostasis, but
the patient was discharged not earlier than after
14 days. Billio et al.9 as well as Kubisz et al.10
published their positive experiences with rFVIIa in patients with FVII deficiency who had to
have their teeth extracted.
In the therapy of FVII deficiency, fresh frozen plasma (FFP), prothrombin complex concentrate (PCC), as well as concentrated FVII
551
Acta Stomatologica Naissi, decembar/December 2005, vol. 21, broj/number 52
kao i koncentrovani FVII dobijen iz plazme
(pd-FVII). Sveža smrznuta plazma iako lako
dostupna, nosi rizik od povećanja cirkulatornog
volumena, dok kod protrombinskog kompleksa
postoji visok rizik od tromboze nakon ponovljene primene, kao i kod pd-FVII.4
Od skoro je u Evropi odobrena upotreba
rekombinantnog aktivisanog FVII (rFVIIaNovoSeven®) i u terapiji kongenitalne deficijencije FVII. Rekombinantni FVIIa je proizvod
savremene biotehnologije, bez humanih derivativa čime se isključuje rizik kontaminacije
ljudskim virusima i obezbeđuje proizvodnja u
većim količinama. U kliničkoj upotrebi nalazi
se od 1996.godine10, a primarno je korišćen u
terapiji hemoragija kod pacijenata koji boluju
od hemofilije A ili B sa inhibitorima FVIII ili
FIX, zašta se i danas najviše koristi. rFVIIa je korišćen i pri ekstrakcijama kod obolelih od
hemofilije A sa inhibitorima.11 Laguna i Klukowska12 navode uspešnu primenu rFVIIa pri
ekstrakcijama kod pet pacijenata sa inhibitorima, pri čemu je kod dva pacijenta korišćen
nakon prethodne neuspešne terapije FEIBAom
(factor eight inhibitor bypassing activity) i
PCC-om (prothrombin complex concentrates).
Ciavarella i sar.13 su uspešno koristili rFVIIa pri
oralnohirurškim intervencijama kod dva pacijenta obolelih od von Willebrandove bolesti sa
inhibitorom von Willebrandovog faktora. Kod
dva pacijenta sa cirozom jetre kod kojih je nakon
ekstrakcije zuba bilo prisutno produženo krvarenje, a koje nije prestajalo ni nakon primene
sveže zamrznute plazme (FFP), uspešno su
tretirani rFVIIa14, kao i u slučaju hirurškog
ukla­njanja impaktiranih zuba kod pacijenata sa
Glanzmannovom trombastenijom.15
Naravno, u svim prethodno navedenim
slučajevima osim sistemske primene rFVIIa
istovremeno su korišćene i lokalne mere hemostaze (najčešće fibrinski lepak), kao i lokalni
tretman antifibrinoliticima.
Osim visoke cene rFVIIa, koja je njegov
glavni nedostatak, problem je (kao i humanog
FVII) kratak polu-život od 2,5-3h, što zahteva
učestaliju primenu u toku lečenja. Preporučena
doza rFVIIa od strane proizvođača u tretmanu
kongenitalne deficijencije FVII iznosi 15-30
μg/kg telesne težine na 4-6h, dok se u tretmanu
hemofilije sa inhibitorima preporučuju znatno
više doze, 90 μg/kg TT na svaka dva sata.
552
obtained from plasma (pd-FVII) have been used
so far. Although easily available, fresh frozen
plasma bears the risk of increasing circulatory
volume, while there is a high risk of thrombosis
upon repeated administration of prothrombin
complex and pd-FVII.4
The usage of recombinant activated FVII
(rFVIIa- NovoSeven®) has recently been permitted in Europe for the therapy of congenital
FVII deficiency, too. The recombinant FVIIa is
the product of modern biotechnology, without
human derivatives, which excludes the risk of
contamination with human viruses and provides the production of larger quantities. It has
been in clinical use since 199610, with primary
application in the therapy of hemorrhages in patients suffering of hemophilia A and B with inhibitors FVIII or FIX, and it is still mostly used
in these cases. The rFVIIa has also been used
for the extractions in hemophilia A patients
with inhibitors.11 Laguna and Klukowska12
report on a successful application of rFVIIa in
the extractions in five patients with inhibitors,
where in two patients it was administered after
the treatment with FEIBA (factor eight inhibitor bypassing activity) and PCC (prothrombin
complex concentrates) had failed. Ciavarella
et al.13 successfully applied rFVIIa in oral surgical interventions in two patients suffering
from von Willebrand’s disease and an inhibitor
against von Willebrand factor. The treatment
with rFVIIa proved successful in two cirrhotic
patients who had prolonged bleeding following
dental extractions, which could not have been
stopped even after the administration of fresh
frozen plasma (FFP)14, as well as in the case of
surgical removal of impacted teeth in patients
with Glanzmann thrombasthenia.15
Of course, in all the mentioned cases, except for the systematic rFVIIa administration,
local methods of hemostasis (most often fibrin
sealant) as well as local treatment with antifibrinolytics were simultaneously applied.
Alongside with a high price of rFVIIa, which
is its major disadvantage, another problem is
(like in the human FVII) its short half-life of
2.5-3 h, as it requires more frequent application
during the treatment. The rFVIIa dose recommended by the producer for the treatment of
congenital FVII deficiency equals 15-30 μg/kg
of bodyweight every 4-6 h, while much higher
doses are recommended for the treatment of hemophilia with inhibitors, amounting to 90 μg/
kg of bodyweight every 2 hours.
Tijanić and Tijanić / Dental extraction in coagulation deficiency with Novo Seven®
Rekombinantni aktivisani FVII je po­
red lečenja krvarenja kod pacijenata sa
poremećajima hemostaze (hemofilia A, B sa
inhibitorima, kongenitalna deficijencija FVII,
XI, von Willebrandova bolest, Glanzmann-ova
trombastenija, trombocitopenia, bolesti jetre),
uspešno korišćen i kod pacijenata sa normalnom hemostazom, a kod kojih je postojala indikacija (intrakranijalne hemoragije, traume,
veće hirurške intervencije i dr.).16,17
Ekstrakcija zuba, iako ne spada u „velike“
hirurške intervencije, s obzirom na specifičnosti
usne duplje predstavlja intervenciju povećanog
rizika od krvarenja kod pacijenata sa kongenitalnom deficijencijom FVII, pa je potrebno
sprovesti sistemske i lokalne mere hemostaze. Recombinant activated FVII was, beside
treating bleeding in patients with hemostasis
disorders (hemophilia A, B with inhibitors, congenital deficiency FVII, XI, von Willebrand’s
disease, Glanzmann thrombasthenia, thrombocytopenia, liver diseases), applied with success
in patients with normal hemostasis, in which
there was an indication (intracranial hemorrhages, traumas, major surgical interventions,
etc.).16, 17
Taking into consideration characteristics of
the oral cavity, dental extraction, although it
does not fall under „major“ surgical interventions, represents an intervention with increased
risk of bleeding in patients with congenital FVII
deficiency. Therefore, it is necessary to conduct
systemic and local methods of hemostasis.
LITERATURA / REFERENCES
1. Roberts HR, Hoffman M. Hemophillia and related
conditions – Inherited deficiencies of prothrombin, factor
V, and factors VII to XIII. In Beutler E, Lichtman MA,
Coller BS, Kipps TJ, eds.Williams Hematology, 5th Ed New York, McGraw Hill, Inc, 1995, 1413-1439.
9. Billio A, Pescosta N, Rosanelli C, Amadii G,
Fontanella F, Coser P. Succesful short-term oral surgery
prophylaxis with rFVIIa in severe congenital factor VII deficiency. Blood Coagul Fibrinolysis 1997 Jun; 8(4):
249-250.
2. Cheng JC, Wong RW, Yan BS. Postoperative
bleeding with factor VII deficiency: case report. Aust
Dent J 1998 Dec;43(6): 382-4.
10. Kubisz P, Staško J. Recombinant activated factor
VII in patients at high risk of Bleeding. Hematology 2004
Oct/Dec; 9(5/6): 317-332.
3. Ingerslev J, Kristensen HL. Clinical picture and
treatment strategies in factor VII deficiency. Haemophilia 1998; 4: 689-696.
11. Morimoto Y, Yoshioka A, Shima M, Kirita T. Intraoral hemostasis using a recombinant activated factor
VII preparationin a hemophilia A patient with inhibitor. J
Oral Maxillofac Surg 2003; 61: 1095-1097.
4. Mariani G, Dolce A, Marchetti G, Bernardi F.
Clinical picture and managment of congenital factor VII 12. Laguna P, Klukowska A. Managment of oral
deficiency. Haemophilia 2004; 10(S4): 180-183.
bleedings with recombinant factor VIIa in children with
5. Tcheng WY, Donkin J, Konzal S, Wong WY. Re- haemophilia A and inhibitor. Haemophilia 2005 Jan;11(1):
combinant factor VIIa prophylaxis in a patient with se- 2-4.
vere congenital factor VII deficiency. Haemophilia 2004;
13. Ciavarella N, Schiavoni M, Valenzano E, Mangi10: 295-298.
ni F, Inchingolo F. Use of recombinant factor VIIa (No6. Perhavec JC, Goldberg JS. Management of a pa- voSeven) in the treatment of two patients with type III
tient with Factor VII deficiency. Oral Surg Oral Med Oral von Willebrand’s disease and an inhibitor against von
Willebrand factor.Haemostasis 1996; 26(S1): 150-154.
Pathol 1980 Jul;50(1):17-20.
7. Sumi Y, Shikimori M, Kaneda T, Kitajima T. Multiple extractions in a patient with factor VII deficiency. J
Oral Maxillofac Surg 1985; 43: 382-384.
8. Wei DC, Wong RW, Robertson EP. Congenital factor VII deficiency presenting as delayed bleeding following dental extraction. A review of the role of factor VII in
coagulation. Pathology 1997 May; 29(2): 234-237.
14. Berthier AM, Guillygomarch A, Messner M,
Pommereuil M, Bader G, De Mello G. Use of recombinant factor VIIa to treat persisting bleeding following
dental extractions in two cirrhotic patients. Vox Sanguinis 2002; 82: 119-121.
15. Chuansumrit A, Suwannuraks M, Sri-Udimporn
N, Pongtanakul B, Worapongpaiboon. Recombinant
553
Acta Stomatologica Naissi, decembar/December 2005, vol. 21, broj/number 52
activated factor VII combined with local measures in
preventing bleeding from invasive dental procedures in
patients with Glanzmann thrombasthenia. Blood Coagul
Fibrinolysis 2003 Feb; 14(2): 187- 190.
17. Khan AZ, Parry JM, Crowley WF, McAllen K,
Davis AT, Bonnell BW, Hoogeboom JE. Recombinant
factor VIIa for the treatment of severe postoperative and
traumatic hemorrhage. Am J Surg 2005; 189: 331-334.
16. Roberts H, Monroe D, White G. The use of recombinant factor VIIa in treatment of bleeding disorders.
Blood 2004 Dec; 104(13): 3858-3864.
Adresa za korespondenciju:
Mr Sc. dr Miloš Tijanić
Klinika za stomatologiju
Odeljenje za oralnu hirurgiju
Bul. Dr Zorana Đinđića 52
18000 Niš, Srbija i Crna Gora
E-mail: [email protected]
554
Address of correspondence:
Miloš Tijanić, DMD, MSD
Clinic for Stomatology
Dep. of Oral Surgery
52 Dr Zorana Đinđića Street
18000 Niš, Serbia and Montenegro
E-mail: [email protected]