Drugs affecting coagulation and dental management

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.

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

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

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

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

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.

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

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)

1- Aspirin

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

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)

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

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 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).

Adverse effect GIT irritation and bleeding Tinnitus

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

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 )

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.

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

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.

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

oral Anticoagulants (Indirect acting) coumarin derivative, including warfarin

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)

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

Pharmacologic Properties (warfarin: Coumadin) Taken orally Metabolized in the liver Half-life: 1.5-2.5 days Duration of action: 2-5 days. Excreted in urine and feces Contraindication : pregnancy and bleeding disorder

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 .

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

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.

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

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 1.5 - 2 Times Control Range Patients on Chronic Aspirin Therapy

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

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

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

Local Measures to Control Postoperative Bleeding Careful, a traumatic surgical technique Post-operative pressure pack (damp gauze for 30-60 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

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,

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; 2.5-25 mg iv, im, sc, or oral