A novel type of macrothrombocytopenia associated with a defect in α2,3-sialylation

Am J Pathol. 2011 Oct;179(4):1969-77. doi: 10.1016/j.ajpath.2011.06.012. Epub 2011 Aug 22.


We describe a novel type of human thrombocytopenia characterized by the appearance of giant platelets and variable neutropenia. Searching for the molecular defect, we found that neutrophils had strongly reduced sialyl-Lewis X and increased Lewis X surface expression, pointing to a deficiency in sialylation. We show that the glycosylation defect is restricted to α2,3-sialylation and can be detected in platelets, neutrophils, and monocytes. Platelets exhibited a distorted structure of the open canalicular system, indicating defective platelet generation. Importantly, patient platelets, but not normal platelets, bound to the asialoglycoprotein receptor (ASGP-R), a liver cell-surface protein that removes desialylated thrombocytes from the circulation in mice. Taken together, this is the first type of human thrombocytopenia in which a specific defect of α2,3-sialylation and an induction of platelet binding to the liver ASGP-R could be detected.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asialoglycoprotein Receptor / metabolism
  • Blood Platelets / metabolism
  • Blood Platelets / pathology
  • Blood Platelets / ultrastructure
  • Child
  • Female
  • Granulocytes / metabolism
  • Humans
  • Interleukin-8 / metabolism
  • Liver / metabolism
  • Mice
  • Mutation / genetics
  • N-Acetylneuraminic Acid / metabolism*
  • Neutropenia / complications
  • Neutropenia / pathology
  • Nucleotide Transport Proteins / genetics
  • Oligosaccharides / metabolism*
  • Phenotype
  • Protein Binding
  • Selectins / metabolism
  • Sialyl Lewis X Antigen
  • Thrombocytopenia / complications
  • Thrombocytopenia / metabolism*
  • Thrombocytopenia / pathology*


  • Asialoglycoprotein Receptor
  • Interleukin-8
  • Nucleotide Transport Proteins
  • Oligosaccharides
  • SLC35A1 protein, human
  • Selectins
  • Sialyl Lewis X Antigen
  • N-Acetylneuraminic Acid