Haemostatic Disarray Following COVID-19 Vaccine – a Case of Acquired Haemophila A

We read with interest Hafeez et al. discussion regarding concern about haemostatic adverse effects post vaccination. ¹ Many haemostatic complications post COVID-19 vaccination have been reported including the syndrome of thrombocytopenia and thrombosis, as discussed by Hafeez et al. ¹

In 2019, a new pandemic of coronavirus arose from China and quickly spread across the world. ² It became a public health emergency. ² Covid-19 infection usually begin with flu like symptoms however, about 10% of the symptomatic subjects may experience more severe course of the disease. ² Vaccination became the cornerstone strategy in disease control and prevention of new and more severe cases of COVID-19 infection. ²

Here we would like to add to the haemostatic adverse events post vaccination reported by Hafeez et al. and report a case of Acquired Haemophilia A (AHA) one week following a Pfizer-BioNTech SARS-CoV-2 vaccine. AHA is a rare bleeding disorder (reported incidence; 1 per million/year) which results in spontaneous bleeding in people with no history of a bleeding disorder. ³ It is believed to be caused by autoantibodies directed against factor VIII (FVIII). ³ It most often seen in elderly patients and is often associated with autoimmune conditions or malignancies but many cases are idiopathic. ³ Here we discuss the rare occurrence of AHA post vaccination.

A 72-year-old gentleman developed forearm, arm and thigh bruising approximately one week after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine in April 2021. He attended his family doctor when the bruising extended, who referred him urgently to hospital. He had a history of successfully treated prostate carcinoma [prostate-specific antigen was 0.07 ng/ml (normal range = 0-4 ng/ml)], non-insulin dependent diabetes and hypertension. His physical examination was unremarkable other than tongue swelling and extensive bruising. Bloods showed anaemia (haemoglobin: 79 g/L), a normal platelet count (288 × 10⁹/L, a prolonged activated partial thromboplastin time [APTT] of 71 s [normal range = 25.1-36.5 s] and a normal prothrombin time and fibrinogen. His lupus anticoagulant screen was negative. The Factor VIII level was reduced [0.01IU/ml [normal range = 0.50 to 1.49 IU/ml]] and Factor VIII inhibitor quantification demonstrated an inhibitor of 70 B.U/ml, consistent with a diagnosis of acquired Haemophilia A. He was treated with one dose [4500 units] of FVIII inhibitor bypassing activity [FEIBA] to control the bleeding and prednisolone 60 mg once daily [reduced dose due to age and history of diabetes]. He experienced no further bleeding episodes. CT imaging showed no evidence of malignancy. He completed four weekly doses of rituximab 375 mg/m² and underwent a slow steroid taper. His FVIII level was normal and his inhibitor screen negative 6 weeks after diagnosis. Remission has persisted despite stopping all immunosuppression.

According to the European Centre for Disease Prevention and Control, 82.2% of adults have had at least one dose of a covid-19 vaccine and this rises to >94% in Ireland. ⁴ Pharmacovigilance is key when new medications or vaccines are introduced, especially to such a large proportion of the worlds’ population as rare complications are likely to be seen. ⁵ Adverse Events Following Immunisation (AEFI) are reported in 53.7 per 100,000 COVID-19 vaccine doses administered. ⁶ The most common adverse events associated with the COVID-19 vaccine to date are allergic skin reactions and pain/redness/swelling at the injection site. Serious AEFI was reported in 2.8 per 100,000 doses of COVID-19 vaccine administered. ⁶ Four other cases of AHA following SARS-CoV-2 vaccination have been reported to date.^7-10 Education about pharmacovigilance and trust in the system is key to limit vaccine scepticism. ⁵

The potential correlation between vaccinations and autoimmune disease has been postulated for a long time. ⁴ The pathogenetic mechanism and aetiology of this is still unclear. ⁵ It has been suggested that the mechanism of autoimmune disease development post vaccination is by molecular mimicry, by which viral or bacterial agents trigger an immune response against autoantigens. ⁵ Another hypothesis is; bystander activation, which involves the activation of quiescent auto-reactive T and B cells. ⁵ However, it is suggested that some people are more susceptible to developing these reactions due to a genetic predisposition to autoimmune diseases. ⁵ This hypothesis may explain the pathogenesis of AHA post SARS-CoV-2 vaccine.

COVID-19 infection rates are rising worldwide. ⁴ Booster doses are being administered and the vaccination programme is being expanded to children. ⁴ More haemostatic adverse events post vaccination are likely to be seen. Therefore, ongoing pharmacovigilance is required.