Original Contributions
Treatment in the dental practice of the patient
This article has an
accompanying online
continuing education activity
available at:
http://jada.ada.org/ce/home.
Copyright ª 2019
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602
receiving anticoagulation therapy
Eric Kaplovitch, MD, FRCPC; Vera Dounaevskaia, MD, FRCPC
ABSTRACT
Background. The use of anticoagulants is ubiquitous in outpatient medical practice, with anti-
coagulants now among the most common classes of medications prescribed in the United States.
Despite its safety, anticoagulation around minimally invasive dental procedures remains a source of
discomfort for dental practitioners and a common reason for referral to specialist anticoagulation
clinics. The introduction of new anticoagulant options, as well as the changing practice pattern in
anticoagulant prescription, somewhat contributes to this situation. Reviewing the commonly used
anticoagulants in outpatient medical practice, as well as their implications in dental practice, is
integral to providing safe oral health care.
Conclusions. Direct oral anticoagulants are now the preferred agents for most patients receiving
anticoagulation therapy. With patients receiving any type of therapeutic anticoagulation, clinicians
usually can perform dental procedures such as restorations, limited dental extractions, endodontic
procedures, soft-tissue biopsies, and scalings safely without anticoagulation therapy interruption.
Although local hemostatic maneuvers are often sufficient during dental procedures, antifibrinolytic
medications, as well as local sponges and glues, can be used to ensure adequate hemostasis. Different
classes of anticoagulants interact with commonly prescribed medications in unique ways and may
require differing management and monitoring.
Practical Implications. Clinicians can perform most dental procedures safely despite patients’
receiving therapeutic anticoagulation. Recognizing common classes of anticoagulants, incorporating
strategies to minimize bleeding, and understanding how commonly prescribed medications in
dentistry interact with anticoagulants are essential to practicing safe, comprehensive care.
Key Words. Anticoagulation; antithrombotics; periprocedural management; dental practice; atrial
fibrillation; venous thromboembolism.
JADA 2019:150(7):602-608
https://doi.org/10.1016/j.adaj.2019.02.011
T
he use of anticoagulation therapy for the prevention of arterial and venous thromboembolism
has been a mainstay in medicine for more than 60 years.1 However, the landscape of anti-
coagulation therapy has changed dramatically over the past decade. Increasing numbers of
outpatients receive prescriptions for oral anticoagulants,2 with direct oral anticoagulants (DOACs)
progressively supplanting vitamin K antagonists (VKAs) as the preferred therapeutic agent for most
indications.2,3
The treatment of the patient receiving anticoagulation therapy has particular import around the
time of invasive procedures. Risks of experiencing bleeding must be balanced against the risk of
developing systemic thrombosis to delineate the optimal plan for each patient. Investigators have
examined dental surgeries in particular because, along with dermatologic and ophthalmologic pro-
cedures, they make up more than 15% of the procedures performed in those receiving antithrombotic
therapy.4 Continuing anticoagulation therapy around the time of dental procedures carries the po-
tential risk of causing minor bleeding, clinically relevant nonmajor bleeding, and true major
bleeding.5 This risk is contrasted by the possibility of stroke, pulmonary embolus, myocardial
infarction, and other local or systemic embolic phenomena when anticoagulant agents are stopped.
Because of the life-threatening nature of these thromboembolic complications, small risks of expe-
riencing minor and clinically relevant nonmajor bleeding often are tolerated in calculating the best
course of action.4,6 Results from 60 years of randomized and observational trials regarding
JADA 150(7) n http://jada.ada.org n July 2019
anticoagulation therapy around dental procedures have led to multiple evidence-based clinical
guidelines constructed to inform clinician practice.7
Despite practice statements from both dental8 and medical4 communities, confusion remains in
the treatment of dental patients receiving therapeutic anticoagulation. As many as 11% of all
patients referred to specialist periprocedural anticoagulation clinics may be referred for questions
about simple dental procedures during which anticoagulation therapy can be continued without
physician input.9 Although general and specialist dentists often do not adjust anticoagulation
therapy independently, they must be well versed in the effect of anticoagulants on dental practice
and when dental surgery can proceed without anticoagulation therapy interruption. Familiarity with
the common anticoagulant agents, as well as the management of surgical, bleeding, and medication
implications for patients receiving anticoagulation therapy, is integral to comprehensive care.

HOW ARE ANTICOAGULANTS USED IN MEDICAL PRACTICE?

Clinicians most often prescribe outpatient anticoagulation therapy for the indications of atrial
fibrillation, mechanical valve implantation, and previous venous or arterial thromboembolism
(Table).
DOACs (rivaroxaban, apixaban, dabigatran, edoxaban) are now the preferred agents in those
with nonvalvular atrial fibrillation,17 as well as in those with venous thromboembolism without
cancer or severe thrombophilia.18 Investigators now have studied the DOACs in large, well-
conducted studies for more than a decade,15,17,18 and they have found them to be at least as safe
and effective as warfarin, if not superior, in most patients with an indication for anticoagulation
therapy.15,17-19 Besides a more favorable profile in balancing bleeding and thrombotic risk, DOACs
have the advantage of not requiring monitoring. DOACs directly inhibit a single key clotting factor
in the coagulation cascade to produce their anticoagulation effect, with dabigatran acting as a direct
thrombin (factor IIa) inhibitor and apixaban, rivaroxaban, and edoxaban acting as direct activated
factor X (factor Xa) inhibitors.19,20 Unlike warfarin, whose anticoagulation effects take many days
to accumulate and dissipate, the DOACs have rapid and predictable onsets (1-4 hours) and a short
half-life.19 This specificity and predictability, as well as a wide therapeutic index, allow DOACs to
have fixed doses without the need for monitoring.15,19
VKAs (warfarin, acenocoumarol) are the preferred anticoagulants in those with rheumatic or arti-
ficial valve disease.17 They are also invaluable in those who require anticoagulation therapy when
alternative agents are untenable, such as in patients who have severe kidney or liver disease or in those
with previous drug sensitivity or interaction. Despite a stated preference for DOACs in nationally
recognized guidelines,17,18 some patients continue receiving warfarin for the sake of familiarity.
Low-molecular-weight heparins (LMWHs) (tinzaparin, enoxaparin, dalteparin) are injectable
anticoagulants occasionally used in the outpatient setting. Excluding those with high-risk valvular
disease, LMWHs are the preferred anticoagulant used during pregnancy.18 Although US guidelines
recommend LMWHs for venous thrombosis associated with cancer,18 2 large trials21,22 with results
showing similar performance and safety of DOACs as those of LMWH in nongastrointestinal cancer
may change this stance in the near future.
Many clinicians are familiar with warfarin monitoring, accomplished with frequent measure-
ment of the international normalized ratio (INR). A therapeutic INR range for most patients is
from 2.0 through 3.0, with some specific high-risk conditions (such as having a mechanical mitral
valve) requiring more elevated targets.17,23 The use of the INR is not validated in those receiving
DOACs or LMWHs and should not be used in monitoring or dose adjustment. Traditional
coagulation times such as the prothrombin time (used in calculating the INR) and partial
thromboplastin time correlate poorly with the levels of DOACs and LMWH and provide
ABBREVIATION KEY
misleading information if used to determine anticoagulation status.20,24 Although DOACs and
LMWHs have the advantage of not requiring routine monitoring, drug-specific levels or surrogate DOAC: Direct oral
anticoagulant.
markers are rarely used in the outpatient setting. LMWHs can be monitored through anti-Xa INR: International
levels, rarely used in cases such as severe renal insufficiency or extremes of weight, though it normalized ratio.
is not clear that making dose adjustments on the basis of these levels results in improved efficacy LMWH: Low-molecular-
or safety.24 DOACs do not have reliable, readily available measurement assays for monitoring15; weight heparin.
NSAID: Nonsteroidal anti-
however, clinicians occasionally use thrombin time (dabigatran) or drug-specific anti-Xa levels
inflammatory drug.
(apixaban, rivaroxaban, edoxaban) in circumstances such as determining emergent medical VKA: Vitamin K
therapy in life-threatening bleeding.15 antagonist.

JADA 150(7) n http://jada.ada.org n July 2019 603

 Table. Common anticoagulants, their indications, and potential interactions with dental medications.

DRUG
INTERACTIONS
NEED FOR WITH COMMON
ROUTINE DENTAL
DRUG CLASS USUAL INDICATION MONITORING MEDICATIONS*
Vitamin K Antagonists Rheumatic atrial fibrillation Yes (international Antibiotics†,10,11
Mechanical heart valve normalized ratio) Clindamycin
Warfarin (Coumadin) Thrombosis with anti- Amoxicillin
Acenocoumarol (Sintrom) phospholipid antibodies Amoxicillin clavulanate
Contraindication to alternative Cephalexin
agents Doxycycline
Metronidazole
Macrolides
Azole antifungals10
Analgesics12-14
Carbamazepine
Oxcarbazepine
NSAIDs‡
Direct Oral Anticoagulants Nonvalvular atrial fibrillation No§ Antibiotics15
Venous thrombosis without Clarithromycin
Apixaban (Eliquis)
cancer or severe thrombophilia Erythromycin{
Rivaroxaban (Xarelto) Azole antifungals15
Dabigatran (Pradaxa) Analgesics15
Edoxaban (Savaysa, Lixiana) Carbamazepine
NSAIDs
Low-Molecular-Weight Thrombosis or prophylaxis in No§ Analgesics16
Heparins pregnancy NSAIDs
Thrombosis in cancer
Tinzaparin (Innohep)
Dalteparin (Fragmin)
Enoxaparin (Lovenox)
* This list is not exhaustive. † Single doses of antibiotics are unlikely to alter anticoagulation effect in a clinically significant manner.
Consider increased monitoring for 2 or more days of therapy. ‡ NSAID: Nonsteroidal anti-inflammatory drug. § Direct drug
levels or surrogate markers (factor Xa, dilute thrombin time) are used in rare circumstances. { Erythromycin predominantly
interacts with dabigatran and edoxaban.

CAN ANTICOAGULANTS BE CONTINUED AROUND DENTAL PROCEDURES?

The decision regarding anticoagulation therapy discontinuation can be complex and dynamic,
relying on both the indication for pharmacotherapy, as well as the timing of previous thromboem-
bolic events. In helping clinicians make these decisions, guidelines stratify patients according to high,
moderate, or low risk of developing systemic thrombosis on the basis of the indication for anti-
coagulation therapy, the recency of the thrombotic event, and comorbidities that increase coagu-
lability (such as active cancer).4,6,25 Guidelines similarly rank the high, moderate, and low bleeding
potential of the particular procedure.4,6,25 Owing to the devastating complications of thrombosis,
anticoagulation therapy is continued in procedures with low bleeding risk in most cases.4,6,25
Procedures with moderate and high bleeding potential necessitate the withholding of antico-
agulants.4,6,25 When warfarin is withheld (often for 5 days before a procedure), a proportion of
patients with high thrombotic risk require a short course of LMWH to bridge the gap in anti-
coagulation therapy.4,6,25 Given the predictable pharmacokinetic properties of DOACs, with
rapid onsets and short half-lives, clinicians do not offer LMWH periprocedurally.4,6,25 The timing
and methods of withholding and resuming any anticoagulation therapy are reliant on the nature
of the procedure, the indication for the anticoagulant, and the parameters affecting drug clear-
ance such as renal function.6,25 Therefore, although a practitioner specializing in anticoagulant
management may individualize the periprocedural management of bleeding risk in procedures
with moderate and high bleeding risk, practitioners systematically can perform procedures with
low bleeding risk, as determined by means of prevailing practice guidelines based on best evi-
dence, without the withholding of anticoagulant. In this way, specific low-risk dental procedures
allow for anticoagulation to be continued without consultation or fear of undue bleeding
requiring further intervention (Box).
According to leading clinical practice guidelines, clinicians typically can perform minor dental
procedures including 1 or 2 dental extractions that are not surgically complex, prosthodontic
procedures (such as fixed and removable dentures, as well as crowns and bridges), implant

604 JADA 150(7) n http://jada.ada.org n July 2019

 Box. Low-risk dental procedures not requiring anticoagulation
therapy interruption.*

Dental scaling
Dental restorations that involve soft-tissue manipulation
Dental extractions that are not surgically complex
Fewer than 3 teeth
Soft-tissue biopsy
Endodontic procedures
Implant placement
Prosthodontic procedures
Fixed and removable dentures
Crowns
Bridges
* If a vitamin K antagonist is the anticoagulant used, international normalized ratio values should be within the therapeutic range
whenever possible.

placements, endodontic procedures, soft-tissue biopsies, dental scalings, and dental restorations that
involve soft-tissue manipulation in patients receiving full therapeutic anticoagulation without the
routine need for physician consultation.4,6,8,25-27 Clinicians likely can perform higher-risk dental
procedures, such as 3 or more extractions or bone augmentation, in patients receiving therapeutic
anticoagulation as well, although a more nuanced decision based on practitioner comfort with or
without physician input may be appropriate.7 As a frame of reference, anticoagulants often are
continued during medical procedures such as pacemaker implantation,6 with some hematologists
continuing therapeutic anticoagulation during bone marrow biopsy as well.28 More invasive pro-
cedures at high risk of producing blood loss, including reconstructive surgery, should prompt referral to
a physician for periprocedural anticoagulation decision support.

WHAT STRATEGIES CAN BE USED TO MINIMIZE DENTAL BLEEDING?

Although clinicians can perform most dental procedures in the presence of therapeutic anti-
coagulation, they can take precautions to minimize periprocedural bleeding. Although limited data
exist about optimal hemostatic measures, most periprocedural dental bleeding can be controlled by
both surgical and pharmacologic local measures.
For most patients taking anticoagulants, local pressure with gauze compression is sufficient for
appropriate hemostasis.29,30 If further measures are required, clinicians have used suturing, cautery,
oxidized cellulose (Surgicel, Ethicon), absorbable sponges (Gelfoam, Pfizer), and fibrin glue for
hemostatic effect.8,27,31
If concern remains, the clinician can use antifibrinolytic medications such as tranexamic acid and
ε-aminocaproic acid in both prevention and treatment.4 The more common tranexamic acid is typically
a 5% formulation administered as a 5-milliliter oral mouthrinse 5 to 10 minutes before the dental
procedure and 3 to 4 times daily for 1 to 2 days after the procedure.4 Although swish-and-spit tra-
nexamic acid yields a salivary concentration high enough to inhibit fibrinolysis for multiple hours,
clinically relevant levels are not detected in the plasma, allaying concerns for systemic adverse effects.27
Although at times these oral solutions are difficult to obtain in community practice, it should not
dissuade dental practitioners from continuing with procedures because nonpharmacologic hemostatic
maneuvers are sufficient in most cases.7 Finally, clinicians should counsel patients about the signs and
symptoms of undue bleeding that should prompt them to seek care at their dental office or hospital.

WHAT DENTAL MEDICATIONS SHOULD BE PRESCRIBED WITH CAUTION IN PATIENTS

RECEIVING ANTICOAGULATION THERAPY?
Anticoagulants are effective in preventing arterial and venous thromboembolism in those with an
appropriate indication for use; however, anticoagulants have the potential for profound adverse

JADA 150(7) n http://jada.ada.org n July 2019 605

 Determine the class of anticoagulant
(DOAC, VKA, LMWH)

No
Is the dental procedure low risk*? Refer to anticoagulation specialist

Continue with
procedure

Yes
Use local hemostatic measures
(pressure, suturing, oxidized cellulose, tranexamic acid) Continue with
procedure

No
Are any new systemic medications prescribed? Routine follow-up

VKA therapy DOAC, LMWH therapy

INR monitoring within Ensure no drug-drug interaction;

2-4 days no laboratory monitoring

Figure. Algorithm for performing dental procedures in patients receiving systemic anticoagulation therapy. * Low-risk
dental procedures include dental scaling, dental restorations that involve soft-tissue manipulation, dental extractions
that are not surgically complex (< 3 teeth), soft-tissue biopsies, endodontic procedures, implant placements, and
prosthodontic procedures (fixed and removable dentures, crowns, and bridges). DOAC: Direct oral anticoagulant. INR:
International normalized ratio. LMWH: Low-molecular-weight heparin. VKA: Vitamin K antagonist.

effects as well. They are the most common cause of an adverse drug event requiring patients to seek
care at the emergency department.32 Although most drug interactions with anticoagulants result in
increased risk of experiencing bleeding, the nature of the interactions can be unpredictable, given
that they manifest through both pharmacokinetic properties and pharmacodynamic mechanisms.
Knowledge of appropriate prescribing, monitoring, and potential for interaction is essential to pa-
tient safety (Table).10-16
Warfarin has a particularly narrow therapeutic window and is susceptible to a multitude of drug and
food interactions.1,12 All antibiotics have the potential for interaction with warfarin because sym-
biotic intestinal bacteria play an integral role in vitamin K homeostasis. Although antibiotics with
greater efficacy against intestinal microorganisms (such as clindamycin and amoxicillin clavulanate)
may have a greater predilection for interaction, even amoxicillin or cephalexin should prompt
increased monitoring. The macrolide antibiotics (clarithromycin, azithromycin, erythromycin), as
well as metronidazole, interact with warfarin through cytochrome P450 enzyme inhibition12 and may
produce drug levels that are out of range. Azole antifungals (fluconazole, ketoconazole, itraconazole),
medications used for oropharyngeal candidiasis, similarly can provoke drug toxicity.12
Among analgesics, those used for trigeminal neuralgia have the highest potential for interaction
with warfarin. Anticonvulsants, such as carbamazepine, may have severe pharmacokinetic in-
teractions.12 Although acetaminophen and opioid analgesics have little pharmacokinetic properties
or pharmacodynamic interaction with VKAs, those with severe dental pain may have altered di-
etary patterns, a risk factor for nontherapeutic drug levels in its own right.1 Warfarin asserts its
anticoagulant effect via suppression of vitamin Kedependent clotting factors, with dietary fluctu-
ations in vitamin K consumption, whether because of dental pain or intercurrent illness, influencing
anticoagulant stability.1,12
The benefit of warfarin is that all of these interacting medications can be prescribed if required, as
long as anticoagulant monitoring (via INR) and adjustment are available. A single dose of such
medications (for example, a single antibiotic dose for endocarditis prophylaxis) is unlikely to affect
anticoagulation status substantially; however, longer courses of therapy should be coupled with
increased INR monitoring. Owing to the extensive list of potential medication interactions, all
patients taking warfarin and prescribed more than 1 day of systemic medication should be

606 JADA 150(7) n http://jada.ada.org n July 2019

considered for more intensive anticoagulant monitoring,1 including a follow-up INR with their
primary practitioner within 2 to 4 days of beginning their medication regimen.
DOACs are often simpler, in that severe interactions and resulting adverse drug events are less
common.32 The danger lies in the clandestine nature of interactions because there is no routine
monitoring for these medications; therefore, clinicians must be vigilant for medications at risk of
severe interactions. Clarithromycin and azole antifungals (particularly ketoconazole and itracona-
zole) are the antimicrobials of predominant concern given their strong enzymatic effects.15 Eryth-
romycin has similar concerns, specifically in patients taking dabigatran or edoxaban.15 These
antimicrobials should be avoided, or consultation should be sought with the patient’s thrombosis
specialist. The other routine antibiotics used in dental practice should not be anticipated to have an
effect requiring anticoagulant titration. Of the analgesics, carbamazepine should be avoided in all
patients taking DOACs, whereas acetaminophen and opioids can be prescribed safely.15 Given the
growing experience with DOACs, routinely assessing for interactions may be prudent, particularly
when prescribing less common dental medications. The use of LMWHs only rarely precipitates
pharmacodynamic or pharmacokinetic properties interactions requiring medication titration.
Finally, all nonsteroidal anti-inflammatory drugs (such as ibuprofen, ketorolac, naproxen, cele-
coxib, aspirin, and indomethacin) should be avoided if possible in those concomitantly receiving
any anticoagulant because platelet inhibition significantly can increase the risk of experiencing
bleeding.13,14

CONCLUSIONS
The use of anticoagulants is ubiquitous in medical practice, with anticoagulants now among the top
15 classes of medications prescribed in the United States.33 Clinicians can perform most dental
procedures safely without interruption of anticoagulation therapy and using only local hemostatic
measures (Figure). Understandably, varying levels of comfort with periprocedural anticoagulation
therapy exist in the medical and dental communities; however, familiarity with anticoagulants in
dental surgery, hemostatic options, and the potential for drug-drug interactions will allow the dental
practitioner confidently and safely to treat a patient receiving anticoagulation therapy. n

Dr. Kaplovitch is a clinical fellow, Department of Medicine, University of
Toronto, Toronto, Ontario, Canada. Address correspondence to Dr.
Kaplovitch at St. Michael’s Hospital, 30 Bond St., 4cc-142, Toronto,
Ontario, M5P 1W8, Canada, e-mail eric.kaplovitch@utoronto.ca.
Dr. Dounaevskaia is an assistant professor, Department of Medicine,
University of Toronto, and an assistant professor, St. Michael’s Hospital,
Toronto, Ontario, Canada.
Disclosure. Drs. Kaplovitch and Dounaevskaia did not report any
disclosures.
The authors thank Dr. Gillian Landzberg, BMSc(Hons), DDS, and Dr. Jordan
Seetner, BSc(H), DMD, Dip Ortho, FRCDC, for their comments and edits on
this manuscript.

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