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| Name | Class |
|---|---|
| Assistance Publique Hopitaux De Marseille | OTHER |
| CENTRE DE REFERENCE DES MALADIES HEMORRAGIQUES CONSTITUTIONNELLES | UNKNOWN |
| URC-CIC Paris Descartes Necker Cochin | OTHER |
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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...)
Patients will be recruited during the exploration visit (v0) or the confirmation/typing visit (v1) according to their follow-up.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Haemostasis consultation | Other | Haemostasis consultation |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Hemorrhagic risk assessment | Evaluation using the ISTH score | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Delphine BORGEL, PhD | APHP | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Necker Enfants Malades - AP-HP | Paris | 75015 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24976115 | Background | 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. | |
| 17339185 |
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| Standard management of patients suspected of thrombopathy | Biological | Standard management of patients suspected of thrombopathy |
|
Delta granules contain calcium, which makes them naturally opaque to electrons and thus allows their direct visualization in electronic microscopy. |
| at 6 months |
| 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) | At 6 months |
| Prothrombin consumption | Evaluated by% of residual Thrombin after plasma coagulation | Baseline (M0) |
| Prothrombin consumption | Evaluated by% of residual Thrombin after plasma coagulation | at 6 months |
| 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. |
| Background | Fiore M, Garcia C, Sié P, et al. δ-storage pool disease: an underestimated cause of unexplained bleeding. Hématologie 2017-8; 243-254. |
| 25403439 | 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. |
| 25879272 | 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. |
| 27304079 | 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. |