Life-Threatening Bleeding in Children: A Prospective Observational Study

Julie C Leonard¹, Cassandra D Josephson², James F Luther³, Stephen R Wisniewski³, Christine Allen⁴, Fabrizio Chiusolo⁵, Adrienne L Davis⁶, Robert A Finkelstein⁷, Julie C Fitzgerald⁸, Barbara A Gaines⁹, Susan M Goobie¹⁰, Sheila J Hanson¹¹, Hilary A Hewes¹², Laurie H Johnson¹³, Mark O McCollum^{14

15}, Jennifer A Muszynski¹⁶, Alison B Nair¹⁷, Robert B Rosenberg¹⁸, Thomas M Rouse¹⁹, Athina Sikavitsas²⁰, Marcy N Singleton²¹, Marie E Steiner²², Jeffrey S Upperman^{23

24}, Adam M Vogel²⁵, Hale Wills^{26

27}, Margaret K Winkler^{28

29}, Philip C Spinella³⁰

Affiliations

¹ Division of Emergency Medicine, Department of Pediatrics, The Ohio State University College of Medicine, Nationwide Children's Hospital, Columbus, OH.
² Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA.
³ Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.
⁴ Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Oklahoma College of Medicine, The Children's Hospital at University of Oklahoma Health Sciences Center, Oklahoma City, OK.
⁵ Department of Anesthesia and Critical Care, ARCO Rome, Bambino Gesù Children's Hospital, Rome, Italy.
⁶ Division of Pediatric Emergency Medicine, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada.
⁷ Division of Pediatric Emergency Medicine, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY.
⁸ Department of Anesthesiology and Critical Care Medicine, Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Children's Hospital of Philadelphia, Philadelphia, PA.
⁹ Division of Pediatric Surgery, Department of Surgery, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA.
¹⁰ Department of Anesthesiology, Critical Care and Pain Medicine, Harvard Medical School, Boston Children's Hospital, Boston, MA.
¹¹ Department of Pediatrics, Critical Care Section, Medical College of Wisconsin, Children's Wisconsin, Milwaukee, WI.
¹² Division of Pediatric Emergency Medicine, Department of Pediatrics, University of Utah School of Medicine, Primary Children's Medical Center, Salt Lake City, UT.
¹³ Division of Emergency Medicine, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
¹⁴ Orange Park Medical Center, Orange Park, FL.
¹⁵ Division of Pediatric Surgery, Akron Children's Hospital, Akron, OH.
¹⁶ Division of Critical Care Medicine, Department of Pediatrics, The Ohio State University College of Medicine, Nationwide Children's Hospital, Columbus, OH.
¹⁷ Division of Neonatology, Department of Pediatrics, University of California San Francisco Pritzker School of Medicine, University of California San Francisco Medical Center Parnassus, San Francisco, CA.
¹⁸ Division of Pediatric Critical Care Medicine, Department of Child Health, University of Arizona College of Medicine, Phoenix Children's Hospital, Phoenix, AZ.
¹⁹ Department of Surgery, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN.
²⁰ Department of Emergency Medicine, University of Michigan, C.S. Mott Children's Hospital, Ann Arbor, MI.
²¹ Department of Pediatrics, Dartmouth Hitchcock Medical Center, Children's Hospital at Dartmouth, Lebanon, NH.
²² Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Minnesota Medical School, Department of Pediatric Critical Care Medicine, University of Minnesota Masonic Children's Hospital, Minneapolis, MN.
²³ Department of Pediatric Surgery, Vanderbilt University College of Medicine, Monroe Carell Jr Children's Hospital Nashville, TN.
²⁴ Keck School of Medicine of University of Southern California, Children's Hospital Los Angeles, Los Angeles, CA.
²⁵ Department of Pediatric Surgery, Baylor College of Medicine, Texas Children's Hospital, Houston, TX.
²⁶ Department of Surgery, Texas A&M University College of Medicine, McLane Children's Hospital, Temple, TX.
²⁷ Division of Pediatric Surgery, Alpert Medical School of Brown University, Hasbro Children's Hospital, Providence, RI.
²⁸ Southlake Pediatrics, Birmingham, AL.
²⁹ Department of Pediatrics, University of Alabama School of Medicine, Children's of Alabama, Birmingham, AL.
³⁰ Division of Critical Care, Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis Children's Hospital, St. Louis, MO.

PMID: 33990098
PMCID: PMC8516672
DOI: 10.1097/CCM.0000000000005075

Observational Study

Life-Threatening Bleeding in Children: A Prospective Observational Study

Julie C Leonard et al. Crit Care Med. 2021.

. 2021 Nov 1;49(11):1943-1954.

doi: 10.1097/CCM.0000000000005075.

Authors

Affiliations

¹ Division of Emergency Medicine, Department of Pediatrics, The Ohio State University College of Medicine, Nationwide Children's Hospital, Columbus, OH.
² Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA.
³ Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.
⁴ Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Oklahoma College of Medicine, The Children's Hospital at University of Oklahoma Health Sciences Center, Oklahoma City, OK.
⁵ Department of Anesthesia and Critical Care, ARCO Rome, Bambino Gesù Children's Hospital, Rome, Italy.
⁶ Division of Pediatric Emergency Medicine, University of Toronto, Hospital for Sick Children, Toronto, ON, Canada.
⁷ Division of Pediatric Emergency Medicine, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY.
⁸ Department of Anesthesiology and Critical Care Medicine, Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Children's Hospital of Philadelphia, Philadelphia, PA.
⁹ Division of Pediatric Surgery, Department of Surgery, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA.
¹⁰ Department of Anesthesiology, Critical Care and Pain Medicine, Harvard Medical School, Boston Children's Hospital, Boston, MA.
¹¹ Department of Pediatrics, Critical Care Section, Medical College of Wisconsin, Children's Wisconsin, Milwaukee, WI.
¹² Division of Pediatric Emergency Medicine, Department of Pediatrics, University of Utah School of Medicine, Primary Children's Medical Center, Salt Lake City, UT.
¹³ Division of Emergency Medicine, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
¹⁴ Orange Park Medical Center, Orange Park, FL.
¹⁵ Division of Pediatric Surgery, Akron Children's Hospital, Akron, OH.
¹⁶ Division of Critical Care Medicine, Department of Pediatrics, The Ohio State University College of Medicine, Nationwide Children's Hospital, Columbus, OH.
¹⁷ Division of Neonatology, Department of Pediatrics, University of California San Francisco Pritzker School of Medicine, University of California San Francisco Medical Center Parnassus, San Francisco, CA.
¹⁸ Division of Pediatric Critical Care Medicine, Department of Child Health, University of Arizona College of Medicine, Phoenix Children's Hospital, Phoenix, AZ.
¹⁹ Department of Surgery, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN.
²⁰ Department of Emergency Medicine, University of Michigan, C.S. Mott Children's Hospital, Ann Arbor, MI.
²¹ Department of Pediatrics, Dartmouth Hitchcock Medical Center, Children's Hospital at Dartmouth, Lebanon, NH.
²² Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Minnesota Medical School, Department of Pediatric Critical Care Medicine, University of Minnesota Masonic Children's Hospital, Minneapolis, MN.
²³ Department of Pediatric Surgery, Vanderbilt University College of Medicine, Monroe Carell Jr Children's Hospital Nashville, TN.
²⁴ Keck School of Medicine of University of Southern California, Children's Hospital Los Angeles, Los Angeles, CA.
²⁵ Department of Pediatric Surgery, Baylor College of Medicine, Texas Children's Hospital, Houston, TX.
²⁶ Department of Surgery, Texas A&M University College of Medicine, McLane Children's Hospital, Temple, TX.
²⁷ Division of Pediatric Surgery, Alpert Medical School of Brown University, Hasbro Children's Hospital, Providence, RI.
²⁸ Southlake Pediatrics, Birmingham, AL.
²⁹ Department of Pediatrics, University of Alabama School of Medicine, Children's of Alabama, Birmingham, AL.
³⁰ Division of Critical Care, Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis Children's Hospital, St. Louis, MO.

PMID: 33990098
PMCID: PMC8516672
DOI: 10.1097/CCM.0000000000005075

Abstract

Objectives: The purpose of our study was to describe children with life-threatening bleeding.

Design: We conducted a prospective observational study of children with life-threatening bleeding events.

Setting: Twenty-four childrens hospitals in the United States, Canada, and Italy participated.

Subjects: Children 0-17 years old who received greater than 40 mL/kg total blood products over 6 hours or were transfused under massive transfusion protocol were included.

Interventions: Children were compared according bleeding etiology: trauma, operative, or medical.

Measurements and main results: Patient characteristics, therapies administered, and clinical outcomes were analyzed. Among 449 enrolled children, 55.0% were male, and the median age was 7.3 years. Bleeding etiology was 46.1% trauma, 34.1% operative, and 19.8% medical. Prior to the life-threatening bleeding event, most had age-adjusted hypotension (61.2%), and 25% were hypothermic. Children with medical bleeding had higher median Pediatric Risk of Mortality scores (18) compared with children with trauma (11) and operative bleeding (12). Median Glasgow Coma Scale scores were lower for children with trauma (3) compared with operative (14) or medical bleeding (10.5). Median time from bleeding onset to first transfusion was 8 minutes for RBCs, 34 minutes for plasma, and 42 minutes for platelets. Postevent acute respiratory distress syndrome (20.3%) and acute kidney injury (18.5%) were common. Twenty-eight-day mortality was 37.5% and higher among children with medical bleeding (65.2%) compared with trauma (36.1%) and operative (23.8%). There were 82 hemorrhage deaths; 65.8% occurred by 6 hours and 86.5% by 24 hours.

Conclusions: Patient characteristics and outcomes among children with life-threatening bleeding varied by cause of bleeding. Mortality was high, and death from hemorrhage in this population occurred rapidly.

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Conflict of interest statement

Drs. Leonard’s, Nair’s, and Spinella’s institutions received funding from the National Heart, Lung, and Blood Institute (NHLBI). Drs. Leonard, Josephson, Davis, Fitzgerald, Muszynski, Steiner, Wills, and Spinella received support for article research from the National Institutes of Health (NIH). Dr. Josephson received funding from Immucor, LLC, and Octapharma. Drs. Allen’s, Hewes’s, Rouse’s, and Steiner’s institutions received funding from the NIH grant administered by Washington University in St. Louis. Drs. Davis’, Nair’s, and Steiner’s institutions received funding from an NIH Exploratory/Developmental Research Grant Award (R21). Dr. Finkelstein received funding from Trauma In Kids Course via the Royal College of Physicians and Surgeons of Canada and the Pediatric Trauma Society from New York Presbyterian Weill Cornell, Carilion Clinic, and Texas Children’s Hospital, Society of Critical Care Medicine as a Faculty Instructor, Giblin, Combs, Schwartz, Cunningham, & Scarpa, LLC, Aaronson Rappaport Feinstein & Deutsch, LLP, and Ruprecht Hart Weeks & Ricciardulli, LLP; he disclosed that his wife has stock in Pfizer and Proctor & Gamble. Drs. Fitzgerald’s, Muszynski’s, and Spinella’s institutions received funding from the NIH. Drs. Johnson’s and Wills’ institutions institution received funding from Massive Transfusion Epidemiology and Outcomes in Children Study, 5R21HL128863-02 NHLBI. The remaining authors have disclosed that they do not have any potential conflicts of interest.

References

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Life-Threatening Bleeding in Children: A Prospective Observational Study

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Life-Threatening Bleeding in Children: A Prospective Observational Study

Authors

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Abstract

Conflict of interest statement

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