# Project 1

> **NIH NIH P01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $440,132

## Abstract

PROJECT 1: PROJECT SUMMARY
Thrombocytopenia is, after anemia, the most common hematological problem among sick neonates, affecting
20-35% of NICU patients. In the U.S., platelet transfusions are frequently given to neonates with mild to
moderate thrombocytopenia (platelet counts 50-100x109/L). A substantial percentage of these transfusions
(58% in our recent multicenter retrospective study) are given to neonates with inflammatory conditions, such as
sepsis or necrotizing enterocolitis (NEC), usually when the platelet count falls below an arbitrary and highly
variable threshold. However, a growing body of evidence supports the fact that platelet counts are poor
predictors of bleeding. Furthermore, it has been recently recognized that platelets play important roles in
inflammation and host defense, and our preliminary data suggest that adult platelets are more pro-
inflammatory than neonatal platelets. Currently, neonatal transfusion decisions are made without taking into
account the differences that exist between neonatal and adult platelets, or the potential consequences of
thrombocytopenia and platelet transfusions on neonatal inflammation or host defense against bacterial
organisms. Our long term goal is to improve the treatment of thrombocytopenic neonates through a better
understanding of the systemic effects of thrombocytopenia and platelet transfusions. Our central hypothesis is
that platelet transfusions will be beneficial to some neonates due to their hemostatic functions and roles in host
defense, but will be harmful to others by exacerbating ongoing inflammation. To test these hypotheses, we
have formulated the following Specific Aims: 1) To define the effects of thrombocytopenia and platelet
transfusions on neonatal inflammation; 2) To establish the impact of neonatal thrombocytopenia and platelet
transfusions on bacterial sepsis; and 3) To characterize the effects of neonatal thrombocytopenia and platelet
transfusions on markers of systemic inflammation and clinical bleeding in human neonates. These aims will be
accomplished using a combination of translational studies applying our published miniaturized human in vitro
platelet transfusion system to evaluate the effects of adult platelets on neonatal blood (S.A. 1 and 2), murine
models of neonatal anemia, inflammation, sepsis, and platelet transfusions (S.A. 1 and 2), and clinical studies
of human thrombocytopenic neonates (S.A. 3). The studies in Specific Aims 1 and 2 will provide mechanistic
insights into the effects of thrombocytopenia and platelet transfusions on neonatal inflammatory responses,
and on bacterial sepsis. Specific Aim 3 will systematically assess the potential beneficial effects of platelet
transfusions on clinical bleeding (utilizing a validated neonatal bleeding score) vs. their potential negative
effects inducing NET formation and amplifying inflammation. These studies will -for the first time- consider the
role of platelets as inflammatory modulators in the cont...

## Key facts

- **NIH application ID:** 10215593
- **Project number:** 5P01HL046925-24
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Martha C. Sola-Visner
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $440,132
- **Award type:** 5
- **Project period:** 1992-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215593

## Citation

> US National Institutes of Health, RePORTER application 10215593, Project 1 (5P01HL046925-24). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10215593. Licensed CC0.

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