1. Drugs affecting coagulation

2. Hemostasis
Prevention of blood loss when vessel rupture .

3. Hemostasis
Hemostasis refers to the finely regulated dynamic process of maintaining fluidity of the blood, repairing vascular injury, and Limiting blood loss while avoiding vessel occlusion (thrombosis) and inadequate perfusion of vital organs

4. HEMOSTASIS 1. VASCULAR PHASE 2. PLATELET PHASE 3. COAGULATION PHASE
4. FIBRINOLYTIC PHASE

5. 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 5

6. COAGULATION PHASE
THROUGH TWO SEPARATE PATHWAYS THE CONVERSION OF FIBRINOGEN TO FIBRIN IS COMPLETE.

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

8. Thrombus formation at the site of the damaged vascular wall (EC, endothelial cell) and the role of platelets and clotting
factors. Platelet membrane receptors include the glycoprotein (GP) Ia receptor, binding to collagen (C); GP Ib receptor, binding von Willebrand
factor (vWF); and GP IIb/IIIa, which binds fibrinogen and other macromolecules. Antiplatelet prostacyclin (PGI 2 ) is released from the endothelium.
Aggregating substances released from the degranulating platelet include adenosine diphosphate (ADP), thromboxane A 2 (TXA 2 ), and
serotonin (5-HT)

9. Patients with defects in the formation of the primary platelet plug (defects in primary hemostasis, eg, platelet function defects, von Willebrand disease) typically bleed from surface sites (gingiva, skin, heavy menses) with injury.

10. In contrast, patients with defects in the clotting mechanism (secondary hemostasis, eg, hemophilia A) tend to bleed into deep tissues (joints, muscle, retroperitoneum), often with no apparent inciting event, and bleeding may recur unpredictably.

11. 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.

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

13. Antithrombotic drug
(Antiplatelet Drugs)

14. Antithrombotic drug (Antiplatelet drugs)
antithrombotic drug interfere with platelet adhesion and aggregation
Aspirin (irreversible effect for life of the platelet ~ 7-10 days)
Clopidogrel
Ticlopidine
Dipyridamole

15. 1- Aspirin

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

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

20. Aspirin and Bleeding
All studies found no significant difference in perioperative or postoperative blood loss between patients taking aspirin and controls
Conclusion: Aspirin should not be withdrawn in most cases

21. If pt is on aspirin, and intraoperative bleeding is feared, a short-acting NSAID can be temporarily substituted.

22. Adverse effect
GIT irritation and bleeding
Tinnitus

23. Clopidogrel
Ticlopidine
mechanisms of action
Inhibits platelet aggregation and platelet - platelet interactions

24. uses in patients contraindication or unresponsive to aspirin
Preventing cerebrovascular and cardiovasculare as well as vascular disease by prevent thrombus formation .

25. Adverse effects
sever bone marrow toxicity including aplastic anemia , agranulocytosis

26. Dipyridamol (vasodilator )
mechanisms of action
Decease platelet adhesion by potentiates action of prostacyclin and inhibits platelet phosphdiestrase

27. uses Used with aspirin to prevent thrombosis
To treat angina pectoris
Used with aspirin to prevent thrombosis
as vasodilator during myocardial perfusion scan (cardiac stress test )

28. Anticoagulant drugs

29. 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

30. 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 )

31. 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.

32. HEPARIN Mechanism of action:
-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 )

33. Therapeutic uses of heparin:
1- for treatment of deep vein thrombosis
2- pulmonary embolism
3. as a prophylactic to prevent post operative venous embolism in some patient .

34. Therapeutic uses of heparin:
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.

35. Pharmacokinetic: Metabolize in liver Excreted in urine
Given parentally:
IV: Onset immediate; peak minutes; duration 2–6 h
SC: Onset 20–60 min; peak 2–4 h; duration 8–12 h
T½: 30–180 min

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

37. Contraindications Hypersensitive to heparin . Bleeding disorder
Alcoholic person
Surgery of brain .

38. Subcutaneous Anticoagulant eg enoxaparin , dalteparin
mechanisms of action
antifactor Xa , antifactor IIa activity

39. Oral Anticoagulants (Indirect acting)
Coumarin Derivatives (dicoumarol, warfarin)

40. 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)

42. 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

43. 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

44. Drug interaction Potentiation of anticoagulant effect of warfarin
1.aspirin , phenylbutazone cause inhibition of platelet aggregation .
2.acute alcohol intoxication ,cimetidine, chloramphenicol ,disulfiram, metronidazole phenylbutazone cause inhibition of warfarin metabolism

45. Drug interaction
Attenuation of anticoagulant
Chronic alcohol ingestion ,barbiturate, grisofulvin cause stimulation of warfarin metabolism

46. Drug interaction Disease state : vit K deficiency
Hepatic disease that impairs synthesis of clotting factors.

47. Fibrinolytic (Thromblytic)drugs
Agent that activate the conversion of plasminogen to plasmin then hydrolyze fibrin and thus dissolve clot .

48. Streptokinase
Mechanism of action
Streptokinase acts indirectly by forming an activator complex with plasminogen
action occurs both within thrombi and circulating blood , leading to lysis of both normal and pathogenic thrombi .
Antidote : aminocaproic or tranexamic acid.

49. Uses of Streptokinase Acute pulmonary embolism Deep venous thrombosis
Myocardial infraction
Atrial thrombosis

50. Adverse effect of Streptokinase
Bleeding disorder
hypersensitivity

51. Alteplase and reteplase
Has low affinity for free plasminogen but rapidly activate plasminogen bound to fibrin in thrombus or haemostatic plug thus is fibrin selective.

52. Uses of Alteplase and reteplase
Treatment of myocardial infraction
Massive pulmonary embolism
Dissolve older clot

53. Hemostatic drugs

54. 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 of prothrombin (factor II) and factorXII , IX, X

55. 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.

56. B- Plasma fraction
Available as factor VIII concentrate and factor IX concentrate , either from pooled human plasma or as recombinant antihemophilic factor .
Uses: hemophilias A and B marked by deficiencies of factor VIII and factor IX.
Adverse effect : risk of AIDS and hepatitis transmission from concentrated plasma fraction .

57. C- Fibrinolytic inhibitor (aminocaproic acid )
Uses : systemic or urinary hyperfibrinolysis (as in aplastic anemia, hepatic cirrhosis )
D - Protamine sulfate
Mechanism of action
Chemical antagonist of heparin
Uses :
hemorrhagic associated with heparin overdose .

58. 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

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

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

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

62. 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

63. 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,

64. Additional Postoperative Measures
For analgesia, consider use of
Acetaminophen.
Codeine
COX 2 inhibitor (rofecoxib)
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

65. Thank you