Spontaneous Induced Unexplained HaemorrhagicAGRADNCT04095715
Anomalies of Dense Platelet Granules
An observational study of Spontaneous Induced Unexplained Haemorrhagic, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Spontaneous Induced Unexplained Haemorrhagic
- What is being tested?
- Haemostasis consultation and Standard management of patients suspected of thrombopathy
- How many people
- 166 participants
- Where
- 1 siteFrance
- Study dates
- 9 Dec 2019to 21 Feb 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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...)
Read the 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
- Being tested
- Haemostasis consultation, Standard management of patients suspected of thrombopathy
- Keywords
- Dense platelet granules, Thrombopathy, Hemorrhagic symptomatology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Haemostasis consultationOther
Haemostasis consultation
Standard management of patients suspected of thrombopathyBiological
Standard management of patients suspected of thrombopathy
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Haemostasis consultation; Biological: Standard management of patients suspected of thrombopathy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Platelet response to different agonists
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
Measured: Baseline (M0)
Platelet response to different agonists
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
Measured: At 6 months
Granular Delta content
Dosage of platelet serotonin by measuring platelet serotonin by HPLC.
Measured: Baseline (M0)
Measurement of ATP
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
Measured: Baseline (M0)
Measurement of ATP
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
Measured: At 6 months
Measurement of granules opacity
Delta granules contain calcium, which makes them naturally opaque to electrons and thus allows their direct visualization in electronic microscopy.
Measured: Baseline (M0)
Measurement of granules opacity
Delta granules contain calcium, which makes them naturally opaque to electrons and thus allows their direct visualization in electronic microscopy.
Measured: at 6 months
Secondary outcomes (5)
Hemorrhagic risk assessment
Evaluation using the ISTH score
Measured: Baseline (M0)
Typage of delta granules anomalies
Fib-SEM technic by focussed ion beam scanning which allows a 3D reconstitution of the platelets and thus to visualize any empty granules
Measured: At 6 months
Genetic anomalies of delta granules
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)
Measured: At 6 months
Prothrombin consumption
Evaluated by% of residual Thrombin after plasma coagulation
Measured: Baseline (M0)
Prothrombin consumption
Evaluated by% of residual Thrombin after plasma coagulation
Measured: at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2019
- Study start9 Dec 2019
- Primary completion21 Feb 2023
- Study completion21 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Spontaneous Induced Unexplained HaemorrhagicStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 166 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Assistance Publique Hopitaux De Marseille, CENTRE DE REFERENCE DES MALADIES HEMORRAGIQUES CONSTITUTIONNELLES, URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Delphine BORGEL, PhD, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04095715
- Sponsor's protocol ID
- APHP190393
- Acronym
- AGRAD
- Status last verified
- Mar 2026
- First submitted
- 18 Jun 2019
- Last updated
- 23 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gresele P, Harrison P, Bury L, Falcinelli E, Gachet C, Hayward CP, Kenny D, Mezzano D, Mumford AD, Nugent D, Nurden AT, Orsini S, Cattaneo M. Diagnosis of suspected inherited platelet function disorders: results of a worldwide survey. J Thromb Haemost. 2014 Sep;12(9):1562-9. doi: 10.1111/jth.12650. Epub 2014 Jul 25.
PubMed 24976115Quiroga T, Goycoolea M, Panes O, Aranda E, Martinez C, Belmont S, Munoz B, Zuniga P, Pereira J, Mezzano D. High prevalence of bleeders of unknown cause among patients with inherited mucocutaneous bleeding. A prospective study of 280 patients and 299 controls. Haematologica. 2007 Mar;92(3):357-65. doi: 10.3324/haematol.10816.
PubMed 17339185Fiore M, Garcia C, Sié P, et al. δ-storage pool disease: an underestimated cause of unexplained bleeding. Hématologie 2017-8; 243-254.
Gresele P; Subcommittee on Platelet Physiology of the International Society on Thrombosis and Hemostasis. Diagnosis of inherited platelet function disorders: guidance from the SSC of the ISTH. J Thromb Haemost. 2015 Feb;13(2):314-22. doi: 10.1111/jth.12792. Epub 2015 Jan 22. No abstract available.
PubMed 25403439Mumford AD, Frelinger AL 3rd, Gachet C, Gresele P, Noris P, Harrison P, Mezzano D. A review of platelet secretion assays for the diagnosis of inherited platelet secretion disorders. Thromb Haemost. 2015 Jul;114(1):14-25. doi: 10.1160/TH14-11-0999. Epub 2015 Apr 16.
PubMed 25879272Selle F, James C, Tuffigo M, Pillois X, Viallard JF, Alessi MC, Fiore M. Clinical and Laboratory Findings in Patients with delta-Storage Pool Disease: A Case Series. Semin Thromb Hemost. 2017 Feb;43(1):48-58. doi: 10.1055/s-0036-1584568. Epub 2016 Jun 15.
PubMed 27304079
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diagnosis of Platelet Dense Granules Anomalies in Unexplained Hemorrhagic Syndromes
- ClinicalTrials.gov ID
- NCT04095715
- Acronym / sponsor ID
- AGRAD / APHP190393
- Keywords
- Dense platelet granules, Thrombopathy, Hemorrhagic symptomatology
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 166 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Assistance Publique Hopitaux De Marseille, CENTRE DE REFERENCE DES MALADIES HEMORRAGIQUES CONSTITUTIONNELLES, URC-CIC Paris Descartes Necker Cochin
- Study start
- 9 Dec 2019 (actual)
- Primary completion
- 21 Feb 2023 (actual)
- Study completion
- 21 Feb 2023 (actual)
- First posted
- 19 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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...)
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Children and adults with unexplained hemorrhagic syndrome | – | Other: Haemostasis consultation, Biological: Standard management of patients suspected of thrombopathyPatients 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. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Haemostasis consultationHaemostasis consultation | Other | Children and adults with unexplained hemorrhagic syndrome |
| Standard management of patients suspected of thrombopathyStandard management of patients suspected of thrombopathy | Biological | Children and adults with unexplained hemorrhagic syndrome |
Primary outcome
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
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
Granular Delta content
Time frame: Baseline (M0)
Dosage of platelet serotonin by measuring platelet serotonin by HPLC.
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
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
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.
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.
5 secondary outcomes
Hemorrhagic risk assessment
Time frame: Baseline (M0)
Typage of delta granules anomalies
Time frame: At 6 months
Genetic anomalies of delta granules
Time frame: At 6 months
Prothrombin consumption
Time frame: Baseline (M0)
Prothrombin consumption
Time frame: at 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2026.
- Background: PubMed 24976115Gresele P, Harrison P, Bury L, Falcinelli E, Gachet C, Hayward CP, Kenny D, Mezzano D, Mumford AD, Nugent D, Nurden AT, Orsini S, Cattaneo M. Diagnosis of suspected inherited platelet function disorders: results of a worldwide survey. J Thromb Haemost. 2014 Sep;12(9):1562-9. doi: 10.1111/jth.12650. Epub 2014 Jul 25.
- Background: PubMed 17339185Quiroga T, Goycoolea M, Panes O, Aranda E, Martinez C, Belmont S, Munoz B, Zuniga P, Pereira J, Mezzano D. High prevalence of bleeders of unknown cause among patients with inherited mucocutaneous bleeding. A prospective study of 280 patients and 299 controls. Haematologica. 2007 Mar;92(3):357-65. doi: 10.3324/haematol.10816.
- BackgroundFiore M, Garcia C, Sié P, et al. δ-storage pool disease: an underestimated cause of unexplained bleeding. Hématologie 2017-8; 243-254.
- Background: PubMed 25403439Gresele P; Subcommittee on Platelet Physiology of the International Society on Thrombosis and Hemostasis. Diagnosis of inherited platelet function disorders: guidance from the SSC of the ISTH. J Thromb Haemost. 2015 Feb;13(2):314-22. doi: 10.1111/jth.12792. Epub 2015 Jan 22. No abstract available.
- Background: PubMed 25879272Mumford AD, Frelinger AL 3rd, Gachet C, Gresele P, Noris P, Harrison P, Mezzano D. A review of platelet secretion assays for the diagnosis of inherited platelet secretion disorders. Thromb Haemost. 2015 Jul;114(1):14-25. doi: 10.1160/TH14-11-0999. Epub 2015 Apr 16.
- Background: PubMed 27304079Selle F, James C, Tuffigo M, Pillois X, Viallard JF, Alessi MC, Fiore M. Clinical and Laboratory Findings in Patients with delta-Storage Pool Disease: A Case Series. Semin Thromb Hemost. 2017 Feb;43(1):48-58. doi: 10.1055/s-0036-1584568. Epub 2016 Jun 15.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Delphine BORGEL, PhD principal investigator
APHP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Spontaneous Induced Unexplained Haemorrhagic, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Platelet response to different agonists (time frame: Baseline (M0)). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04095715, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2026.