Dental Management of Patients on Anticoagulant

and Antiplatelet Drugs

Donald A. Falace, DMDProfessor and Division Chief

Oral Diagnosis and Oral MedicineUniversity of Kentucky College of Dentistry

Normal HemostasisFollowing injury to a blood vessel:1. Vascular retraction (vasoconstriction)

to slow blood loss2. Adherence of platelets to the vessel

wall (endothelium) and then to eachother to form a platelet plug

3. Initiation of the coagulation cascaderesulting in the formation and deposition of fibrin to form a clot

Coagulation Cascade

Extrinsic pathway: Factor VII is activated by tissue factor (phospholipid) that is released by injured perivascular or vascular tissues; very rapid reactionIntrinsic pathway: Factor XII is activated by exposure to collagen from vessel wall (endothelium) or blood cell membrane; slower reaction

Each activated factor, in turn, activates the next factor-thus the term “cascade” ultimately resulting in the formation of fibrin

Anticoagulants:– Inhibit the production of clotting factors

Antiplatelet Agents:– Interfere with the functioning of

platelets, thus inhibiting platelet aggregation

AnticoagulantsCoumarin Derivitives (dicoumarol,

warfarin: Coumadin, Panwarfin)

Coumadin antagonizes the production of vitamin K Vitamin K is necessary for the synthesis of four of the coagulation factors (VII, IX, X and prothrombin)

Pharmacologic Properties(warfarin: Coumadin)

Taken orallyMetabolized in the liverHalf-life: 1.5-2.5 daysDuration of action: 2-5 days (it takes several days for dosage changes to take effect)Increased anticoagulant effect when combined with:– Antibiotics– Aspirin– NSAIDs– Antifungals– Tramadol– Tricyclic antidepressants– Certain herbals (gingko,

ginsing, ginger, garlic)

Co-morbid Conditions That Can Contribute to Increased Bleeding

Liver diseaseKidney diseaseTumorBone marrow failureChemotherapyAutoimmune diseases

Conditions for which Coumadin is prescribed to prevent unwanted blood clotting

Prophylaxis/Treatment of:– Venous thrombosis (DVT)– Pulmonary embolism– Atrial fibrillation– Myocardial infarction– Mechanical prosthetic

heart valves– Recurrent systemic

embolism

Laboratory Tests to Monitor the Activity of Coumadin

Prothrombin Time (PT): time for fibrin formation via the extrinsic pathway-factor VII– Test performed by taking a

sample of the Pt’s blood and adding a reagent (thromboplastin) and calculating the time required to form a clot; expressed in seconds

PT Ratio: Pt’s PT/Normal PTNormal PT ration = 1Problem: There is variation among thromboplastin reagents, therefore the results from lab to lab are not comparable

Same patient- Same blood5 different laboratories - 5 different PT Ratios!

Sample Patient’s PT Control PT PT Ratio

A 17 sec 12 sec 1.4

B 18 sec 12 sec 1.5

C 21 sec 13 sec 1.6

D 24 sec 11 sec 2.2

E 38 sec 14.5 sec 2.6

Solution:International Normalized Ratio (INR)

– A mathematical “correction” that corrects for the differences in the sensitivity of thromboplastin reagents

– Each thromboplastin is assigned an ISI number which is a sensitivity index

– This correction makes INR values comparable from lab to lab

– Normal INR = 1 (an INR of 2 means that their INR is 2 times higher than normal)

Same Patient-Same BloodReported by INR

Sample Patient PT

Mean Normal

PTR ISI INR

A 17 sec 12 sec 1.4 2.8 2.6

B 18 sec 12 sec 1.5 2.4 2.6

C 21 sec 13 sec 1.6 2.0 2.6

D 24 sec 11 sec 2.2 1.2 2.6

E 38 sec 14.5 2.6 1.0 2.6

Recommended Therapeutic Range for Oral Anticoagulant Therapy

(American College of Chest Physicians: Chest 1998; 114(suppl): 439-769s)

INR: 2.0-3.0Prophylaxis or treatment of venous thrombosisTreatment of pulmonary embolusPrevention of systemic embolismTissue heart valvesAcute MIAtrial fibrillation

Recommended Therapeutic Range for Oral Anticoagulant Therapy

(American College of Chest Physicians: Chest 1998; 114(suppl): 439-769s)

INR: 2.5-3.5– Mechanical prosthetic valves (high risk)– Acute MI (to prevent recurrent MI)– Certain patients with thrombosis and the

antiphospholipid antibody syndrome (antibodies that interfere with the assembly of phospholipid complexes and thus inhibit coagulation)

Dental Management GuidelinesThere are no uniformly accepted guidelines for managing anticoagulated patients during dental treatment

Previous AMA/ADA recommendation was that it was safe to perform surgery on a patient if the PT was 1.5-2.5x normal. This, however, is equivalent to an INR of 2.6-5.0 depending on the sensitivity of the various thromboplastins; an average PT of 1.6 = INR of 3!

This clinical problem is not amenable to a “cookbook” approachEach patient must be considered individually and you must take into consideration the risk-benefit of stopping vs continuing anticoagulation (they are on anticoagulants because they are at risk for thromboembolism)Your decision depends upon:– Medical condition/stability– Degree of anticoagulation– Magnitude of planned

surgery– Scientific evidence

If questionable, decision should be a shared with physician

What does the scientific literature tell us?

Wahl,MJ: Myths of dental surgery in patients receiving anticoagulant therapy JADA

2000:131;77-81

Updated a previous study (Wahl,MJ: Dental surgery in

anticoagulated patients. Arch Int Med. 1998;158:1610-1616) and added more cases (26 studies)A review of more than 2400 cases of dentoalveolar surgery on more than 950 patients undergoing multiple extractions, full mouth exts, alveoloplasties whose anticoagulant was continued (many with INR > than therapeutic levels) – 12 cases (0.5%) experienced bleeding that was

uncontrollable by local measures alone– Of these 12, 7 had an INR> than therapeutic levels

& 3 were on antibiotics– 3 required vitamin K administration to stop the

bleeding

Wahl,M: Dental surgery in anticoagulated patients Arch Int Med 1998; 158;1610-1616

Reviewed case reports of 493 patients whose anticoagulant had been discontinued prior to dental extractions and other dental procedures5 pts (1%) suffered significant adverse outcomes– 4 patients had fatal embolisms– 1 patient had a non-fatal embolism

Devani,P: Dental extractions in patients on warfarin: Is alteration of anticoagulant

regime necessary? Brit JOMFS 1998;36;107-111

Compared 2 groups of extraction patients undergoing an average of 2 extractions (range of 1-9 teeth)– 32 pts with anticoagulant discontinued prior to surg

with INR 1.5-2.1, and – 33 pts with anticoagulant continued with INR of 2.3-

3.4. Local measures only for hemostasis (atraumatic technique, sutures, gauze, etc)

None in either group had significant post-op bleeding; 1 pt in each group required additional local measures to control delayed oozing

Campbell, JH: Anticoagulation and minor oral surgery: Should the antibiotic regimen be

altered? JOMFS 2000; 58;131-135

Compared blood loss of 3 groups of dentoalveolar surgery pts– 12 pts who continued anticoagulant with INR

1.2-2.9– 13 pts who discontinued anticoagulant 3-4

days with INR 1.1-3.0 – 10 pts who were never on anticoagulant (INR

not tested)No significant difference in blood loss among groups and no serious postoperative bleeding requiring intervention

Dunn, A: Perioperative management of patients receiving oral anticoagulants

Arch Int Med 2003; 163: 901-908 Conducted a systematic review and synthesis of the English language literature from 1966-2001 examining the perioperative management and outcomes of patients receiving long term oral anticoagulant therapy; included a comprehensive review of 26 case reports and studies examining bleeding and thromboembolism after dental procedures (minor ext, fmx, alveolectomies)Conclusion: Most patients undergoing dental procedures can undergo the procedure without alteration of the OAC regimen. The current literature suggests that the perioperative stroke rate for patients who have OAC withheld may be substantially greater than would be normally predicted

Conclusions

It would thus appear that most patients who are on anticoagulant therapy (Coumadin) can undergo minor dentoalveolar surgery without discontinuance of anticoagulant using local/topical measures if:– INR is within the therapeutic range (<3.5)– No assoc aggravating conditions (e.g. antibiotics, liver or

kidney disease) – Planned surgery is “minor” (extractions, alveoloplasty,

biopsy)

If anticoagulant needs to be adjusted (INR>3.5), this is the responsibility of the physician

Antiplatelet AgentsNormal Platelet Function

Platelets adhere to the areaof injured endothelium (mediated by von Willebrand factor)

Platelets adhere to each other and form a scaffolding for fibrindeposition (von Willebrand factor is a carrier protein forfactor VIII)

Uses for Antiplatelet Drugs

Prevention of heart diseaseDuring heart attackUnstable anginaFollowing heart attackDuring or following angioplasty and stentingPrevention of stroke or TIAAtrial fibrillation (low risk patient)Peripheral vascular disease

Antiplatelet DrugsAspirin (irreversible effect for life of the platelet ~ 7-10 days)NSAIDs (reversible effect; limited to duration of drug)– Cox-1 (renal blood flow, fluid/electrolyte

transport, stomach mucosal integrity, vasomotor tone, platelet aggregation)

– Cox-2 (inflammation)Clopidogrel (Plavix)Ticlopidine (Ticlid)Dipyridamole (Persantine)

Action of Antiplatelet Drugs

*The life of a platelet is about 7-10 days

Laboratory Tests to Monitor the Effects of Antiplatelet Drugs

Ivy Bleeding time: measures the length of time a patient bleeds after a standardized incision. – low reproducibility – questionable sensitivity – poor correlation to clinical bleeding tendency– normal: 1-6 or 7 minutes– conventionally, a bleeding time >20 minutes has been

considered likely to result in clinically significant bleeding

Platelet Function Analyzer (PFA-100)– currently the most widely used autoanalyzer– not yet available in all laboratories– measures the time it takes to form a platelet plug across the

aperature of a capillary tube– normals: 60-120 seconds– guidelines not currently available for application of PFA-100

results to clinical bleeding probability

Antiplatelet Drugs and Postoperative Bleeding?

Very limited literature on this topicMost of the studies deal with aspirinLittle information available on the other antiplatelet drugsMost of the recommendations are based upon clinical experience, case reports and expert opinion

Aspirin and BleedingPawlak,D: J Oral Surg, 36:944-7,1978 (43 pts undergoing tooth extraction)Amrein,P: JAMA, 245:1825-8, 1981(129 pts undergoing total hip replacement)Ferraris,V: Surg Gynecol Obstet 156:439-42, 1983 (52 pts having various types of general surgery)

In all studies, aspirin was continuedAll three studies found no significant difference in perioperative or postoperative blood loss between patients taking aspirin and controls

Fijnheer,R:Nederlands tijdschrift voor geneeshunde 2003;147(1);21-25

Medline review and analysis of all articles from 1966-2002 on surgery and bleeding complications due to aspirinNo clinically relevant bleeding complications were reported for cardiovascular, vascular, or orthopedic surgery, or epidural anesthesia; there was an increase in clinically non-relevant bleeding induced by aspirin Conclusion: There is no scientific evidence to support the withdrawal of aspirin in patients prior to surgery

Current Practice in Great Britain

Smout,J: Current practice in the use of antiplatelet agents in the perioperative period by UK vascular surgeons. Ann Roy Coll Surg Engl 2003:85(2);97-101

The general consensus of opinion from this survey suggests that most vascular surgeons do not stop antiplatelet drugs preoperatively

Expert Opinion CanadaSamama,C: Antiplatelet agents in the perioperative period: Expert recommendations of the French Society of Anesthesiology and Intensive Care Can J Anesth 2002:49(6); S26-35

Conclusion: Aspirin should not be withdrawn in most cases– If pt is on aspirin, clopidogrel or ticlopidine and

intraoperative bleeding is feared, a short-acting NSAID can be temporarily substituted

Summary: Antiplatelet Agents

Clinical experience, expert opinion, anecdotal reports and available studies suggest that for most patients undergoing dentoalveolar surgery, it is not necessary to discontinue the use of aspirin or other antiplatelet agents if used alone. The use of these agents is not usually associated with significant (serious) operative or postoperative bleeding.If two agents are used together (e.g. aspirin and clopidogrel), the risk for bleeding is likely increased, and depending upon the extent of the surgery, should be discussed with the physician

Local Measures to Control Postoperative Bleeding

Careful, atraumatic surgical techniqueUse of absobable hemostatic agent in socket (e.g. Gelfoam,Avitene,Surgicel)Careful suturing; primary closure over sockets not essentialPost-operative pressure pack (damp gauze for 30-60 minutes); especially important for flap compressionMay use antifibrinolytic agents: tranexamic acid [Cyklokapron Oral] or epsilon amino caproic acid [Amicar] as a mouthwash or to soak pressure gauzes

Antifibrinolytic Mouthrinses

Epsilon amino caproic acid (Amicar)– Syrup (1.25 gm/5cc) , 5-10 mL QID X 7 days– Use either as mouthwash or as a soak for the

pressure gauze

Tranexamic acid (Cyklokapron)– Used topically as 10 mL of a 4.8% -5%

weight/volume solution as a mouthwash for 2 minutes, QID, for 7 days

– Unfortunately, the 4.8% elixir is not FDA approved for use in the USA market

Additional Postoperative Measures

For analgesia, consider use of– Acetaminophen (Tylenol)– Codeine – COX 2 inhibitor (Celebrex)

Avoid drugs and herbals that increase bleeding

For continued bleeding,– 25% Amicar soaked gauze pressure pack– Consider intranasal desmopressin acetate (DDAVP)

spray; 2.5 ml bottle; 2 nostril sprays BID for 1-2 days; Stimulates the release of factor VIII and vWFactor

– Vitamin K (phytonadione; AquaMEPHYTON) 2.5-25 mg iv, im, sc, or oral