cardiovascular

Drugs affecting coagulation

Hemostasis
Prevention of blood loss when vessel rupture .

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

HEMOSTASIS

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

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

COAGULATION PHASE

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

THE CLOTTING MECHANISM

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



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.


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.

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

Antithrombotic drug (Antiplatelet Drugs)

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

1- Aspirin

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)


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.

Adverse effect

GIT irritation and bleeding Tinnitus


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

uses

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

Adverse effects sever bone marrow toxicity including aplastic anemia , agranulocytosis

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

uses

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

Anticoagulant drugs

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

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 )

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 .

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.

Pharmacokinetic:

Metabolize in liver Excreted in urine
IV: Onset immediate; peak minutes; duration 2–6 hSC: Onset 20–60 min; peak 2–4 h; duration 8–12 h Given parentally:
TЅ: 30–180 min

Adverse effect 

1.bleeding complication 2. hypersensitivity reaction 3.thrombocytopenia

Contraindications

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

Subcutaneous Anticoagulant eg enoxaparin , dalteparin 

mechanisms of action antifactor Xa , antifactor IIa activity


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

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

Drug interaction

Attenuation of anticoagulant Chronic alcohol ingestion ,barbiturate, grisofulvin cause stimulation of warfarin metabolism

Drug interaction

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


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

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.

Uses of Streptokinase

Acute pulmonary embolism Deep venous thrombosis Myocardial infraction Atrial thrombosis

Adverse effect of Streptokinase

Bleeding disorder hypersensitivity

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.

Uses of Alteplase and reteplase

Treatment of myocardial infraction Massive pulmonary embolism Dissolve older clot


Hemostatic drugs

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

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- 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 .

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 .

DENTAL PATIENTS

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

DENTAL MANAGEMENT

HIGH RISK PATIENTS 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 (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; 2.5-25 mg iv, im, sc, or oral

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