ChAdOx1 nCov-19 vaccine-induced thrombotic thrombocytopenic purpura successfully treated with plasmapheresis.

Dear Editor,

Appropriate vaccination remains the most effective approach against contracting the severe acute respiratory syndrome coronavirus 2 infection and the resulting coronavirus disease 2019 (COVID-19) [1, 2]. Although most adverse events due to both adenoviral vector-based (ChAdOx1 nCov-19 and Ad26.COV2.S) and mRNA-based (BNT162b2 mRNA and mRNA-1273) vaccines are tolerable, thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal event [3, 4]. Herein, we present the case of a patient with ChAdOx1 nCov-19 vaccine-induced TTP successfully treated with plasmapheresis.

A 75-year-old man experienced bleeding from the tongue 30 days after administration of the ChAdOx1 nCov-19 vaccine. His initial hemogram revealed leukocytosis (leukocyte count: 9520/μL; reference: 4000–8000/μL), anemia (hemoglobin: 10.5 g/dL; reference: 13.5–17.5 g/dL), and thrombocytopenia (platelet: 9000/μL; reference: 150000–400000/μL). Furthermore, increased d-dimer (2.74 mg/FEU; reference: < 0.55 mg/FEU) and lactate dehydrogenase (1675 IU/L; reference: 120–240 IU/L) levels and decreased haptoglobin (< 0.0781 g/L; reference: 0.3–2.0 g/L) levels were noted. Prothrombin time, activated partial thromboplastin time, and fibrinogen level were within normal ranges. To further investigate the possibility of vaccine-induced immune thrombotic thrombocytopenia, we performed the enzyme-linked immunosorbent assay to detect antibodies against the PF4-heparin/complex, which tested negative (optical density: 0.127; reference: < 0.400). Multidetector computed tomography did not reveal peripheral vascular or pulmonary artery thrombosis. Autoimmune panel workup was unremarkable. Human immunodeficiency virus, hepatitis B virus, Epstein–Barr virus, and cytomegalovirus all tested negative. However, we found abundant schistocytes on the peripheral blood smear (Fig. 1a), and the ADAMTS-13 activity was only 0.8% (reference: 40–130%). Considering TTP, we initiated plasmapheresis for five consecutive days. Thrombocytopenia substantially improved from 9000 to 235000/μL (Fig. 1b).

Fig. 1

A Abundant schistocytes on the peripheral blood smear (arrows) (Liu’s stain, 400×). B Thrombocytopenia substantially improved from 9000 to 235000/μL after plasmapheresis (arrows)

Although cases of TTP after various vaccinations have been previously reported [5], the pathophysiology of the ChAdOx1 nCov-19 vaccine-induced TTP remains unclear. Autoantibodies against ADAMTS-13 induced by the ChAdOx1 nCov-19 vaccine could be a potential mechanism [3]. In addition to vaccine-induced immune thrombotic thrombocytopenia [6], TTP needs to be considered in patients presenting with thrombocytopenia after any COVID-19 vaccination. Early diagnosis and plasmapheresis are crucial to prevent mortality in these patients.