Observational Study

. 2025 Jul 1;26(7):e889-e899.

doi: 10.1097/PCC.0000000000003751. Epub 2025 Apr 25.

Massive Bleeding in Children With Cancer or Hematopoietic Cell Transplant: International, Multicenter Retrospective Study, 2017-2021

Marianne E Nellis¹, Marie E Steiner², Saleh Bhar³, Jennifer McArthur⁴, Ali McMichael⁵, April L Rahrig⁶, Christine Leeper⁷, Salvatore Perdichizzi⁸, Fabrizio Chiusolo⁸, Jacob Shamash¹, Nora Bruns⁹, Hilary Schreiber¹⁰, Matthew P Sharron¹¹, Laura Butragueño-Laiseca¹², James S Killinger¹³, Charlene P Pringle¹⁴, Samantha M Koenig¹⁵, Cassandra Josephson^{16

17}, David Crawford¹⁸, Briana L Scott¹⁹, Kenneth E Remy²⁰, Christine Puthawala²¹, Philip C Spinella²²; Massive Transfusion In Children (MATIC)-Cancer Investigators, and in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet) subgroup and the Hematopoietic Cell Transplant subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network

Collaborators, Affiliations

Collaborators

Massive Transfusion In Children (MATIC)-Cancer Investigators, and in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet) subgroup and the Hematopoietic Cell Transplant subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network:
Amir Navaei²³, Matteo DiNardo²⁴, Luigi Dei Giudici²⁴, Courtney M Rowan²⁵, Katarina Barukcic²⁶, Michael Schündeln²⁶, Asumthia Jeyapalan²⁷, Maria Guedes²⁸, Yvonne Avent²⁹, Michael Frett²⁹, Saad Ghafoor²⁹, Rebekah Lassiter²⁹, Yan Zheng²⁹, Robert T Russell³⁰, Nikhila Juluri³¹, Rajashri Rasal³¹, Oliver Karam³², Erin Kreml³³, Robert DeSimone³⁴

Affiliations

¹ Division of Pediatric Critical Care, Department of Pediatrics, Weill Cornell Medicine, New York, NY.
² Divisions of Hematology and Critical Care, Department of Pediatrics, University of Minnesota, Minneapolis, MN.
³ Pediatric Critical Care Medicine and Hematology Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
⁴ Department of Pediatric Critical Care Medicine, St Jude Children's Research Hospital, Memphis, TN.
⁵ Phoenix Children's, Division of Pediatric Critical Care, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ.
⁶ Department of Pediatrics, Division of Hematology/Oncology/Stem Cell Transplant, Indiana University School of Medicine, Indianapolis, IN.
⁷ Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.
⁸ Anesthesia and Critical Care Medicine, Department of Pediatric Critical Care, Bambino Gesù Children's Hospital, Rome, Italy.
⁹ Department of Pediatrics I, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
¹⁰ Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI.
¹¹ Pediatric Critical Care Medicine, Department of Pediatrics, Children's National Hospital/George Washington University School of Medicine, Washington, DC.
¹² Pediatric Intensive Care Unit, Department of Pediatric Critical Care, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
¹³ Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
¹⁴ Department of Pediatrics, Critical Care Medicine, University of Florida, Gainesville, FL.
¹⁵ Department of Surgery, Division of Pediatric Surgery, University of Alabama at Birmingham, Children's of Alabama, Birmingham, AL.
¹⁶ Departments of Oncology, Pediatrics, and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.
¹⁷ Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St. Petersburg, FL.
¹⁸ Department of Pediatrics, Division of Hematology and Oncology, University of Miami Miller School of Medicine, Miami, FL.
¹⁹ Division of Critical Care Medicine, University of Rochester Medical Center, Rochester, NY.
²⁰ Departments of Internal Medicine and Pediatrics, Case Western University School of Medicine, University Hospitals of Cleveland, Cleveland, OH.
²¹ Pediatric Critical Care Medicine, Department of Pediatrics, Yale School of Medicine, New Haven, CT.
²² Trauma and Transfusion Medicine Research Center, Department of Surgery, University of Pittsburgh, Pittsburgh, PA.
²³ (Baylor College of Medicine, Houston, TX).
²⁴ (Bambino Gesù Children's Hospital, Rome, Italy).
²⁵ (Indiana University School of Medicine, Indianapolis, IN).
²⁶ (University Hospital Essen, Essen, Germany).
²⁷ (University of Miami, Coral Gables, FL).
²⁸ (University of Florida, Gainesville, FL).
²⁹ (St Jude Children's Research Hospital, Memphis, TN).
³⁰ (University of Alabama at Birmingham, Birmingham, AL).
³¹ (Case Western Reserve University, Cleveland, OH).
³² (Yale University, New Haven, CT).
³³ (Phoenix Children's, Phoenix, AZ).
³⁴ (Weill Cornell Medicine, New York, NY).

PMID: 40277427
PMCID: PMC12221796 (available on 2026-04-25)
DOI: 10.1097/PCC.0000000000003751

Observational Study

Massive Bleeding in Children With Cancer or Hematopoietic Cell Transplant: International, Multicenter Retrospective Study, 2017-2021

Marianne E Nellis et al. Pediatr Crit Care Med. 2025.

. 2025 Jul 1;26(7):e889-e899.

doi: 10.1097/PCC.0000000000003751. Epub 2025 Apr 25.

Authors

Collaborators

Massive Transfusion In Children (MATIC)-Cancer Investigators, and in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet) subgroup and the Hematopoietic Cell Transplant subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network:
Amir Navaei²³, Matteo DiNardo²⁴, Luigi Dei Giudici²⁴, Courtney M Rowan²⁵, Katarina Barukcic²⁶, Michael Schündeln²⁶, Asumthia Jeyapalan²⁷, Maria Guedes²⁸, Yvonne Avent²⁹, Michael Frett²⁹, Saad Ghafoor²⁹, Rebekah Lassiter²⁹, Yan Zheng²⁹, Robert T Russell³⁰, Nikhila Juluri³¹, Rajashri Rasal³¹, Oliver Karam³², Erin Kreml³³, Robert DeSimone³⁴

Affiliations

¹ Division of Pediatric Critical Care, Department of Pediatrics, Weill Cornell Medicine, New York, NY.
² Divisions of Hematology and Critical Care, Department of Pediatrics, University of Minnesota, Minneapolis, MN.
³ Pediatric Critical Care Medicine and Hematology Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
⁴ Department of Pediatric Critical Care Medicine, St Jude Children's Research Hospital, Memphis, TN.
⁵ Phoenix Children's, Division of Pediatric Critical Care, Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ.
⁶ Department of Pediatrics, Division of Hematology/Oncology/Stem Cell Transplant, Indiana University School of Medicine, Indianapolis, IN.
⁷ Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA.
⁸ Anesthesia and Critical Care Medicine, Department of Pediatric Critical Care, Bambino Gesù Children's Hospital, Rome, Italy.
⁹ Department of Pediatrics I, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
¹⁰ Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI.
¹¹ Pediatric Critical Care Medicine, Department of Pediatrics, Children's National Hospital/George Washington University School of Medicine, Washington, DC.
¹² Pediatric Intensive Care Unit, Department of Pediatric Critical Care, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
¹³ Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
¹⁴ Department of Pediatrics, Critical Care Medicine, University of Florida, Gainesville, FL.
¹⁵ Department of Surgery, Division of Pediatric Surgery, University of Alabama at Birmingham, Children's of Alabama, Birmingham, AL.
¹⁶ Departments of Oncology, Pediatrics, and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.
¹⁷ Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St. Petersburg, FL.
¹⁸ Department of Pediatrics, Division of Hematology and Oncology, University of Miami Miller School of Medicine, Miami, FL.
¹⁹ Division of Critical Care Medicine, University of Rochester Medical Center, Rochester, NY.
²⁰ Departments of Internal Medicine and Pediatrics, Case Western University School of Medicine, University Hospitals of Cleveland, Cleveland, OH.
²¹ Pediatric Critical Care Medicine, Department of Pediatrics, Yale School of Medicine, New Haven, CT.
²² Trauma and Transfusion Medicine Research Center, Department of Surgery, University of Pittsburgh, Pittsburgh, PA.
²³ (Baylor College of Medicine, Houston, TX).
²⁴ (Bambino Gesù Children's Hospital, Rome, Italy).
²⁵ (Indiana University School of Medicine, Indianapolis, IN).
²⁶ (University Hospital Essen, Essen, Germany).
²⁷ (University of Miami, Coral Gables, FL).
²⁸ (University of Florida, Gainesville, FL).
²⁹ (St Jude Children's Research Hospital, Memphis, TN).
³⁰ (University of Alabama at Birmingham, Birmingham, AL).
³¹ (Case Western Reserve University, Cleveland, OH).
³² (Yale University, New Haven, CT).
³³ (Phoenix Children's, Phoenix, AZ).
³⁴ (Weill Cornell Medicine, New York, NY).

PMID: 40277427
PMCID: PMC12221796 (available on 2026-04-25)
DOI: 10.1097/PCC.0000000000003751

Abstract

Objectives: To characterize the epidemiology and management of massive bleeding events in children with cancer and/or hematopoietic cell transplant (HCT).

Design: Multicenter, retrospective cohort study.

Setting: Nineteen pediatric hospitals in Europe and United States.

Subjects: Children ages 0-21 years old with malignancy and/or HCT and massive bleeding admitted from January 1, 2017, to December 31, 2021.

Interventions: None.

Measurements and main results: Demographics, oncologic history, laboratory values, interventions, and PICU outcomes were collected. One hundred fifty-two bleeding episodes from 135 patients were analyzed. The median (interquartile range [IQR]) age was 7 years (2-14 yr). Forty-three percent (58/135) were female sex. Nineteen percent of children (26/135) had death attributable to hemorrhage. Forty percent had solid tumors and one-third had undergone at least one HCT. The majority of bleeding events occurred in the PICU (81/152, 53%). The median (IQR) platelet count at time of bleeding was 52 × 10 9 /L (24-115 × 10 9 /L), prothrombin time 18.5 seconds (15.2-24.8 s), activated partial thromboplastin time 42.2 seconds (33.2-56.0 s), and international normalized ratio 1.51 (1.21-2.11). To treat these bleeding events, 99% (148/152) of the time children received RBC transfusions, 84% (126/152) of the time plasma transfusions, 88% (132/152) of the time platelet transfusions, and less than one-fifth hemostatic medications. Half (77/152, 52%) of the time the children received high plasma ratios and half (73/152, 49%) received high platelet ratios. Pulmonary bleeding, oral/nasal bleeding, and receipt of prothrombin complex concentrate were each associated with greater odds of death attributed to hemorrhage: odds ratio (95% CI), respectively: 5.44 (2.250-13.171; p < 0.001); 3.30 (1.20-9.09; p = 0.021); and 3.24 (1.18-8.93; p = 0.023).

Conclusions: Children with malignancy and/or HCT have a high mortality rate from hemorrhage despite being hospitalized at the time of their bleeding event. The majority of children received balanced resuscitation. Definitive trials are needed to determine optimal hemostatic resuscitation practice in this population.

Keywords: bleeding; cancer; children; critical illness; hematopoietic cell transplant; hemorrhage.

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Conflict of interest statement

Drs. Nellis and Puthawala received support for article research from the National Institutes of Health (NIH). Dr. Steiner received funding from the NIH and Department of Defense; she disclosed off-label use of recombinant factor 7a; and she has a teaching contract with MedTronic and receives honoraria from National Heart, Lung, and Blood Institute as Data Safety Monitoring Board Chair for Pumps for Kids, Infants and Neonates (PumpKIN). Dr. Josephson received funding from Westat. Dr. Spinella is a consultant for Cerus, on the scientific advisory board for Octapharma and Haima, and Chief Medical Officer of KaloCyte. The remaining authors have disclosed that they do not have any potential conflicts of interest.

References

1. Leonard JC, Josephson CD, Luther JF, et al. Life-Threatening Bleeding in Children: A Prospective Observational Study. Crit Care Med 2021; 49:1943–1954. - PMC - PubMed
1. Karam O, Russell RT, Stricker P, et al. Recommendations on RBC Transfusion in Critically Ill Children With Nonlife-Threatening Bleeding or Hemorrhagic Shock From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. Pediatr Crit Care Med 2018;19:S127–s132. - PMC - PubMed
1. Russell R, Bauer DF, Goobie SM, et al. Plasma and Platelet Transfusion Strategies in Critically Ill Children Following Severe Trauma, Traumatic Brain Injury, and/or Intracranial Hemorrhage: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding. Pediatr Crit Care Med 2022;23:e14–e24. - PMC - PubMed
1. Russell RT, Esparaz JR, Beckwith MA, et al. Pediatric traumatic hemorrhagic shock consensus conference recommendations. J Trauma Acute Care Surg 2023;94:S2–S10. - PMC - PubMed
1. Spinella PC, Leonard JC, Gaines BA, et al. Use of Antifibrinolytics in Pediatric Life-Threatening Hemorrhage: A Prospective Observational Multicenter Study. Crit Care Med 2022;50:e382–e392. - PubMed

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Massive Bleeding in Children With Cancer or Hematopoietic Cell Transplant: International, Multicenter Retrospective Study, 2017-2021

Collaborators

Affiliations

Massive Bleeding in Children With Cancer or Hematopoietic Cell Transplant: International, Multicenter Retrospective Study, 2017-2021

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical