This document discusses dental management in patients receiving anticoagulation or antiplatelet treatment. It presents two clinical scenarios: 1) A 45-year-old man on warfarin for atrial fibrillation who needs a tooth extraction, and 2) A 75-year-old woman 6 months post-drug eluting stent placement for a heart attack who is on aspirin and clopidogrel and needs a tooth extraction. The document reviews the risks of bleeding versus thromboembolism from stopping or continuing anticoagulation/antiplatelet therapy and recommends an individualized approach based on each patient's risk factors and the invasiveness of the dental procedure.

1. DENTALDENTAL
MANAGEMENT INMANAGEMENT IN
PATIENTSPATIENTS
RECEIVINGRECEIVING
ANTICOAGULATIONANTICOAGULATION
OR ANTIPLATELETOR ANTIPLATELET
TREATMENTTREATMENT
IS STOPPING OF THE
THERAPY REALLY
REQUIRED IN MINOR
DENTAL SURGERY ?
Piti Niyomsirivanich, MD.

2. CLINICAL SCENARIO
 ผู้ชาย 45 ปี
 Old CVA with AF with MR S/P MVR
 on warfarin 22 mg/week INR 3.0
 จะถอนฟัน ทำาไงดี ?
 หยุดยา warfarin ก่อนไปถอนฟัน
 ไปถอนฟันเลย

3. CLINICAL SCENARIO
 ผู้หญิง 75 ปี
 Previous STEMI S/P PCI Drug Eluting Stent
เมื่อ 6 เดือนก่อน
 ASA 81 mg/d + Clopidogrel 75 mg/d
 จะไปถอนฟัน ทำาไงดี
 หยุดยา ASA + Clopidogrel ก่อนไปถอนฟัน
 หยุดยา ASA ก่อนไปถอนฟัน
 หยุดยา Clopidogrel ก่อนไปถอนฟัน
 ไปถอนฟันได้เลย

4. TUTORIAL IN ORAL
ANTITHROMBOTIC
THERAPY

5. ANTITHROMBOTIC DRUGS CATEGORIZED BY
PHARMACODYNAMICS
Anti thrombotic drug categories Generic names and subgroup
Antiplatelet agents COX-1 inhibitor
Aspirin
ADP receptor inhibitor:
Clopidogrel ,Prasugrel ,Ticlopidine ,Ticagrelor
Gp IIb/IIIa inhibitor
Abciximab ,Eptifibatide , Triofiban
Phosphodiesterase inhibitor
Cilostazol , Dipyridamole
Vitamin K antagonist Warfarin , Coumarin , Dicoumarol , Phenprocoumon ,
Acenocoumarol
Factor Xa inhibitor Enoxaparin (SC), Fundaparinux (SC), rivaroxaban(SC)
Direct thrombin inhibitor dabigatran
Thrombolytic drugs tPA
Alteplase , Tenecteplase , Reteplase , Streptokinase ,
Urokinase
Adapted from Cochrane Database Syst. Rev,CD 001820.

6. OVERVIEW OF CLOT FORMATION
injury
TF Thrombin
Coagulation cascade
Collagen
vWF
ADP
Thromboxane A2
P2Y12
PAR-1
GP IIb/IIIa
Fibrin  platelet aggregation
Xa/Va prothrominase complex

7. OVERVIEW OF CLOT FORMATION
injury
TF Thrombin
Coagulation cascade
Collagen
vWF
ADP
Thromboxane A2
P2Y12
PAR-1
GP Iib/IIIa
Fibrin  platelet aggregation
Xa/Va prothrominase complex

8. CONCEPTS ON EARLY COAGULATION
CASCADE
Intrinsic pathway extrinsic pathway
TF/VIIa
XI XIa
IX  IXa
XaX X
XII,HMK , PK
Prothrombin(II)  Thrombin
Fibinogen(I)  Fibrin
PL ,VIIIa Ca PL, Ca
PL ,Va Ca
Adapted from Thromb Haemost 85(6):958-65

9. CONCEPTS ON EARLY COAGULATION
CASCADE
Intrinsic pathway extrinsic pathway
TF/VIIa
XI XIa
IX  IXa
XaX X
XII,HMK , PK
Prothrombin(II)  Thrombin
Fibinogen(I)  Fibrin
VKA e.g. warfarin
Inh. II , VII ,IX ,X
PL ,VIIIa Ca PL, Ca
PL ,Va Ca
Adapted from Thromb Haemost 85(6):958-65

10. CONCEPTS ON EARLY COAGULATION
CASCADE
Intrinsic pathway extrinsic pathway
XI XIa
Xa
XII,HMK , PK
Fibinogen(I)  Fibrin
Factor Xa inhibitor : Enoxaparin ,
Fundaparinux
PL ,VIIIa Ca PL, Ca
PL ,Va Ca
TF/VIIaIX  IXa
Prothrombin(II)  Thrombin
Adapted from Thromb Haemost 85(6):958-65
X X

11. CONCEPTS ON EARLY COAGULATION
CASCADE
Intrinsic pathway extrinsic pathway
XI XIa
XII,HMK , PK
Fibinogen(I)  Fibrin
Direct thrombin inhibitor :
dabigatran
PL ,VIIIa Ca PL, Ca
PL ,Va Ca
TF/VIIaIX  IXa
Prothrombin(II)  Thrombin
XaX X
Adapted from Thromb Haemost 85(6):958-65

12. CONCEPTS ON THE NEW, CELL-BASED
COAGULATION MODEL
Initiation
TF –bearing cell
e.g. fibroblast TF
Adapted from Thromb Haemost 85(6):958-65
Arterioscler Thromb Vasc Biol 2006:26(1):41-8

13. CONCEPTS ON THE NEW, CELL-BASED
COAGULATION MODEL
Initiation
TF –bearing cell
e.g. fibroblast TF
VII
VIIa
Adapted from Thromb Haemost 85(6):958-65
Arterioscler Thromb Vasc Biol 2006:26(1):41-8

14. CONCEPTS ON THE NEW, CELL-BASED
COAGULATION MODEL
Initiation
TF –bearing cell
e.g. fibroblast TF
VIIa
TF/VII complex
X
Xa
IX
IXa
Adapted from Thromb Haemost 85(6):958-65
Arterioscler Thromb Vasc Biol 2006:26(1):41-8

15. CONCEPTS ON THE NEW, CELL-BASED
COAGULATION MODEL
Initiation
TF –bearing cell
e.g. fibroblast TF
VIIa
TF/VII complex
IXa
Xa/Va complex
VaXa
Adapted from Thromb Haemost 85(6):958-65
Arterioscler Thromb Vasc Biol 2006:26(1):41-8

16. CONCEPTS ON THE NEW, CELL-BASED
COAGULATION MODEL
Amplification
TF –bearing cell
e.g. fibroblast TF
VIIa
TF/VII complex
VaXa
IXa
Xa/Va complex
prothrombin
Thrombin
Adapted from Thromb Haemost 85(6):958-65
Arterioscler Thromb Vasc Biol 2006:26(1):41-8

17. CONCEPTS ON THE NEW, CELL-BASED
COAGULATION MODEL
Amplification
TF –
bearing
cell
e.g.
fibroblas
t
T
F
V
I
I
a
V
a
X
a
IXa
Thrombin
Adapted from Thromb Haemost 85(6):958-65
Arterioscler Thromb Vasc Biol 2006:26(1):41-8

18. CONCEPTS ON THE NEW, CELL-BASED
COAGULATION MODEL
Amplification
TF –
bearing
cell
e.g.
fibroblas
t
T
F
V
I
I
a
V
a
X
a
Thrombin
Platelet Activation
VaV
vWF/VIII
VIIIa
IXa
IX
PAR1,PAR4
Adapted from Thromb Haemost 85(6):958-65
Arterioscler Thromb Vasc Biol 2006:26(1):41-8
Thromboxane A2 synthesis

19. CONCEPTS ON THE NEW, CELL-BASED
COAGULATION MODEL
Propagation
TF –
bearing
cell
e.g.
fibroblas
t
T
F
V
I
I
a
V
a
X
a
Activated Platelet
Va
VIIIa IXa
Intrinsic tenase
X Xa
Adapted from Thromb Haemost 85(6):958-65
Arterioscler Thromb Vasc Biol 2006:26(1):41-8

20. CONCEPS ON THE NEW, CELL-BASED
COAGULATION MODEL
Propagation
TF –
bearing
cell
e.g.
fibroblas
t
T
F
V
I
I
a
V
a
X
a
Activated Platelet
Va
VIIIa IXa
Intrinsic tenase
Xa
Va/Xa complex
(Prothrombinase)
Fibrinogen  Fibrin
Prothrombin  Thrombin
Adapted from Thromb Haemost 85(6):958-65
Arterioscler Thromb Vasc Biol 2006:26(1):41-8

21. PRE-OPERATIVE EVALUATION FOR
ANTICOAGULANTS
Bleeding Risk Procedure
Versus
Risk of thromboembolic events
Whether to off anticoagulants ?

22. PATIENT VERSUS SURGICAL RISK
FACTORS
 Patient Risk Factors
 Prior thromboembolism ?
 Mechanical valve ?
 AF ?
 Surgical Risk Factors
 Procedure type ?
 Quantify Risk of bleeding ?
 Quantify Risk of
thromboembolism ?

23. RISK OF THROMBOEMBOLISM
 Michael et al.
 After discontinue OAT in 169 patients
 22%  thromboembolic event
 7%  died
 Tulloch and Wright et al.
 Case Report
 Discontinue OAT for 8 days before oral surgery
 Post operative day 2  CVA
 Post operative day 4  branchial artery emboli
Br Heart J 1970;32:359-364
Circulation 1954;9:823-834

24. RISK OF THROMBOEMBOLISM
Wahl et al.
 Review > 2400 cases
 950 cases continued oral antithrombotic
 12 cases experienced post-operative bleeding
 Which controlled by local measures
 Incidence of thromboembolic complication was about 1%
Small but outcome serious !!!
Arch Intern Med 1998;158:1610-1616

25. RISK OF HEMORRHAGE
 Cambell et al.
 Randomized controlled trial
 Continue OAT versus withdrawn OAT
 No significant difference in total blood loss
 Madrid and Sanz
 Systemic review
 Continue OAT with INR 2-4 and discontinue OAT
 No significant in post operative hemorrhage
J oral Maxillofac Surg 2000;58:131-135
Clin Oral Implants Res 2009;20 Suppl 4:96-106

26. MEANING OF INR VALUE
 Most anticoagulation therapy
INR 2.0 - 3.0
 Few
INR 3.0 - 4.0
 Blinder et al.
 INR value did not significantly influence the incident
of perioperative bleeding (INR 2.0 -4.0)
 INR 2.0-4.0 post operative hemorrhage can
not be so serious
Int J Oral Maxillo Surg 2008;66:51-57

27. CONCLUSION
ThromboembolismThromboembolism
RiskRisk
Bleeding Risk
Local control
Small but outcome serious !!!
Arch Intern Med 1998;158:1610-1616

28. CHEST 2012; 141:326-350S

29. CLINICAL SCENARIO
 ผู้ชาย 45 ปี
 Old CVA with AF with MR S/P MVR
 on warfarin 22 mg/week INR 3.0
 จะถอนฟัน ทำาไงดี ?
 หยุดยา warfarin ก่อนไปถอนฟัน
 ไปถอนฟันเลย

30. OVERVIEW OF CLOT FORMATION
injury
TF Thrombin
Coagulation cascade
Collagen
vWF
ADP
Thromboxane A2
P2Y12
PPAR-1
GP Iib/IIIa
Fibrin  platelet aggregation
Xa/Va prothrominase complex

31. ANTIPLATELET
promote
vWFvWF

32. ASPIRIN
ARACHIDONIC ACID METABOLISM
Phospholipid-Arachidonic acid
Phospholipases
Arachidonic acid
Prostaglandin G2
Prostaglandin H2
Tissue Specific Isomerases
COX1
HOX
Arachidonic acid
Prostaglandin G2
Prostaglandin H2
COX2
HOX
Thromboxane A2
(Promote Thrombosis)
Prostaglandin D2 Prostaglandin E2 Prostaglandin F2a
Prostacyclin
(inhibit Plt aggregation)
Low dose ASA High dose ASA(Inflammatory dose)
Higher dose block
Adapted from: CHEST 2012; 141(2) (Suppl) : e89S-e119S
Platelets & vascular endothelial cells

33. Dipyridamole.
effects of dipyridamole on NO/cGMP and prostaglandin/cAMP signal transduction in human
platelets.
Adapted from :Aktas B et al. Stroke. 2003;34:764-769
Copyright © American Heart Association, Inc. All rights reserved.
Platelet aggregationPlatelet aggregation

34. DIPYRIDAMOLE.
PROMOTE PROSTACYCLIN
promote

35. CILOSTAZOL
PHOSPHODIESTERASE III INHIBITORS
Eur Heart J (2008) 29 (18): 2202-2211.
Vasodilatory stimulating phosphoprotein

36. THIENOPYRIDINES
TICLOPIDINE ,CLOPIDOGREL ,
PRASUGREL
Eur Heart J (2008) 29 (18): 2202-2211.

37. ANTIPLATELET AND ORAL SURGERY
 Ardekian et al.
 39 patients taking ASA 100 mg
19 continued
20 stopped
Bleeding time 3.1 min versus 1.8 min (p=0.004)
None of them had prolong bleeding time >10
min
No patient experienced uncontrolled bleeding
 Antiplatelet should not be discontinued prior to
dental procedure
J Am Dent Assoc 131,331-335

38. DUAL ANTIPLATELET OR SINGLE
ANTIPLATELET?
 Nepanas et al.
 Retrospective study
 43 patients who were receiving single or dual
antiplatelet therapy
 Twenty-nine patients (67 percent) were receiving
dual antiplatelet therapy.
 The authors found no differences between patients
receiving single or dual antiplatelet therapy for all
variables.
J Am Dent Assoc. 2009 Jun;140(6):690-5

39. COMPLICATION RATES FROM
DISCONTINUATION OF ANTIPLATELETE < 6
WKS AFTER PCI W/WO STENT

40. CHEST 2012; 141:326-350S

41. CLINICAL SCENARIO
 ผู้หญิง 75 ปี
 Previous STEMI S/P PCI Drug Eluting Stent
เมื่อ 6 เดือนก่อน
 ASA 81 mg/d + Clopidogrel 75 mg/d
 จะไปถอนฟัน ทำำไงดี
 หยุดยำ ASA + Clopidogrel ก่อนไปถอนฟัน
 หยุดยำ ASA ก่อนไปถอนฟัน
 หยุดยำ Clopidogrel ก่อนไปถอนฟัน
 ไปถอนฟันได้เลย

42. CLINICAL SCENARIO
 ผู้หญิง 75 ปี
 Previous STEMI S/P PCI Drug Eluting Stent
เมื่อ 6 เดือนก่อน
 ASA 81 mg/d + Clopidogrel 75 mg/d
 จะไปถอนฟัน ทำำไงดี
 หยุดยำ ASA + Clopidogrel ก่อนไปถอนฟัน
 หยุดยำ ASA ก่อนไปถอนฟัน
 หยุดยำ Clopidogrel ก่อนไปถอนฟัน
 ไปถอนฟันได้เลย

43. LOCAL BLEEDING CONTROL
 Local anesthesia with vasoconstrictor
 Local hemostatic material (bonewax ,surgicel)
 Local hemostatic agent (epinephrine solution )
 Suture
 Pressure
 Dressing
 Peridontal pack application
 Tranexamic acid
 Mouth wash
Journal of Oral Science,Vol.49,No.4,253-258,2007

44. TAKE HOME MESSAGE
 Warfarin
 ถ้ำ INR 2 - 4 ไม่ต้องหยุด
 ถ้ำ INR > 4 ไม่ต้องผ่ำ/ทำำฟันทุกกรณี
 Antiplatelets
 ASA , clopidogrel ,prasugrel , ticlopidine , cilostazole ,
Tegagrelor etc.
 ไม่ต้องหยุดทุกรณี ไม่ว่ำจะ on ด้วย indication primary
prevention , secondary prevention , S/P stent ก็ตำม ทั้ง
single หรือ dual antiplatelet

45. HIGH ALERT DON’T STOP OAT!!!
 Warfarin
 Mechanical valve , Hypercoagulable state
 Antiplatelet
 S/P w Stent [DES , BMS] within 1 years

46. สุดท้ำย
หำก INR สองถึงสี่นั้น บ่หยุด
INR เกิน 4 ให้ ผ่ำไม่
antiplatelet ไซร้ อย่ำได้
หยุดเลย
บ่หยุดOATไว้ จักได้
ปลอดภัย

47. THANK YOU