1. Drugs affecting coagulation and dental management

2. DEFINITION
Hemostasis: is a complex process depending on the interactions between the vessel wall, platelets and coagulation and fibrinolytic mechanisms.
Bleeding disorders are conditions that alter the ability of blood vessels, platelets, and coagulation factors to maintain hemostasis.

4. Normal Hemostasis Following injury to a blood vessel:
Vascular retraction (vasoconstriction)
to slow blood loss
2. Adherence of platelets to the vessel
wall (endothelium) and then to each
other to form a platelet plug
3. Initiation of the coagulation cascade
resulting in the formation and
deposition of fibrin to form a clot 4

6. Coagulation Cascade
Extrinsic pathway: Factor VII is activated by tissue factor (phospholipid) that is released by injured perivascular or vascular tissues; very rapid reaction
Intrinsic 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

7. THE CLOTTING MECHANISM
INTRINSIC
EXTRINSIC
Collagen
Tissue Thromboplastin
XII XI
VII IX
VIII X V
FIBRINOGEN
(I)
PROTHROMBIN THROMBIN
(II)
(III)
FIBRIN

8. Calcium ion (factor IV )are essential for many of the stage of blood coagulation and help to accelerate the reaction between thrombin and fibrinogen .
Vit K is essential for normal hepatic biosynthesis of factor ( II ,VII, IX ,X )
Is a fat soluble

9. FIBRINOLYTIC PHASE
Anticlotting mechanisms are activated to allow clot disintegration and repair of the damaged vessel.
Blood clot are broken down by plasmin which is derived from plasma protein plasminogen.

10. Drug used to break up thrombi
A- antithrombotic drug
B- anticoagulant drug
C- fibrinolytic drug

11. A- antithrombotic drug(Antiplatelet Drugs)
antithrombotic drug interfere with platelet adhesion and aggregation
Aspirin (irreversible effect for life of the platelet ~ 7-10 days)
Clopidogrel (Plavix)
Ticlopidine (Ticlid)
Dipyridamole (Persantine)

12. 1- Aspirin

13. mechanism of action
Aspirin block thromboxane A2 (TA2) synthesis, a potent platelet aggregation , by irreversible acetylation of cyclooxygenase
The resulting suppression of platelet aggregation last for the life of the platelet Approximately 7 to 10 days

14. Low dose aspirin therapy inhibits cyclooxygenase to prevent synthesis of TA2 without decreasing the synthesis of prostacyclin (PGI2), which inhibit platelet aggregation.
High doses of aspirin inhibits of both TA2 and (PGI2)

15. uses in the prophylactic of cerebral ischemia
to reduce The incidence of recurrent myocardial infraction
to decrease mortality in postmyocardial infraction patient.

16. Aspirin and Bleeding
All studies found no significant difference in perioperative or postoperative blood loss between patients taking aspirin and controls

17. Conclusion: Aspirin should not be withdrawn in most cases
If pt is on aspirin, and intraoperative bleeding is feared, a short-acting NSAID can be temporarily substituted ( NSAIDs like ibuprofen, taken concomitantly with or 2 hours prior to aspirin , can obstruct the serine residue).

18. Adverse effect
GIT irritation and bleeding
Tinnitus

19. Anticoagulant drugs Differentiated on basis of
A- route of administration
1- Parenteral Anticoagulant eg heparin .
2- subcutaneous Anticoagulant eg enoxaparin , dalteparin
3- oral Anticoagulant eg coumarin derivative , including warfarin

20. Anticoagulant drugs
B- Direct or indirect interfere with the normal clotting mechanism of blood and reduce the incidence of thrombembolic disorder
Either inhibit of the coagulation factors ( heparin )
(direct interfere )
Or interfere with synthesis of coagulation factors (warfarin ) . (indirect interfere )

21. Patient receiving anticoagulant therapy include those with history of :
1- myocardial infraction
2 - cerebrovascular thrombosis
3- venous thrombosis ,
4- pulmonary embolism ,
5 - before and during dialysis.

22. HEPARIN Pharmacodynamic
Interfere with blood coagulation by inhibit the conversion of prothrombin to thrombin and fibrinogen to fibrin
- Heparin accelerate the action of antithrombine III to neutralize thrombin (factor IIa )
Therapeutic uses :
1- for treatment of deep vein thrombosis
2- pulmonary embolism

23. 3. as a prophylactic to prevent post operative venous embolism in some patient .
4. in acute case of myocardial infraction .
5. in dialysis mechanism to prevent thrombosis.
6. it is drug of choice for treating pregnant women with prosthetic heart valves or venous thromboembolism because it dose not cross the placenta.

24. Adverse effect 1.bleeding complication 2. hypersensitivity reaction
3.thrombocytopenia

25. oral Anticoagulants (Indirect acting)
coumarin derivative, including warfarin

26. oral Anticoagulants (Indirect acting) Coumarin Derivatives (dicoumarol, warfarin)
Coumarin antagonizes the production of vitamin K,
Vitamin K is necessary for the synthesis of four of the
coagulation factors (VII, IX, X and prothrombin)

27. Conditions for which Coumarin is prescribed to prevent unwanted blood clotting
Prophylaxis/Treatment of:
Venous thrombosis
Pulmonary embolism
Atrial fibrillation
Myocardial infarction
Mechanical prosthetic heart valves
Recurrent systemic embolism

28. Pharmacologic Properties (warfarin: Coumadin)
Taken orally
Metabolized in the liver
Half-life: days
Duration of action: 2-5 days.
Excreted in urine and feces
Contraindication : pregnancy and bleeding disorder

29. Fibrinolytic (Thromblytic)drugs
Agent that activate the conversion of plasminogen to plasmin then hydrolyze fibrin and thus dissolve clot .the thrombolytic drugs must be given within 6 to 12 hours of myocardial infraction to limited damage .

30. Hemostatic drugs A-Vitamin K
This fat-soluble vitamin is found in leafy green vegetables
Its produced by bacteria that colonize the human intestine and needs bile salt for absorption .
Its require in synthesis prothrombin (factor II) and factorXII , IX, X

31. Uses Prevention of hemorrhagic disease of the newborn (I.M , S.C)
Treatment of dietary Vit K deficiencies and reversal of the effect of warfarin (oral or parentral )
Adverse effect
Hemolysis , jaundice , and hyperbilirubinemia occasionally occur in newborn.

32. B-Fibrinolytic inhibitor (aminocaproic acid )
Uses : systemic or urinary hyperfibrinolysis (as in aplastic anemia hepatic cirrhosis )

33. DENTAL PATIENTS LOW RISK MODERATE RISK Normal Laboratory Results
Patients with No Hx of Bleeding Disorders
Normal Laboratory Results
MODERATE RISK
Patients on Chronic Oral Anticoagulant Therapy. PT is Times Control Range
Patients on Chronic Aspirin Therapy

34. DENTAL PATIENTS HIGH RISK
Patients with Known Bleeding Disorders
Patients without Known Bleeding Disorders Who Have Abnormal Laboratory Results

35. DENTAL MANAGEMENT LOW RISK PATIENTS MODERATE RISK PATIENTS
Normal Protocol
MODERATE RISK PATIENTS
Anticoagulants - Consult Physician
Aspirin Therapy - BT, Consult Physician

36. DENTAL MANAGEMENT HIGH RISK PATIENTS (Factor Replacement)
Close Coordination with Physician
Hospitalization (Platelet Transfusion)
(Factor Replacement)
(Vit K Therapy)
(Dialysis)

37. Local Measures to Control Postoperative Bleeding
Careful, a traumatic surgical technique
Post-operative pressure pack (damp gauze for minutes); especially important for flap compression
Use of absorbable hemostatic agent in socket (e.g. Gelfoam,Avitene,Surgicel)
Careful suturing; primary closure over sockets not essential
May use antifibrinolytic agents: tranexamic acid [Cyklokapron Oral] or epsilon amino caproic acid [Amicar] as a mouthwash or to soak pressure gauzes

38. Antifibrinolytic Mouthrinses
Epsilon amino caproic acid (Amicar)
Syrup (1.25 gm/5cc) ,
Use either as mouthwash or as a soak for the pressure gauze
Tranexamic acid (Cyklokapron)
Used topically as a mouthwash for 2 minutes,

39. Additional Postoperative Measures
For analgesia, consider use of
Acetaminophen.
Codeine
COX 2 inhibitor (celcoxib)
Avoid drugs that increase bleeding
For continued bleeding,
25% Amicar soaked gauze pressure pack
Consider intranasal desmopressin acetate spray; for 1-2 days; Stimulates the release of factor VIII and vWFactor
Vitamin K; mg iv, im, sc, or oral