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

Crit Care Med. 2008 Oct;36(10):2878-87. doi: 10.1097/ccm.0b013e318186aa49.


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.

Objectives: 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.

Design: First study: observational. Second study: randomized control trial.

Setting: Single center university pediatric intensive care unit.

Patients: 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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / blood*
  • ADAM Proteins / drug effects
  • ADAMTS13 Protein
  • Adolescent
  • Adult
  • Age Factors
  • Analysis of Variance
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Critical Illness / mortality
  • Critical Illness / therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Infant, Newborn
  • Logistic Models
  • Male
  • Multiple Organ Failure / blood
  • Multiple Organ Failure / complications
  • Multiple Organ Failure / mortality
  • Multiple Organ Failure / therapy*
  • Plasma Exchange / methods*
  • Reference Values
  • Risk Assessment
  • Statistics, Nonparametric
  • Survival Rate
  • Thrombocytopenia / blood
  • Thrombocytopenia / complications
  • Thrombocytopenia / mortality
  • Thrombocytopenia / therapy*
  • Treatment Outcome


  • Biomarkers
  • ADAM Proteins
  • ADAMTS13 Protein
  • ADAMTS13 protein, human