Mechanisms of enhanced thrombus formation in cerebral microvessels of mice expressing hemoglobin-S

Felicity N E Gavins, Janice Russell, Elena L. Senchenkova, Lidiana De Almeida Paula, Amílcar S. Damazo, Charles T. Esmon, Daniel Kirchhofer, Robert P. Hebbel, D. Neil Granger

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

The microvasculature assumes an inflammatory and procoagulant state in a variety of different diseases, including sickle cell disease (SCD), which may contribute to the high incidence of ischemic stroke in these patients. This study provides evidence for accelerated thrombus formation in arterioles and venules in the cerebral vasculature of mice that express hemoglobin-S (β s mice). Enhanced microvascular thrombosis in β s mice was blunted by immunologic or genetic interventions that target tissue factor, endothelial protein C receptor, activated protein C, or thrombin. Platelets from β s mice also exhibited enhanced aggregation velocity after stimulation with thrombin but not ADP. Neutropenia also protected against the enhanced thrombosis response in β s mice. These results indicate that the cerebral microvasculature is rendered vulnerable to thrombus formation in |5s mice via a neutrophil-dependent mechanism that is associated with an increased formation of and enhanced platelet sensitivity to thrombin.

Original languageEnglish (US)
Pages (from-to)4125-4133
Number of pages9
JournalBlood
Volume117
Issue number15
DOIs
StatePublished - Apr 14 2011

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