688 Letters to the Editor
exercise in patients with IDDM. Thromb Haemost 2003; 90:
References
1 Laing SP, Swerdlow AJ, Slater SD, Burden AC, Morris A, Waugh
NR, Gatling W, Bingley PJ, Patterson CC. Mortality from heart
disease in a cohort of 23.000 patients with insulin-treated diabetes.
Diabetologia 2003; 46: 760–5.
2 Larsen J, Brekke M, Sandvik L, Arnesen H, Hanssen KF, Dahl-
Jørgensen K. Silent coronary atheromatosis in type-1 diabetic patients
and relation to long-term glycemic control. Diabetes 2002; 51: 2637–41.
3 Lehto S, Ronnemaa T, Pyorala K, Laakso M. Poor glycemic control
predicts coronary heart disease events in patients with type-1 diabetes
without nephropathy. Arteroscler Thromb Vasc Biol 1999; 19: 1014–9.
4 Dahl-Jørgensen K, Brinchmann-Hansen O, Hansen KF, Ganes T,
Kierulf P, Smeland E, Sandvik L, Aagenes O. Effects of near
normoglycemia for two years on progression of early diabetes retin-
opathy, nephropathy, and neuropathy: the Oslo study. BMJ 1986; 293:
1195–9.
5 The Diabetes Control and Complications Trial Research Group. The
effects of intensive insulin treatment of diabetes on the development
and progression of long-term complications in insulin-dependent
diabetes mellitus. N Eng J Med 1993; 329: 977–86.
6 Juhan-Vague I, Thompson SG, Jespersen J. Involvement of the
hemostatic system in the insulin resistance syndrome. A study of 1500
patients with angina pectoris. Arteroscler Thromb 1993; 13: 1865–73.
7 Wieczorek I, Pell ACH, McIver B, MacGregor IR. Coagulation and
fibrinolytic systems in type 1 diabetes: effects of venous occlusion and
insulin-induced hypoglycaemia. Clin Sci 1993; 84: 79–86.
8 Hilberg T, Eichler E, Gläser D, Prasa D, Stürzebecher J, Gabriel
HHW. Blood coagulation and fibrinolysis before and after exhaustive
Oral surgery in patients on oral anticoagulant therapy:
a randomized comparison of different INR targets
R . S A C C O , * M . S A C C O ,   M . C A R P E N E D O à and M . M O I A à
*Department of Maxillo-Facial Surgery, Italian Stomatology Institute, Milan;  Department of Clinical Epidemiology, Mario Negri Sud
Consortium, S. Maria Imbaro; and àA. Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Mangiagalli and Regina
Elena Foundation and University of Milan, Milan, Italy
To cite this article: Sacco R, Sacco M, Carpenedo M, Moia M. Oral surgery in patients on oral anticoagulant therapy: a randomized comparison of
different INR targets. J Thromb Haemost 2006; 4: 688–9.
Patients receiving oral anticoagulant therapy (OAT) are a
clinical challenge when therapy has to be interrupted to carry
out invasive procedures. Dental procedures represent a partic-
ularly common intervention for these patients. A number of
reports indicate that in most cases it is not necessary to change
the intensity of OAT [1–5]. Nevertheless, there is still a
widespread belief among dental practitioners and physicians
that OAT must be discontinued to prevent hemorrhagic
complications, particularly in case of invasive procedures such
as dental extractions or fixture insertions. However, OAT
Correspondence: M. Moia, Via Pace 9, 20122 Milan, Italy.
E-mail: moia@policlinico.mi.it
Received 27 October 2005, accepted 28 October 2005
1065–73.
9 Seljeflot I, Arnesen H, Eritsland J, Smith P. D-dimer test after stan-
dardized coagulation. A new assay for evaluation of the unstimulated
fibrinolytic system. Fibrinolysis 1993; 7: 303–7.
10 Dahl-Jørgensen K, Larsen AE. HbA1c determination by agar gel
electrophoresis after elimination of labile HbA1c: a comparison with
ion-exchange chromatography. Scand J Clin Lab Invest 1982; 42:
27–33.
11 Ahmed N. Advanced glycation endproducts – role in pathology of
diabetic complications. Diabetes Res Clin Pract 2005; 67: 3–21.
12 Bonnefont-Rousselot D. Glucose and reactive oxygen species. Curr
Opin Clin Metab Care 2002; 5: 561–8.
13 Uchida Y, Ohba K, Yoshioka T, Irie K, Muraki T, Maru Y. Cellular
carbonyl stress enhances the expression of plasminogen activator
inhibitor-1 in rat white adipocytes via reactive oxygen species-
dependent pathways. J Biol Chem 2004; 279: 4075–83.
14 Nielsen VG, Crow JP, Zhou F, Parks DA. Peroxynitrite inactivates
tissue plasminogen activator. Anesth Analg 2004; 98: 1312–7.
15 Basta G, Schmidt AM, De Caterina R. Advanced glycation end
products and vascular inflammation: implication for accelerated
atherosclerosis in diabetes. Cardiovasc Res 2004; 63: 582–92.
16 Hansen TK, Thiel S, Knudsen ST, Gravholt CH, Christiansen JS,
Mogensen CE, Poulsen PL. Elevated levels of mannan-binding lectin
in patients with type 1 diabetes. J Clin Endocrinol Metab 2003; 88:
4857–61.
17 Chase HP, Cooper S, Osberg I, Stene LC, Barriga K, Norris J,
Eisenbarth GS, Rewers M. Elevated C-reactive protein levels in
the development of type 2 diabetes. Diabetes 2004; 53: 2569–73.
discontinuation may engender the risk of thromboembolism,
particularly in patients with atrial fibrillation. With this as the
background, we designed a prospective, randomized, open-
label study to evaluate the outcome of oral surgery in patients
on OAT operated upon conditions of reduced International
Normalized Ratio (INR) values, compared with patients
maintained in their usual therapeutic ranges.
Eligible cases were individuals of any age on OAT for at least
1 month for any reason. A clinical evaluation, including a
general medical evaluation and a surgical and radiological
evaluation through orthopantomography, was carried out.
Each patient’s medical history was evaluated, with special
emphasis on the indication for OAT, its dosage, length of
treatment and the type of drug prescribed. We included in the
study 131 consecutive patients on long-term OAT because of a
prosthetic valve (45%), atrial fibrillation (30%), venous

2006 International Society on Thrombosis and Haemostasis
 Letters to the Editor 689

thromboembolism (12%), heart valvulopathy (10%), and
other indications (3%). All the procedures were carried out
by the same oral surgeon. Before undertaking 511 dental
extractions (in average four teeth per patient), six fixture
insertions and six exeresis of cystic neoformations, patients
were randomized to two treatment groups. In group A (mean
age 64 ± 11 years), OAT dosage was reduced during the 72 h
before surgery to attain INR values between 1.5 and 2.0 (target
1.8) on the day of surgery. The mean INR value actually
attained in this group was 1.77 ± 0.26. In group B (mean age
61 ± 12 years), OAT dosage was not reduced, but hemostatic
agents such as tranexamic acid, oxidized cellulose or collagen
sponges were applied on the surgically treated region. The
mean INR measured in this group was 2.89 ± 0.42 on the day
of surgery.
After 2 h of postsurgical observation, all patients were
discharged and received written instructions to avoid non-
steroidal anti-inflammatory drugs (only paracetamol was
allowed), to record the length and severity of any bleeding
and to contact the center immediately in case of bleeding not
controlled by compression for 20 min. Patients in group A
were required to restore oral anticoagulant treatment to return
to their regular INR on the day after the procedure, while those
of group B were asked to continue their regular dosage. All
patients were summoned 7 days after the procedure for the
removal of the sutures. During this examination, the presence
or absence of late bleeding was also recorded. Only patients in
group B (OAT not reduced) were instructed to perform
mouthwashing with tranexamic acid at home (10 mL for
2 min, four times daily, for 6 days after procedure), and a daily
telephonic contact by a nurse was arranged for 6 days after the
procedure. Bleeding was considered as an ‘event’ if any
intervention by the surgeon was needed to stop it either with
a new suture or with placement of other local hemostatic
agents. Bleeding successfully managed at home by patients
were not considered an event.
Bleeding excessive enough to warrant adoption of supple-
mentary local hemostatic measures was observed, in 10 cases
(15.1%) in group A (reduced dosage) and in six (9.2%) in group
B (unmodified dosage). Bleeding, irrespective of the group, was
treated with the insertion of oxidized cellulose inside the
procedural area. There was no thrombotic complication in
these patients. This randomized study shows that, using simple
and inexpensive measures for local hemostasis, it is not necessary
to reduce OAT intensity in patients undergoing oral surgery.
The adoption of this procedure may prevent thromboembolic
complications associated with subtherapeutic INR values.
References
1 Ramstrom G, Sindet-Pedersen S, Hall G, Blomback M, Alander U.
Prevention of postsurgical bleeding in oral surgery using tranexamic
acid without dose modification of oral anticoagulants. J Oral
Maxillofac Surg 1993; 51: 1211–6.
2 Souto JC, Oliver A, ZuaZu-Jausoro I, Vives A, Fontcuberta J. Oral
surgery in anticoagulated patients without reducing the dose of oral
anticoagulant: a prospective randomized study. J Oral Maxillofac Surg
1996; 54: 27–32.
3 Wahl MJ. Dental surgery in anticoagulated patients. Arch Intern Med
1998; 158: 1610–6.
4 Blinder D, Manor Y, Martinowitz U, Taicher S, Hashomer T. Dental
extractions in patients maintained on continued oral anticoagulant:
comparison of local hemostatic modalities. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 1999; 88: 137–40.
5 Vicente BM, Knezevic M, Tapia MM, Viejo LA, Orengo Valverde JC,
Garcia JF, Lopez PO, Dominguez SS, Diaz Cremades JM, Castellano
RJ. Oral surgery in patients undergoing oral anticoagulant therapy.
Med Oral 2002; 7: 63–70.

Thromboembolic risk and bleeding in patients maintaining or

stopping oral anticoagulant therapy during dental extraction
S . A L - M U B A R A K , * M . A . R A S S ,   A . A L S U W Y E D , à A . A L A B D U L A A L Y § and S . C I A N C I O –
*Dental Department, Sultan Bin Abdulaziz Humanitarian City;  Prince Abdulrahman Advanced Dental Institute; àDental Department, King
Abdulaziz Medical City; §Hematology Department, Riyadh Armed Forces Hospital, Riyadh, Saudi Arabia; –Department of Periodontic
and Endodontics, School of Dental Medicine, State University of New York at Bualo, New York, NY, USA

To cite this article: Al-Mubarak S, Rass MA, Alsuwyed A, Alabdulaaly A, Ciancio S. Thromboembolic risk and bleeding in patients maintaining or
stopping oral anticoagulant therapy during dental extraction. J Thromb Haemost 2006; 4: 689–91.

Most patients on oral anticoagulant therapy (OAT) belong to

Correspondence: Sultan Al-Mubarak, Consultant Periodontist,
Chairman of Dental Department, Chairman of Research & Ethics
Committee, PO Box 64399, Riyadh 11536, Saudi Arabia.
Tel.: 9661 5620000 ext. 1807; fax: 9661 5620000 ext. 1824; e-mail:
smubarak@humanitariancity.org.sa
Received 22 November 2005, accepted 20 December 2005
an old age characterized by high incidence of dental diseases
that necessitate surgical interventions [1]. Therefore, the
evaluation of the risks of bleeding (with OAT) or thrombo-
embolism (stopping OAT) is important. Owing to serious
complications associated with the modification [2] or cessa-
tion of OAT before during or after oral surgery [3,4], the
dilemma continues to exist and no universal consensus has

2006 International Society on Thrombosis and Haemostasis