Anomalies of Dense Platelet Granules

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...)

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

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