the effects of combined oral anticoagulant–aspirin therapy in patients undergoing tooth...

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B. PetrovicBranislav V. Bajkin, Ivana A. Bajkin and Bojanstudyundergoing tooth extractions: A prospectiveanticoagulant-aspirin therapy in patients The effects of combined oral

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A nticoagulant and anti-platelet drugs are usedwidely for long-term pre-vention of arterial and

venous thrombosis. In addition tothe increasing number of patientsreceiving oral anticoagulant therapy(OAT), a growing number of pa-tients are taking combined OAT andantiplatelet (mostly aspirin) ther-apy.1 It is estimated that about fourof 10 patients receiving OAT in theUnited States also are receiving anantiplatelet agent.2 It has beenstrongly recommended that com-bined OAT-aspirin therapy be usedonly in patients with prostheticheart valves.3-5 Although the bene-fits of receiving combined OAT-aspirin therapy for stroke preven-tion in patients with atrial fibril-lation often do not outweigh therisks, study results have shown that20 to 25 percent of patients withatrial fibrillation were receivingDr. Branislav Bajkin is an assistant professor, Depart-ment of Oral Surgery, Dental Clinic of Vojvodina, Fac-ulty of Medicine Novi Sad, University of Novi Sad,Hajduk Veljkova 12, 21000 Novi Sad, Serbia, [email protected]. Address reprints to Dr. Bajkin.Dr. Ivana Bajkin is a teaching assistant, EmergencyCentre, Clinical Centre of Vojvodina, Faculty of Medi-cine Novi Sad, Serbia.Dr. Petrovic is an assistant professor, Department ofPreventive and Pediatric Dentistry, Dental Clinic ofVojvodina, Faculty of Medicine Novi Sad, University ofNovi Sad, Serbia.

The effects of combined oralanticoagulant–aspirin therapyin patients undergoing tooth extractionsA prospective study

Branislav V. Bajkin, DDS, MD, PhD; Ivana A. Bajkin, MD; Bojan B. Petrovic, DDS, MSc, PhD

ABSTRACTBackground. The authors conducted a studyto evaluate the effect of combined oralanticoagulant–aspirin therapy on postoperativebleeding in patients undergoing tooth extractions.Methods. A total of 213 patients were dividedinto three groups of 71 participants each. Patients ingroupA received combined anticoagulant-aspirin (100-milligramprophylactic dose) therapy. Patients in group B received oral antico-agulant therapy. Patients in group C received aspirin therapy (100-mg prophylactic dose). Bleeding was marked as an “event” if it metthe following criteria: the bleeding continued beyond 12 hours,patient had to call the surgeon or return to dental practice or emer-gency department, bleeding resolved with large hematoma or ecchy-mosis within the oral soft tissues, or required a blood transfusion.Results. Mean international normalized ratio (INR) (standarddeviation) was 2.43 (0.61) in groupA, and 2.45 (0.60) in group B.Postoperative bleeding occurred in three (4.2 percent) participantsin groupA, two (2.8 percent) participants in group B and no (0.0percent) participants in group C. The authors found no statisticalsignificance in postoperative bleeding between these three groups(χ2 = 2.867, P = .238). All cases of hemorrhage were controlled easilyby using local hemostatic measures.Conclusion. Tooth extractions can be performed safely while pa-tients continue to receive combined anticoagulant-aspirin therapy.Clinical Implications. In patients receiving combinedanticoagulant-aspirin therapy, simple tooth extractions can be per-formed safely without discontinuing either oral anticoagulant orantiplatelet therapy if their INRs are within therapeutic range andappropriate local hemostasis measures are provided.Key Words. Anticoagulants; anticoagulation therapy; aspirin;hemostasis; oral surgery; tooth extraction.JADA 2012;143(7):771-776.

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combined anticoagulant-antiplatelet therapy.6,7Adding aspirin to OAT is a rational therapeuticapproach for patients receiving anticoagulationtherapy in whom cardiovascular prophylaxis isindicated. Despite the advantages of this com-bined therapy, the incidence of major bleedingincreases in nonsurgical patients who are re-ceiving combined therapy,5,7,8 and there is ahigher risk of experiencing prolonged and exces-sive bleeding during and after undergoing sur-gical procedures. Nevertheless, discontinuingeither OAT or aspirin therapy preoperativelycan expose patients to the risk of experiencing athromboembolism.9-14

Managing the care of patients who are under-going oral surgery and are receiving OAT haschanged during the past decade, and mostreports do not support discontinuing OAT forpatients undergoing tooth extractions.9,15-19 Sim-ilar recommendations are given for patientswho are undergoing oral surgery and receivingantiplatelet therapy.19-24 To our knowledge, noprospective clinical studies of postoperativebleeding risk in dentistry that included patientsreceiving combined OAT-aspirin therapy havebeen published. This category of patients usu-ally has been excluded from research concerningoral surgery in patients taking OAT, becausethe main focus of previous studies was the iso-lated effects of OAT on postoperative bleeding.

We conducted a prospective study to evaluatethe effect of combined OAT-aspirin therapy onpostoperative bleeding in patients undergoingtooth extractions.

METHODSThe Ethics Committee of the Dental Clinic ofVojvodina, Faculty of Medicine Novi Sad, Serbia,approved the study protocol, and we obtainedwritten informed consent from all of the partici-pants. We conducted a prospective clinical studyfrom March 1, 2005, through March 31, 2011.We recruited consecutively patients who hadbeen referred by their dentists and physicians tothe Department of Oral Surgery, Dental Clinic ofVojvodina, University of Novi Sad, Serbia, fortooth extraction.

We included in the study patients who re-quired simple extraction of one or more teethinvolving the use of local anesthetic but withoutthe need for a mucoperiosteal flap. We excludedfrom the study patients with liver or renal dis-eases, those taking medications that affecthemostasis (combined antiplatelet therapy, non-sterioidal anti-inflammatory drugs, heparin)and those with history of serious hemorrhageafter tooth extractions before they began

receiving OAT or aspirin therapy.After complete data collection, which in-

cluded patients’ histories, we assigned partici-pants who received combined OAT-aspirin (adaily 100 milligram prophylactic dose) therapyto group A. One author (B.B.P.), who did notperform surgery and was masked as to the out-comes, selected participants for group B (thosewho received oral anticoagulant therapy) andgroup C (those who received aspirin therapy [adaily 100 mg prophylactic dose]) who had thesame number of extractions as did those ingroup A. We also selected participants for groupB who matched those in group A with respect tointernational normalized ratio (INR) value. Allparticipants continued to take their medicationsbefore and after oral surgery.

In accordance with American Heart Associa-tion guidelines,25 we administered antibioticprophylaxis to participants who were at risk ofdeveloping endocarditis. We determined theINR value for each participant in groups A andB on the day of the dental procedure. The sameoral surgeon (B.V.B.) performed all extractionson an outpatient basis with minimal surgicaltrauma. Local anesthesia was achieved bymeans of 2 percent lidocaine with 1:80,000 epi-nephrine, and we did not use more than twoampoules (4 milliliters) for each participant. Weused the local infiltration method and intraliga-mentary injection technique whenever possible,although in some cases we also had to use theinferior alveolar nerve block.26

We used the same local hemostatic modalitiesfor all three groups of participants. We packedextraction sockets with collagen sponge, withoutprimary wound suturing. Local pressure wasapplied afterward; we instructed participants tohold sterile gauze in a firm bite for 30 minutes.We examined all participants for postoperativebleeding 30 minutes and two hours after theprocedure, as well as on the first, second andfifth days after the procedure. We determinedbleeding to be an “event” by using Lockhart andcolleagues’27 definition: the bleeding continuedfor more than 12 hours, the patient had to callthe surgeon, return to dental practice or go tothe emergency department, the bleeding re-solved with large hematoma or ecchymosiswithin the oral soft tissues, or the patient re-quired a blood transfusion.

In cases of postoperative bleeding, the firstmeasure we used was applying a superficialgauze tamponade to the wound for 10 minutes.

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ABBREVIATION KEY. INR: International normalizedratio. OAT: Oral anticoagulant therapy.





This was repeated, if needed, onlytwice. We sutured the wound witha figure-of-eight nonresorbablesuture (black silk 3-0) in case pre-vious measures failed. We consid-ered all cases in which the addi-tional measures for local hemo-stasis were used in the first twohours and resulted in cessation ofbleeding to be successful primarylocal hemostasis. We recorded allcases in which we sutured thewound as successful primary localhemostasis, but we did not con-sider them to be bleeding events.

We gave all participants a listof postoperative instructions andthe telephone number of a sur-geon to be contacted in case ofpostoperative bleeding. We recom-mended they take paracetamol(acetaminophen) for pain relief.

For participants who had pro-longed hemorrhage that could notbe controlled by using local meas-ures, we consulted the attendingphysician to assess the need foradministration of vitamin K, pro-thrombin complex concentrate orfresh frozen plasma.

We analyzed data regardingpostoperative bleeding by using aχ2 test to evaluate the relative fre-quencies of postoperative bleedingin patients in different groups. We tested differ-ences of parametric variables by using analysis ofvariance with the level of significance set at .05.

RESULTSThe sample initially comprised 233 patients.Twenty patients were excluded from the study:five underwent extraction with a raised mucope-riosteal flap; three were receiving three medica-tions (OAT-aspirin-clopidogrel); two discontinuedOAT without consulting their physicians; six dis-continued aspirin therapy without consultingtheir physicians; four patients did not attend thecontrol examinations (those that took place atthe first, second and fifth days) at all but werecontacted by telephone to inquire about postoper-ative hemorrhaging. The final number of partici-pants was 213 patients, with 71 in each group.

All patients in groups A and B received theanticoagulant acenocoumarol. Table 1 lists theindications for anticoagulant and antiplatelettherapy.

Table 2 lists the basic characteristics of par-

ticipants in all three groups. We found no statis-tically significant differences among the threegroups in regard to sex (P = .777), but we didnote a significant difference in regard to age(P = .026). Groups A and B did not differ signifi-cantly in regard to INR values (P = .844). Fivepatients receiving combined OAT-aspirintherapy had INR values greater than 3.5. Thetotal number of tooth extractions in group A was115 (mean, 1.62 per patient). We extracted 56 ofthese teeth owing to severe periodontitis and 59owing to deep carious lesions. In group B, thetotal number of extracted teeth was 120 (mean,1.69 per patient). We extracted 62 of these teethowing to periodontal disease and 58 owing todeep caries. In group C, the total number oftooth extractions was 119 (mean, 1.68 per pa-tient). We extracted 64 of these teeth owing tosevere periodontitis and 55 owing to deep caries.The highest number of extracted teeth in asingle participant was four in all three groups.We found no statistically significant differencesbetween groups in regard to number of extrac-

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TABLE 1

Indications for anticoagulantand antiplatelet therapy.INDICATION PATIENTS, NO.

Group A* Group B† Group C‡

Prosthetic Valve Replacement 11 15 0

Prosthetic Valve Replacement andIschemic Heart Disease

10 4 0

Valvular Heart Disease and DilatedCardiomyopathy

3 1 0

Atrial Fibrillation 8 19 0

Atrial Fibrillation and Ischemic HeartDisease

22 4 0

Atrial Fibrillation and Valvular HeartDisease

4 4 0

Atrial Fibrillation and DilatedCardiomyopathy

2 1 0

Atrial Fibrillation and CerebrovascularAccident

4 7 0

Atrial Fibrillation, VenousThromboembolic Disease and IschemicHeart Disease

3 2 0

Atrial Fibrillation and MesentericThrombosis

1 0 0

Ischemic Heart Disease andCerebrovascular Accident

3 0 2

Ischemic Heart Disease 0 4 65

Cerebrovascular Accident 0 2 4

Venous Thromboemboembolic Disease 0 8 0

* Combined oral anticoagulant therapy–aspirin therapy.† Oral anticoagulant therapy.‡ Aspirin therapy.





tions (P = .826).To achieve successful primary local hemo-

stasis, we sutured the wounds in six patientswho were receiving combined OAT-aspirintherapy (Table 3). Four of these six patients hadan INR greater than 3.1 and had undergonemultiple tooth extractions. We also needed tosuture the wounds of two patients receivingOAT and one patient receiving aspirin toachieve successful primary local hemostasis.

We noted postoperative bleeding in three (4.2percent) participants in group A, in two (2.8 per-cent) participants in group B and in no (0.0 per-cent) participants in group C. None of thesenumbers was statistically significant (χ2 = 2.867,P = .238). We saw all of the participants with apostoperative bleeding event on the day of theintervention when they returned after dismissal.We treated them with only local hemostaticmeasures, which easily resolved the bleeding.

We noted the first incident involving postop-erative bleeding in group A in a participant whohad undergone the extraction of two adjacentmaxillary molars. Although the participant’spostoperative wounds were sutured, the partici-pant returned to our clinic six hours after theprocedure because bleeding occurred again.After removing coagulum, which extended fromthe wound to the adjacent teeth and sutures, westopped the bleeding by inserting oxidized cellu-lose into the wound and resuturing the wound.In the second incident, a participant returned tothe clinic the afternoon of the day he underwent

the extraction of amaxillary canine anda third molar. Wecould see bleeding inthe region of thirdmolar. In a similarsituation, a third pa-tient with bleedingsought help the eve-ning of the day heunderwent the ex-traction of a maxil-lary lateral incisorand first molar. Wenoted bleeding only inthe region of the ex-tracted molar. In bothcases, we stopped thebleeding by suturingthe wounds.

One participant ingroup B returned tothe clinic the after-noon of the day he

underwent the extraction of two mandibularcentral incisors because of postoperativebleeding. The bleeding probably was caused bysevere local inflammation, and we stopped it byplacing oxidized cellulose into the wound andsuturing the wound. A second participant ingroup B experienced bleeding after undergoingthe extraction of two adjacent maxillary molars.We used only local compression to stop thebleeding (Table 3).

DISCUSSIONPerioperative management of the care of pa-tients receiving OAT and antiplatelet therapyincludes balancing the risk of thromboembolismand bleeding. Among other factors, it dependson the type of surgery. American College ofChest Physicians guidelines recommendbridging OAT with unfractionated heparin orlow-molecular-weight heparins during majorsurgery in patients at high risk of developing athromboembolism.28 For minor surgery, such astooth extractions, this approach is not recom-mended16; instead, procedures can be performedsafely without discontinuing OAT by using localhemostatic measures.

Investigators have described successful oralsurgical procedures in patients receiving antico-agulation therapy in which OAT was not discon-tinued.9,15-19 The results of several studies andreview articles showed there was no need forpatients to discontinue prophylactic antiplatelettherapy before undergoing tooth extractions.19-24

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TABLE 2

Characteristics of participants in all three groups.CHARACTERISTIC GROUP A* (N = 71) GROUP B† (N = 71) GROUP C‡ (N = 71)

Sex, No.Male 42 38 43Female 29 33 28

Mean Age (SD§),Years (Range)

65.2 (8.0) (41-78) 65.9 (8.7) (37-80) 62.1 (9.7) (36-80)

Mean InternationalNormalized Ratio(SD) (Range)

2.43 (0.61) (1.62-3.90) 2.45 (0.60) (1.67-3.90) Not applicable

Tooth Extractions, No.Total 115 120 119Mean per patient (range) 1.62 (1-4) 1.69 (1-4) 1.68 (1-4)

Cause of Extraction,No. of TeethPeriodontal disease 56 62 64Deep carious lesions 59 58 55

Inferior Alveolar NerveBlock, No. Administered

27 24 26

* Combined oral anticoagulant therapy–aspirin therapy.† Oral anticoagulant therapy.‡ Aspirin therapy.§ SD: Standard deviation.





Nevertheless, there is lack of dataregarding the treatment of pa-tients who are receiving combinedanticoagulant-antiplatelet therapyduring oral surgical procedures. Toour knowledge, there are no pro-spective trials addressing this spe-cific topic.

There is only one retrospectivestudy by Morimoto and colleagues17

regarding tooth extractions inpatients receiving combined oralanticoagulant-antiplatelet therapy.A total of 66 patients were re-ceiving combined therapy, and theincidence of postoperative bleedingwas 8.2 percent (six of 73 extrac-tions). Morimoto and colleagues17

did not find any statistical signifi-cance in postoperative bleedingdepending on antithrombotic therapy regimen.

The results of our study showed that therewas a slightly higher incidence of postoperativebleeding in participants who were receiving com-bined therapy (three of 71 participants [4.2 per-cent]) than in participants receiving OAT (two of71 participants [2.8 percent]) or aspirin therapy(zero of 71 participants). This finding was notstatistically significant. Results of our study alsoindicated that there is no reason for patients todiscontinue either OAT or aspirin therapy beforeundergoing tooth extractions. All participants ingroups A and C were taking prophylactic doses ofaspirin (100 mg). Local hemostasis withoutsuturing of the wound was a successful treat-ment for patients receiving OAT in our earlierreport16; thus, we used the same approach in thisstudy. We needed to only suture wounds for eightparticipants who were receiving combined OAT-aspirin therapy; in six participants we did it toachieve primary local hemostasis, and in twoparticipants we did it because of postoperativebleeding (for one of these participants, the woundhad to be resutured). For most participants inwhom the wounds were sutured, their INR wasgreater than 3.0 on the day of the procedure, andthey underwent the extraction of more than onetooth. Since the sample size in our study is rela-tively small, this finding could indicate that cau-tion is necessary when performing extensive oralsurgical procedures in patients receiving com-bined OAT-aspirin therapy who have high INRvalues.

For patients receiving anticoagulant or anti-platelet therapy, dentists should use safe tech-niques to achieve local anesthesia such as thelocal infiltration method or intraligamentary

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injection technique. The results of a recentstudy showed that using the inferior alveolarnerve block in patients with INRs within thetherapeutic range (2.0-4.0) also is safe.26 In ourstudy, we did not notice any bleeding complica-tions after 27, 24 and 26 inferior alveolar nerveblocks administered in groups A, B and C,respectively (Table 2).

Patients taking aspirin did not undergo ableeding time test. This laboratory test is notperformed routinely at our clinic before patientsreceiving antiplatelet therapy undergo dentalprocedures. In addition, a bleeding time test isnot considered reliable enough to predict thebleeding risk in patients after they undergo oralsurgery.23,29 The results of studies regardingtooth extractions in patients receiving anti-platelet therapy showed that bleeding timealmost always was within the normal range.20,21A platelet aggregation test is more sensitive, butit is not used in everyday practice.23

We did not include a control group of healthypatients in our study. Because of the recommen-dations in the literature for continuing anti-platelet therapy19-24 or OAT9,15-19 when tooth ex-tractions are indicated, we decided to comparepatients receiving these types of therapy withpatients receiving combined anticoagulant-antiplatelet therapy.

Our study had some potential drawbacks andlimitations: its relatively small sample size, thatit included only oral surgery procedures thathad low bleeding risks for patients (simplesingle and multiple tooth extractions), and thatthe number of patients with an INR of 3.5 orgreater who received combined OAT-aspirintherapy was small (only five patients).

TABLE 3

Postoperative hemorrhage casesand treatment.PATIENTS’ CHARACTERISTICS GROUP

A*GROUPB†

GROUPC‡

Patients With Postoperative Bleeding,No. (%)

3 (4.2) 2 (2.8) 0

International Normalized Ratio, Range 2.81-3.20 2.32-3.45 0

Tooth Extractions, Mean No. (Range) 2 (2-2) 2 (2-2) 0

Local Hemostatic Measures,No. of PatientsCompression 0 1 0Suturing 2 0 0Inserting oxidized cellulose and suturing 1 1 0

Suturing to Achieve Successful PrimaryLocal Hemostasis, No. of Patients (%)

6 (8.4) 2 (2.8) 1 (1.4)

* Combined oral anticoagulant therapy–aspirin therapy.† Oral anticoagulant therapy.‡ Aspirin therapy.





The strengths of our study were its prospec-tive design, its clearly defined sample and thecomprehensiveness of clinical follow-up.

CONCLUSIONPatients who were receiving combined anticoag-ulant and aspirin therapy were able to undergosimple tooth extractions safely without havingto discontinue either OAT or antiplatelet ther-apy, as long as INR was within therapeuticrange and local hemostasis measures were used.Further studies are needed to justify using thistherapeutic approach, especially in patients whohave higher INRs and in whom major oral sur-gical procedures are indicated. �

Disclosure. None of the authors reported any disclosures.

The authors thank the staff members affiliated with the Centre forLaboratory Medicine, Department of Thrombosis, Hemostasis andHematological Diagnostics, Clinical Centre of Vojvodina, Novi Sad,Serbia, for their help and cooperation during this study.

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2. Johnson SG, Witt DM, Eddy TR, Delate T. Warfarin andantiplatelet combination use among commercially insured patientsenrolled in an anticoagulant management service. Chest 2007;131(5):1500-1507.

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