Incorrect community dosing leading to high apixaban levels in a patient with a hip fracture

An 86‐year‐old woman presented to a district general hospital with a fractured neck of femur and was listed for a hemiarthroplasty. Her past medical history included atrial fibrillation. Her only medication was the direct oral anti‐coagulant (DOAC) apixaban.

During the anaesthetic review on the morning of her planned procedure, she reported taking her last dose of apixaban 5 mg approximately 48 h previously, and expressed a preference for spinal anaesthesia. The recommended safe interval for neuraxial blockade following the last dose of apixaban in the UK guidance on Regional Anaesthesia and Patients with Abnormalities of Coagulation is 48 h [1]. However, her renal function on admission (36 h previously) was noted to be mildly deranged (urea 9.4 mmol.l⁻¹, creatinine 74 μmol.l⁻¹ and her estimated glomerular filtration rate was 63 ml.min⁻¹ (Modification of Diet in Renal Disease formula) so her case was discussed with the haematologist regarding her risk of vertebral canal haematoma (VCH).

We were advised that if a continued anticoagulant effect could not be excluded, then neuraxial anaesthesia should be avoided [2]. Given that assurance could not be provided based on renal function, dose and weight alone, and considering the patient's anaesthetic preference, assessment of the patient's apixaban level was recommended.

The Association of Anaesthetists Guideline for the Management of Hip Fractures advises that the anti‐Xa level should be < 50 ng.ml⁻¹ for the safe performance of central neuraxial blockade [3]. Apixaban anti‐Xa levels were measured using a calibrated anti‐Xa assay (Hyphen Biomed SAS, Neuville‐sur‐Oise, France) along with repeat urea and electrolytes. This showed an apixaban anti‐Xa level of 123.6 ng.ml⁻¹, and also deterioration of her renal function (urea 18.8 mmol.l⁻¹, creatinine 99 μmol.l⁻¹). On further discussion with the haematologist, it was recommended that neuraxial anaesthesia was unsuitable.

Current recommendations are that apixaban anti‐Xa levels should be checked when creatinine clearance is < 30 ml.min⁻¹ [1, 3]. Our patient's height of 1.63 m and measured weight of 54 kg gave an initial Cockcroft‐Gault calculated creatinine clearance of 41 ml.min⁻¹, which did not meet this threshold. On review of her community prescription, however, it was noted that given her age and weight, she should have been taking a reduced dose of 2.5 mg (rather than 5 mg) of apixaban twice daily [4] (Table 1). This, in addition to her impaired renal function, was considered to have been the main cause for her elevated apixaban level.

Table 1.

Apixaban dosing for stroke prophylaxis in non‐valvular atrial fibrillation with one risk factor, according to the British National Formulary [4].

Standard dose	5 mg twice daily
Reduced dose*	2.5 mg twice daily

^*Recommended if two of the three characteristics present: Age > 80 years, weight < 60 kg, serum creatinine > 133 μmol.l⁻¹.

The patient's operation was delayed until the following day, when hemiarthroplasty was performed uneventfully under spinal anaesthesia, as per the patient's wishes.

Anticoagulant use and advancing age were noted as risk factors for VCH following central neuraxial blockade in the Third National Audit Project (NAP3) [5]. However, it is worth considering when evaluating risk for individual patients that the overall risk of VCH caused by spinal anaesthesia is extremely low, with no incidences recorded across the 324,950 procedures included in NAP3.

This case highlights the importance of checking community dosing of DOACs and the possible need to check pre‐operative apixaban levels to help assess risk. Apixaban clearance is adversely affected by increasing age, low weight and reduced renal function. Clinicians are perhaps not yet as familiar with typical DOAC dosing as they are with warfarin. The guidelines and evidence base for their management and dosing in the peri‐operative period continue to evolve.