Foudroyant cerebral venous (sinus) thrombosis triggered through CLEC-2 and GPIIb/IIIa dependent platelet activation.

ABSTRACT: Cerebral venous (sinus) thrombosis (CVT) is an unusual manifestation of venous thrombosis causing severe neurological impairment and seizures^1,2. Molecular mechanisms underlying CVT, potentially involving pathological platelet activation, are unknown. Here we show that antibody-(INU1-fab)-induced cooperative signaling of two platelet receptors, C-type lectin-like receptor-2 (CLEC-2) and GPIIb/IIIa, triggers within minutes a CVT-like thrombotic syndrome in mice, characterized by tonic-myoclonic seizures, platelet consumption and death. Brain autopsy showed thrombi mainly in the cortical venules, but no intracranial hemorrhages or edema formation. Transcranial intravital microscopy revealed rapidly progressing thrombosis in the superior sagittal sinus, a main site of CVT in humans

SUBMITTER: Stegner D 

PROVIDER: S-EPMC11358028 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature