Cerebral venous sinus thrombosis after COVID-19 vaccination ‘rare but severe’

Researchers noted a high mortality rate among patients with cerebral venous sinus thrombosis due to thrombosis with thrombocytopenia syndrome after COVID-19 vaccination.

“Our aim was to provide detailed insights into the clinical manifestations and outcomes of cerebral venous sinus thrombosis (CVST) due to thrombosis with thrombocytopenia syndrome (TTS) after COVID-19 vaccination,” study co-author Jonathan M. Coutinho, MD, PhD, of the department of neurology at Amsterdam University Medical Center, the Netherlands, told Healio Neurology. “For this, we used the existing International CVST Consortium, which is an academic research network that has been in existence since 2015.

“Since the data from this study come from a wide range of countries (19 in total), the study has a high external validity,” Coutinho added.

Several countries have restricted the use of certain COVID-19 vaccines, particularly among younger patients, following reports of CVST and other thromboses at unusual sites combined with thrombocytopenia that occurred between 4 and 28 days after vaccination with the Oxford-AstraZeneca and Janssen/Johnson & Johnson vaccines. Investigators found circulating platelet-activating platelet factor 4 antibodies in many of these patients after observing similarities between their clinical syndrome and spontaneous heparin-induced thrombocytopenia. The condition is now referred to as vaccine-induced immune thrombotic thrombocytopenia.

The Brighton Collaboration sought to pinpoint cases and promote research to determine the possible vaccination link with this condition by proposing a definition of TTS, which uses evidence of thrombosis and new-onset thrombocytopenia without known recent heparin exposure.

Coutinho and colleagues analyzed data of 116 patients included in an international registry of consecutive patients with CVST within 28 days after COVID-19 vaccination between March 29 and June 18 from 81 hospitals. They used an existing international registry to obtain data from 207 patients with CVST between 2015 and 2018 as reference. They detailed clinical characteristics and the mortality rate for adults with CVST in the setting of COVID-19 vaccine-induced immune thrombotic thrombocytopenia, CVST following COVID-19 vaccination that did not meet criteria for TTS and CVST not linked to COVID-19 vaccination.

The researchers classified patients with new-onset thrombocytopenia without recent heparin exposure as having TTS, which met the Brighton Collaboration interim criteria.

Results showed 67.2% of those with CVST after vaccination had TTS. Of these, 76 received the Oxford-AstraZeneca vaccine, and 32.8% had no indication of TTS. The researchers noted concomitant thromboembolism among 25 of 70 (36%) patients in the TTS group, two of 35 (6%) in the group without TTS and 10 of 206 (4.9%) in the control group, with in-hospital mortality rates of 47%, 5% and 3.9%, respectively.

Patients in the TTS group diagnosed before the condition received attention in the scientific community had a mortality rate of 61%, whereas those diagnosed later had a mortality rate of 42%.

Among patients with TTS, 24% were comatose at presentation, 68% had intracerebral hemorrhage and concomitant thromboembolism, and 47% died during hospitalization.

“CVST due to TTS after COVID-19 vaccination is a rare but severe clinical condition with high rates of coma and intracerebral hemorrhage at presentation,” Coutinho said. “The mortality rate of CVST-TTS is high, almost 50% in our study, which is considerably higher than is usually seen in patients with CVST (4% in our control group).

“Still, it remains important to stress that TTS is a very rare side effect of the adenovirus-based COVID-19 vaccines, and that the positive effects of the vaccines vastly outweigh the risks,” Coutinho added.