Edward Francis Small Teaching Hospital.

Anticoagulation guideline March 2023, V1

Anticoagulation guide
Please note that this is intended to be a pragmatic guide, not a formal guideline,
understanding of the need for compromises with regards to best treatments, due to
difficulties (including financial) in accessing certain drugs or tests.

Anticoagulants are used to reduce the risk of blood clot formation. The clinician should
always weigh the risks of clotting vs the risk of bleeding with anticoagulation. The prices and
availability of these drugs is variable and therefore enquiries should be made with the
pharmacies prior to prescribing the drugs to assist in decision making.

1. Indications for anticoagulation

Indications include the treatment of venous thromboembolism (VTE), prevention of stroke in

atrial fibrillation and prosthetic heart valves and prevention of VTE in high-risk patients. This
guideline only covers treatment-dose anticoagulation.

2. Anticoagulant drugs

Advantages and disadvantages of the most commonly used drugs are listed in table 1.

Table 1 - Advantages and disadvantages of anticoagulant drugs

Drug Advantages Disadvantages

Unfractionated heparin Lower cost Injectable
Safe in pregnancy and Risk of heparin-induced
breastfeeding thrombocytopenia (HIT) and
osteoporosis
Low molecular weight Low risk of HIT Expensive
heparin Safe in pregnancy and Not widely available
breastfeeding Injectable (sc)
No need for monitoring
Warfarin Oral therapy Narrow therapeutic range
Low cost Needs INR monitoring
Widely available Contraindicated in 1st
trimester and last month of
pregnancy
Direct oral anticoagulants Oral therapy Expensive
No need for monitoring Contraindicated in
pregnancy and breastfeeding
Edward Francis Small Teaching Hospital. Anticoagulation guideline March 2023, V1

3. Dosing of anticoagulants

3.1 Unfractionated heparin (UFH)

Intravenous UFH requires 4-6 hourly APTT monitoring and is therefore impractical in this
setting.

UFH can also be given as a subcutaneous injection (see figure 1).

Due to the risk of HIT, a platelet count should be checked prior to starting heparin, and then
every 2-3 days from days 4-14.

APTT monitoring is not necessary with weight-based dosing of UFH. However, if morbid
obesity or renal failure with creatinine clearance <30ml/min, APTT should be checked at
least once (4 hours post dose) to aim for APTT 1.5 – 2.5 x the control. APTT ration can be
calculated by dividing the patient’s APTT by the laboratory mean of normal range APTT.

Figure 1 - subcutaneous UFH dosing

3.2 Low molecular weight heparin (LMWH)

LMWHs includes e.g. Enoxaparin (Clexane) and Dalteparin (Fragmin). Enoxaparin is the
most available in The Gambia currently. Monitoring is not usually required in the absence of
several renal impairment.

Enoxaparin dose:
- 1.5mg/kg once daily
- 1mg/kg twice daily if: obesity, symptomatic pulmonary embolism (PE), underlying
cancer, recurrent VTE or proximal/extensive thrombosis
Edward Francis Small Teaching Hospital. Anticoagulation guideline March 2023, V1

3.3 Warfarin

Use of warfarin is challenging due to its narrow therapeutic range. It therefore requires
regular INR monitoring.

Warfarin interacts with many drugs and foods.

Patients should be counselled with the following information:
- Take warfarin at the same time every day and avoid missing doses
- Foods that interact with warfarin include green leafy vegetables, e.g. in plasas, liver
and also alcohol. Patients should be advised to take the same quantity of these each
week
- Many medications interact with warfarin: patients should inform anyone prescribing
medicines for them that they are taking warfarin. Increased INR monitoring may be
required if drug interactions present.
- Compliance with INR monitoring is essential

Tips for warfarin dosing:

- If the INR trend is within range, but persistently increasing or decreasing, it will likely
soon become out of range. A small adjustment to the dose may be needed
- Always think about why the dose may be out of range:
o Check compliance
o Has there been a change in diet / medications?
- Always check there have been no missed doses prior to changing the dose

Warfarin initiation

Warfarin should be commenced simultaneously with therapeutic dose LMWH/UFH.

Heparin can be stopped after 5 days if INR is in target range (e.g. 2-3 for VTE). Heparin and
warfarin should overlap for at least 5 days due to hypercoagulability within the first few
days of warfarin treatment. Baseline INR should be <1.4 prior to commencing warfarin.

Table 2 - Warfarin initiation for target INR 2-3

Day INR Warfarin dose (mg)

1 10
2 5
3 < 1.5 5 – 7.5
1.5 – 1.9 2.5 – 5
2 – 2.5 2.5
> 2.5 Hold and re-check INR next
day
4 Same as previous day
5 Same as previous day
6 < 1.5 7.5 – 10
1.5 – 1.9 5 – 10
2–3 2.5 – 5
>3 Hold and re-check INR next
day
Edward Francis Small Teaching Hospital. Anticoagulation guideline March 2023, V1

Warfarin maintenance dosing

Warfarin maintenance dosing should be based on the total weekly dose requirement. This
avoids big swings in INR levels. It takes around 3-4 days for any change in dose to affect the
INR. In general, dose changes should only be up to +/- 10% per week.

Frequency of INR monitoring

- Every 3 days until INR within target range, then:
- Weekly until INR within target range on 2 consecutive occasions, then:
- 2 weekly until INR within target range on 2 consecutive occasions, then:
- Monthly until INR within target range on 2 consecutive occasions

Table 3 - maintenance warfarin dosing

INR
< 1.5 1.5 – 1.9 2 – 3 3.1 – 4 4.1 – 5 5.1 – 9 >9
Dose Give Increase No Decrease Withhold Withhold Withhold
alteration extra total change total 1 dose 2 doses AND
dose weekly weekly AND AND admit
AND dose by dose by decrease decrease patient
increase 5% 5% weekly weekly
total dose by dose by
weekly 10% 20%
dose by
10%
Management of over anticoagulation or bleeding with warfarin

Please note, it is important to only use vitamin K when necessary – especially for
patients with metallic heart valves. It is advisable to use small doses of vitamin K
wherever possible, to avoid over-correction of the INR or warfarin resistance.
Cause of bleeding should always be investigated.

Adverse effect / INR Management

Life or limb threatening bleeding at any Withhold warfarin and give Vit K 10mg IV
INR

Clinically relevant minor bleeding Withhold warfarin and give Vit K 1-2mg
+ INR >4.5 PO/IV*

INR > 8 without bleeding Withhold warfarin and give Vit K 1mg
PO/IV)*

INR 4.5 – 8 without bleeding Withhold warfarin. Give Vit K IF patient

considered at high risk for bleeding**

Unexpected bleeding with INR 2 – 4.5 Continue warfarin and investigate for cause
of bleeding

Emergency admission for surgery Withhold warfarin and give Vit K 10mg IV
Edward Francis Small Teaching Hospital. Anticoagulation guideline March 2023, V1

*IV vitamin K is active within 6-8 hours. Oral vitamin K is active within 12-24 hours

**High risk for bleeding = e.g. age >65y, previous GI/intracranial bleeding, renal/liver failure,
anaemia, cancer, recent stroke, recent surgery

4. Special situations

Anticoagulation decisions are often complex due to the need to weigh up the risks of bleeding
versus the risks of clotting. There are certain situations that should be considered very
carefully, for example, renal failure and pregnancy.

4.1 Renal failure

Renal failure is complicated due to many drugs being unsuitable. Below is a summary of the
possible options in patients with renal failure.

• Warfarin
• Relatively safe in renal failure
• Needs INR monitoring

• Intravenous UFH
• Safe in renal failure
• Needs 4-6 hourly APTT

• Subcutaneous UFH
• Safe in renal failure
• Needs APTT monitoring initially, as per section 3.1

• LWMH*
• Risk of accumulation, especially with Enoxaparin – up to 2-3x increased risk
of major bleeding with creatinine clearance <30ml/min (Dalteparin may be
safer if available)
• For Enoxaparin – reduce dose if CrCl 15-30ml/min, avoid if CrCl<15ml/min

• DOAC
• DOACs are excreted via the kidneys to variable degrees: dabigatran (80%),
edoxaban (35%), rivaroxaban (33%), apixaban (25%)
• Advice is to use with caution if CrCL 15-30ml/min and avoid if CrCL
<15ml/min (lack of data)

*For practical reasons, there may be occasions when LMWH is the most pragmatic option.
However, this should be discussed with a renal consultant before commencing.
Edward Francis Small Teaching Hospital. Anticoagulation guideline March 2023, V1

4.2 Pregnancy

All anticoagulation increases risk of bleeding – especially around time of delivery. Options
should be clearly discussed with the patient, given that there is potential harm to mother
and/or fetus with all drugs.

It is likely that, unless the patient has significant financial means, the most pragmatic option
will often be LMWH for the first trimester and last month of pregnancy, with warfarin from
the second trimester until 36-37/40. LMWH should always be used if affordable/available.

• LMWH:
• Safest but expensive and not always available

• Warfarin:
• Teratogenic in 1st trimester, but can be used in 2rd/3rd trimester
• Increased risk of fetal bleeding throughout pregnancy
• Needs stopping at least 2/52 prior to delivery as crosses placenta and may
result in unacceptable bleeding risk for fetus during delivery
• Needs INR monitoring, as per section 3.3

• UFH:
• Can be used in pregnancy but needs monitoring and risks of HIT and
osteoporosis

• Not enough evidence yet to recommend DOACs

• Rivaroxaban shows fetal toxicity in animal studies, apixaban does not

References

https://www.medicines.org.uk/emc/product/8987/smpc
Accessed on 16/03/2023

https://www.medicines.org.uk/emc/product/4245/smpc
Accessed on 16/03/2023

Prandoni P, Carnovali M, Marchiori A, Galilei Investigators. Subcutaneous adjusted-dose

unfractionated heparin vs fixed-dose low-molecular-weight heparin in the initial treatment of
venous thromboembolism. Arch Intern Med. 2004 May 24;164(10):1077-83.

https://www.uptodate.com/contents/warfarin-and-other-vkas-dosing-and-adverse-effects?
search=warfarin&source=search_result&selectedTitle=2~148&usage_type=default&display_
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Accessed on 16/03/2023

South Africa Adult Hospital level Standard treatment guidelines and Essential medicines list
for 2019

Sheffield Teaching Hospitals. Warfarin prescription and monitoring chart. 2019