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NHS England: Specific information regarding the management of anticoagulant services (from NHS England (NHSE)) during the Coronavirus (COVID-19) pandemic can be found here.
Information contained in the document includes:
Information and support for patients:
NICE COVID-19 rapid guideline: managing COVID-19 (NG191). This guideline includes pharmacological prophylaxis of venous thromboembolism (VTE) for patients with COVID-19 managed in hospital or in hospital-led acute care in the community (see here).
For women with COVID-19 who are pregnant or have given birth within the past 6 weeks, the recommendation is to follow the advice on VTE prevention in the Royal College of Obstetricians and Gynaecologists guidance on coronavirus (COVID-19) in pregnancy
MHRA advice (October 2020): Warfarin and other anticoagulants – monitoring of patients during the COVID-19 pandemic. Please see here
National Patient Safety Alert (14 July 2021): Inappropriate anticoagulation of patients with a mechanical heart valve.
Formulary Guidance: Management of suspected deep vein thrombosis (DVT) and pulmonary embolism (PE)
Formulary Guidance: Management of Atrial Fibrillation
Discuss the relative risks and benefits of warfarin and Direct-acting oral anticoagulants (DOACs) with patients, with particular reference to the level of INR control.
Categories of patients in whom DOACs may be a useful option:
Warfarin may be the preferred option for people who have an eGFR less than 30 mL/min/1.73m2.
*National Patient Safety Alert (14 July 2021): Inappropriate anticoagulation of patients with a mechanical heart valve: All patients with prosthetic mechanical heart valves require life-long oral anticoagulation with a vitamin K antagonist (VKA), usually warfarin, and should not be switched to an alternative anticoagulant (e.g. low molecular weight heparin or DOAC)
*NHS England: Management of anticoagulant services during the Coronavirus (COVID-19) pandemic: page 4 includes patient groups who should not be considered for switching from warfarin to DOACs
Dosing regimen guidance can be viewed under the individual drug monographs – see 2.8.2 Oral anticoagulants
DOACs are associated with increased risk of serious haemorrhage in patients with renal impairment. Assessment of renal function for DOAC use should be based upon creatinine clearance calculated using the Cockcroft-Gault formula.
MHRA Drug Safety Update (October 2019): Using the appropriate estimate of renal function to avoid the risk of adverse drug reactions
Since eGFR is normalised to a standard body surface area (BSA) of 1.73m2, there is the potential for under, or over-dosing patients at extremes of body weight (BMI of less than 18.5 kg/m2 or greater than 30 kg/m2). This is particularly important for people with reduced muscle mass, including the frail, elderly, or critically ill. Use the Cockcroft & Gault formula to calculate creatinine clearance for determining dose adjustment for DOACs in patients with renal impairment. In all DOAC studies renal function has been expressed in terms of CrCl, no dose recommendation can be made in terms of eGFR.
The Cockcroft & Gault formula:
Estimated Creatinine Clearance (mL/minute) = (140 – Ageyrs) x *MassKg x Constant# / Serum Creatinine
*Weight (mass) - use actual body weight in the calculation. (In underweight patients, actual body weight should still be used. In overweight patients, ideal body weight should be used)
#Constant= 1.23 for men, 1.04 in women
The Specialist Pharmacy Service (SPS) and local specialist renal teams recommend the use of a web based application such as MDCalc where actual bodyweight is used to calculate the Cockcroft-Gault CrCl. If height is added the different methods of adjusting for weight can be seen, providing a range of possible values for CrCl.
Where these results cross or are close to a CrCl level that may require a dose change, this can support the clinician making a dosing decision.
For dose adjustments required in renal impairment, refer to individual drug entries (2.8.2 Oral anticoagulants):
National Patient Safety Alert (14 July 2021): Inappropriate anticoagulation of patients with a mechanical heart valve: All patients with prosthetic mechanical heart valves require life-long oral anticoagulation with a vitamin K antagonist (VKA), usually warfarin, and should not be switched to an alternative anticoagulant (e.g. low molecular weight heparin or DOAC)
NHS England: Management of anticoagulant services during the Coronavirus (COVID-19) pandemic: page 4 includes patient groups who should not be considered for switching from warfarin to DOACs
Patients should be aware of the risks and benefits of anticoagulation and should be advised to carry an appropriate anticoagulant alert card. Cards are available for each non-vitamin K oral anticoagulant, and can be obtained from the individual manufacturers:
Advise patients to omit their anticoagulant medication and seek medical advice in the event of haemorrhage or significant acute illness. Ensure patients and carers keep a copy of the patient information leaflet.
Determining the time since last dose of therapy is vital as interruption of treatment may be sufficient. The estimated time for restoration of haemostasis after cessation of therapeutic doses with adequate renal function is usually within 12 hours for dabigatran and apixaban, and 24 hours for rivaroxaban and edoxaban.
Initiate resuscitation with compression, IV fluids, blood transfusion and other supportive measures as necessary.
Check FBC, U&E's and a coagulation screen (PT, Thrombin Time and APTT). A normal Thrombin Time can be used to exclude any clinical relevant level of dabigatran. However, a normal PT or APTT cannot be used to rule out a therapeutic concentration of the factor Xa inhibitors rivaroxaban, apixaban or edoxaban.
An agent to rapidly reverse the anticoagulant effect of dabigatran (idarucizumab [Praxbind] as a single 5g bolus injection) is available.
Dried prothrombin complex (4-factor prothrombin complex concentrate, PCC) may reverse the effect of the factor Xa inhibitors and may be considered (at a dose of 50 IU/kg), but there is very limited clinical experience with its use in patients taking new oral anticoagulants.
MHRA Drug Safety Update (October 2013, September 2016) New oral anticoagulants apixaban, dabigatran and rivaroxaban: risk of serious haemorrhage.
The following contraindications now apply to all DOACs, for all doses and indications:
Additional advice and information for healthcare professionals:
Please consult the product information for advice on treatment in the event of bleeding complications, or overdose.
Women are advised to avoid pregnancy if taking a DOAC
Apixaban: Not recommended (secreted into breastmilk)
Dabigatran: Discontinue breastfeeding if taking dabigatran (clinical safety not established)
Edoxaban: Contraindicated. (Secreted into breastmilk; women should consider whether to stop breastfeeding or stop treatment)
Rivaroxaban: Contraindicated in breastfeeding (secreted in breastmilk).
If possible, wait 12 hours (dabigatran) or 24 hours (rivaroxaban, edoxaban and apixaban) after the last dose.
Guidance only, targets and durations should be determined based on individual cases
An INR which is within 0.5 units of the target value is generally satisfactory; larger deviations require dosage adjustment
Patients with low risk atrial fibrillation who do not need rapid anticoagulation can be prescribed 2mg of warfarin per day usually without heparin. INR should be checked after 1 week.
Slow induction is not suitable for patients who:
The INR at the end of two weeks of 2mg can be used as approximate guide of an individual patient's daily warfarin requirements. Please note the gender differences in the dose per day.
See Chapter 2, section 2.8.2 Oral anticoagulants
Estimate of maintenance dose based on INR at day 14:
Male
INR at day 14 | Maintenance dose |
1.0 | 6mg |
1.1-1.2 | 5mg |
1.3-1.5 | 4mg |
1.6-2.1 | 3mg |
2.2-3.0 | 2mg |
greater than 3.0 | 1mg |
Female
INR at day 14 | Maintenance dose |
1.0-1.1 | 5mg |
1.2-1.3 | 4mg |
1.4-1.9 | 3mg |
2.0-3.0 | 2mg |
greater than 3.0 | 1mg |
The objective of rapid initiation is to achieve full anticoagulation and reach the target INR as quickly yet safely as possible.
Rapid induction of warfarin should only take place in a hospital setting, see individual trust policies for further details.
Monitoring INR; in early days of treatment it is essential to determine INR daily or on alternate days, then at longer intervals (depending on response), then up to every 12 weeks.
The main adverse effect of all oral anticoagulants is haemorrhage. The following recommendations (which take into account the recommendations of the British Society for Haematology) are based on the result of the INR and whether there is major or minor bleeding; the recommendations apply to patients taking warfarin: