PICU Transfusion Study: Harmful Effects of Red Blood Cell Transfusions

Harmful Effects of Red Blood Cell Transfusions Are Mediated by Iron: Pediatric ICU Aim

The investigators hypothesize that the storage-damaged red cells are responsible for some of the adverse effects of transfusion. In this observational study, the investigators will measure various laboratory parameters both before and after transfusion in a pediatric intensive care unit to determine at what duration of storage is there laboratory evidence of refrigerator storage damage.

The investigators hypothesize that increasing storage time of packed red blood cells (PRBCs) transfused will be associated with increasing non-transferrin-bound iron (NTBI), pro-inflammatory cytokine concentrations, and enhanced microbial growth in vitro in pediatric patients.

Study Overview

• Status: Completed
• Conditions: Iron, Abnormal Blood Level
• Intervention / Treatment: Biological: Transfusion of red blood cells; Biological: Infusion of albumin/saline

Detailed Description

Transfusions of red blood cells (RBCs) stored for longer durations are associated with adverse effects in hospitalized patients. During storage, RBCs undergo cumulative changes that reduce their survival in vivo, and have been associated with impairment in oxygen transport and adverse outcomes. Transfusion of older RBCs results in increased NTBI levels in healthy adults, and elevated NTBI levels have been associated with increased morbidity and mortality in hospitalized patients. Transfusion of PRBCs has also been associated with up-regulation of inflammatory cytokines. Pediatric patients are exposed to PRBC transfusions; however, this patient population has not been previously studied for these outcomes.

According to current practice guidelines, PRBCs are stored in the blood bank up to 42 days prior to transfusion. In this study, blood sample will be collected from pediatric ICU patients prior to every PRBC transfusion and again 2-6 hours post-transfusion to determine iron parameters, inflammatory marker concentrations, and growth of microbial pathogens in vitro.

The investigators hopes to further the understanding of the effects of blood storage on outcome in children, thereby making transfusion safer and more effective.

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Weill Cornell Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Hospitalized pediatric patients admitted to the Columbia University Medical Center's Pediatric ICU

Description

Inclusion Criteria:

• Less than 21 years of age;
• Greater than 5kg weight;
• Parents or legal guardian have signed informed consent;
• Will be receiving transfusion of packed, leukoreduced RBCs stored in an additive saline (AS) solution (standard practice).

Exclusion Criteria:

• Patients have undergone transfusion of platelets or fresh frozen plasma 4 hours before or will receive these products after transfusion of the RBC unit;
• Transfusion of RBC from more than one donor at the test transfusion event.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Transfused pediatric patients; Children who might receive packed red blood cell (PRBC) transfusion will be enrolled after obtaining consent from their parents/legal guardians and assent from the patient, if possible. Transfusion of red blood cells will be done according to standard of care.	Biological: Transfusion of red blood cells; (non-experimental) PRBC transfusion; Other Names: Packed Red Blood Cells (PRBCs)
Saline/Albumin infusion; Children who might receive albumin or saline for volume resuscitation will be enrolled after obtaining consent from their parents/legal guardians and assent from the patient, if possible. Infusion will be done according to standard of care.	Biological: Infusion of albumin/saline; (non-experimental) albumin/saline infusion; Other Names: Albumin/Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-transferrin-bound iron level	Circulating non-transferrin-bound iron level post-transfusion (taken between 2-6 hours post-transfusion and 8-12 hours post-transfusion) vs the pre-transfusion level.	Up to 12-hours post-transfusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Hepcidin level	Up to 12-hours post-transfusion
Level of C-Reactive Protein (CRP)	Up to 12 hours post-transfusion
Level of Monocyte Chemoattractant Protein (MCP)-1	Up to 12 hours post-transfusion
Level of Interleukin (IL)-6	Up to 12 hours post-transfusion

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Eldad A Hod, MD, Columbia University

Publications and helpful links

General Publications

• L'Acqua C, Bandyopadhyay S, Francis RO, McMahon DJ, Nellis M, Sheth S, Kernie SG, Brittenham GM, Spitalnik SL, Hod EA. Red blood cell transfusion is associated with increased hemolysis and an acute phase response in a subset of critically ill children. Am J Hematol. 2015 Oct;90(10):915-20. doi: 10.1002/ajh.24119.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2013
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: March 12, 2014
• First Submitted That Met QC Criteria: March 12, 2014
• First Posted (Estimate): March 14, 2014

Study Record Updates

• Last Update Posted (Actual): March 27, 2019
• Last Update Submitted That Met QC Criteria: March 25, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Blood Transfusion; Iron; PRBC; NTBI; Packed Red Blood Cells
• Other Study ID Numbers: AAAM5050; R01HL115557 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED