The typology of coagulation disorders is extremely heterogeneous. Today, we
patients taking oral anticoagulant therapy (OAT), a prophylaxis against the
thromboembolic events [1-2] .
Recent studies on the Italian population indicate an estimated 250.000 patients
taking OAT to date.
Indications for use of this pharmacological prophylaxis [3-4] are confirmed by
vasculopathies with thromboembolic etiology, a few enzymatic-receptorial
anomalies, as well as
qualitative/quantitative alterations of some cellular hematic components [5-6] .
Today, we deal with patients undergoing dicoumarolics therapy, which interfere
metabolism of vitamin K and therefore with the synthesis of coagulation factors?
II, VII, IX, and
X [7-8]. These patients often take the most frequent OAT, such as:
acenocoumarol: intermediate action, which begins within 24?48 h and ends within
warfarin: long and delayed action from 3 to 7 days.
Warfarin has a more permanent and long-lasting effect, because of its longer
(about 36 h).
The aim of the present study was to apply a protocol, which could provide a safe
postoperative management of patients on OAT.
Materials and Methods
In the present multicentric study, we focused on a cohort of 193 patients (119
men aged between 46
and 82 years and 74 women aged between 54 and 76 years) undergoing OAT for more
than 5 years.
This study is carried out in compliance with the Helsinki Declaration; it is
divided into a
preoperative phase, an intraoperative phase, and a postoperative phase including
a) Preoperative Phase
Medical history was carried out through specific questionnaires for the
diagnosis of hemorrhagic
disorders  . We asked the patients if they ever had hemorrhagic diathesis,
its type (spontaneous or
post-traumatic/post-surgical), and outcome. It is important to ask the patients
if they drink alcohol
or take unnecessary substances  . A careful assessment of the ongoing
should be carried out. Some currently used drugs (such as penicillin and
trimetoprim, gentamicin, rifampicin, analgesics and non-steroidal
(NSAIDS), cardiovascular and anti-diabetic drugs, diuretics, platelet
anti-aggregants, heparins, gold
salts, and anti H2) can produce thrombocytopenia  .
On the day of the surgery, the dental surgeon has to investigate the patient?s
hemocoagulative structure through a series of hematoclinical examinations.
Counseling between the dental surgeon, patient, and hygienist is necessary to
make patients aware
of the importance of dental hygiene in preventing dental and periodontal
pathologies, which could
later require more destructive and invasive therapies  .
In addition to this, inflammatory or degenerative pathologies of the oral cavity
play a crucial role in
the genesis of bacterial endocarditis, a non-rare phenomenon among chronic
and among those with valvular prostheses  .
Bacterial Endocarditis (BE) is a potentially lethal disease, even if patients
are on antibiotics.
Mortality can reach up to 30% of cases.
The British Society Antimicrobial Chemotherapy (BSAC) has revised the cardiac
table of patients
risking BE. According to these new indications, there are 3 types of patients
1) patients with previous BE;
2) patients with cardiac valve replacement; and
3) patients who
underwent surgical shunt creation, especially in the cardiopulmonary area.
These new guidelines are no longer ambiguous about performing an antibiotic
prophylaxis (table 1)
apart from the routinely removal of infections during the days preceding the
The aim of antibiotic prophylaxis is to have an effective serum concentration
of the active principle
during the whole perioperative period.
The antibiotic therapy should be given shortly after the beginning of the
treatment (1?2 h) and
within 6?8 h from surgery; a longer therapy is justified only in case of
infected tissues or delayed
b) Intra-operative phase
Fifteen days before surgery, periodontal preparation of patients through tartar
ablation by means of
an ultrasonic equipment. To avoid periodontal hemorrhages, it is necessary to
invite patients (before
ablation) to do oral rinses for 1 min, with 10 ml of 4.8% solution of tranexamic
acid. Moreover, it is
important to prescribe to patients oral rinses with chlorhexidine digluconate
0.12%, 2 times a day
for 14 days before surgery.
The day of surgery, it is necessary to assess the hemocoagulative parameters by
taking a blood
sample, which will allow to evaluate PT, PTT, and especially the INR measured 24
h before surgery.
In the last 3 years, we treated 193 patients on OAT with a standardized
management and a 2-months
follow-up. Although we evaluated every single clinical case in its uniqueness,
we wanted to apply a
protocol providing for a safe intra- and postoperative management of patients
There are not any contraindications to the use of local anesthetics:
mepivacaine, lidocaine, or
articaine are recommended (articaine is needed when an intense ischemia is
required and when
surgery lasts more than 1 h, thanks to its longer action than mepivacaine and to
effectiveness in controlling postoperative pain).
The literature does not recommend the use of vasoconstrictors as they could
episodes ; nevertheless, we think that a safe use of a vasoconstrictor is
possible by means of an
aspirating syringe (carpule) and a good anesthesia technique, except for
patients who recently had a
myocardial infarction or coronary artery bypass surgery (≤ 8 months).
This will bring 2 advantages:
1) The vasoconstrictor will guarantee an optimal zonal ischemia and a longer
which is very useful when treating hemorrhagic patients  ;
2) The vasoconstrictor (red phials) allows for an effective anesthesia, using a
smaller quantity of
anesthetic compared to green phials (anesthetic without vasoconstrictor).
Among the hemostatic agents that a dental surgeon can use, there are ferric
cellulose, gelatin sponges, and anti-fibrinolytics.
Oxidized regenerated cellulose  (Surgicel, Tabotamp) consists of a sterile
gauze and oxidized
cellulose. First, it acts as a mechanical barrier and then as a viscous mass,
which works as an
Antifibrinolytics (Tranex, Ugurol) perform a good local hemostatic action.
Local use of tranexamic acid to prevent and treat hemorrhage in the oral cavity
The use of this active principle encourages clot formation and reduces the
bleeding time  .
Before surgery, we perform a standardized preoperative procedure.
We recommend a pre-anesthesia by administering benzodiazepines (15 gtts, 20 min.
surgery). As a matter of fact, premedication allows for greater patient
compliance during surgery,
and the adrenalin plateau caused by intraoperative stress will be avoided.
We suggest to our patients oral rinses with chlorhexidine digluconate 0.2%
solution  .
A careful disinfection of perioral and intraoral mucus-dental tissues by using
an iodized solution is
also necessary. Rinsing the operating field with tranexamic acid solution (4.8%)
allows to control
hemostasis since initial dieresis.
Performing a venous access allows to operate quickly in case of hemorrhagic
emergency. In this
case, patients could have hypotensive phenomena, which involve difficult
identification of the
venous access, because vessels could be partially collapsed.
In major oral surgery, 2 g of tranexamic acid are administered intravenously
(IV) 1 h before surgery
(divided into 4 x 0.5g doses every 15 min) and after preparing the venous access
The cardiac activity and the pressure status have to be steadily monitored
using specific equipment
The surgical procedure is performed following a standardized controlled
A plexus, intraligamentous, or locoregional anesthesia is performed using a slow
mepivacaine 3%; we have described above what we think about the use of
will bring more benefits than objective risks. Following a periotome
syndesmotomy, a luxation of
the dental-alveolar gomphosis will be performed. We suggest to reduce to a
minimum the use of
surgical elevators, because the moments of force of these instruments cause
severe trauma to soft
tissues along with microlesions to the alveolar ridge. After avulsion, manual
reduction of the
?greenstick? fracture 
of the post-extractive alveolus will be performed by two-finger
compression of the vestibular and lingual-palatal alveolus portions, in order to
reduce the fracture
occurred during avulsion.
Accurate alveolar bone cleaning is to perform: by means of an alveolar spoon, we
will remove all
the possible granulation tissues representing the primum movens in the residual
namely post-extractive alveolites [1-2] .
A bone rongeur or a bone mill with a turbine motor (continuous irrigation)
allows to eliminate the
bone roughness, which could damage the soft tissues of the antagonist arch. We
post-extraction alveolus with oxidized regenerated cellulose.
we suggest an absorbable suture (Vicryl 3/0 or 4/0 to avoid trauma of suture
removal) using a
?simple running stitch,? with a further safety suture using a ?simple
interrupted stitch? ; then, there
will be a 30 minute compression of the surgical area, followed by sterile gauze
with tranexamic acid. If bleeding stops about 30 min later, it is the clinical
demonstration of the
technical success of surgery.
c) Post-operative phase
Patients should be discharged at least 60 minutes after surgery (in order to
verify the absence of
hemorrhagy); we advise a cold and liquid diet during the next 3 days and a tepid
and semiliquid diet
during the following 3 days.
Patients should perform oral rinses for 2 minutes with 10 ml of tranexamic acid,
4 times a day for 7
days  . After rinsing, patients should not drink or eat for about an hour.
During the first 30 days after surgery, we suggest patients to rinse their mouth
every 12 h with
chlorhexidine digluconate 0.12% solution; anti-inflammatory therapy should be
prescribed only in
case of complex surgeries or if patients experience postoperative pain: 500 mg
of paracetamol every
8 hours will be a precaution against hemorrhagic problems caused by the NSAIDs.
The highest risk of postoperative hemorrhagic diathesis is during the first 12 h
after the surgery; our
follow-ups allow us to exclude hemorrhagic relapse from the 6th day after the
In case of postoperative hemorrhage, a buffer imbibed in tranexamic acid should
together with compression of the area ; if bleeding persists, up to 2 g of
tranexamic acid divided
into 4 doses of 0.5 g has to be administered. In incoercible cases, it is
indispensable to consult the
hematologist in order to reduce OAT and develop a strategy to stop hemorrhagic
diathesis [19-20] .
We recommend the use of absorbable sutures (Vicryl 3/0 or 4/0) to avoid trauma
caused by suture
removal. Non-absorbable sutures are particularly indicated for areas presenting
muscles, frenula, etc. Removal should nonetheless be performed on the 8th day
and in the less
traumatic way. In case of slight hemorrhages, it is enough to apply a tampon of
tranexamic acid and
repeat oral rinses for 1 or 2 days.
Regular follow-ups should be planned (7, 15, 30, and 60 days after surgery).
They include intra- and
extraoral examinations, a measurement of symptoms of pain by visual analogue
scale (VAS), the
motivation of patients to oral hygiene, and the possibility of further dental
Out of 193 treated patients, just 2 of them (only 1.03% of cases) had problems
related to surgery:
the 1st one had a slight hematoma in the area of labial commissure, due to the
trauma caused by the
Farabeuf retractor, but it regressed in a few days.
The 2nd one had pains and
did not present clot
formation in the post-extractive site. Intraoral examination confirmed the
diagnosis of post-extractive alveolitis, while the forthcoming pathological medical history
indicated that the patient
did not follow hygiene rules (smoker) in the immediate postoperative period; the
cleaned and the symptoms significantly reduced in the follow-up period.
The results of this study show a protocol which allows a safe treatment of
patients on OAT.
The problems that may principally arise in this type of surgical patients are
related to a deficient or
excessive clotting, we may also have problems of excessive susceptibility to
With this protocol we have treated 193 patients and we have had none of these
problems, except in
only 2 cases. These data are significant and show that the management of these
patients is possible
if we follow a proper protocol such as this one here described.
Dental procedures represent a particularly common intervention for patients
therapy. The most recent literature indicated that in most cases, no change in
the intensity of
anticoagulation is needed. As we can highlight in the literature, there are no
of severe bleeding in this setting, but there are many documented cases of
embolic events in
patients whose warfarin therapy was discontinued for dental treatment. If there
is a need to control
local bleeding, tranexamic acid administration has been used successfully
anticoagulant therapy [18-19] .
The diathesis of bleeding is significantly related to the intensity of the
Therefore, in patients who show a severe bleeding, every effort should be made
to maintain the INR
at the lower limit of the therapeutic range. For patients with mechanical
prosthetic valves (and a persisting risk of increased bleeding), it would be reasonable to aim for an
INR range of 2.0 to 2.5.
For patients with atrial fibrillation (and a persisting risk of increased
bleeding), the anticoagulant
intensity can be reduced to an INR range of 1.5 to 2.0 with the expectation that
efficacy will be
reduced but not abolished. Alternatively, aspirin can be used to replace
warfarin in patients with
atrial fibrillation, but also with a reduced efficacy in high-risk patients 
In the past, the scientific literature often recommended OAT interruption in
order to avoid intra- and
postoperative hemorrhagic risk: in a research carried out in 1996 in the USA,
around 70% of
clinicians recommended their patients to interrupt anticoagulant treatment
before undergoing dental
treatments, with a risk of hemorrhage. In this light, we want to underline how
the interruption of an
anticoagulant therapy, even for a short time, exposes the patient to
thromboembolic risks, even
many days after treatment: the analysis of 500 documented cases of patients who
anticoagulant therapy to undergo oral surgery revealed that 5 patients (0.95%)
episodes; 4 of them had fatal thromboembolism, while 1 patient had 2 embolic
A randomized study showed how OAT interruption to perform minor oral surgery
does not imply
any real clinical benefit [4-5] .
Even in those cases in which we are performing surgical treatments particularly
invasive, or we are
treating a syndromic condition closely related to an augmented bleeding risk, we
can emphasize the
effectiveness of the association between a conscious administration of
tranexamic acid and a well
done surgical performance, especially if we follow a well documented protocol
We think that the protocol analyzed in the present study can be used in complete
safety for the
treatment patients receiving OAT, even though a few factors can alter the
patient response to the
protocol. The recommendations that urge to maintain the INR at the lower limit
of the therapeutic
range are still actual, although, the evaluations to do are closely related to
each patient, to his
general conditions and to the typology of oral surgery to perform.
Table 1: Pattern of Antibiotic Prophylaxis
|Adults: 2 gm per os, 1 hour before surgery 1,5 gm per os, 6 hours after
Children: 50 mg/Kg per os, 1 hour before surgery
PATIENTS UNABLE TO TAKE DRUGS PER OS
| Adults: 2 gm i.m., before surgery
Children: 50 mg/Kg ev or im, 30 min before surgery
|Adults: 600 mg per os, 1 hour before surgery
Children: 20 mg/Kg per os, 1 hour before surgery Cephalexin* or
Adults: 2 gr per os, 1 hour before surgery
Children: 50 mg/Kg per os, 1 hour before surgery Azithromycin or
Adults: 500 mg x os 1 hour before surgery
Children: 15 mg/Kg per os, 1 hour before surgery
|Adults 600 mg ev, 30 min before surgery
Children: 20 mg/Kg ev, 30 min before surgery Cephazolin*
Adults: 1 gr im, 30 min before surgery
Children: 25 mg/Kg im or ev, 30 min before surgery *provided that there
are no serious allergic reactions to penicillin
Written informed consent was obtained from the patients for publication of this
case report and
accompanying images. A copy of the written consent is available for review by
of this journal.
The authors declare that they have no competing interests.
FI and FMA participated in the surgical treatment and in the follow-up
examinations. MT and SS
drafted the manuscript and revised the literature sources. MM and GD
participated in the follow-up
examinations. Dr. Papa analyzed the data carried out from the multicentric study
and revised the
ADI revised the literature sources. AMI managed the data collection and
contributed to writing the
paper. All authors read and approved the final manuscript.
Department of Dental Sciences and Surgery, University
of Bari, Bari, Italy
Department of Medical Biochemistry, Medical Biology and
Physics, University of Bari, Bari, Italy
Department of ?Head and Neck Diseases? , Hospital ?Fatebenefratelli?,
Department of Maxillofacial Surgery, Calabrodental,
Department of Dental Sciences and Surgery, Dental
School , Bari, Italy
Department of Surgical, Reconstructive and Diagnostic
Sciences, University of Milano, Milano, Italy
Corresponding author: Prof. Francesco Inchingolo, Place
Giulio Cesare – Policlinico 70124 – Bari. E-mail: firstname.lastname@example.org.
Tel.: 00390805593343 – Infoline: 00393312111104.
Oral Anticoagulant Therapy (OAT); Tranexamic Acid; Oral Surgery
Inchingolo F, Tatullo M, Abenavoli FM, Marrelli M, Inchingolo AD, Scacco
S, Papa F, Inchingolo AM, Dipalma G.