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Therapeutic Plasma Exchange in Children With Thrombocytopenia-Associated Multiple Organ Failure

The Thrombocytopenia-Associated Multiple Organ Failure Network Prospective Experience

Fortenberry, James D., MD, MCCM1; Nguyen, Trung, MD2; Grunwell, Jocelyn R., MD, PhD1; Aneja, Rajesh K., MD3; Wheeler, Derek, MD4; Hall, Mark, MD5; Fleming, Geoffrey, MD6; Tarrago, Rod, MD7; Buttram, Sandra, MD8; Dalton, Heidi, MD9; Han, Yong, MD10; Easley, Kirk A., MS11; Knezevic, Andrea, MS11; Dai, Tian, PhD11; Paden, Matthew, MD1; Carcillo, Joseph A., MD3 for the Thrombocytopenia-Associated Multiple Organ Failure (TAMOF) Network Study Group

doi: 10.1097/CCM.0000000000003559
Online Clinical Investigations
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Objective: The objective was to compare the resolution of organ dysfunction, 28-day mortality, and biochemical markers in children with thrombocytopenia-associated multiple organ failure who received therapeutic plasma exchange versus no therapeutic plasma exchange.

Design: Observational longitudinal cohort study.

Setting: Nine U.S. PICUs.

Patients: Eighty-one children with sepsis-induced thrombocytopenia-associated multiple organ failure.

Interventions: Therapeutic plasma exchange.

Measurements and Main Results: Adjusted relative risk for 28-day mortality was modeled using standard multivariate regression with propensity score weighting to reduce covariate confounding. Change from baseline Pediatric Logistic Organ Dysfunction scores between therapeutic plasma exchange and no therapeutic plasma exchange differed in temporal pattern during the first week (p = 0.009). By day 4, mean Pediatric Logistic Organ Dysfunction score declined by 7.9 points (95% CI, –10.8 to –5.1) in the therapeutic plasma exchange–treated group compared with no change with no therapeutic plasma exchange. Use of therapeutic plasma exchange was associated with reduced 28-day mortality by multivariate analysis (adjusted relative risk, 0.45; 95% CI, 0.23–0.90; p = 0.02) and by propensity score weighting (adjusted relative risk, 0.46; 95% CI, 0.22–0.97; p = 0.04).

Conclusions: Therapeutic plasma exchange use in thrombocytopenia-associated multiple organ failure was associated with a decrease in organ dysfunction. After accounting for several risk factors, 28-day all-cause mortality was lower in children treated with therapeutic plasma exchange compared with those receiving no therapeutic plasma exchange. A multicenter randomized clinical trial is necessary to determine a causal relationship.

1Department of Pediatrics, Emory University School of Medicine, Children’s Healthcare of Atlanta at Egleston, Atlanta, GA.

2Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX.

3Department of Anesthesia and Critical Care Medicine, University of Pittsburgh School of Medicine, Children’s Hospital of Pittsburgh, Pittsburgh, PA.

4Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati Children’s Medical Center, Cincinnati, OH.

5Department of Pediatrics, The Ohio State University School of Medicine, Nationwide Children’s Hospital, Columbus, OH.

6Department of Pediatrics, Vanderbilt University School of Medicine, Monroe Carell Jr Children’s Hospital, Nashville, TN.

7Department of Pediatric Intensive Care, Children’s Hospital and Clinics of Minnesota, Minneapolis, MN.

8Department of Pediatric Critical Care, Phoenix Children’s Hospital, Phoenix, AZ.

9Department of Pediatric Critical Care Medicine, Children’s National Medical Center, Washington, DC.

10Department of Pediatrics, University of Michigan School of Medicine, C.S. Mott Children’s Hospital, Ann Arbor, MI.

11Department of Biostatistics and Bioinformatics, Emory University, Rollins School of Public Health, Atlanta, GA.

Drs. Fortenberry, Nguyen, and Carcillo conceived and designed the study. Drs. Fortenberry and Nguyen drafted the initial article. Mr. Easley, Ms. Knezevic, and Dr. Dai conducted statistical analyses, aided with data interpretation, and edited the article. Dr. Grunwell interpreted the data, and drafted and provided critical revision of the article. Drs. Aneja, Wheeler, Hall¸ Fleming, Tarrago, Buttram, Dalton, Han, and Paden recruited patients, and acquired data. All authors read and provided final approval of the version submitted for publication.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported, in part, by a grant from The Children’s Miracle Network. Dr. Grunwell is supported by the Atlanta Pediatric Scholars Program grant K12HD072245. Dr. Carcillo received funding through the National Institutes of Health GM108618.

Dr. Nguyen’s institution received funding from the National Institutes of Health (NIH). Drs. Nguyen, Grunwell, and Carcillo received support for article research from the NIH. Dr. Grunwell’s institution received funding from the Children’s Miracle Network, and she is supported by the Atlanta Pediatric Scholars Program grant K12HD072245. Dr. Aneja received funding from UptoDate. Drs. Grunwell, Wheeler, and Dalton disclosed off-label product use of therapeutic plasma exchange for sepsis-induced thrombocytopenia–associated multiple organ failure in children. Dr. Hall received funding from Bristol Myers-Squibb (advisory board) and La Jolla Pharmaceuticals (consultant). Dr. Fleming disclosed that he is a member of the American Board of Medical Specialties Vision Commission. Dr. Dalton received funding fromInnovative ECMO Concepts (consultant). Dr. Dai was paid as a graduate research assistant to work on clinical research studies, but was not paid for her analysis work for the Thrombocytopenia-Associated Multiple Organ Failure study. Dr. Paden received funding from expert witness work, and he disclosed off-label product use of apheresis for sepsis. Dr. Carcillo received funding through the NIH GM108618 and the National Institute of General Medical Sciences. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Current address for Dr. Tarrago: Seattle Children’s Hospital, Seattle, WA; Dr. Han: Children’s Mercy, Kansas City, MO; Dr. Knezevic: Memorial Sloan Kettering Cancer Center, New York City, NY; Dr. Dai: Amgen, Thousand Oaks, CA.

For information regarding this article, E-mail: james.fortenberry@choa.org

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