Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A

Nat Med. 2003 Aug;9(8):1020-5. doi: 10.1038/nm899. Epub 2003 Jul 13.


High plasma levels of soluble P-selectin are associated with thrombotic disorders and may predict future cardiovascular events. Mice with high levels of soluble P-selectin have more microparticles in their plasma than do normal mice. Here we show that chimeras of P-selectin and immunoglobulin (P-sel-Ig) induced formation of procoagulant microparticles in human blood through P-selectin glycoprotein ligand-1 (PSGL-1; encoded by the Psgl1 gene, officially known as Selpl). In addition, Psgl1-/- mice produced fewer microparticles after P-sel-Ig infusion and did not spontaneously increase their microparticle count in old age as do wild-type mice. Injected microparticles specifically bound to thrombi and thus could be involved in thrombin generation at sites of injury. Infusion of P-sel-Ig into hemophilia A mice produced a 20-fold increase over control immunoglobulin in microparticles containing tissue factor. This significantly improved the kinetics of fibrin formation in the hemophilia A mice and normalized their tail-bleeding time. P-sel-Ig treatment could become a new approach to sustained control of bleeding in hemophilia.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Blood Coagulation / physiology
  • Disease Models, Animal
  • Factor VIII / metabolism
  • Hemophilia A / metabolism
  • Hemophilia A / therapy*
  • Hemostasis / physiology*
  • Humans
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Knockout
  • Middle Aged
  • P-Selectin / genetics
  • P-Selectin / metabolism*
  • Phenotype
  • Recombinant Fusion Proteins / metabolism


  • Immunoglobulins
  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein
  • Recombinant Fusion Proteins
  • Factor VIII