This document discusses hemostasis, anticoagulation, and various anticoagulant medications. It covers the three steps of hemostasis - vasoconstriction, platelet activation, and coagulation cascade formation. It then discusses indications for anticoagulation like VTE, ACS, AFib, and prosthetic heart valves. Types of anticoagulants discussed include injectable anticoagulants like LMWH and oral anticoagulants like warfarin and new oral anticoagulants like rivaroxaban, apixaban, and dabigatran. Details are provided on dosing, monitoring, and managing these anticoagulant medications.

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.