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Medicines Q&As
Q&A 436.1
How do we assess and manage bleeding risks in patients requiring
oral anticoagulation for atrial fibrillation?
Prepared for NHS healthcare professionals by the HAT Committee of the UK Clinical Pharmacy Association
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: July 2014
Background
Oral anticoagulants are widely used in the prevention and treatment of thromboembolism, as well as
stroke prevention in atrial fibrillation. They have been demonstrated to be highly effective, however
the benefits of anticoagulation have to be weighed against associated bleeding risks; a major
complication of anticoagulation therapy (1).
There have been recent advances in oral anticoagulation with the introduction of the newer oral
anticoagulants dabigatran, apixaban and rivaroxaban. The number of patients requiring oral
anticoagulation is increasing due to a number of factors including, the call to increase identification of
Atrial Fibrillation (AF); recognition that stroke prevention is the first priority in the treatment plan for
AF; the move away from aspirin to oral anticoagulation as a treatment option for stroke prevention in
AF. In addition, recommendations from the latest National Institute for Health and Care Excellence
(NICE) Clinical Guideline for AF increase the proportion of AF patients that should be offered
anticoagulation from 57% to 84%. The risk of atrial fibrillation is related to age and prevalence rises
exponentially as the population ages. However, whilst elderly patients are most likely to require
anticoagulation therapy, they are also the cohort of patients most at risk of anticoagulation associated
bleeding due to coexisting co-morbidities, polypharmacy and the increased likelihood that these
patients will become unwell and require acute treatment such as antibiotics. With the wider choice in
oral anticoagulants and a growing population requiring anticoagulation particularly those of an older
age, healthcare professionals must make a careful assessment of the risks of bleeding as well as the
risks of thromboembolism to support appropriate decision making.
Answer
Risk assessing patients’ bleeding risk
There are several individual clinical risk factors which are associated with increased bleeding risks in
patients taking oral anticoagulants, these typically include increased age, anaemia and renal
impairment, factors which are commonly present in elderly patients presenting with thrombosis risk
factors. In order to quantify a patient’s bleeding risk, it is recommended that a risk prediction tool is
utilised to allow the risk of bleeding to be balanced against the benefits of anticoagulant therapy.
The HAS-BLED score is currently the risk stratification tool of choice in AF (2) (Figure 1). It predicts
the 1 year risk of major bleeding in patients with AF and is recommended in both European (3,4) and
Canadian guidelines (5) and most recently in the 2014 NICE Clinical Guideline for AF (6) as a method
of allowing clinicians to make an informed assessment of patients’ bleeding risk. In addition, American
guidelines also describe the HAS-BLED scoring system as more accurate in discriminating bleeding
risks compared to other scoring systems (7). Studies have demonstrated the HAS-BLED score to
have better predictive value than other available bleeding risk scores and increasing HAS-BLED
scores have been shown to positively correlate to intracerebral haemorrhage risk (8).
The HAS-BLED scoring system assigns 1 point for each of the characteristics detailed in Figure 1
below, up to a maximum score of 9.
Available through NICE Evidence Search at www.evidence.nhs.uk
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Figure 1: Bleed risk assessment in patients with Atrial Fibrillation using the HAS-BLED tool
Letter
Clinical Characteristic and Definition
H
Hypertension defined as uncontrolled systolic >160mmHg
A
Abnormal renal function defined as serum creatinine >200micromol/L,
or creatinine clearance <30mls/min, or need for dialysis
AND
Abnormal liver function defined as chronic hepatic disease e.g. cirrhosis
or deranged liver enzymes >2x upper limit of normal
S
Stroke
Points
Awarded
1
1 or 2
1
B
L
E
D
Bleeding defined as history of bleeding or predisposition to bleeding
e.g. anaemia
Labile INRs defined as unstable / high INRs or low therapeutic time in
range e.g. <60%
Elderly defined as age >65 years
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Drugs defined as use of concomitant drugs associated with increased
bleeding risk (e.g. NSAIDs, antiplatelets, SSRIs etc.)
Or
Alcohol defined as >8 alcoholic drinks per week or alcohol excess /
abuse, which is essentially an intake where the clinician assesses there
would be an impact on health or bleeding risk
1 or 2
1
1
Maximum 9
points
Adapted from Pisters et al (2)
A HAS-BLED score of 3 or more is regarded as a high risk of bleeding and recommendations suggest
that patients with a score of ≥3, require regular review and caution is necessary. However, it is
important to note that the HAS-BLED score should not be used to exclude oral anticoagulant
therapies but allow healthcare professionals to identify modifiable risk factors such as uncontrolled
blood pressure, labile INRs or concomitant antiplatelet treatment.
The assignment of one point in the HAS-BLED score for increased alcohol intake, indicates it is
associated with an increased risk of bleeding. The interaction of warfarin with alcohol is well
established with binge drinking resulting in increased INR readings due to acute hepatic dysfunction
and chronic excess alcohol consumption causing low INR readings due to increased P450
metabolism of warfarin. Alcohol consumption is considered a modifiable risk factor and the decision to
anticoagulate patients known to have excessive alcohol intake should be highly personalised.
Patients should be advised to keep their alcohol consumption within the recognised healthy limits and
avoid binge drinking or fluctuations in their intake. Current recommendations suggest men should limit
their alcohol intake to 21 units a week, drink no more than 4 units in one day and aim for 2 alcohol
free days a week. Women are recommended to limit their weekly alcohol intake to 14 units a week,
drink no more than 3 units in one day and aim to have at least 2 alcohol free days a week. The newer
oral anticoagulants do not interact in the same manner with alcohol as warfarin therefore they may be
considered in patients where there are anxieties with regards to fluctuating alcohol intake. However, it
is still considered good practice to advise patients to keep within acceptable limits. It must be noted
that in patients with alcoholic liver disease, significant bleeding risks will still apply for patients on
newer oral anticoagulants and careful consideration must be applied before initiation of dabigatran,
rivaroxaban or apixaban. This is not only because hepatic impairment directly affects the metabolism
of the direct factor Xa inhibitors (rivaroxaban and apixaban), but also because moderate to severe
liver impairment reduces coagulation factor synthesis increasing bleeding risks.
Available through NICE Evidence Search at www.evidence.nhs.uk
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One of the most common reasons for withholding oral anticoagulant therapy in the elderly is related to
the risks of falls in this patient group. Many healthcare professionals consider the combination of oral
anticoagulant therapy and the risk of falls as an excessively high risk for developing subdural
haematomas or intracerebral haemorrhage (9). However, it is important to quantify this risk with
regards to the elderly population and put this into context with their stroke risk or risk of developing
further thrombotic events. Although elderly patients may have an increased risk of falling, studies
have shown that on average only 1 in 10 falls results in major injury or fractures. In addition, analytical
models estimate that elderly patients would need to fall 295 times a year for their risk of developing
subdural haematomas to outweigh the benefit of being anticoagulated with warfarin (9). Therefore it
can be concluded that propensity to fall is not an absolute contraindication to oral anticoagulant
therapy. This is reflected in the 2014 NICE Clinical Guideline for AF which states anticoagulation
should not be withheld solely because the person is at risk of having a fall (6). Where clinicians feel a
patient’s falls pose a real risk, modifiable risk factors such as concomitant drug therapy (e.g. drugs
associated with increased bleeding, dizziness or excessively low blood pressure) should be assessed
with discussions and decisions involving the patient or carer. In addition, as appropriate consideration
should be given to referring the patient to a falls clinic.
Combined use of anticoagulants with antiplatelets
The increased use of anticoagulant and antiplatelet therapy for a number of thromboembolic
conditions has resulted in clinical situations where the combined use of antiplatelets and
anticoagulants occurs. There is sufficient evidence to show that dual therapy with anticoagulants and
antiplatelets results in an increased risk of major bleeding. In addition, one study has shown triple
therapy with dual antiplatelets and anticoagulation to be associated with a three-fold increased risk of
major bleeding compared to warfarin alone (10).
In consideration of the increased risk of major bleeding, the British Committee for Standards in
Haematology (BCSH) Guidelines for oral anticoagulation with warfarin recommend that patients with
stable ischaemic heart disease1 who develop an indication for anticoagulation should have their
antiplatelet discontinued upon initiation of anticoagulation (11). However, for patients who are
anticoagulated and go on to develop acute coronary syndromes (ACS), a decision needs to be made
and may involve a number of members of the patient’s healthcare team including the cardiologist as
triple or dual therapy may be indicated representing a significant increased risk of bleeding. In
general the advice is that such patients should be treated with the minimum appropriate number of
antithrombotic agents for the minimum appropriate duration, this may influence treatment decisions
e.g. use of bare metal stent which only requires four weeks of antiplatelet therapy (3,12).
Summary
With a growing elderly population requiring anticoagulation and also having a greater bleeding risk,
decisions regarding anticoagulation can be challenging; clinicians must make careful assessments of
the risks and benefits of anticoagulation for each patient. The HAS-BLED score is a useful clinical
prediction tool for assessing bleeding risks in AF patients however, it should not be used to exclude
anticoagulation. Rather, it should be used to identify and address modifiable risk factors such as
uncontrolled hypertension, poor anticoagulation control (labile INRs) concomitant use of drugs
associated with bleeding and excessive alcohol consumption.
Limitations
There is limited evidence with regards to managing patients with bleeding risks on anticoagulation.
Healthcare professionals must make clinical decisions based on the individual patient and in depth
discussions regarding the options for anticoagulation should be undertaken with each patient.
1
BCSH guidance states that stable ischaemic heart disease is often defined as >12 months following acute
myocardial infarction (11). The Practical Guide on the use of new oral anticoagulants in patients with nonvalvular atrial fibrillation from the European Heart Rhythm Association defines stable coronary heart disease as a
history of coronary heart disease, but without ACS within the last year, without an elective bare metal stent during
the last month or a drug-eluting stent over the last 6 months (13).
Available through NICE Evidence Search at www.evidence.nhs.uk
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References
(1) Hylek EM, Evans-Molina C, Shea C et al. Major hemorrhage and tolerability of warfarin in the first
year of therapy among elderly patients with atrial fibrillation. Circulation 2007;115:2689-2696.
(2) Pisters R, Lane DA, Nieuwlaat R et al. A novel user friendly score (HAS-Bled) to assess 1-year
risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010;138:10931100.
(3) Camm J, Lip GY et al. 2012 focused update of the ESC Guidelines for the management of atrial
fibrillation. European Heart Journal 2012;33:2719-2747.
(4) Lip GY, Andreotti F, Fauchier L et al. Bleeding risk assessment, management in atrial fibrillation
patients. Executive Summary of a position Document from the European Heart Rhythm Association
(ESC), endorsed by the European Society of Cardiology (ESC) Working Group on Thrombosis.
Europace 2011;13:723-746.
(5) Skanes AC, Healey JS, Cairns JAet al. Canadian Cardiovascular Society Atrial Fibrillation
Guidelines Committee. Focused 2012 Update of the Canadian Cardiovascular Society Atrial
Fibrillation Guidelines: recommendations for stroke prevention and rate/rhythm control. Can J
Cardiology 2012;28:125-136.
(6) National Institute for Health and Care Excellence: CG 180 Atrial fibrillation: the management of
atrial fibrillation. June 2014. Available at http://www.nice.org.uk/guidance/CG180.
(7) January CT, Wann LS, Alpert JS et al 2014 AHA/ACC/HRS guideline for the management of
patients with atrial fibrillation: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation
2014;129:000-000. Available at:
http://circ.ahajournals.org/content/early/2014/04/10/CIR.0000000000000041.citation
(8) Apostolakis S, Lane DA, Guo Y et al. Performance of the HEMORR2HAGES, ATRIA and HASBLED bleeding risk prediction scores in anticoagulated patients with atrial fibrillation: The AMADEUS
study. J Am Coll Cardiol 2012:60:861–867.
(9) Man-Son-Hing M, Nichol G, Lau A et al Choosing Antithrombotic Therapy for Elderly Patients With
Atrial Fibrillation Who Are at Risk for Falls. Arch Intern Med1999;159(7):677-685.
(10) Hansen ML, Sørensen R, Clausen MT et al. Risk of bleeding with single, dual, or triple therapy
with warfarin, aspirin and clopidogrel in patients with atrial fibrillation. Arch Intern Med
2010;170(16):1433 – 1441.
(11) Keeling, D, Baglin, T, Tait, C, et al. British Committee for Standards in Haematology (2011),
Guidelines on oral anticoagulation with warfarin – fourth edition. British Journal of Haematology 2011;
154: 311–324.
(12) American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis
Panel. Antithrombotic Therapy and Prevention of Thrombosis, 9th Ed: American College of Chest
Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: (2_suppl): 7S-47S.
(13) Heidbuchel, H, Verhamme, P, Alings, M, et al. European Heart Rhythm Association Practical
Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Executive
Summary. European Heart Journal 2013; 34: 2094-106.
Quality Assurance
Prepared by
Jannat Muen, Anticoagulation & Thrombosis Prevention Pharmacist, Sheffield Teaching Hospitals on
behalf of Haemostasis, Anticoagulation & Thrombosis (HAT) Committee, UK Clinical Pharmacy
Association.
Date Prepared
July 2014
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
Checked by
Frances Akor, Consultant Pharmacist Anticoagulation, Imperial College Healthcare NHS Trust,
Haemostasis, Anticoagulation & Thrombosis (HAT) Committee, UK Clinical Pharmacy Association.
Quality assurance assisted by UKMi.
Date of check
July 2014
Available through NICE Evidence Search at www.evidence.nhs.uk
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