Lactadherin promotes microvesicle clearance to prevent coagulopathy and improves survival of severe TBI mice

Blood. 2018 Feb 1;131(5):563-572. doi: 10.1182/blood-2017-08-801738. Epub 2017 Nov 21.


Coagulopathy is common in patients with traumatic brain injury (TBI) and predicts poor clinical outcomes. We have shown that brain-derived extracellular microvesicles, including extracellular mitochondria, play a key role in the development of TBI-induced coagulopathy. Here, we further show in mouse models that the apoptotic cell-scavenging factor lactadherin, given at a single dose of 400 μg/kg 30 minutes before (preconditioning) or 30 minutes after cerebral fluid percussion injury, prevented coagulopathy as defined by clotting time, fibrinolysis, intravascular fibrin deposition, and microvascular bleeding of the lungs. Lactadherin also reduced cerebral edema, improved neurological function, and increased survival. It achieved these protective effects by enhancing the clearance of circulating microvesicles through phosphatidylserine-mediated phagocytosis. Together, these results identify the scavenging system for apoptotic cells as a potential therapeutic target to prevent TBI-induced coagulopathy and improve the outcome of TBI.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, Surface / genetics
  • Antigens, Surface / pharmacology
  • Antigens, Surface / therapeutic use*
  • Blood Coagulation Disorders / genetics
  • Blood Coagulation Disorders / mortality
  • Blood Coagulation Disorders / prevention & control*
  • Brain Injuries, Traumatic / drug therapy*
  • Brain Injuries, Traumatic / genetics*
  • Brain Injuries, Traumatic / mortality
  • Brain Injuries, Traumatic / pathology
  • Cell-Derived Microparticles / drug effects*
  • Cell-Derived Microparticles / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Milk Proteins / genetics
  • Milk Proteins / pharmacology
  • Milk Proteins / therapeutic use*
  • Phagocytosis / drug effects*
  • Phagocytosis / genetics
  • Survival
  • Trauma Severity Indices


  • Antigens, Surface
  • Mfge8 protein, mouse
  • Milk Proteins