Spontaneous Induced Unexplained Haemorrhagic Clinical Trial
— AGRADOfficial title:
Diagnosis of Platelet Dense Granules Anomalies in Unexplained Hemorrhagic Syndromes
| Verified date | October 2023 |
| Source | Assistance Publique - Hôpitaux de Paris |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Observational |
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...)
| Status | Completed |
| Enrollment | 166 |
| Est. completion date | February 21, 2023 |
| Est. primary completion date | February 21, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 2 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| France | Hôpital Necker Enfants Malades - AP-HP | Paris |
| Lead Sponsor | Collaborator |
|---|---|
| Assistance Publique - Hôpitaux de Paris | Assistance Publique Hopitaux De Marseille, CENTRE DE REFERENCE DES MALADIES HEMORRAGIQUES CONSTITUTIONNELLES |
France,
Fiore M, Garcia C, Sié P, et al. d-storage pool disease: an underestimated cause of unexplained bleeding. Hématologie 2017-8; 243-254.
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. — View 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. — View Citation
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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. — View 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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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) | |
| Primary | 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 | |
| Primary | Granular Delta content | Dosage of platelet serotonin by measuring platelet serotonin by HPLC. | Baseline (M0) | |
| Primary | 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) | |
| Primary | 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 | |
| Primary | 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) | |
| Primary | 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 | Hemorrhagic risk assessment | Evaluation using the ISTH score | Baseline (M0) | |
| Secondary | 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 | At 6 months | |
| Secondary | 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) | At 6 months | |
| Secondary | Prothrombin consumption | Evaluated by% of residual Thrombin after plasma coagulation | Baseline (M0) | |
| Secondary | Prothrombin consumption | Evaluated by% of residual Thrombin after plasma coagulation | at 6 months |