Prednisolone/tozinameran

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A man in his 80s [exact age at onset not stated] developed acquired haemophilia (AHA) following vaccination with the first dose of tozinameran. Additionally, he developed COVID-19 pneumoniae during immunosuppression treatment with prednisolone for AHA.

The man presented to a hospital clinic with a 4-day history of bruising on his lower and upper limbs. His medical history was significant for type-2 diabetes mellitus, glaucoma in both eyes, benign prostatic hyperplasia (BPH), chronic kidney disease stage 3a, dyslipidaemia, hypertension and an ischaemic stroke (7 years ago) with associated cognitive impairment. His ongoing medications included metformin, bisoprolol, atorvastatin, pantoprazole, aspirin/glycine [Cardiprin], alfuzosin and calcium carbonate. Two weeks prior to the onset of his symptoms, he had undergone vaccination with the first dose tozinameran [Pfizer COVID-19 vaccine; route and dosage not stated]. Examination (at current admission) revealed pulse 73 beats/min, BP 128/68mm Hg and temperature 36.8°C. He had bruises on his left upper limb and on right posterior thigh. Blood tests showed creatinine 136 µmol/L and an isolated prolonged activated partial thromboplastin time (aPTT) of 90s. A compression bandage was applied to the haematoma, following to which he was discharged and scheduled for a follow-up 1 week later. He was recommended to postpone his second dose of tozinameran. Five days later, he presented to the emergency unit with painful and swollen left lower limb and tiredness. His appearance was also frail. Examination showed oxygen saturation 99% on breathing ambient air, RR 20 breaths/min, pulse 98 beats/min, BP 127/64mm Hg and temperature 36.5°C. Numerous ecchymoses were seen over his right arm extending up to the forearm, left wrist and left cubital fossa. A painful swelling over the anteromedial aspect of the left thigh along with associated oedema were also noted. Investigations revealed severe anaemia with isolated prolonged aPTT at 78.7s and Hb 73g/L. Further laboratory findings upon admission revealed WBC count 11.6 × 10 ⁹/L, prothrombin time (PT) 13.1s, INR 1.26, creatinine 134 µmol/L, serum albumin 31g/L, carcinoembryonic antigen 6.2 ng/mL, prostate-specific antigen 9.234 ng/mL, CRP 8.8 mg/L, total iron binding capacity 41.4 µmol/L, serum iron 7.6 µmol/L, unsaturated iron-binding capacity 33.8 µmol/L, serum vitamin B12 level 103 pmol/L, serum folate level 12.9 nmol/L, factor VIII (FVIII) assay 6.7% and FVIII inhibitor 7.5BU. Left thigh ultrasound showed an intramuscular haematoma at the anteromedial region measuring 4.0cm × 6.5cm × 10.9cm and measuring 0.8cm × 1.2cm × 9.1cm over the posterior part of the thigh. Various differential diagnoses were ruled out with findings. Subsequently, the presence of a clotting factor inhibitor, low FVIII level and an FVIII inhibitor titre at 7.5BU confirmed a diagnosis of AHA secondary to vaccination with tozinameran.

The man started receiving treatment with tranexamic acid and underwent transfusion with 4 units of fresh frozen plasma and 2 units of packed RBC. Later, he was shifted to a specialist centre, where he received treatment with methylprednisolone and eptacog-alfa [recombinant activated FVII] to achieve haemostasis. Following response to treatment, he was additionally prescribed with azathioprine and oral prednisolone 60mg daily in divided doses (30mg twice daily for 9 days) with a tapering-down schedule of over 6 weeks (20mg twice daily for 7 days, followed by 15mg twice daily for 4 days and 20mg daily for 5 days). He also received mecobalamin for vitamin B12 and folate deficiency. As per earlier recommendation, his second dose of tozinameran was postponed. However, during week 3 of tapering prednisolone treatment, he developed COVID-19 pneumoniae secondary to immunosuppressive treatment with prednisolone [duration of treatment to reaction onset and outcome not stated]. Thus, he was hospitalised a second time. Irrespective of his condition, his AHA remained under control with dissipation of ecchymosis and decrease in the size of haematoma. His prednisolone therapy was replaced with dexamethasone under haematologist's advice. At the same time, azathioprine was also continued and he was subsequently discharged. Later, FVIII titre normalised and FVIII inhibitors were undetectable, following to which dexamethasone was discontinued and azathioprine was retained. His clinical course was complicated with acute urinary retention and a urosepsis episode after 2 months of AHA diagnosis. Both these complications responded well to an unspecified antibacterial [antibiotic] treatment. At the 6-month follow-up, he remained in remission (AHA) under azathioprine and treatment with azathioprine was further continued.