# RBC TRANSFUSION IN ANEMIC NEONATES LEADS TO SYSTEMIC INFLAMMATORY RESPONSE SYNDROME

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2022 · $28,616

## Abstract

Project summary
Transfusions of Red Blood Cells (RBCT) are necessary and life-saving in premature and critically
ill infants, who experience severe anemia due to both physiologic and iatrogenic factors. Recently,
we have shown that severe anemia was associated with increased intestinal permeability,
demonstrated by the identification of endotoxin in the bloodstream. Additionally, there is
increasing recognition of the dangers of the necessary step of blood bank storage prior to
transfusion. Transfusions of stored RBCs are rapidly cleared by liver macrophages, producing
non-transferrin bound iron (NTBI) to circulate in plasma, acutely inducing inflammation through
iron deposition in tissues. The risks of experiencing severe anemia during critical developmental
periods must be balanced with the risks of transfusions, which can lead to Systemic Inflammatory
Response Syndrome (SIRS) and potentially Multi Organ Dysfunction Syndrome (MODS). The
underlying mechanism(s) by which anemia and transfusion directly or indirectly correlate with the
development of SIRS remain unclear. Critical evaluation of the association between RBC
transfusion and SIRS is necessary to improve clinical practice and develop therapeutic strategies
to prevent and/or ameliorate anemia-RBCT associated SIRS. To investigate RBCT associated
SIRS, the investigators used an existing murine model in which 10-day-old mouse pups were
subjected to timed phlebotomy between postnatal days (P) 2-10 to induce severe anemia
(hematocrits 18%-22%), at which point they received an intravenous RBC transfusion, then
observed for up to 24h. Based on preliminary data, the investigators propose a novel hypothesis
that anemic neonates are uniquely predisposed to SIRS because of direct transmigration of
bacterial products from the hypoxic intestine due to loss of intestinal barrier function, facilitating
the hepatic monocyte response with preformed cytokines; RBCT can potentiate this effect. There
are two specific aims: (1) Determine the pathophysiological role of neonatal liver (NL)-derived
monocytes in the development of SIRS during anemia and RBC transfusion. (2) Determine
whether blocking trem1 activity on liver monocyte and/or restoration of anemia-associated
intestinal permeability can prevent/ameliorate anemia-transfusion associated
SIRS. Accomplishment of the proposed aims will explain the mechanisms and potential
strategies to prevent and/or treat anemia-RBCT transfusion associated SIRS in critically-ill
neonates.

## Key facts

- **NIH application ID:** 10463828
- **Project number:** 5R21HD105880-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Mohan Kumar Krishnan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $28,616
- **Award type:** 5
- **Project period:** 2021-08-06 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463828

## Citation

> US National Institutes of Health, RePORTER application 10463828, RBC TRANSFUSION IN ANEMIC NEONATES LEADS TO SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (5R21HD105880-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10463828. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*