title: Intensive plasma exchange increases a disintegrin and metalloprotease with thrombospondin motifs-13 activity and reverses organ dysfunction in children with thrombocytopenia-associated multiple organ failure.
abstract: BACKGROUND
  Thrombocytopenia-associated multiple organ failure (TAMOF) is a poorly understood syndrome in critically ill children. A disintegrin and metalloprotease with thrombospondin motifs (ADAMTS-13), formerly known as von Willebrand factor (VWF) cleaving protease, is decreased in adults with VWF-mediated thrombotic microangiopathy, and intensive plasma exchange (PEx) both replenishes ADAMTS-13 and improves outcome in these patients.
  
  
  OBJECTIVE
  To determine whether: 1) critically ill children with TAMOF syndrome have decreased ADAMTS-13 activity, 2) ADAMTS-13 activity correlates with platelet counts and VWF antigen, 3) the autopsies from patients who died with reduced ADAMTS-13 activity have VWF-rich microthrombi, and 4) intensive PEx will restore ADAMTS-13 activity and facilitate organ failure resolution.
  
  
  METHODS
  First study: observational. Second study: randomized control trial.
  
  
  METHODS
  Single center university pediatric intensive care unit.
  
  
  METHODS
  First study: thirty-seven consecutive children (17 males and 20 females; ages ranging from 9 days to 23 years) identified with > or = 2 organs dysfunction were enrolled. Seventy-six percent of these children had thrombocytopenia (platelet counts < 100,000/mm3). Five additional critically ill children without MOF were also enrolled. In the second study, children with severe TAMOF (platelet counts < 100,000/mm3 and > 3 organ failure) were randomized to PEx or standard therapy. Primary physicians and parents agreed to enrollment in 10 of the 20 eligible patients with ages ranging from 1 year to 18 years. Five patients received PEx and 5 patients received standard therapy.
  
  
  RESULTS
  First study: children with TAMOF (n = 28) had decreased ADAMTS-13 activity, but similar plasminogen activator inhibitor-1 activity and prothrombin time compared to children with MOF without thrombocytopenia (n = 9, p < 0.05). All non-survivors (n = 7) had TAMOF, reduced ADAMTS-13 activity, and VWF-rich microvascular thromboses at autopsy. In the second study, PEx (n = 5, median 12 days, 4-28 days) restored ADAMTS-13 activity and organ function, compared to standard therapy (n = 5, p < 0.05).
  
  
  CONCLUSIONS
  Children with TAMOF syndrome can have VWF-mediated thrombotic microangiopathy. Similar to adult experience, PEx can replenish ADAMTS-13 activity and reverse organ failure.
authors.affiliation: Section of Critical Care, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. tcnguyen@texaschildrenshospital.org
authors.forename: Trung C
authors.initials: TC
authors.lastname: Nguyen
authors.forename: Yong Y
authors.initials: YY
authors.lastname: Han
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Kiss
authors.forename: Mark W
authors.initials: MW
authors.lastname: Hall
authors.forename: Andrea Cortese
authors.initials: AC
authors.lastname: Hassett
authors.forename: Ron
authors.initials: R
authors.lastname: Jaffe
authors.forename: Richard A
authors.initials: RA
authors.lastname: Orr
authors.forename: Janine
authors.initials: J
authors.lastname: Janosky
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Carcillo
mesh_terms: D051722:ADAM Proteins / Q000097:blood* / Q000187:drug effects; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness / Q000401:mortality / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D009102:Multiple Organ Failure / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy*; D010951:Plasma Exchange / Q000379:methods*; D012016:Reference Values; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D015996:Survival Rate; D013921:Thrombocytopenia / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human