Association of Platelet Parameters With Bleeding Severity in Children With ITP (ITP-APPS)

Association of Platelet Parameters Identified by the Sysmex XN-1000 and Flow Cytometry With Concurrent and Subsequent Bleeding Severity in Children With Immune Thrombocytopenia (ITP): A Multicenter Study

Patients with severe immune thrombocytopenia (ITP) present with similarly low platelet counts but varying bleeding symptoms, making it difficult to predict the disease course and to decide on an appropriate treatment plan. In a single-center study, platelet parameters including the immature platelet fraction, the absolute immature platelet count , and functional response markers were found to be significantly associated with patient bleeding severity, independent of platelet count. This study aims to confirm and replicate these findings in a multi-center patient population and to investigate the use of these parameters to better predict disease severity and bleeding events.

Study Overview

• Status: Completed
• Conditions: Immune Thrombocytopenia

Detailed Description

Many children with severe immune thrombocytopenia (ITP) present with mild symptoms and their disease spontaneously resolves within 3 to 6 months. However, a subset of pediatric ITP patients experience severe bleeds and their symptoms persist for more than 6 to 12 months. Both patient populations present with similarly low platelet counts, making it difficult to predict the disease course and to decide on a treatment plan. The current American Society of Hematology treatment guidelines advise that most cases of ITP may be managed through close observation, while pharmacological interventions that may result in treatment-related toxicities may be used in patients with more severe bleeding symptoms. In order to improve the care and management of pediatric patients with ITP, it is necessary to develop a better predictor of bleeding events and disease severity than the patient's platelet count.

In a previous single-center study, investigators studied the association of different platelet parameters with patient bleeding severity. Using whole blood from patients diagnosed with severe ITP, investigators measured the immature platelet fraction (IPF) and absolute immature platelet count (IPC) through a hematology analyzer (Sysmex XN-1000). Investigators performed functional tests on the platelets and analyzed them through flow cytometry. In this study, the investigators found that the IPF and IPC is associated with patient bleeding severity, independent of platelet count. It was also determined that functional activation markers such as P-selectin and glycoprotein (GP) IIb-IIIa are significantly associated with subsequent bleeding severity in children, independent of platelet count. The results of these proposed studies in ITP patients may suggest clinically relevant uses of these assays.

To confirm these findings, this trial will repeat the previous study in a multi-center patient population, including a greater number of patients with severe bleeding and low platelet counts.

• Study Type: Observational
• Enrollment (Actual): 95

Contacts and Locations

• Study Contact: Name: Andrew L. Frelinger, PhD; Phone Number: 617-919-2537; Email: andrew.frelinger@childrens.harvard.edu
• Study Contact Backup: Name: Micaela Hayton; Phone Number: 617-355-3748; Email: Micaela.Hayton@childrens.harvard.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 20 years (Child, Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Pediatric patients diagnosed with primary or secondary immune thrombocytopenia.

Description

Inclusion Criteria:

• Diagnosed with primary or secondary immune thrombocytopenia.
• Platelet count of < 50 x 10^9/L

Exclusion Criteria:

• May not have received aspirin 10 days prior to study entry.
• May not have received nonsteroidal anti-inflammatory drugs (NSAIDs) 3 days prior to study entry.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with ITP; Patients with primary or secondary immune thrombocytopenia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of IPF with concurrent, subsequent and worst-ever bleeding in children with ITP.	Evaluate in a multi-center study the association, independent of platelet count, of IPF measured by the Sysmex XN-1000 with concurrent, subsequent, and worst-ever bleeding in children with ITP.	February 2019-August 2022
Association of IPC with concurrent, subsequent, and worst-ever bleeding in children with ITP	Evaluate in a multi-center study the association, independent of platelet count, of immature platelet parameters measured by the Sysmex XN-1000 (IPC, Plt-F, and FSC and other research parameters as applicable) with concurrent, subsequent, and worst-ever bleeding in children with ITP.	February 2019-August 2022
Association of platelet function markers with concurrent, subsequent, and worst-ever bleeding in children with ITP.	Evaluate in a multi-center study the association, independent of platelet count, off circulating andd agonist-stimulated platelet surface P-selectin and activated GPIIb-IIIa with concurrent, subsequent, and worst-ever bleeding in children with ITP.	February 2019-August 2022

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: Baylor College of Medicine; Children's Hospital of Philadelphia; Columbia University; Children's Hospital Colorado; Duke University; Sysmex America, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2019
• Primary Completion (Actual): November 26, 2023
• Study Completion (Actual): November 26, 2023

Study Registration Dates

• First Submitted: January 16, 2019
• First Submitted That Met QC Criteria: January 16, 2019
• First Posted (Actual): January 18, 2019

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: platelet function; ITP; Sysmex
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Cytopenia; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
• Other Study ID Numbers: P00030227

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No