Brief Title
Impact of Thrombocytopenia and Platelet Transfusions on Neonatal Bleeding and Inflammation
Official Title
Impact of Thrombocytopenia and Platelet Transfusions on Neonatal Bleeding and Inflammation
Brief Summary
This is a prospective observational study that was designed with the following two Specific
Aims:
1. To determine whether the Immature Platelet Fraction percentage (IPF%) and the Immature
Platelet Count (IPC) are better predictors of bleeding than the platelet count alone in
neonates of different gestational and post-conceptional ages and with different
etiologies of thrombocytopenia; and
2. To characterize the effects of neonatal thrombocytopenia and platelet transfusions (PLT
Tx) on bleeding and on markers of systemic inflammation, thrombosis, and neutrophil
extracellular traps (NET) formation in neonates with different underlying conditions.
Detailed Description
This is a prospective observational study designed to contrast the potential positive effects
of neonatal platelet transfusion on clinical bleeding vs. their potentially negative effects
on NET formation, intravascular thrombosis and elevation of pro-inflammatory cytokines.
Importantly, patients will be consented when they have a platelet count <100 x 109/L, but
they will enter study only when the platelet count falls to <50 x 109/L.
After obtaining signed Informed Consent, enrolled infants will undergo the following:
1. Prospective collection of clinical and laboratory data, including:
1. Baseline demographic and clinical information from infants and mothers;
2. Clinical diagnoses at the time of enrollment (if NEC, then Bell's stage) and illness
severity (SNAP scores) at the time of diagnosis;
3. All hemoglobins, hematocrits, PLT counts, IPF% and IPCs obtained during study. An IPF
(the PLT equivalent of the reticulocyte count) is automatically run on every
thrombocytopenic sample at all participating hospitals, and will provide information
regarding mechanism of thrombocytopenia;
4. All blood culture results, and all markers of liver and renal function;
5. All PLT, RBC and plasma transfusions, including product characteristics, transfusion
times, and volume; and
6. Neonatal outcomes including IVH (any grade), chronic lung disease (oxygen requirement at
36 wks post-conception), retinopathy of prematurity (any grade), and mortality.
Infants will be followed until resolution of the severe thrombocytopenia (PLT count >50x109/L
without PLT Tx x 72 hours), death or discharge, whichever comes first.
2. Study-specific procedures. In addition to the data collected as above, enrolled infants
will undergo the following study-specific measurements:
1. A bleeding score (Neo-BAT, see Appendix) will be obtained by the bedside nurse within 2
hours of every PLT count and IPF% checked. NeoBAT scores will include any bleeding since
the last PLT count or over the prior 24 hours, whichever is shortest. This will serve to
correlate bleeding scores with PLT counts, and to quantify changes following PLT Tx;
2. Two optional blood samples will be obtained within 2 hours prior to and 4±2 hours (see
below) following the first clinically indicated PLT Tx after enrollment. These 2
study-specific blood samples (0.5-1.0 cc each) will be taken to the study laboratory for
a CBC and plasma separation and storage for future measurements of dsDNA and MPO-DNA
ELISA, markers of NET formation, TAT complexes (markers of intravascular coagulation),
and for a panel of serum cytokines/vascular injury markers (IFNɣ, IL-6, IL-8, IL-10,
IL-17, IL-18, TNFα/β, IP-10, MCP-1, ICAM, VCAM, and VEGF) by Luminex;
3. In addition, left-over plasma samples from clinical tests will be collected daily from
the clinical laboratory, aliquoted, and frozen for future cytokine measurements, as we
did to generate the preliminary data for this study.
Study Type
Observational
Primary Outcome
Assessment of the bleeding score using the Neo-BAT (Neonatal Bleeding Assessment Tool),
Secondary Outcome
Measurement of changes in cytokine levels and markers of intravascular coagulation and NET formation following PLT Tx
Condition
Neonatal Thrombocytopenia
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
160
Start Date
August 19, 2019
Completion Date
September 1, 2024
Primary Completion Date
March 1, 2024
Eligibility Criteria
Inclusion Criteria:
1. Have a post-menstrual age between 23 and 44 weeks;
2. Have a PLT count <100 x 109/L; and
3. Have a parent/guardian willing to provide written informed consent.
Exclusion Criteria:
1. Are not expected to survive for >5 days by the Attending Neonatologist;
2. Are thought to have a congenital thrombocytopenia or platelet dysfunction, based on
family history or clinical presentation (e.g. congenital malformations, platelet
morphology); or
3. Are on extracorporeal membrane oxygenation (ECMO).
Importantly, patients will be consented when they have a platelet count <100 x 109/L, but
they will enter study only when the platelet count falls to <50 x 109/L.
Gender
All
Ages
0 Days - 6 Months
Accepts Healthy Volunteers
No
Contacts
Martha Sola-Visner, MD, 617-919-4845, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03848923
Organization ID
IRB-P00029482
Secondary IDs
2P01HL046925-21A1
Responsible Party
Principal Investigator
Study Sponsor
Boston Children's Hospital
Collaborators
Beth Israel Deaconess Medical Center
Study Sponsor
Martha Sola-Visner, MD, Principal Investigator, Boston Children's Hospital
Verification Date
April 2022