Format

Send to:

Choose Destination
See comment in PubMed Commons below
Blood. 2011 Apr 14;117(15):4125-33. doi: 10.1182/blood-2010-08-301366. Epub 2011 Feb 8.

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

Author information

  • 1Wolfson Neuroscience Laboratories, Faculty of Medicine, Imperial College, London, UK. f.gavins@imperial.ac.uk

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 β(s) mice via a neutrophil-dependent mechanism that is associated with an increased formation of and enhanced platelet sensitivity to thrombin.

PMID:
21304105
[PubMed - indexed for MEDLINE]
PMCID:
PMC3087535
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk