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

Autor: Stegner D; Institute of Experimental Biomedicine, University Hospital, University of Würzburg, Würzburg, Germany.; Rudolf Virchow Center, University of Würzburg, Würzburg, Germany., Göb V; Institute of Experimental Biomedicine, University Hospital, University of Würzburg, Würzburg, Germany.; Rudolf Virchow Center, University of Würzburg, Würzburg, Germany., Krenzlin V; Institute of Experimental Biomedicine, University Hospital, University of Würzburg, Würzburg, Germany.; Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.; Center for Thrombosis and Hemostasis, Johannes Gutenberg University Medical Center, Mainz, Germany., Beck S; Institute of Experimental Biomedicine, University Hospital, University of Würzburg, Würzburg, Germany.; Rudolf Virchow Center, University of Würzburg, Würzburg, Germany., Hemmen K; Rudolf Virchow Center, University of Würzburg, Würzburg, Germany., Schuhmann MK; Department of Neurology, University Hospital Würzburg, Würzburg, Germany., Schörg BF; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of Tübingen, Tübingen, Germany., Hackenbroch C; Institute of Experimental Biomedicine, University Hospital, University of Würzburg, Würzburg, Germany., May F; Institute of Experimental Biomedicine, University Hospital, University of Würzburg, Würzburg, Germany.; Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.; CSL Behring Innovation GmbH, Marburg, Germany., Burkard P; Institute of Experimental Biomedicine, University Hospital, University of Würzburg, Würzburg, Germany.; Rudolf Virchow Center, University of Würzburg, Würzburg, Germany., Pinnecker J; Rudolf Virchow Center, University of Würzburg, Würzburg, Germany., Zernecke A; Institute of Experimental Biomedicine, University Hospital, University of Würzburg, Würzburg, Germany., Rosenberger P; Department of Anesthesiology and Intensive Care Medicine, University Hospital, Tübingen, Germany., Greinacher A; Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany., Pichler BJ; Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', Eberhard Karls University Tübingen, Tübingen, Germany., Heinze KG; Rudolf Virchow Center, University of Würzburg, Würzburg, Germany., Stoll G; Department of Neurology, University Hospital Würzburg, Würzburg, Germany., Nieswandt B; Institute of Experimental Biomedicine, University Hospital, University of Würzburg, Würzburg, Germany. bernhard.nieswandt@virchow.uni-wuerzburg.de.; Rudolf Virchow Center, University of Würzburg, Würzburg, Germany. bernhard.nieswandt@virchow.uni-wuerzburg.de.
Jazyk: angličtina
Zdroj: Nature cardiovascular research [Nat Cardiovasc Res] 2022 Feb; Vol. 1 (2), pp. 132-141. Date of Electronic Publication: 2022 Feb 10.
DOI: 10.1038/s44161-021-00017-1
Abstrakt: 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. Interfering with CLEC-2 signaling or inhibition of GPIIb/IIIa completely blocked platelet activation and CVT. Blocking GPIIb/IIIa after onset of neurological symptoms protected mice from platelet consumption, CVT and death, which was not seen after treatment with heparin. These results point to aberrant platelet activation as a major trigger of CVT and potential target for treatment.
(© 2022. The Author(s).)
Databáze: MEDLINE
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