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.
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.
First study: Observational.
Randomized control trial.
Single center university pediatric intensive care unit.
First study: thirty-seven consecutive children (17 males and 20 females; ages ranging from 9 days to 23 years) identified with ≥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.
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).
Children with TAMOF syndrome can have VWF-mediated thrombotic microangiopathy. Similar to adult experience, PEx can replenish ADAMTS-13 activity and reverse organ failure.
From the Section of Critical Care (TCN), Department of Pediatrics, Baylor College of Medicine, Houston, TX; Division of Critical Care (YYH), Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI; Division of Hematology/Oncology and the Department of Medicine (JEK), University of Pittsburgh School of Medicine, Pittsburgh, PA; The Institute for Transfusion Medicine (JEK, ACH), Pittsburgh, PA; Division of Critical Care (MWH), Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH; Department of Family Medicine and Epidemiology (JJ), University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA; Departments of Pathology (RJ), Critical Care Medicine and Pediatrics (RAO, JAC), University of Pittsburgh School of Medicine, Pittsburgh, PA.
Supported in part by grant NICHD/NIH 5T32-HD40686 (TCN, YYH), AHA Beginning grant-in-aid (TCN), Department of Anesthesiology, University of Pittsburgh School of Medicine Charles Research Fellowship (MWH), and NCRR 3M01RR0056GCRC (JAC).
The authors have not disclosed any potential conflicts of interest.
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