ANTICOAGULANTSBY:

Danial hassan

Hemostasis• Hemostasis is the prevention or stoppage of

blood loss from an injured blood vessel

• Process involves: formation of a platelet plug, activation of clotting factors and growth of fibrin meshwork into the blood clot making it more stable.

Blood Platelets•Platelets are formed from the cytoplasm of bone marrow and are the smallest of the blood cells.

 Normal platelet count lies between 150-450 x 109/L

Primary HemostasisEnzymes and Receptors involved in Primary Hemostasis:1- Thromboxane A2– Increases platelet activation and aggregation 2- Adenosine Diphosphate (ADP)– Induce platelet aggregation 3- glycoprotein II B/ III A receptors on platelet surface: for attaching with the blood vessel’s endothelial wall (aggregation) 

Glycoprotein IIb/IIIa Receptors forPlatelet Aggregation

ADPCollagen

Thrombin

Epinephrine

Tx A2

Serotonin

GP IIb/IIIareceptoractivation

IIb/IIIa

Shear forces

SECONDARY HEMOSTASISClotting factors activation• Factor X converts prothombin into thrombin• Thrombin converts fibrinogen into fibrin• Fibrin threads stabilize the blood clot already

formed.

TERTIARY HEMOSTASIS

• Tissue plasminogen activator released from endothelium---- converts plasminogen in the clot to plasmin---- fibrinolysis---- fibrin dissolution to limit the clot (removing extra part)

Definition of Anticoagulation

• Therapeutic interference with the clotting mechanism of the blood (blood-thinning) to prevent or treat thrombosis.

Indications of Anticoagulant Therapy

• Treatment and Prevention of Deep Venous Thrombosis (DVT), especially in CBR patients– most high risk for DVT

• Pulmonary Emboli• Prevention of stroke in patients with atrial

fibrillation, artificial heart valves, cardiac thrombus.

• Ischemic heart disease• During procedures such as cardiac

catheterisation (angioplasty).

No ST elevation ST elevation

Acute coronary syndrome

Antiplatelet Rx

Antithrombin Rx

Complete obstruction

Partial flow

UA/NSTEMI STEMI

Drugs Affecting Primary Hemostasis

Antiplatelet Drugs

• Antiplatelet drugs act by inhibiting platelet activation, adhesion and aggregation.

• Include drugs that inhibit thromboxane A2, ADP, glycoprotein IIb/IIIa receptors

• Platelet count is essential to be checked with all anti platelet drugs.

Thromboxane A2 Inhibitors• Work by inhibiting synthesis of

prostaglandins, thereby inhibiting cyclooxygenase, the enzyme in platelets that synthesizes thromboxane A2 (which causes platelet aggregation).

• Aspirin is an example. It affects the platelets for the life of the platelet i.e. 7-10 days.

• Must be stopped atleast 7 days before surgeries after consultation with the physician.

Platelet Activation:Effect of ASA

ADP

CollagenThrombin

Epinephrine

Tx A2

Serotonin

Ca++

PGG2-PGH2

AA release

Tx A2

COX

Tx Syn

Tx A2

RBCs

Endothelial cells

ASA

Adenosine Diphosphate Receptor Antagonists

• Example: Clopidogrel (Plavix), Ticlopidine• Inhibit platelet aggregation by preventing

ADP-induced binding of platelets. This reaction inhibits platelet aggregation and persist for the lifespan of the platelet (7-10 days)

• Must be stopped atleast 7 days before surgeries after consultation with the physician.

COX (cyclo-oxygenase)ADP (adenosine diphosphate)TxA2 (thromboxane A2)

CLOPIDOGREL

ASA COX

ADP

ADP

C

GPllb/llla Collagen thrombinTXA2

Activation

TXA2

ASA

Mode of Action of Clopidogrel1

1. Schafer AI. Am J Med 1996; 101: 199–209.

Glycoprotein IIb/IIIa Receptor Inhibitors

• Aggrastat and Reopro (Abciximab) are the drugs that prevent the binding of GP IIb/IIIa receptors on platelets with the vessel wall. This action inhibits platelet aggregation.

• Indication: Used during and after percutaneous transluminal coronary angioplasty (PTCA) i.e. removal of atherosclerotic plaque, to prevent rethrombosis

Glycoprotein IIb/IIIa Receptor Inhibitors cont.

• Contraindications: include active bleeding, thrombocytopenia, history of hemorrhagic stroke, surgery or trauma within past 6 weeks, uncontrolled hypertension or hypersensitivity.

Glycoprotein IIb/IIIa Receptor Inhibitors

ADPCollagen

Thrombin

Epinephrine

Tx A2

Serotonin

GP IIb/IIIareceptoractivation

IIb/IIIa

Shear forces IIb/IIIa inhibitor

Antiplatelet AgentsMechanism of Action

ADP

(FibrinogenReceptor)

ADP = adenosine diphosphate, TXA2 = thromboxane A2, COX = cyclooxygenase. Schafer AI. Am J Med. 1996;101:199–209.

clopidogrel bisulfate

TXA2

ADP

dipyridamole

phosphodiesterase

ADP

Gp IIb/IIIa Activation

COX

ticlopidine HCl

aspirin

CollagenThrombin

TXA2

Gp IIb/IIIa antagonists

Drugs Affecting Secondary Hemostasis

HEPARINE• Binds to naturally occurring antithrombin III---

enhances its ability to inhibit thrombin (IIA), thereby inhibiting fibrinogen conversion into fibrin

Monitoring required with Heparin

• Activated Partial Thromboplastin Time (APTT)--- Normal range: 25-30 seconds

• Timing– Baseline APTT (before starting Heparine therapy– Then, APTT is checked 6 hours after starting

Heparin infusion, and then after every 6 hours till the infusion is in progress; based on the values of APTT, dosage of heparin infusion is adjusted as per the protocol

Low Molecular Weight Heparin

• Example : Enoxaparine• Enriched with short molecular chains • No monitoring required via APTT and lesser incidence of

thrombocytopenia----- due to lesser effect on thrombin (II A); it primarily affects factor Xa

• However, PT and INR is to be checked with Enoxaparine • Higher bioavailability than heparin (90% versus 60%)• Longer half life than heparin (6 hours versus 1 hour)• Must be stopped 12 hours before angiography in order to

avoid bleeding

WARFARIN

• Antagonizes vit K produced by the liver

Vitamin K

Synthesis of Functional

Coagulation Factors

VIIIXXII

Vitamin K-Dependent Clotting Factors

Warfarin

No Synthesis of

Coagulation Factors

Antagonismof

Vitamin K

Warfarin Mechanism of Action

Vitamin K

VIIIXX

II

Enhances Antithrombin Activity

Warfarin

Nursing Care for Patients on Warfarin

• For patients on Warfarin, their Prothrombin time (PT) and International Normalized Ratio (INR) has to be checked regularly and informed to the physician; Warfarin dose is adjusted according to the PT and INR results

• Instruct patient to avoid eating green leafy vegetables (rich in vitamin K) as they reduce the effectiveness of Warfarin

Drugs Affecting Tertiary Hemostasis

FIBRINOLYTICS/ THROMBOLYTICS• Enhances the natural process of conversion

of plasminogen into plasmin--- dissolve fibrin threads---dissolve the already formed clots/ plaque

• Revascularize the myocardium or brain tissue by dissolving clots in coronary or cerebral arteries

• Indicated in STEMI (100% blocked coronary artery) or Acute Ischemic stroke

• Contraindicated in hemorrhagic stroke• Examples: Streptokinase, tPA (tissue

Plasminogen Activator)

Nursing Care and Teaching for Patients on Anticoagulants

• Explain the patient that their bleeding tendency has increased, and that they are at high risk for bleeding

• Instruct patient to observe for bleeding from all orifices nose, moth, anus, and to observe blood in sputum, urine and stool; also instruct to report any bleeding

• Instruct patient to prevent themselves from injuries and cuts

• Instruct patient to use sharps very cautiously such as razors, knives, needles, scissors etc.

Nursing Care and Teaching for Patients on Anticoagulants

• Instruct patient for no Intramuscular injections and no tooth brush

• In case of injury, instruct patient to apply direct pressure over the area for ten to fifteen minutes in order to stop bleeding.

• Instruct patient to monitor appropriate lab results (Platelet count with antiplatelets, APTT with Heparin, PT and INR with Enoxaparine and Warfarin.

• Anticoagulants are contraindicated in all conditions of hemorrhage i.e. hemorrhagic stroke, major bleeding from surgical sites etc.

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