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.

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.

• Authors: Trung C Nguyen, Yong Y Han, Joseph E Kiss, Mark W Hall, Andrea Cortese Hassett, Ron Jaffe, Richard A Orr, Janine Janosky, Joseph A Carcillo
• Journal: Critical care medicine (Crit Care Med) Vol. 36 Issue 10 Pg. 2878-87 (Oct 2008) ISSN: 1530-0293 [Electronic] United States
• PMID: 18828196 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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