Research for Plasma Biomarkers Associated With Fatigue in Thrombocytopenic Patients (FAGPLAQ)

Thrombocytopenia is a clinical problem defined by a platelet count lower than 150×10⁹/L. It can be linked to various pathologies of central origin, such as decreased platelet production in the bone marrow, or peripheral origin with increased platelet destruction through autoimmune mechanisms, increased splenic sequestration, or excessive platelet consumption. Significant fatigue is often reported in association with thrombocytopenia, but its underlying pathophysiology remains unclear. One hypothesis is the role played by neurotrophic factors contained in platelets and released into the circulation following their activation, in particular the Brain-Derived Neurotrophic Factor (BDNF), which promotes the survival, growth, differentiation, and plasticity of neurons in both the central and peripheral nervous systems. Consequently, BDNF plays a key role in long-term memory, intellectual abilities, and neuroprotection.

In this context, this project aims to confirm whether platelet-origin neurotrophic biomarkers could explain the fatigue experienced by thrombocytopenic patients and whether it depends on the etiology of the thrombocytopenia.

Study Overview

• Status: Recruiting
• Conditions: Thrombopenia
• Intervention / Treatment: Biological: blood sampling; Other: self-administrated questionaires

Detailed Description

Thrombocytopenia is defined as a platelet count below 150×109/L. The mechanisms leading to thrombocytopenia are multiple, and may be linked to :

• reduced platelet production in the bone marrow;
• increased destruction of peripheral platelets;
• increased splenic sequestration. In the event of a vascular breach, platelets contribute to hemostasis by sealing the lesion, thereby stopping bleeding. In thrombocytopenic patients, the best-known clinical signs are excessive mucocutaneous bleeding. Patients with severe thrombocytopenia (< 20×109 /L) may be at risk of life-threatening bleeding (cerebral bleeding).

In the case of autoimmune thrombocytopenia, cognitive disorders have been reported, detected by appropriate questionnaires, the pathophysiological mechanism of which remains unclear. In a study of 1871 patients with thrombocytopenia, 39% of patients in the UK and 22% in the USA reported severe asthenia. Asthenia appears to be related to thrombocytopenia, but the mechanism has not been identified either. Asthenia is a recognized symptom in other autoimmune pathologies, such as primary biliary cirrhosis (autoimmune liver disease), in which asthenia has been shown to be mainly associated with autonomic nervous system dysfunction.

While thrombocytopenia is primarily associated with bleeding risk, at least half of thrombocytopenic patients report fatigue and impaired mental and emotional health and social functioning, even though anemia is corrected and the association with autoimmune disease does not explain fatigue in all thrombocytopenic patients.

The hypothesis is that thrombocytopenia is associated with a decrease in circulating neurotrophic factor levels through reduced platelet granule secretion, which may explain the fatigue.

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nadine Ajzenberg; Phone Number: 01 40.25.62.73; Email: nadine.ajzenberg@aphp.fr
• Study Contact Backup: Name: Georges Jourdi; Phone Number: 01.49.95.64.11; Email: georges.jourdi@aphp.fr

Study Locations

• France
  • Paris, France, 75018
    • Recruiting
    • Hopital Bichat-Claude Bernard
    • Contact: Nadine Ajzenberg; Phone Number: 01 40.25.62.73; Email: nadine.ajzenberg@aphp.fr
    • Contact: Georges Jourdi; Phone Number: 01.49.95.64.11; Email: georges.jourdi@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria for patients (adults or minors):

• Patients with constitutional or autoimmune (chronic or persistent ITP with last treatment administration ≥ 3 weeks) thrombocytopenia (platelet count < 150×109/L) already diagnosed
• patient not being treated and not receiving serotonin reuptake inhibitor (SSRI) or norepinephrine (SNRI) or antithrombotic treatments (antiplatelet or anticoagulant) in the 10 days prior to inclusion
• affiliation to social security (beneficiary or assignee)
• patient followed in consultation in one of the recruiting haematology departments
• Patient (or parent) having received a detailed explanation of the research project and having consent by signing the consent form before any research-specific procedure

Inclusion criteria for healthy volunteers:

• Age- (± 5 years) and sex-matched healthy adult controls
• Non-thrombocytopenic patients and not receiving antithrombotic, SNRI or SSRI therapy or if applicable, last treatment ≥ 10 days
• affiliation to social security (beneficiary or assignee)
• adults who received a detailed explanation of the research project and having consent by signing the consent form before any research-specific procedure

Non inclusion criteria (adults and minors):

• Adult patients under legal protection (guardianship or curatorship) Thrombocytopenic patients treated with antithrombotics, serotonin reuptake inhibitors (SSRIs) or noradrenaline reuptake inhibitors (SNRIs)
• Minor patients weighing less than 20 kg

Non inclusion criteria for healthy adult controls:

• Healthy adult volunteers under legal protection (guardianship, curatorship or safeguard of justice).
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients; Minor patients (8 years of age or older) and adult patients seen consecutively in a hematology consultation as part of the follow-up of their thrombocytopenia.	Biological: blood sampling; 3 blood tubes will be taken during a standard check-up; Other: self-administrated questionaires; 4 self administrated questionaires and scales at the inclusion
Other: Control group; Control group (n=80) who will consist of healthy adult subjects (without pathology and without treatment) matched by age (± 5 years) and sex to adult patients included in the study given the possible influence of age and sex on circulating BDNF concentrations	Biological: blood sampling; 3 blood tubes will be taken during a standard check-up; Other: self-administrated questionaires; 4 self administrated questionaires and scales at the inclusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood BDNF levels in thrombocytopenic adult and pediatric patients	Measurement of BDNF levels in thrombocytopenic patients Adults and children with excessive fatigue	At the inclusion
Fatigue questionnaire scores for adult and pediatric patients	Fatigue questionnaire scores for adult and pediatric patients with excessive fatigue	At the inclusion
BDNF blood level in Healthy volunteers	Measurement of BDNF blood level in Healthy volunteers	At the inclusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Measurement of pro-BDNF blood level in thrombopenic adult and pediatric patients	At the inclusion
measurement of p75NTR blood level in thrombopenic adult and pediatric patients	At the inclusion
measurement of TrkB blood level in thrombopenic adult and pediatric patients	At the inclusion
measurement of MMP9 blood level in thrombopenic adult and pediatric patients	At the inclusion
measurement of Serotonin blood level in thrombopenic adult and pediatric patients	At the inclusion
measurement of Dopamin blood level in thrombopenic adult and pediatric patients	At the inclusion
measurement of P-selectin blood level in thrombopenic adult and pediatric patients	At the inclusion
measurement of CD40 ligand blood level in thrombopenic adult and pediatric patients	At the inclusion
anxiety questionnaire sub score of adult and pediatric patients	At the inclusion
Depression questionnaire sub score of adult and pediatric patients	At the inclusion
cognition questionnaire sub score of adult and pediatric patients	At the inclusion
measurement of pro-BDNF blood level in Healthy volunteers	At the inclusion
measurement of p75NTR blood level in Healthy volunteers	At the inclusion
measurement of TrkB blood level in Healthy volunteers	At the inclusion
measurement of MMP9 blood level in Healthy volunteers	At the inclusion
measurement of Serotonin blood level in Healthy volunteers	At the inclusion
measurement of Dopamin blood level in Healthy volunteers	At the inclusion
measurement of P-selectin blood level in Healthy volunteers	At the inclusion
measurement of CD40 ligand blood level in Healthy volunteers	At the inclusion
anxiety questionnaire sub score in Healthy volunteers	At the inclusion
Depression questionnaire sub score in Healthy volunteers	At the inclusion
cognition questionnaire sub score in Healthy volunteers	At the inclusion

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Nadine Ajzenberg, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2025
• Primary Completion (Estimated): March 26, 2028
• Study Completion (Estimated): June 26, 2028

Study Registration Dates

• First Submitted: May 12, 2025
• First Submitted That Met QC Criteria: May 12, 2025
• First Posted (Actual): May 20, 2025

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Thrombopenia
• Additional Relevant MeSH Terms: Cytopenia; Hematologic Diseases; Blood Platelet Disorders; Hemic and Lymphatic Diseases; Thrombocytopenia; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: APHP240854; 2024-A01225-42 (Other Identifier: ANSM)

Drug and device information, study documents

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