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ESOC 2022 | Cerebral venous thrombosis in the setting of COVID-19 vaccination

Cerebral venous thrombosis (CVT) has been reported as a rare adverse event associated with COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT). Diana Aguiar de Sousa, MD, PhD, Lisbon Central University Hospital Center, University of Lisbon, Lisbon, Portugal, discusses what we know about these rare cases of CVT after vaccination against SARS-CoV-2 infection. Data from the CVT after SARS-CoV-2 vaccination registry was used to identify more than 100 cases of VITT-related CVT. The presence of platelet factor 4 (PF4) antibodies in several of these patients led to suggestions that the underlying mechanisms were similar to those behind heparin-induced thrombocytopenia. CVT cases occurring after vaccination were typically severe in presentation, often presenting with brain hemorrhagic lesions and intracranial hypertension with brain herniation, and fatality rates are reported to be significantly higher than those in patients with CVT in the pre-pandemic era. Research is ongoing to understand the underlying mechanisms and treatment strategies. This interview took place at European Stroke Organisation Conference 2022 in Lyon, France.

Transcript (edited for clarity)

So probably you remember that early on during the vaccination campaign for COVID-19, about one year ago in March 2021, several cases of thromboembolic events were reported in people given the Astrazeneca vaccine in Europe. Although this was apparently very extremely rare event, several countries immediately suspended the use of this vaccine. Then shortly thereafter, just a few days after, a German group and more or less at the same time also an English group and the Norwegian group, they identified in these patients with CVT and thrombocytopenia that they had positive antibodies against platelet factor 4, PF4...

So probably you remember that early on during the vaccination campaign for COVID-19, about one year ago in March 2021, several cases of thromboembolic events were reported in people given the Astrazeneca vaccine in Europe. Although this was apparently very extremely rare event, several countries immediately suspended the use of this vaccine. Then shortly thereafter, just a few days after, a German group and more or less at the same time also an English group and the Norwegian group, they identified in these patients with CVT and thrombocytopenia that they had positive antibodies against platelet factor 4, PF4. So this seemed to be a similar mechanism to heparin-induced thrombocytopenia, but it was unknown what was the mechanism. Then in April, so one months later, FDA also paused the vaccination with the Johnson & Johnson vaccine, because there were similar reports of CVT and thrombocytopenia and positive PF4 antibodies in patients receiving this also adenoviral based vaccine.

So at this point in Europe, we started the registry of cerebral venous thrombosis after vaccination with any of the vaccines against SARS-CoV-2. This was then within a network of CVT researchers, which is the International CVT Consortium. So very quickly we could gather several cases across Europe and other countries and by June we had data already on more than 100 cases. What we found was that patients with CVT and thrombocytopenia, after vaccination with these vaccines, had a different specific presentation, which was much more severe compared with patients with CVT in the pre-pandemic years, which was our control group. These patients had higher rates of common at presentation, about one quarter, and about two thirds had ICH at baseline as well. And the mortality rates were around 50% while usually it is four or five percent in the acute phase for CVT in the pre-pandemic period.

Also, we have been exploring why is it so common that these patients have CVT while for example, patients with heparin-induced thrombocytopenia, we have the impression that it was quite rare that they had CVT. And indeed we did the systematic review on that and it is quite rare. About 1-2% of patients with the heparin-induced thrombocytopenia have CVT while patients with vaccine-induced thrombocytopenia, about one half have this severe form of CVT. So indeed, there should be something else than the PF4 antibodies and the pathophysiology to explain this tropism of the thrombosis for this cerebral venous system in this new condition but we still don’t know. We are still exploring and we hope that this and other questions in future research, we can learn more from this condition.

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