Anomalies of Dense Platelet Granules (AGRAD)

March 19, 2026 updated by: Assistance Publique - Hôpitaux de Paris

Diagnosis of Platelet Dense Granules Anomalies in Unexplained Hemorrhagic Syndromes

The study aims to know the overall prevalence of granular deficits and their breakdown by type (anomaly of number, content or secretion) in a population of patients with hemorrhagic symptomatology after exclusion of other known causes.

This study consists also to evaluate the association between the presence of a deficit in dense granules and (1) the intensity of the hemorrhagic phenotype (hemorrhagic score) (2) the nature of hemorrhages (post-operative, spontaneous, atypical...)

-Evaluate the association between the type of deficit in dense granules and (1) the intensity of the hemorrhagic phenotype (hemorrhagic score) (2) the nature of hemorrhages (post-operative, spontaneous, atypical...)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients will be recruited during the exploration visit (v0) or the confirmation/typing visit (v1) according to their follow-up.

  • Exploration visit (v0): inclusion of patients without prior platelet exploration, and study of their dense platelet granules.
  • Confirmation/typing visit (v1): verification of the persistence of anomalies detected in patients with an abnormality identified during v0 (no later than 6 months after v0) and in patients for whom a dense granules anomaly has already been identified during their standard management prior to the start of the study. Completion of complementary examinations to complement the typing of the granular anomaly and molecular analysis for family cases

Study Type

Observational

Enrollment (Actual)

166

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

  • France
      • Paris, France, 75015
        • Hôpital Necker Enfants Malades - AP-HP

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

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Patients addressed to the specialized haemostasis consultations of the various services associated with the project for the exploration of haemorrhagic symptomatology referring to a primary haemostasis anomaly.

Description

Inclusion Criteria:

  • Adult or child patient ≥ 2 years
  • Having a hemorrhagic score ISTH > 3 for men, > 5 for women and > 2 for children.
  • With no abnormal coagulation (defined by normal TP and TCK or activity ≥ 50% of FII, FV, FVII, FX, FVIII, FIX, FXI)
  • no deficiency of Willebrand factor (defined by a cofactor activity with Ristoctin (VWF: RCo < 50%))
  • no a known major thrombocytopenia/thrombopathy linked to a deficiency of one of the major platelet receptors
  • Information of the patient and/or his legal representative present

Exclusion Criteria:

  • Inability or refusal of compliance with research requirements
  • Thrombocytopenia < 100 G/L
  • Treatments interfering with platelet functions within 10 days prior to inclusion
  • Malignant hemopathy

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
Children and adults with unexplained hemorrhagic syndrome
Patients with spontaneous or induced hemorrhagic manifestations who are present for a consultation to investigate a thrombopathy or during follow-up consultations as part of their usual care.
Other: Haemostasis consultation
Haemostasis consultation
Biological: Standard management of patients suspected of thrombopathy
Standard management of patients suspected of thrombopathy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Platelet response to different agonists
Time Frame: Baseline (M0)
Us of some low-dose agonists such as ADP, epinephrine or collagen, which are particularly susceptible to granular defects, on platelet-rich plasma (PRP) prepared from the patient's blood sample to be explored
Baseline (M0)
Platelet response to different agonists
Time Frame: At 6 months
Use of some low-dose agonists such as ADP, epinephrine or collagen, which are particularly susceptible to granular defects, on platelet-rich plasma (PRP) prepared from the patient's blood sample to be explored
At 6 months
Granular Delta content
Time Frame: Baseline (M0)
Dosage of platelet serotonin by measuring platelet serotonin by HPLC.
Baseline (M0)
Measurement of ATP
Time Frame: Baseline (M0)
The measurement is based on the principle of bioluminescence with a two-step transformation reaction of luciferin in the presence of luciferase, this reaction requiring the presence of ATP
Baseline (M0)
Measurement of ATP
Time Frame: At 6 months
The measurement is based on the principle of bioluminescence with a two-step transformation reaction of luciferin in the presence of luciferase, this reaction requiring the presence of ATP
At 6 months
Measurement of granules opacity
Time Frame: Baseline (M0)
Delta granules contain calcium, which makes them naturally opaque to electrons and thus allows their direct visualization in electronic microscopy.
Baseline (M0)
Measurement of granules opacity
Time Frame: at 6 months
Delta granules contain calcium, which makes them naturally opaque to electrons and thus allows their direct visualization in electronic microscopy.
at 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemorrhagic risk assessment
Time Frame: Baseline (M0)
Evaluation using the ISTH score
Baseline (M0)
Typage of delta granules anomalies
Time Frame: At 6 months
Fib-SEM technic by focussed ion beam scanning which allows a 3D reconstitution of the platelets and thus to visualize any empty granules
At 6 months
Genetic anomalies of delta granules
Time Frame: At 6 months
Sequencing on a broad set of genes involved in platelet function. Bioinformatic analysis is carried out using BWA-MEM software (Alignment on the genome version HG19)
At 6 months
Prothrombin consumption
Time Frame: Baseline (M0)
Evaluated by% of residual Thrombin after plasma coagulation
Baseline (M0)
Prothrombin consumption
Time Frame: at 6 months
Evaluated by% of residual Thrombin after plasma coagulation
at 6 months

Collaborators and Investigators

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

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Assistance Publique Hopitaux De Marseille
URC-CIC Paris Descartes Necker Cochin
CENTRE DE REFERENCE DES MALADIES HEMORRAGIQUES CONSTITUTIONNELLES

Investigators

  • Principal Investigator: Delphine BORGEL, PhD, APHP

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 9, 2019

Primary Completion (Actual)

February 21, 2023

Study Completion (Actual)

February 21, 2023

Study Registration Dates

First Submitted

June 18, 2019

First Submitted That Met QC Criteria

September 17, 2019

First Posted (Actual)

September 19, 2019

Study Record Updates

Last Update Posted (Actual)

March 23, 2026

Last Update Submitted That Met QC Criteria

March 19, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APHP190393

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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