PICU Transfusion Study: Harmful Effects of Red Blood Cell Transfusions

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Iron, Abnormal Blood Level

Intervention / Treatment
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* Biological: Transfusion of red blood cells
* Biological: Infusion of albumin/saline


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Transfused pediatric patients<br>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<br>* (non-experimental) PRBC transfusion<br>* Other names: Packed Red Blood Cells (PRBCs);|
| Saline/Albumin infusion<br>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<br>* (non-experimental) albumin/saline infusion<br>* Other names: Albumin/Saline;|

What is the study measuring?
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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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron, Blood Transfusion, Packed Red Blood Cells, PRBC, NTBI