The need for anticoagulation is increasing due to a rise in the prevalence of the two common indications: atrial fibrillation (AF), and venous thromboembolism (VTE). Quality and Outcomes Framework (QOF) figures indicate that 2.5 % of the population have AF, ~87% estimated to be at high stroke risk according to a CHA2DS2VaSc score of 2 or more.

Of the high risk group, 90% receive anticoagulation. Thus, roughly 2% of the population are on anticoagulation therapy for AF. In addition, the availability of newer alternatives to warfarin called direct oral anti-coagulants (DOACs) has increased the applicability of anticoagulation to frailer and older groups, as the DOACs have fixed dosing, and an overall lower risk of major bleeding compared to standard warfarin.

Data from the UK national stroke audit (SSNAP) show a steady rise in the proportion of patients with pre-stroke atrial fibrillation on anticoagulation (from 50-64% over the last 10 years).1 Moreover, the DOACs are more attractive from a practical perspective requiring less frequent monitoring, with fewer drug and food interactions. All these factors combined are resulting in an increasing cohort of people on anticoagulation, who receive monitoring mostly in primary care.

Primary care monitoring of anticoagulation

Most primary care clinicians are familiar with warfarin management, and the dosing is supported by electronic systems like INRstar, making it less onerous for the clinician. With availability of near patient INR testing, the vast majority of issues can be dealt in primary care, with recourse to secondary care only where there is major bleeding or need for further investigation.

Whilst the principles of DOAC monitoring are similar, there is one key difference: there is no easily available test to quantify degree of anticoagulation. Whilst familiarity with these agents is rising in primary care, several novel issues with ongoing management have become apparent, which will be explored further.

Licensed usage

It is important that the indication of anticoagulation is clearly documented. The two key licensed indications are: atrial fibrillation and venous thromboembolism (VTE). VTE other than DVT and PE is not included in the licensing.

Clearly recognised contraindications are: moderate to severe mitral valve disease; severe renal impairment (calculated creatinine clearance <15 ml/min; <30 ml/min for dabigatran), metallic heart valves, antiphospholipid syndrome, left ventricular thrombus and cancer-associated VTE. However, there may be certain situations where anticoagulation may be employed in unlicensed scenarios. 

In such circumstances, it is essential that the prescribing specialist is clearly identified; there has been a discussion with the patient about the “unlicensed” use, and the rationale for such use. For example, in the setting of cancer patients may decline the use of ongoing dalteparin injections and warfarin, and DOAC may be preferable to no anticoagulation treatment. Stroke physicians may initiate anticoagulation in the setting of recurrent stroke with a presumption of paroxysmal AF (where such paroxysms may not have been demonstrated).

Correct dosing

There are several reports of incorrect DOAC dose usage. This can be due to lack of familiarity with the relatively new agents, or more likely a conservative use with the intent to reduce bleeding risk. Retrospective analysis of large datasets confirm that the use of an “inappropriately reduced dose” is common, does not reduce bleeding risk, and significantly increases embolic stroke risk.2

There is also evidence of a smaller cohort of people on standard DOAC dose inappropriately (where dose should have been reduced in accordance with the summary of product characteristics) who are potentially exposed to higher bleeding risk.

Management of bleeding

The lack of a test to measure the anticoagulation effect of DOACs is unnerving to clinicians who are used to INR to test for warfarin. However, the relatively stable and predictable pharmacodynamics should reassure clinicians and inform the management of the vast majority of bleeds encountered during monitoring, which are minor and require no interruption of treatment.

Brief interruption may be reasonable for recurrent or moderate bleeding, with recourse to emergency hospital referral for moderate to severe bleeding. It is important to consider the underlying cause of bleeding or anaemia (e.g. colonic neoplasms are detected earlier for people on anticoagulation) and always seek an underlying cause for anaemia and not attribute it solely to anticoagulation.

The recurrent faller

The issue of falls and anticoagulation cessation is a matter of constant debate. In the absence of robust trial evidence, mathematical modelling using data on the number of falls and the number of significant intracranial bleeds suggests that a person needs to fall 295 times a year (about 5-6 falls a week), for the risk of major bleeding to become dominant. However, one must take into account the quality and impact of the fall eg. a fall causing a hip fracture carries much higher risk than minor trips and slips which are the commonest. NICE guidelines are clear that “falls are not a contraindication to anticoagulation in AF” and interventions to reduce fall risk should be instituted e.g. referral to falls clinic.3

Peri-procedural management

The increased risk of bleeding when undertaking procedures in the setting of anticoagulation is well recognised. Anticoagulation cessation pre-operatively is often undertaken for a longer than appropriate time frame exposing patients to a high risk of embolic complications. In select cases, intervention (left atrial appendage occlusion, specialist commissioning) may be appropriate.

It is essential that robust local protocols are developed in accordance with international guidelines (e.g. EHRA guidance4) to ensure safer peri-operative anticoagulation management. These should incorporate formal assessment of thrombotic and bleeding risk, to minimise overall patient risk (a combination of bleeding and embolic risk).

Anticoagulation cessation

As already mentioned, brief anticoagulation cessation may be required for minor recurrent or moderate bleeding. A clear plan for review must be ensured to keep this duration to a minimum. In certain situations, it will be essential to review the overall risk-benefit balance and consider permanent cessation. In select cases, intervention (left atrial appendage occlusion, specialist commissioning5) may be appropriate.

This will usually be informed by specialist opinion. Specific examples include: demonstration of multiple micro-haemorrhages on MRI brain scan; gastrointestinal (GI) haemorrhage with a non-modifiable cause like angiodysplasia. Most GI haemorrhage is secondary to ulcer disease or neoplastic disease, and if the underlying cause is treated successfully, anticoagulation can be resumed with specialist input, if required.

In addition, when people become frail (e.g. severe frailty score of 7-9 on the Clinical Frailty Score, significantly limited oral intake), the focus of management may shift to conservative and symptom focused treatment, and anticoagulation may not be appropriate. Such decisions should involve the patient, or relatives/carers if the patient lacks capacity. 

Secondary care advice

Most anticoagulation initiation and monitoring for AF can be undertaken in primary care. VTE diagnosis usually occurs in secondary care with provided guidance on duration of anticoagulation. Reasons for seeking advice from secondary care about anticoagulation may include:

At initiation

  • Second opinion on anticoagulation for AF (or rate versus rhythm strategy for AF)
  • Abnormal blood tests at anticoagulation initiation e.g. anaemia, newly identified moderate to severe renal impairment
  • Evaluation of suspected VTE

Whilst monitoring

  • Investigation of significant or recurrent bleeding or anaemia
  • Emergency admission for moderate to severe bleeding
  • Specialist advice on choice of anticoagulant in unlicensed scenarios

Conclusion

About 2% of the population are on anticoagulation and monitored almost exclusively in primary care. Thus, primary care clinicians need to be aware of the specifics of warfarin and DOACs. Robust local guidance should be developed in partnership to inform safe anticoagulation monitoring and referral pathways. 

National guidance to inform anticoagulation practice during the current pandemic6 is not covered in this article.

 


Mistri H – Forest Medical Group, Leicestershire
Mistri AK - University Hospitals of Leicester NHS Trust

Conflict of interest: none declared


References

  1. SSNAP. https://www.strokeaudit.org/
  2.  Yao et al. J Am Coll Cardiol 2017;69:2779–90.
  3. NICE Guidelines for Atrial Fibrillation – available online at https://www.nice.org.uk/guidance/cg180
  4. https://www.escardio.org/Guidelines/Recommended-Reading/Heart-Rhythm/Novel-Oral-Anticoagulants-for-Atrial-Fibrillation
  5. https://www.nice.org.uk/guidance/ipg349
  6. https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/03/C0077-Specialty-guide_Anticoagulant-services-and-coronavirus-v1-31-March.pdf