Long-term outcome of patients with vaccine-induced immune thrombotic thrombocytopenia and cerebral venous sinus thrombosis

ABSTRACT

Introduction In early 2021, unanticipated thromboses, including cerebral venous sinus thrombosis (CVST) with thrombocytopenia, emerged as an adverse reaction (ADR) in patients who had been vaccinated with the AstraZeneca ChAdOx1 nCoV-19 vaccine. This ADR was termed vaccine-induced immune thrombotic thrombocytopenia (VITT) or thrombosis with thrombocytopenia syndrome (TTS). Although sporadic in nature, VITT can result in severe disease in the individual vaccinee. We followed up on the outcomes and status of neurological recovery of 49 cases of VITT with CVST that were reported to PEI. Method Assessment of the Extended Glasgow Outcome Scale (GOS-E) was performed within 3-6 months after the initial hospital admissions. Individual Glasgow Coma Scale (GCS) scores were reported by phone or electronically via a questionnaire or medical report by the treating physician of the hospital to which the patient was initially admitted. If a GCS score was not reported, an expert determined a score based on the patient's medical report. For most patients, follow-up was pursued about 3-6 months after hospital admission. The reported outcomes describe the patients' neurological status at 5-38 weeks (mean 20 weeks) after hospital admission. Outcomes were identified in 44 of the original 49 cases. Results Patient outcomes ranged from good recovery (13 patients, 29.6 %) to moderate disability (11 patients, 25.0 %) and severe disability or vegetative state (6 patients, 13.6 %). Fatal outcomes were reported in 14 patients (31.8 %). As anticipated, initial low GCS scores were associated with poor outcomes. By contrast, GCS scores > 10 were typically associated with improved neurological outcomes. Moreover, platelet count nadirs were correlated with patient outcomes. Low platelet counts were observed in fatal cases (GOS-E 1) with a mean count of 17,000 platelets/muL). Likewise, patients with better neurological outcomes (GOS-E scores of 5-6 and 7-8) presented with mean counts of 61,000 thrombocytes/muL. However, the course of the disease was not always predictable and showed significant individual variability. Conclusion We provide data on the outcome of VITT cases with CVST upon vaccination with the AstraZeneca adenoviral vector ChAdOx1 nCoV-19 COVID- 19 vaccine and found that the recovery of patients from CVST was very heterogeneous. While some patients exhibited good recoveries, others developed severe disabilities and major long-term complications. Collectively, our findings highlight the importance of paying attention to early signs of increased intracranial pressure and the onset of thrombocytopenia in patients with a recent history of vaccination with the AstraZeneca adenoviral vector ChAdOx1 nCoV-19 COVID-19 vaccine.