DIAGNOSIS/TREATMENT/PROGNOSIS

ARTICLE ANALYSIS & EVALUATION

ARTICLE TITLE ANDBIBLIOGRAPHICINFORMATION

A retrospective review of clinicalinternational normalized ratioresults and their implications.

Kassab MM, Radmer TW, Glore JW,Visotcky A, Robertson J, Degroot B.

J Am Dent Assoc 2011;142(11):1252-7.

REVIEWER

Mariano Sanz, MD, DDS, DrMed

PURPOSE/QUESTION

To measure the day-of-surgeryinternational normalized ratiovalues in dental patients receivingoral anticoagulants and to assesswhether these values were withinthe therapeutic range status for themedical condition diagnosed

SOURCE OF FUNDING

Information not available

TYPE OF STUDY/DESIGN

Case series

LEVEL OF EVIDENCE

Level 3: Other evidence

STRENGTH OFRECOMMENDATION GRADE

Not applicable

J Evid Base Dent Pract 2012;12:164-1661532-3382/$36.00� 2012 Elsevier Inc. All rights reserved.http://dx.doi.org/10.1016/j.jebdp.2012.06.006

Screening for International NormalizedRatio in the Dental Office may ProvideUseful Information to Prevent BothHemorrhagic and Thromboembolic Events

SUMMARY

SubjectsThe authors conducted a search of all the clinical charts (16,017) of activepatient records from the 3 campuses in the Marquette University (MU)School of Dentistry for 2009 and 2010 that contained information on inter-national normalized ratio (INR) entries within their medical history. A totalof 315 patient records fulfilling the search criteria were manually searched,and 68 contained an INR entry but no provisional medical diagnosis. Theremaining 247 patient records contained INR entries and a provisional di-agnosis, with 206 of these patients having 1, 36 patients having 2, and 5 pa-tients having 3 of the following conditions: atrial fibrillation, deep venousthrombosis (DVT), stroke, or cardiac valve replacement. These 247 identi-fied records were included in this retrospective case series.

Key Exposure/Study FactorWarfarin is an oral anticoagulant commonly used to treat patients with con-ditions such as atrial fibrillation, DVT, stroke (cerebrovascular accident),and cardiac valve replacement. Warfarin affects the extrinsic clotting path-way by preventing the reduction of vitamin K into its active form. Its effec-tiveness in the patient is measured by the INR, which is the ratio of thepatient’s prothrombin time to a normalized control sample. Dependingon the reason for the anticoagulation (cardiovascular thrombo-embolicrisk), the patient’s target INR therapeutic ranges will be different. Patientswith atrial fibrillation, DVT, or stroke have a target INR of 2.0 to 3.0,whereas after undergoing cardiac valve replacement surgery, patientshave a target range of 2.5 to 3.5. An INR below the therapeutic range in-creases the risk of a thrombotic event, and an INR above the therapeuticrange increases the risk of a hemorrhagic event.

Main Outcome MeasureAt the MU School of Dentistry, INR values from patients requiring antico-agulation were measured by faculty members and dental students beforeany dental intervention by means of a point-of-care (POC) device. This de-vice was the INRatio PT Monitoring System Professional Kit (Alere, SanDiego, CA), which used the patient’s capillary blood with disposable teststrips containing a recombinant thromboplastin reagent as the reactivecomponent. The investigators correlated the values registered in the se-lected patient’s records with the expected therapeutic range status accord-ing to their medical diagnosis.

Main ResultsFrom the total MU dental clinic patient population, almost 2% had a his-tory of warfarin use. When evaluating the INR therapeutic ranges accord-ing to the patient diagnoses, 107 (43%) of the 247 patients had values

JOURNAL OF EVIDENCE-BASED DENTAL PRACTICE

that were not within the accepted therapeutic range.When the therapeutic ranges were studied with each diag-nosis, the INRs of 34.6% of patients with atrial fibrillation,55.1% of patients with DVT, 14.0% of patients with stroke,and 12.1% of patients with cardiac valve replacementwere not within therapeutic range. The obtained rangefor any diagnosis was between 0.2 and 7.0, which impliesa patient’s potential risk of experiencing thromboembo-lism in values below the therapeutic range or hemorrhagein the values above.

ConclusionsThis investigation demonstrates that an importantnumber of patients under warfarin therapy do not haveINR values within the therapeutic range when attendinga dental practice, which might increase the risk of bleed-ing or a thromboembolic event as a consequence of thedental intervention. INR testing should, therefore, be in-corporated into any dental practice in which invasiveprocedures are performed. POC devices provide valuableinformation comparable with that derived fromlaboratory-based testing, and either method should be in-corporated into regular dental practice.

COMMENTARYANDANALYSIS

This retrospective case series has limited significance, as itis based on the study of patients’ historical clinical re-cords, and, hence, the study did not have any controlon the accuracy of the retrieved information. The factthat the MU Dental School has medical records contain-ing electronic progress notes allowed the investigatorsto easily search all existing active patient electronic re-cords using the key term INR. The obtained prevalenceof warfarin users in this population (about 2%) has not,however, been verified in any direct manner, and thenumber of false-negatives is unknown. Furthermore,this institution has a policy of evaluating the INR valuesfrom these patients before any invasive dental procedureusing a POC device that, when used under the manufac-turer’s recommendations, provides values comparablewith laboratory-based testing. Because these INR valuesare incorporated into the patient’s progress notes in hisor her clinical charts, these values were easily retrievedelectronically and matched with the patient’s working di-agnosis. In this manner, the expected patient’s INR ther-apeutic range according to his or her medical diagnosiscould be correlated with the real value obtained. This in-formation, however, was not verified for accuracy orreproducibility, nor did the operators have specific train-ing to undertake the tests. The results, however, aremainly descriptive, without trying to verify any hypothesis,and clearly demonstrate that an important number of pa-tients receiving warfarin medication do not have INRvalues within the commonly established therapeuticranges and, therefore, are at risk of developing bleeding

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or a thromboembolic event as a consequence of a dentalintervention.

Clinical Application of the StudyMost general practitioners may not be aware of the riskswhen implementing invasive dental interventions in pa-tients on oral anticoagulation therapy (OAT). Althoughmany may be alert to the possible occurrence of a hemor-rhagic event at the intervention or during the postopera-tive period, they may not be aware of the significance ofhaving INR values within the therapeutic range for theprevention of the patient’s perioperative risk of arterialor venous thromboembolism. Madrid and Sanz1 pub-lished a systematic review of all published studies assess-ing the risks (both thromboembolic and bleeding) ofa patient on OAT undergoing implant therapy and pro-vided recommendations for the implant treatment ofthese patients. Nineteen studies were identified reportingoutcomes after oral surgery procedures (mostly dental ex-tractions in patients on OAT following different manage-ment protocols and hemostatic therapies). Five studieswere randomized-controlled trials, 11 were controlledclinical trials, and 3 were prospective case series.

TheOATmanagement strategies, as well as the protocolsduring and after surgery, were quite different, and thisheterogeneity prevented any possible data aggregationand synthesis.2,3 The results from these studies, however,clearly showed that the occurrence of hemorrhages wasvery small, with reporting of only minor bleeding in veryfew patients and without a significant difference betweenthe patients on OAT (INR 2-4) who continued withwarfarin medication and patients who stopped thismedication before surgery.4 When these postoperativebleeding events occurred, they were effectively controlledwith only local hemostatic measures. Postoperative bleed-ing did not correlate with the INR status, and in none ofthe studieswas a thromboembolic event reported, althoughmost of the studies were of very short duration. In light ofthis evidence, the authors of this review concluded thatOAT discontinuation is not recommended for minor oralsurgery, such as single tooth extraction or implant place-ment, provided that these interventions do not require ex-tensive flaps or osteotomy preparations extending outsidethe bony envelope.

The results from the present study provide evidencethat about half of the patients on OATattending a dentalclinic do not have INR values within the therapeuticranges either for thromboembolic or hemorrhagic risk.5

These results are clinically relevant, as there are an in-creasing number of patients on OAT undergoing minororal surgery procedures and dental practitioners shouldbe very well aware of their patient’s medical history andof any anticoagulation therapy they might be receiving.This study also points out that easy-to-use POC testerscan be used in the dental office to retrieve relevant

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information on the INR values before beginning invasivedental procedures. In spite of the low number of reportedbleeding or thromboembolic complications, it seems pru-dent for dental practitioners to consider adopting preop-erative testing for minor oral surgical procedures andthus provide safer treatment for their patients, and alsodevelop an avenue for collaboration with other healthcare professionals to yield more comprehensive care forpatients.

REFERENCES

1. Madrid C, Sanz M. What influence do anticoagulants have on oral im-plant therapy? A systematic review. Clin Oral Implant Res 2009;20(Suppl. 4):96-106.

2. Aframian DJ, Lalla RV, Peterson DE. Management of dentalpatients taking common hemostasis-altering medications. OralSurg Oral Med Oral Pathol Oral Radiol Endod 2007;103(Suppl):S45.e1-11.

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3. Akopov SE, Suzuki S, FredieuA, Kidwell CS, Saver JL, Cohen SN.With-drawal of warfarin prior to a surgical procedure: time to follow theguidelines? Cerebrovas Dis 2005;19:337-42.

4. Campbell JH, Alvarado F, Murray RA. Anticoagulation and minor oralsurgery: should the anticoagulation regimen be altered? J Oral Maxil-lofac Surg 2000;58:131-5.

5. Hirsh J, Poller L, Deykin D, Levine M, Dalen JE. Optimal therapeuticrange for oral anticoagulants. Chest 1989;95:5S-11.

REVIEWER

Mariano Sanz, MD, DDS, DrMedDecano, Facultad de OdontologiaUniversidad Complutense de MadridPlaza Ramon y Cajal28040 MadridSpainPhone: þ34913941901Fax: þ 34913941910marianosanz@odon.ucm.es

September 2012