In conjunction with additional public health measures, vaccination against COVID-19 has been vital in protecting population health. In the United Kingdom, real-time modelling1 has demonstrated that vaccination has reduced the number of deaths in those infected whilst preventing transmission. In the United States, data reported for the period March–August 2021 demonstrated that all three vaccines approved by the Food and Drug Administration proved effective at preventing hospitalisation from infection with COVID-19.2

Several effective vaccines are now in use worldwide. The two-dose mRNA COVID-19 vaccines from Pfizer-BioNTech and Moderna have been approved for use in the UK and USA. The single-dose viral vector vaccine from Janssen is approved in the USA and the two-doses viral vector vaccine from Oxford-AstraZeneca is approved in the UK.

The Russian two-dose Sputnik V viral vector vaccine has been distributed worldwide but is yet to be approved by the World Health Organisation or the European Medicines Agency owing to ongoing data and safety concerns.3

In China, multiple vaccine developers have used an inactivated version of the COVID-19 virus to generate an effective immunogenic response in trial participants.4 However, to date, for none of the Chinese-developed vaccines have phase 3 clinical trial data been published in any peer-reviewed journals.5

As of 1 November 2021 over 6.8 billion COVID-19 vaccine doses have been administered globally6 and as expected this has resulted in a number of adverse effects being reported.

Minor side effects included fever, headache, lethargy, myalgia, arthralgia, nausea, swelling and pain at the site of injection.7

Rare but serious side effects included anaphylactic reactions,7 myocarditis,8 Guillain–Barré Syndrome (GBS)8 and Thrombotic Thrombocytopenia Syndrome (TTS).8

Here, we report a case whose presentation to hospital coincided with electronic communication from the Medical Directors Office for the South East alerting hospital consultants of an emerging syndrome associated with low platelets, thromboses, elevated D-dimer and anti-platelet-factor 4 antibodies. More specific notification regarding the condition was released by the Medicines & Healthcare Products Regulatory Agency (MHRA) one week later. This reported a total of 79 cases of probable vaccine-induced immune-mediated thrombosis with thrombocytopenia (VITT) up to 31 March 2021, 44 cases of cerebral venous sinus thrombosis, 34 cases of other site venous thrombosis, and one case of arterial thrombosis subsequently described.

A 59-year-old woman presented 14 days after receiving the first dose of ChAdOx1 nCoV-19 vaccine. She described a four-day history of a persistent headache and a one-day history of intermittent coolness in her left foot. The headache had started gradually with a severity of 7/10 and remained frontal. There was no limb weakness, visual disturbance, photophobia, neck stiffness or rash.

Her past medical history included hypertension, acquired hypothyroidism, depression, post-traumatic stress disorder (PTSD), and a right total knee replacement for osteoarthritis. Her regular medications included losartan 50 mg oral once daily (PO OD), lansoprazole 30 mg PO OD, levothyroxine 125 mcg PO OD and sertraline 100 mg PO OD.

Cardiovascular, respiratory, abdominal and neurological examinations were unremarkable and there were no features of meningism or rash. Dorsalis pedis pulses were initially difficult to palpate but were documented as present on subsequent clinical examinations performed that day.

The patient's laboratory tests performed one day prior to vaccination were normal.

Her laboratory tests performed on admission confirmed a thrombocytopenia of 23 × 109/L, fibrinogen 2.5 g/L and an elevated D-dimer of 2767 fibrinogen equivalent units. SARS-CoV-2 antibody was not detected. The blood film was reported as ‘platelet count confirmed by microscopy — no clumps or fibrin strands seen. Red blood cells appear normal. Neutrophils show some toxic granulation — uncertain cause.’

A computed tomography (CT) venogram was performed and reported as within normal parameters, thus excluding a cerebral sinus venous thrombosis as the cause of her headache.

The following day, the patient reported that her left leg felt painful and cold. Clinical examination revealed absent pulses throughout. Ultrasound Colour Doppler (Figure 1) showed a large femoral thrombus with minimal circumferential flow. A CT angiogram of the lower limbs showed multiple arterial thromboses in the distal aorta and both femoral arteries (Figure 2). Laboratory tests were repeated and confirmed a reduced platelet count of 16 × 109/L and a D-dimer elevated to 8 543 fibrinogen equivalent units. Anti-platelet-factor 4 antibodies were sent and subsequently positive with an optical density value of 0.312 units.

Ultrasound Colour Doppler showed large femoral thrombus with minimal circumferential flow

Computed tomography angiogram with 3D reconstruction of the lower limbs showed multiple arterial thromboses in the distal aorta and both femoral arteries

The patient was urgently transferred to the Intensive Care Unit at a tertiary vascular centre. Medical management followed newly released guidelines,9 with intravenous steroids and immunoglobulin. Initial anticoagulation was with argatroban but this was later switched to fondaparinux.

Eight days after the patient's initial presentation to hospital, the vascular team deemed the left leg non-viable due to the unresolved occlusion of the left common femoral artery and an above knee amputation of the left leg was performed.

Post-operative care included intravenous antibiotics and fondaparinux. Laboratory tests, prior to discharge from hospital, demonstrated a normal platelet count: 172 × 109/L, D-dimer was 646 fibrinogen equivalent units, and anti-platelet-factor 4 antibodies were not detected (0.1518 optical density units). The patient was commenced on rivaroxaban and aspirin and discharged to a prosthetic centre.

In the UK, as of 20 October 2021, the MHRA had been alerted to 423 cases of major thromboembolic events with thrombocytopenia following vaccination with the Oxford-AstraZeneca vaccine, via Yellow Card reports.10 Like the patient described in this case report, 88% (377/423) of major thromboembolic events with thrombocytopenia occurred after the first vaccine dose.10

This patient consented to vaccination in the hope of avoiding morbidity and/or mortality from COVID19. The tragic physical and psychological consequences of such rare events are difficult to measure.

This patient has required an uptitration of sertraline to address more frequent depressive mood disturbance. Gabapentin has been commenced to manage phantom limb pain. Physical support has been provided in the form of life-long aftercare from the prosthetic clinic. Input from social workers, physiotherapy, occupational therapy and musculoskeletal rehabilitation will support the patient as she adjusts to activities of daily living using her limb prosthesis and wheelchair. Psychological support has been provided informally by her family and friends, and professionally by trauma psychologists.