Impact of Thrombocytopenia and Platelet Transfusions on Neonatal Bleeding and Inflammation

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, 2022

Primary Completion Date

March 1, 2022

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

N/A - 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

January 2020