Anomalies of Dense Platelet Granules

NCT04095715 | Completed

• 1 other identifier: APHP190393
• Study Type: observational
• Target: 166
• Locations: 1 country
• Sites: 1

Brief 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. 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...)

Conditions

Spontaneous Induced Unexplained Haemorrhagic

Keywords

Dense platelet granules; Thrombopathy; Hemorrhagic symptomatology

Outcome Measures

Primary Outcomes (7)

• 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

  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

  At 6 months

• Granular Delta content

  Dosage of platelet serotonin by measuring platelet serotonin by HPLC.

  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

  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

  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.

  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.

  at 6 months

Secondary Outcomes (5)

• Hemorrhagic risk assessment

  Baseline (M0)

• Typage of delta granules anomalies

  At 6 months

• Genetic anomalies of delta granules

  At 6 months

• Prothrombin consumption

  Baseline (M0)

• Prothrombin consumption

  at 6 months

Study Arms (1)

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; Biological: Standard management of patients suspected of thrombopathy

Interventions

Standard management of patients suspected of thrombopathy BIOLOGICAL

Standard management of patients suspected of thrombopathy

Children and adults with unexplained hemorrhagic syndrome

Haemostasis consultation OTHER

Haemostasis consultation

Children and adults with unexplained hemorrhagic syndrome

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• Inability or refusal of compliance with research requirements
• Thrombocytopenia \< 100 G/L
• Malignant hemopathy

Sponsors & Collaborators

• CENTRE DE REFERENCE DES MALADIES HEMORRAGIQUES CONSTITUTIONNELLES: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator
• Assistance Publique - Hôpitaux de Paris: lead
• Assistance Publique Hopitaux De Marseille: collaborator

Study Sites (1)

Hôpital Necker Enfants Malades - AP-HP

Paris, 75015, France

Location

Related Publications (6)

• 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.

  PMID: 24976115 BACKGROUND

• Quiroga 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.

  PMID: 17339185 BACKGROUND

• Fiore M, Garcia C, Sié P, et al. δ-storage pool disease: an underestimated cause of unexplained bleeding. Hématologie 2017-8; 243-254.

  BACKGROUND

• 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.

  PMID: 25403439 BACKGROUND

• Mumford 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.

  PMID: 25879272 BACKGROUND

• Selle 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.

  PMID: 27304079 BACKGROUND

Study Officials

• Delphine BORGEL, PhD

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: September 19, 2019
• Study Start: December 9, 2019
• Primary Completion: February 21, 2023
• Study Completion: February 21, 2023
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)