title: Decreased activity of soluble thrombomodulin and plasma procoagulant phospholipids in childhood bone marrow transplantation with severe complications.
abstract: BACKGROUND
  Complications of bone marrow transplantation (BMT) are usually considered to be related to the secretion of inflammatory cytokines, which generate membrane microparticles rich in procoagulant phospholipids (PPL) from different cellular origins and release of endothelial proteins such as thrombomodulin (TM). The use of soluble TM quantified by ELISA (TM:Ag) as a marker of endothelial injury is complex in children since it is age-dependent.
  
  
  METHODS
  Using a functional assay which quantifies the activity of sTM activity (TMa), we performed a pilot study to analyze the ratio TMa/TM:Ag in a control group of 25 healthy children, 8 children with autologous and 16 children with allogeneic BMT. In this last group, 8 experienced BMT complications. In addition, we used a functional assay which quantifies PPL.
  
  
  RESULTS
  In healthy children the ratio TMa/TM:Ag was independent of age and stable in children with a favorable outcome but significantly (p<0.05) reduced by the use of antithymocyte globulin during the conditioning regimen, and regularly decreased in children with BMT complications. Surprisingly, low plasma PPL levels were associated with a poor outcome.
  
  
  CONCLUSIONS
  The ratio TMa/TM:Ag could constitute a marker of endothelium injury, and its follow-up could be of interest for an early discrimination of children with high risk of complications during allogeneic BMT. The decrease of PPL could be also another marker of a poor evolution and deserves further investigations.
authors.affiliation: Pediatric Haematology and Oncology & IHU, Rouen University Hospital, 1, rue de Germont, 76000, Rouen, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Schneider
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Dreden
authors.forename: Aurélie
authors.initials: A
authors.lastname: Rousseau
authors.forename: Aude
authors.initials: A
authors.lastname: Marie-Cardine
authors.forename: Estelle
authors.initials: E
authors.lastname: Houivet
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vannier
authors.forename: Marc
authors.initials: M
authors.lastname: Vasse
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D001779:Blood Coagulation Factors / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D010743:Phospholipids / Q000097:blood*; D018180:Thrombomodulin / Q000097:blood*
chemical_list: D015415:Biomarkers; D001779:Blood Coagulation Factors; D010743:Phospholipids; D018180:Thrombomodulin