Clinical trial NCT04095715: Anomalies of Dense Platelet Granules
Official title: Diagnosis of Platelet Dense Granules Anomalies in Unexplained Hemorrhagic Syndromes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Spontaneous Induced Unexplained Haemorrhagic
Keywords: Dense platelet granules
Thrombopathy
Hemorrhagic symptomatology
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Assistance Publique Hopitaux De Marseille
name: CENTRE DE REFERENCE DES MALADIES HEMORRAGIQUES CONSTITUTIONNELLES
First posted: 2019-09-19
Enrollment: 166
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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...)

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

Eligibility criteria: 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

Primary outcomes:
measure: Platelet response to different agonists
timeFrame: Baseline (M0)
measure: Platelet response to different agonists
timeFrame: At 6 months
measure: Granular Delta content
timeFrame: Baseline (M0)
measure: Measurement of ATP
timeFrame: Baseline (M0)
measure: Measurement of ATP
timeFrame: At 6 months
measure: Measurement of granules opacity
timeFrame: Baseline (M0)
measure: Measurement of granules opacity
timeFrame: at 6 months
Secondary outcomes:
measure: Hemorrhagic risk assessment
timeFrame: Baseline (M0)
measure: Typage of delta granules anomalies
timeFrame: At 6 months
measure: Genetic anomalies of delta granules
timeFrame: At 6 months
measure: Prothrombin consumption
timeFrame: Baseline (M0)
measure: Prothrombin consumption
timeFrame: at 6 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker Enfants Malades - AP-HP
Study officials:
affiliation: APHP
name: Delphine BORGEL, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: Fiore M, Garcia C, Sié P, et al. δ-storage pool disease: an underestimated cause of unexplained bleeding. Hématologie 2017-8; 243-254.
citation: 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.
citation: 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.
citation: 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.