Clinical approach to new anticoagulants therapy

1. BY: DR. NADEEM AKBAR
HOUSE OFFICER CARDIOLOGY UNIT

2.  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.

4.  The coagulation cascade has two initial pathways
which lead to Fibrin formation.
1. INTRINSIC PATHWAY
2. EXTRINSIC PATHWAY

6.  the process of hindering the clotting of blood especially by
treatment with an anticoagulant.
INDICATIONS FOR ANTICOAGULANTION:
1. Venous Thromboembolism Phenomenon.
2. Acute Coronary Syndrome
3. Atrial Fibrillation
4. TIA/Stroke
5. DIC
6. Prosthetic Heart Valves
7. Vascular Surgeries

7. TYPES OF ANTICOAGULANTS:
1. Injectable Anticoagulants
LMWH
Unfractionated Heparins
1. Oral Anticoagulants
Warfarin
New Oral Anticoagulants
* Factor Xa inhibitors (Rivaroxaban, Apixaban)
* Direct Thrombin inhibitors ( Dabigatran)

9.  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.

10.  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.

12.  Warfarin bioavailability of nearly 100%.
 Highly bound to plasma protein , mainly Albumin.
 Half life of warfarin is 40 hours
 Metabolized by Hepatic P-450 enzyme to inactive
metabolites and excreted through Bile and Kidney.

13.  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.

14.  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

15.  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

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

18. Indication INR
Treatment of venous thrombosis 2.0–3.0
Treatment 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 2.0–3.0
Bileaflet 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

19.  IN NON-BLEEDING PATIENTS
 IN BLEEDING PATIENTS

20. TARGET INR
2.0-3.0
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

21.  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

22. 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)

25.  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

26.  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

27. MODERATE CKD: 20 mg OD after evening meal
SEVERE CKD: 15 mg OD after evening meal
END STAGE CKD or ON DIALYSIS: NOT
RECOMENDED

28.  Major adverse efffect is INTERNAL BLEEDING.
 It has yet no antidote of rivaroxaban.
 Possible antidote ANDEXANET ALFA is under
investigation.

29.  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

30.  1: DVT or PE
150 mg BD PO.
 2: DVT Prophylaxis ( orthopadec surgery)
Hip replacement: 220 mg PO OD for 35 days
 3: Nonvalvular Atrial Fibrillation
150 mg/bd PO.
IN CKD:
Severe CKD: 75mg BD
END stage CKD: NOT RECOMENDED

31.  Idarucizumab is the specific antidote for Dabigatran.

32.  WARFARIN TO RIVAROXABIN
Discontinue Warfarin and Start Rivaroxaban when
INR <3.0
 WARFARIN 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.