Vagus nerve stimulation primes platelets and reduces bleeding in hemophilia A male mice

Carlos E. Bravo-Iñiguez, Jason R. Fritz, Shilpa Shukla, Susmita Sarangi, Dane A. Thompson, Seema G. Amin, Tea Tsaava, Saher Chaudhry, Sara P. Valentino, Hannah B. Hoffman, Catherine W. Imossi, Meghan E. Addorisio, Sergio I. Valdes-Ferrer, Sangeeta S. Chavan, Lionel Blanc, Christopher J. Czura, Kevin J. Tracey and Jared M. Huston ()
Additional contact information
Carlos E. Bravo-Iñiguez: The Feinstein Institutes for Medical Research at Northwell Health
Jason R. Fritz: The Feinstein Institutes for Medical Research at Northwell Health
Shilpa Shukla: The Feinstein Institutes for Medical Research at Northwell Health
Susmita Sarangi: The Feinstein Institutes for Medical Research at Northwell Health
Dane A. Thompson: The Feinstein Institutes for Medical Research at Northwell Health
Seema G. Amin: The Feinstein Institutes for Medical Research at Northwell Health
Tea Tsaava: The Feinstein Institutes for Medical Research at Northwell Health
Saher Chaudhry: The Feinstein Institutes for Medical Research at Northwell Health
Sara P. Valentino: The Feinstein Institutes for Medical Research at Northwell Health
Hannah B. Hoffman: Northwell Health
Catherine W. Imossi: The Feinstein Institutes for Medical Research at Northwell Health
Meghan E. Addorisio: The Feinstein Institutes for Medical Research at Northwell Health
Sergio I. Valdes-Ferrer: The Feinstein Institutes for Medical Research at Northwell Health
Sangeeta S. Chavan: The Feinstein Institutes for Medical Research at Northwell Health
Lionel Blanc: Elmezzi Graduate School of Molecular Medicine at Northwell Health
Christopher J. Czura: The Feinstein Institutes for Medical Research at Northwell Health
Kevin J. Tracey: The Feinstein Institutes for Medical Research at Northwell Health
Jared M. Huston: The Feinstein Institutes for Medical Research at Northwell Health

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract Deficiency of coagulation factor VIII in hemophilia A disrupts clotting and prolongs bleeding. While the current mainstay of therapy is infusion of factor VIII concentrates, inhibitor antibodies often render these ineffective. Because preclinical evidence shows electrical vagus nerve stimulation accelerates clotting to reduce hemorrhage without precipitating systemic thrombosis, we reasoned it might reduce bleeding in hemophilia A. Using two different male murine hemorrhage and thrombosis models, we show vagus nerve stimulation bypasses the factor VIII deficiency of hemophilia A to decrease bleeding and accelerate clotting. Vagus nerve stimulation targets acetylcholine-producing T lymphocytes in spleen and α7 nicotinic acetylcholine receptors (α7nAChR) on platelets to increase calcium uptake and enhance alpha granule release. Splenectomy or genetic deletion of T cells or α7nAChR abolishes vagal control of platelet activation, thrombus formation, and bleeding in male mice. Vagus nerve stimulation warrants clinical study as a therapy for coagulation disorders and surgical or traumatic bleeding.

Date: 2023
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DOI: 10.1038/s41467-023-38505-6

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