ANTICOAGULANTS

Dr. Joy Biswas, RMO, AAH ICU

We will cover

TYPES MECHANISM OF USES IN ICU

ACTION
TYPES
In simple terms
COAGULATION
CASCADE
Prothrombi
n time/ INR:
Measures activity of
clotting factors of extrinsic
and common pathways,
also helps to monitor
warfarin.
APTT:
Measures activity of
clotting factors of intrinsic
and common pathways,
also helps to monitor
heparin.
 PARENTERAL
ANTICOAGULANTS
Common Parenteral Anticoagulants

1. Unfractionated heparin
2. Low-molecular weight heparins (LMWHs)

Enoxaparin
Dalteparin
3. Factor Xa Inhibitor

Fondaparinux
4. Direct Thrombin Inhibitors

Bivalirudin
Argatroban
Heparins generally act by activating antithrombin III.
Unfractionated heparin forms a complex which
inhibits thrombin, factors Xa, IXa, XIa and XIIa. Heparin
Adverse effects of heparins include:
bleeding
thrombocytopenia - see below
osteoporosis and an increased risk of fractures
hyperkalaemia - this is thought to be caused by
inhibition of aldosterone secretion

The anticoagulant effect of heparin is monitored by

the activated partial thromboplastin time (APTT)
Indication of heparin:
. Treatment of pulmonary embolism,
. Treatment of unstable angina
. Treatment of deep-vein thrombosis
. Thromboprophylaxis in medical patients, surgical patients and pregnant patients.
. Haemodialysis
. To maintain patency of catheters, cannulas, other indwelling intravenous infusion devices
. Prevention of clotting in extracorporeal circuits
Heparin overdose

Heparin overdose may be

reversed by protamine sulphate,
although this only partially
reverses the effect of LMWH.
 LMWHs can be administered by subcutaneous injection
and usually do not require laboratory monitoring, making them Low molecular
more convenient for outpatient treatment compared to
unfractionated heparin. weight heparin
LMWH however only increases the action of antithrombin III on
factor Xa
LMWHs have different approved indications. Enoxaparin is the
only LMWH that is approved for both venous thromboembolism
(VTE) prophylaxis and treatment.

LMWHs can be administered once or twice daily by SC injection,

without routine coagulation monitoring. However, in certain clinical
situations (e.g., morbid obesity, renal failure), monitoring of anti-
factor Xa concentrations may be helpful
 INDICATIONS AND
DOSE OF
ENOXAPARIN SODIUM
Dosing of
Enoxaparin in
Renal
Impairment
 

The table below shows

the differences
between standard
heparin and LMWH:
 ORAL
ANTICOAGULANTS
Types of Oral Anticoagulation:

Vitamin K Antagonists :
Warfarin
Direct (or Novel) Oral Anticoagulants (DOAC’s/NOAC’s)
Direct Xa Inhibitor (Rivaroxaban, Apixaban)
Direct Thrombin Inhibitors (Dabigatran)
Mechanism of action
inhibits epoxide reductase preventing the reduction of vitamin K to
its active hydroquinone form Warfarin
this in turn acts as a cofactor in the carboxylation of clotting factor II,
VII, IX and X (mnemonic = 1972) and protein C.
Factors that may potentiate warfarin
liver disease
P450 enzyme inhibitors, e.g.: amiodarone, ciprofloxacin
cranberry juice
drugs which displace warfarin from plasma albumin, e.g. NSAIDs
inhibit platelet function: NSAIDs
Side-effects
haemorrhage
teratogenic, although can be used in breastfeeding mothers
skin necrosis
purple toes
Indications of warfarin:

Prophylaxis of embolisation in rheumatic heart disease and atrial fibrillation,

Prophylaxis after insertion of prosthetic heart valve,
Prophylaxis and treatment of venous thrombosis and pulmonary embolism,
Transient ischaemic attacks
WHAT IS THE STARTING DOSE WHEN
WARFARIN TREATMENT IS INITIATED?
Baseline prothrombin measurements should be taken before starting treatment with
warfarin.
The typical induction dose of warfarin is 10 mg daily for 2 days, but this should
be tailored to individual requirements.
A low starting dose (5 mg) is often more suitable for frail or elderly people,
people with a low body weight, people with liver disease or cardiac failure, and
people at high risk of bleeding.
The daily maintenance dose of warfarin is usually 3–9 mg, taken at the same
time each day.
Where an immediate effect is required (for example in deep venous
thrombosis or a pulmonary embolism), heparin or a low molecular weight
heparin is given concurrently — this is done in secondary care.
Should warfarin be stopped before planned
surgery or dental treatment?
Minor surgical procedures with low risk of bleeding can be performed in general
with an international normalized ratio (INR) of less than 2.5.
For surgery or other surgical procedures where there is a risk of severe bleeding:
Warfarin should be stopped 3–5 days prior to the surgery or procedure.
Where it is necessary to continue anticoagulation, for example with life-
threatening thromboembolism, the INR should be reduced to less than 2.5
and heparin therapy should be started.
If surgery is required and warfarin cannot be stopped 3 days beforehand,
anticoagulation should be reversed with low-dose vitamin K.
For dental procedures:
In most cases, warfarin need not be stopped before routine dental surgery, for
example tooth extraction.
HOW TO REVERSE EFFECTS
OF WARFARIN?

If surgery can wait for 6-8 hours - give How to

reverse effects of warfarin?
If surgery can't wait - 25-50 units/kg four-factor
prothrombin complex
How to monitor warfarin?
INR
Mode of action:
Apixaban, edoxaban, and rivaroxaban are direct and reversible inhibitors
of factor Xa (inhibition of factor Xa prevents thrombin generation and Direct oral
thrombus development).
anticoagulant
Dabigatran is a reversible inhibitor of free thrombin, fibrin-bound thrombin,
and thrombin-induced platelet aggregation.

Advantage:
Unlike warfarin, DOACs do not require regular international normalised ratio
(INR) monitoring. However, regular follow up is required to review the
treatment.

The most common adverse effect of anticoagulants is bleeding.

Warfarin, apixaban, dabigatran, and rivaroxaban have antidotes for
reversing their anticoagulant effects. There is currently no antidote for
edoxaban.
Indications of DOACs:
Apixaban, dabigatran, edoxaban, and rivaroxaban may be prescribed instead of warfarin for
prevention of stroke and systemic embolism in adults with non-valvular atrial fibrillation and
at least one risk factor, such as heart failure, hypertension, previous stroke or transient ischaemic
attack, age 75 years or older, or diabetes mellitus.
Apixaban, dabigatran, edoxaban, and rivaroxaban are licensed for the treatment of PE and deep
vein thrombosis (DVT), and prevention of recurrent DVT and PE.
Apixaban, dabigatran, and rivaroxaban are licensed for the prophylaxis of venous
thromboembolism after elective hip or knee replacement surgery.
Rivaroxaban is licensed for prophylaxis of atherothrombotic events following an acute coronary
syndrome with elevated cardiac biomarkers (in combination with aspirin alone or aspirin and
clopidogrel) and for prophylaxis of atherothrombotic events in adults with coronary artery disease or
symptomatic peripheral artery disease at high risk of ischaemic events (in combination with aspirin).
Dabigatran
Developed as an alternative to warfarin.
Advantage: Doesn’t require regular monitoring.
Mechanism of action: Factor 2a inhibitor , also
known as thrombin (DaBIgatran)
Antidote: Idarucizumab ( I inhibits Da dabigatran)
What is the recommended dose and duration of
treatment for dabigatran?

For the prophylaxis of stroke and deep vein thrombosis (DVT) and pulmonary embolism (PE) and the prevention of recurrent DVT and
PE, following initial use of parenteral anticoagulation for at least 5 days:
The recommended dose is 150 mg twice a day.
A reduced dose of 110–150 mg twice daily is recommended if the person:
Is aged 75–79 years.
Has moderate renal impairment (creatinine clearance [CrCl] 30–50 mL/minute), based on individual assessment of thromboembolic
risk and risk of bleeding.
For the prevention of venous thromboembolism (VTE) in people who have undergone knee replacement surgery:
The recommended dose is 110 mg to be taken 1–4 hours after surgery, followed by 220 mg once daily for 10 days.
A reduced dose of 75 mg taken 1–4 hours after surgery, followed by 150 mg once daily for 10 days is recommended if the person:
Is aged 75 years or older..
Has moderate renal impairment (CrCl 30–50 mL/minute).
For the prevention of VTE in people who have undergone hip replacement surgery:
The recommended dose is 110 mg to be taken 1–4 hours after surgery, followed by 220 mg once daily for 28–35 days.
References:
https://cks.nice.org.uk/topics/anticoagulation-oral
The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral
anticoagulants in patients with atrial fibrillation [ Steffel, 2018], the British Committee for Standards in
Haematology (BCSH) Guidelines on oral anticoagulation with warfarin - fourth edition [ Keeling, 2011], the
Scottish Intercollegiate Guidelines Network (SIGN) guideline Antithrombotics: indications and management [
SIGN, 2013], and on information in manufacturers' Summaries of Product Characteristics (SPCs) and the British
National Formulary (BNF).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358682/
https://bnf.nice.org.uk/drugs/heparin-unfractionated/
https://bnf.nice.org.uk/treatment-summaries/parenteral-anticoagulants
https://bnf.nice.org.uk/drugs/enoxaparin-sodium
https://elsevier.health/en-US/preview/low-molecular-weight-heparins
THANK YOU