Acquired thrombotic thrombocytopenic purpura with possible association with AstraZeneca‐Oxford COVID‐19 vaccine

Abstract Acquired thrombotic thrombocytopenic purpura is characterized by the microvascular aggregation of platelets and microangiopathic hemolytic anemia causing ischemia of multiple organs including the brain mainly and less likely the kidney and the heart. The disease is caused by severe reduction in the activity of ADAMTS 13 due to presence of inhibitory antibodies.


covid-19, thrombocytopenia, TTP, vaccines
We report a case of a 37-year-old man with acquired thrombotic thrombocytopenic purpura (aTTP) that developed after AstraZeneca-Oxford COVID -19 vaccination. He presented with progressive dizziness, fatigue, and headache associated with exertional shortness of breath and palpitation 10-15 days after vaccination. Laboratory investigation showed hemolytic anemia, thrombocytopenia, and blood smear showed fragmented erythrocytes. aTTP was diagnosed based on the clinical presentation and was confirmed later by low level of ADAMTS13 activity and the presence of inhibitory antibodies. He was successfully treated using eight sessions of plasma exchange, corticosteroids, and rituximab.
To our knowledge, this case appears to represent the first report of aTTP following coronavirus disease 2019 (COVID-19) vaccination.

CASE REPORT
A 37-year-old Kuwaiti gentleman presented to the emergency department of a general hospital complaining of a gradually progressive dizziness, fatigue, and headache associated with exertional shortness of breath and palpitation for 1 week, and he also noticed dark urine and red spots over his extremities 1 day prior to admission.
The patient is a heavy smoker who is complicated by secondary polycythemia for which he donates blood once every year. ADAMTS13 activity was 2.6% and antibodies assay was positive (these tests were sent before the start of plasma exchange and the results were received with 3 days). Chest X-ray was done with no obvious pathology.

DIAGNOSIS
Patient

TREATMENT AND OUTCOME
Plasma exchange was started immediately planned for daily exchange with 1.5 plasma volume. Methylprednisolone at a dose of 1 g intravenous was started for 3 days initially and was followed by prednisolone 1 mg/kg/day. Rituximab 375 mg/m 2 was added as once weekly infusion for 4 weeks.
The patient received total of eight sessions of plasma exchange while in hospital. The patient symptomatology has improved, and his blood investigations were back to normal with LDH of 199 IU/L, platelet count of 340 × 10 9 /L, and Hg level of 123 g/L on discharge.
The patient had completed the remaining of the four doses of rituximab as an outpatient and he had a rapid taper off the steroid dose over 3 weeks.

DISCUSSION
aTTP is a rare disease with an incidence of 3 to 10 cases per million adult per year [1]. It is caused by severe reduction in the activity of Von Willebrand factor cleaving metalloprotease (ADAMTS13). This is, in turn, caused by the presence of inhibitory antibodies.
The disease is characterized by small vessel platelet-rich microthrombi that results in MAHA, thrombocytopenia, and thrombosis.
The historical pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms, and renal insufficiency appears obsolete, as these symptoms were present in <10% of patients with aTTP [2].
The symptoms of the disease initially include fatigue, shortness of breath, abdominal pain, nausea, vomiting, and petechial rash or minor bleeding.
As the disease progresses and becomes more aggressive, the dis- Plasma infusion can be given as a temporary measure for patient with an expected delay in initiation TPE. The addition of immunosuppressive agent including corticosteroid and rituximab has improved the outcome of the aTTP and it has decreased the duration of TPE. These agents are given to patient with intermediate to high PLASMIC score [12].
Vaccination in general is an important part of preventative medicine and COVID-19 vaccination is proven to reduce morbidity and mortality of the disease.
Rarely vaccination, especially against viral infection, has been associated with autoimmune pathology including aTTP. Three case reports have linked influenza vaccine with aTTP [13][14][15]: one case report has linked pneumococcal vaccination with aTTP [16], one case report has described aTTP after H1N1 vaccination [17], and one case report of aTTP shortly after Rabies vaccination [18].
To our knowledge, this case report is the only case showing a possible connection of AstraZeneca-Oxford COVID-19 vaccination to aTTP.
The patient had no prior history of any form of thrombocytopenia or other hematological disorder, and no medication apart from the vaccination. Screening for secondary causes of aTTP was all negative.

CONCLUSION
This report suggests the potential, but not proven role, of AstraZeneca-Oxford COVID-19 vaccination in the pathogenesis of aTTP. Vaccinerelated aTTP, like other forms of aTTP, can be successfully treated by plasmapheresis, corticosteroids, and rituximab.

CONFLICT OF INTEREST
The authors have no conflicts of interest to declare

AUTHORS CONTRIBUTION
MA and EJ initiated and coordinated the development of the paper and worked on data collection, analysis, and writing up the paper. NA and JN analyzed and interpreted the results and helped in writing up introduction. NA, JN, and EJ were major contributors in writing up the manuscript. All authors read and approved the final manuscript.