BY: DR. NADEEM AKBARHOUSE OFFICER CARDIOLOGY UNIT

CLINICAL APPROACH TO

ANTICOAGULATION

Is a process which causes bleeding to stop.Has three steps: 1. Reflex Vasoconstriction 2. Primary Hemostasis ( Platelet Activation) 3. Secondary Hemostasis ( Coagulation Cascade)

This process results in the formation of Blood clot.

NORMAL HEMOSTASIS:

The coagulation cascade has two initial pathways which lead to Fibrin formation.

1. INTRINSIC PATHWAY 2. EXTRINSIC PATHWAY

COAGULATION CASCADE

the process of hindering the clotting of blood especially by treatment with an anticoagulant.

INDICATIONS FOR ANTICOAGULANTION:1. Venous Thromboembolism Phenomenon.2. Acute Coronary Syndrome3. Atrial Fibrillation4. TIA/Stroke5. DIC6. Prosthetic Heart Valves7. Vascular Surgeries

ANTICOAGULATION

TYPES OF ANTICOAGULANTS:

1. Injectable Anticoagulants LMWH Unfractionated Heparins

2. Oral Anticoagulants Warfarin New Oral Anticoagulants * Factor Xa inhibitors (Rivaroxaban, Apixaban) * Direct Thrombin inhibitors ( Dabigatran)

ORAL ANTICOAGULANTS

Warfarin is an oral Coumarin anticoagulant.Clinically Warfarin is available in mixture of

two racemic forms: R- and S-Warfarin.S- form has 3-5 times greater potency than R-

Warfarin.

WARFARIN

Warfarin acts by antagonizing the anti-hemorrhagic effects of Vitamin K.

It inhibits hepatic sysnthesis of Vitamin K dependent

Coagulation factors II, VII, IX and X by inhibiting Vitamin K1 -2,3 epoxide reductase enzyme, preventing vitamin K from being reduced to its active form.

MECHANISM OF ACTION

Warfarin bioavailability of nearly 100%.Highly bound to plasma protein , mainly

Albumin.Half life of warfarin is 40 hoursMetabolized by Hepatic P-450 enzyme to

inactive metabolites and excreted through Bile and Kidney.

PHARMAKOKINETIC

An anticoagulation effect generally occurs within 24 hours after warfarin administration.

Peak anticoagulant effect may occur in 24 to 96 hours.

The duration of action of a single dose of racemic warfarin is 2 to 5 days.

ANTICOAGULATION EFFECT

Start with loading dose of 10 mg stat and do INR after 16 hours.

If: INR <1.8 : The 2nd dose is 5 mg given 24 hour

after 1st dose. INR >1.8 : The 2nd dose is just 0.5 mg given 24

hour after 1st dose

WARFARIN DOSAGE

Then repeat INR after 16 hours of 2nd dose.The 3rd dose should be given accordingly

INR 3rd Dose Maintenance dose

<2 10 mg 6 mg 2 5 mg 5.5 mg 2.5 4 mg 4.5 mg 2.9 3 mg 4 mg 3.3 2 mg 3.5 mg 3.6 0.5 mg 3 mg 4.1 0 mg 1-2 mg next

day >4.5 miss 2 doses

Effect of Warfarin is monitored by PT/INR.INR = Patient’s PT in sec ISI Mean Normal PT in secISI= International Sensitivity Index.

WARFARIN MONITORING

Indication INRTreatment of venous thrombosis 2.0–3.0Treatment of pulmonary embolism

2.0–3.0

Prophylaxis of venous thrombosis (high-risk surgery)

2.0–3.0

Prevention of systemic embolism 2.0–3.0  Tissue heart valves 2.0–3.0  AMI (to prevent systemic embolism)†

2.0–3.0

  Valvular heart disease 2.0–3.0  Atrial fibrillation 2.0–3.0Bileaflet mechanical valve in aortic position

2.0–3.0

Mechanical prosthetic valves (high risk)

2.5–3.5

Systemic recurrent emboli 2.5–3.5

WARFARIN INDICATIONS ALONG INR

IN NON-BLEEDING PATIENTSIN BLEEDING PATIENTS

WARFARIN DOSE TITRATION

DOSE TITRATION IN NON BLEEDING PATIENTS

TARGET INR2.0-3.0

INR 4.1-8.9INR 3.6- 4.0INR 3.1-3.5 INR >9.0INR <2.0

INCREASE BY 10%

DECREASE BY 0-10%

HOLD 1 DOSE,

DECREASE BY 10%

HOLD 2 DOSES,

DECREASE BY 15%, +/- 2.5mg Vit

K

HOLD 2 DOSES,

DECREASE BY 20%, +/- 2.5mg Vit

K

REPEAT INR IN 2 WEEKS

REPEAT INR IN 1

WEEK

REPEAT INR IN 2

DAYS

REPEAT INR NEXT

DAY

REPEAT INR

WITHIN 1 WEEK

MINOR BLEEDING: STOP WARFARIN 2.5 mg VIT.K P/O CHECCK INR DAILY

MAJOR BLEEDING: STOP WARFARIN INJ. VIT K 5-10 mg IV SLOWLY PROTHROMBIN COMPLEX CONCENTRATE 50

U/kg OR FFP 15ml/kg

DOSE TITRATION IN BLEEDING PATIENTS

H  Hypertension -( systolic blood pressure >160 mmHg) (Points: 1 )

A  Abnormal renal function ( defined as the presence of chronic dialysis or renal transplantation                   or serum creatinine 200µmol/L (>~2.3 mg/dL)) (Points: 1 )     Abnormal liver function ( defined as chronic hepatic disease (eg. cirrhosis) or biochemical              evidence of significant hepatic derangement (eg. bilirubin >2x upper limit of normal, in association              with AST/ALT/ALP >3x uper limit normal) (Points: 1 )

S  Stroke (Previous history of stroke) (Points: 1 )

B  Bleeding (Major bleeding history (anemia or predisposition to bleeding))  (Points: 1 )

L  Labile INRs (refers to unstable/high INRs or poor time in therapeutic range(eg<60%))(Points: 1)E  Elderly (age >/= 65) (Points: 1 )

D  Drug Therapy (concomitant therapy such as antiplatelet agents, NSAID's)   (Points: 1 )     Alcohol intake (consuming 8 or more alcoholic drinks per week)   (Points: 1)

ASSESSING BLEEDING RISK IN PATIENTS ON ANTICOAGULANTS: HAS-BLED SCORE

WARFARIN CONTRAINDICATIONS:

WARFARIN INTERACTION

It is new oral anticoagulant.

MECHANISM OF ACTION:It is direct inhibitor of Factor Xa and thus inhibits both Intrinsic and Extrinsic pathways.

INDICATIONS: DVT or PE Treatment DVT Prophylaxis ( orthopadec surgery) Nonvalvular Atrial Fibrillation

RIVAROXABAN

1: DVT or PE 15 mg BD PO for 21 days with food, THEN 20 mg OD PO for 6 months. 2: DVT Prophylaxis ( orthopadec surgery) Knee replacement: 10 mg PO OD for 12 days Hip replacement: 10 mg PO OD for 35 days 3: Nonvalvular Atrial Fibrillation 20 mg/day PO with the evening meal

DOSE OF RIVAROXABAN

MODERATE CKD: 20 mg OD after evening meal

SEVERE CKD: 15 mg OD after evening meal

END STAGE CKD or ON DIALYSIS: NOT RECOMENDED

RIVAROXABAN DOSE IN CKD:

Major adverse efffect is INTERNAL BLEEDING.

It has yet no antidote of rivaroxaban.Possible antidote ANDEXANET ALFA is under

investigation.

REVERSAL OF RIVAROXABAN ANTICOAGULATION

It is also new oral anticoagulant.

MECHANISM OF ACTION:It is direct inhibitor of Thrombin.

INDICATIONS: DVT or PE Treatment DVT Prophylaxis ( orthopadec surgery) Nonvalvular Atrial Fibrillation

DABIGATRAN

1: DVT or PE 150 mg BD PO.2: DVT Prophylaxis ( orthopadec surgery) Hip replacement: 220 mg PO OD for 35 days3: Nonvalvular Atrial Fibrillation 150 mg/bd PO.IN CKD: Severe CKD: 75mg BD END stage CKD: NOT RECOMENDED

DOSAGE OF DABIGATRAN

Idarucizumab  is the specific antidote for Dabigatran.

REVERSAL OF DABIGATRAN ANTICOAGULATION:

WARFARIN TO RIVAROXABIN Discontinue Warfarin and Start Rivaroxaban when INR <3.0WARFARIN TO DABIGATRAN Discontinue Warfarin and Start Dabigatran when INR <2.0 RIVAROXABAN TO WARFARIN initiate warfarin and a parenteral anticoagulant 24 hour after discontinuation of rivaroxaban.

CONVERTING BETWEEN ORAL ANTICOAGULANTS