Impact of Thrombocytopenia and Platelet Transfusions on Neonatal Bleeding and Inflammation

Neonatal Thrombocytopenia Clinical Trial

Official title:

Impact of Thrombocytopenia and Platelet Transfusions on Neonatal Bleeding and Inflammation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03848923
• Other study ID #: IRB-P00029482
• Secondary ID: 2P01HL046925-21A
• Status: Recruiting
• Start date: August 19, 2019
• Est. completion date: September 1, 2026

Study information

• Verified date: May 2024
• Source: Boston Children's Hospital
• Contact: Martha Sola-Visner, MD
• Phone: 617-919-4845
• Email: martha.sola-visner[@]childrens.harvard.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: September 1, 2026
• Est. primary completion date: March 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Days to 6 Months

Eligibility

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.

Related Conditions & MeSH terms

• Inflammation
• Neonatal Thrombocytopenia
• Thrombocytopenia

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Children's Hospital	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Boston Children's Hospital	Beth Israel Deaconess Medical Center, National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of the bleeding score using the Neo-BAT (Neonatal Bleeding Assessment Tool),	The Neo-BAT categorizes bleeding as none (0), minor (1), moderate (2), severe (3), and major (4). A bleeding score 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.	Approximately 3 years
Secondary	Measurement of changes in cytokine levels and markers of intravascular coagulation and NET formation following PLT Tx	Cytokines will be measured within 2 hours before and 4 hours following a platelet transfusion using a Millipore multiplex immunoassay, analyzed with a BioPlex 200. All cytokine concentrations will be expressed in pg/mL. To measure NET formation at the same time points, we will use a newly described and validated ELISA to quantify citrullinated histone H3 (H3Cit) in plasma. This ELISA measures H3Cit in ng/mL. Increases in thrombin generation induced by platelet transfusions will be measured using a commercially available Thrombin-Antithrombin (TAT) Complex ELISA from Abcam, which measures TAT complexes in ng/mL.	Approximately 3 years