Immunohistologic Features of Cerebral Venous Thrombosis Due to Vaccine-Induced Immune Thrombotic Thrombocytopenia

"Methods: Detailed neuropathologic studies were performed in 3 cases of cerebral venous thrombosis related to VITT [vaccine-induced immune thrombotic thrombocytopenia] after adenoviral COVID-19 vaccination.

Results: Autopsy revealed extensive cerebral vein thrombosis in all 3 cases. Polarized thrombi were observed with a high density of neutrophils in the core and a low density in the tail. Endothelial cells adjacent to the thrombus were largely destroyed. Markers of neutrophil extracellular trap and complement activation were present at the border and within the cerebral vein thrombi. SARS-CoV-2 spike protein was detected within the thrombus and in the adjacent vessel wall...

Of note, anti-PF4 IgG (Immucor), able to promote platelet serotonin secretion, were detected in premortem blood in all 3 patients. At autopsy, venous thrombi were observed in the brain, liver, and lungs, but not in other organs.

Discussion

To gain a better insight into the mechanisms responsible for the rare but severe and sometimes dramatic side effect of adenovirus-based SARS-CoV-2 vaccines, we performed a detailed neuropathologic analysis of 3 cases with VITT. A remarkable architecture of the thrombi, with a high cell density, mostly neutrophils, and platelets in the core and a low leukocyte density in the tail, rich in red blood cells and fibrin, was observed. Moreover, we confirm that thrombi are associated with NET formation and reveal signs of complement activation, both processes being highly thrombogenic. These data provide strong evidence for immunothrombosis during VITT.

Strikingly, SARS-CoV-2 spike protein was also detected within neutrophils in the thrombus and in the adjacent vessel wall. In experimental mouse models, the vaccine antigen could be detected in the serum for 7 days and the vaccine DNA in tissues for up to 29 days after an IM injection of ChAdOX1-nCoV-19."