The Association Between Platelet Reactivity and Bleeding Risk in Adult ITP

December 14, 2017 updated by: Ming Hou, Shandong University

The Association Between Platelet Reactivity and Bleeding Risk in Adult ITP Patients: a Prospective Multicenter Double-blind Study

It seems reasonable to assume that patients who present significant bleeding symptoms may have different quality of platelets than those without bleeding. This question was addressed in a study that examined platelet function in adult ITP patients, which try to determine whether this correlated with bleeding risk. Previous reports have suggested that measuring platelet function may help define patients at highest risk of bleeding. In addition, Middelburg and colleagues corrected platelet function for quartile of platelet count, using <32×10^9/L as the lowest cohort and >132×10^9/L as the top quartile. They demonstrated that increased platelet reactivity (as measured by flow cytometry) was associated with decreased risk of bleeding but particularly for those patients with the lowest platelet counts. Further studies in a larger cohort are needed to confirm this correlation. Our study aimed at standardizing a prediction model to evaluate the bleeding risk of adult ITP patients with the use of platelet function tests.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The investigators are undertaking a prospective multicenter double-blind study of 400 adult patients with immune thrombocytopenia from 6 medical centers in China. We adopted three different assays that examined platelet function and reactivity. 1) Flow cytometry: Citrate anticoagulated whole blood was diluted in PBS to result in 20×10^9/L platelets, and 20 μl was aliquoted into polystyrene test tubes. Ten microliters of anti-CD42b-PE was added and incubated at room temperature for 10 min. Agonists (TRAP-6 12.5 μMol/L, Collagen 20 μg/mL, ADP 2 μM, Epinephrin 20 μM, Arachidonic acid 0.275 mM, Ristocetin 1.5 mg/mL) or PBS were added (10 μl each) and incubated again for 10 min. Then mAb PAC-1-FITC or anti-CD62p-FITC (10 μl each) or the corresponding isotype-matched controls were added. After 15-min incubation in the dark, the reaction was stopped with 500 μl PBS. Samples were analyzed on a flow cytometer (FACScan, Becton-Dickinson) by measuring 10,000 events in the CD42b-positive fraction. 2) Filopodia quantification: Briefly, platelets in Tyrode's buffer were allowed to adhere to VWF (9×10^6 cells/coverslip) in the presence of botrocetin (1 μg/mL) and Integrilin (40 μg/mL) at 37°C. After 15 min, non-adherent platelets were removed by washing and adherent platelets were fixed with 4% PFA, stained with TRITC-phalloidin (2 μg/mL) and viewed by epifluorescence microscopy for filopodia count. 3) Platelet aggregation: Measured on an automated platelet aggregation analyzer.

Understanding bleeding risk and underlying determinants of bleeding is important in order to help recognize patients that will require pharmacologic therapy even at higher platelet counts. Previous studies have suggested that low platelet counts, increased patient age, use of concurrent medications, and male sex are associated with increased bleeding risk. The present investigation will answer whether platelet function predicts the severity of bleeding in adult ITP patients. Clinical information of recruited participants includes gender, age, platelet count and physical/laboratory examination. Blinding was set between investigators who evaluated bleeding risks and those who performed experiments.

Study Type

Observational

Enrollment (Anticipated)

400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shandong
      • Jinan, Shandong, China, 250012
        • Recruiting
        • Qilu Hospital, Shandong University
        • Principal Investigator:
          • Ming Hou, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Untreated adult ITP patients of both genders between the ages of 18 and 80 years.

Description

Inclusion Criteria:

  1. Untreated adult ITP patients of both genders between the ages of 18 and 80 years.
  2. Participants of either acute or chronic phase; with or without thrombocytopenia; with or without bleeding manifestation.

Exclusion Criteria:

  1. Received high-dose steroids or IVIG within 3 weeks prior to the test.
  2. Received second-line ITP-specific treatments (eg, cyclophosphamide, 6-mercaptopurine, vincristine, vinblastine, etc) within 3 months prior to the test.
  3. Current HIV infection, hepatitis B virus or hepatitis C virus infections.
  4. Severe medical condition (liver and kidney function impairment).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group A
Participants with platelet counts <32×10^9/L.
Other: Platelet function tests
Platelet reactivity was measured by flow cytometry, filopodia detection and the platelet aggregation analyzer.
Group B
Participants with platelet counts between 32×10^9/L and 132×10^9/L.
Other: Platelet function tests
Platelet reactivity was measured by flow cytometry, filopodia detection and the platelet aggregation analyzer.
Group C
Participants with platelet counts >132×10^9/L.
Other: Platelet function tests
Platelet reactivity was measured by flow cytometry, filopodia detection and the platelet aggregation analyzer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The severity of bleeding manifestations at onset was assessed using a previously described clinical scoring system with minor modifications. The total bleeding score was calculated by adding the scores for each item.
Time Frame: No more than three months after platelet function assessment.
The bleeding score system: 1) Age: Age over 65 years (2'); Age over 75 years (5'). 2) Cutaneous bleeding: Localized petechial purpura (1'); Localized ecchymotic purpura (2'); Two locations of petechial purpura (2'); Generalized petechial purpura (3'); Generalized ecchymotic purpura (4'). 3) Mucosal bleeding: Unilateral epistaxis (2'); Bilateral epistaxis (3'); Hemorrhagic oral bullae and/or gingival bleeding (5'). 4) Gastrointestinal bleeding: Gastrointestinal hemorrhage without anemia (4'); Gastrointestinal hemorrhage with acute anemia and/or shock (15'). 5) Urinary bleeding: Macroscopic hematuria without anemia (4'); Macroscopic hematuria with acute anemia (10'). 6) Genitourinary tract bleeding: Major meno/metrorrhagia without anemia (4'); Major meno/metrorrhagia with acute anemia (10'). 7) Central nervous system bleeding: Central nervous system bleeding and/or life-threatening hemorrhage (15').
No more than three months after platelet function assessment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shandong University

Collaborators

Shandong Provincial Hospital
Qianfoshan Hospital
Traditional Chinese Medicine Hospital Affiliated to Shandong University
Jinan Central Hospital
Shandong University Second Hospital

Investigators

  • Study Director: Jun Peng, MD, PhD, Qilu Hospital, Shandong University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2017

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

December 1, 2018

Study Registration Dates

First Submitted

December 14, 2017

First Submitted That Met QC Criteria

December 14, 2017

First Posted (Actual)

December 19, 2017

Study Record Updates

Last Update Posted (Actual)

December 19, 2017

Last Update Submitted That Met QC Criteria

December 14, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Plt function and bleeding risk

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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