"During a 2-week period, we have encountered five cases presenting with the combination of cerebral venous thrombosis (CVT), intracerebral hemorrhage and thrombocytopenia. A clinical hallmark was the rapid and severe progression of disease in spite of maximum treatment efforts, resulting in fatal outcome in for 4 out of 5 patients. All cases had received ChAdOx1 nCov-19 vaccine 1–2 weeks earlier and developed a characteristic syndrome thereafter. The rapid progressive clinical course and high fatality rate of CVT in combination with thrombocytopenia in such a cluster and in otherwise healthy adults is a recent phenomenon. Cerebral autopsy findings were those of venous hemorrhagic infarctions and thrombi in dural venous sinuses, including thrombus material apparently rich in thrombocytes, leukocytes and fibrin. Vessel walls were free of inflammation. Extra-cerebral manifestations included leech-like thrombi in large veins, fibrin clots in small venules and scattered hemorrhages on skin and membranes...
Discussion
... VITT seems to occur about 1–2 weeks after vaccination with ChAdOx1 nCoV-19 and describes the rapid development of thrombosis at unusual sites (e.g., cerebral and splanchnic veins)...
The diagnosis of CVT in context with COVID-19 vaccination can be challenging as the symptoms initially can be discrete and unspecific. Headache, the most common initial symptom of CVT, is also commonly encountered after COVID-19 vaccination and does therefore not rise any red flags. However, the flu-like symptoms after COVID-19 vaccination mostly occur in the first days, in contrary [sic] to the increasing symptoms about a week after vaccination, as experienced by our patients. Petechiae and ecchymosis were observed in 4 of 5 patients and may represent an early clinical finding. The presence of neurological symptoms after ChAdOx1 nCoV-19 vaccine should prompt further investigations, including platelet count, ELISA testing for platelet factor 4 (PF4) –polyanion antibodies and cerebral imaging with venography...
Blood clots generated in the arterial circulation are generally rich in platelets and appear white at autopsy. Clots from the venous circulation are rich in fibrin and erythrocytes, with a more red/brownish appearance and are typically found in CVT. In light of the unusual hematological process related to the thrombus formation in our five patients and macroscopic appearance of some of the thrombus material, one may question whether the thrombi present in our cases may differ from those more commonly formed in classical arterial and venous thromboembolic processes...
We describe the clinical, radiological and pathological findings of severe thrombocytopenic, hemorrhagic cerebral venous thrombosis in VITT after ChAdOx1 nCoV-19 vaccine. Although an association with ChAdOx1 nCoV-19 vaccine seems obvious, the exact cause of this immune reaction is not yet clear. Outcome in our cohort was extremely poor..."
Copyright © 2021 Wiedmann, Skattør, Stray-Pedersen, Romundstad, Antal, Marthinsen, Sørvoll, Leiknes Ernstsen, Lund, Holme, Johansen, Brunborg, Aamodt, Schultz, Skagen and Skjelland.
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