Platelet dense granule defect: experience in the French population

Platelet dense granule defect (DGD) is a frequent inherited disorder that is underdiagnosed due to its complexity and poor standardization of diagnostic tools.

To assess the prevalence of DGD in a large real-life French cohort of patients with an abnormal bleeding score.

Patients with abnormal International Society on Thrombosis and Haemostasis Bleeding Assessment Tool scores, but no deficiency of coagulation or von Willebrand factor, and platelet counts > 100 × 10⁹/L, were recruited between December 2019 and March 2023 across 8 French expert centers. At the first visit, platelet function testing included light transmission aggregometry, whole-mount transmission electron microscopy, the mepacrine assay, and evaluation of CD63 expression. Patients with suspected DGD, based on prior testing, were included directly at the confirmatory visit (V2). DGD was defined by abnormal results on whole-mount transmission electron microscopy, mepacrine assay, or CD63 assay, and was considered confirmed if abnormalities were reproducible across both visits.

Of the 119 patients included at the inclusion visit, 66 had at least 1 abnormal dense granule test, including 19 with ≤2. Among the 54 patients seen at confirmatory visit , 40 had confirmed abnormalities, including 8 with at least 2 abnormal tests. Depending on diagnostic criteria, DGD prevalence ranged from 7.5% (≥2 abnormalities) to 37.4% (≥1 abnormality). Among 46 patients included at confirmatory visit, 30 had a confirmed DGD, including 11 with at least 2 abnormalities. No significant differences in age, sex, International Society on Thrombosis and Haemostasis Bleeding Assessment Tool scores, or bleeding history were observed between patients with or without DGD.

DGD diagnosis in clinical practice depends on the criteria used. Standardized guidelines and repeated testing are essential for improving diagnostic accuracy.