Evaluation of platelet dense granules by transmission electron microscopy in healthy pediatric donors and pediatric patients with suspected platelet disorders

Whole mount (WM) platelet transmission electron microscopy (PTEM) is a standard method for evaluating platelet dense granules (DG). However, because of the lack of a pediatric/adolescent mean DG/platelet reference range (RR), the prevalence of platelet DG deficiency in patients with suspected inherited platelet disorders (IPD) is mostly unknown in our practice. This study aimed to establish a local pediatric/adolescent RR for mean DG/platelet in a cohort of pediatric patients with clinical suspicion of IPD, which was used to determine the prevalence and clinical and laboratory features of platelet DG deficiency. WM-PTEM was performed on healthy donors. The mean DG/platelet RR was calculated by averaging the DG of 100 platelets per donor. Patients who underwent laboratory evaluation of suspected IPD were evaluated. PTEM results, clinical histories, other laboratory testing results, and pediatric ISTH BAT scores (normal &lt; 3; abnormal ≥3) were collected and analyzed. Healthy donors (<i>n</i> = 77, 41.6% female), ages 3–18 years, had a mean of 2.7 DG/platelet (±0.5), ranging from 1.9 to 3.8 per platelet. The mean DG/platelet did not correlate with age or gender. The tentative RR was calculated to be 1.9 to 3.8 DG/platelet. Of the 72 patients with suspected IPD (age 3–18 years, 69.4% female), 31 patients had BAT scores &lt; 3 and 41 patients had BAT scores ≥3 (range 0–11). Eighteen patients (25%) were diagnosed with DG deficiency. The mean DG/platelet in patients with bleeding scores ≥3 vs. those with bleeding scores &lt; 3 was similar. There was no difference in the number of patients with normal or abnormal bleeding scores in groups with normal vs decreased mean DG/platelet (<i>p</i> = .42) based on the pediatric DG/platelet RR. Platelet DG deficiency was also not correlated with abnormal platelet function testing results. Approximately 25% of pediatric patients with suspected IPD were found to have platelet DG deficiency. However, the mean DG/platelet did not correlate with the ISTH BAT scores or platelet function testing results. <b>What is the context?</b>Platelets have essential roles in primary hemostasis. They contain dense granules and alpha granules that are essential for their function.Whole-mount platelet transmission electron microscopy has become a preferred method to assess platelet dense granules. Platelets have essential roles in primary hemostasis. They contain dense granules and alpha granules that are essential for their function. Whole-mount platelet transmission electron microscopy has become a preferred method to assess platelet dense granules. <b>What is new?</b>Using our established reference range, we found that approximately 25% of patients who had suspected inherited platelet disorders in our cohort had platelet dense granule deficiency.We examined both bleeding and laboratory findings of the patients with platelet dense granule deficiency and failed to demonstrate a strong correlation with the severity of bleeding symptoms or a specific laboratory feature. Using our established reference range, we found that approximately 25% of patients who had suspected inherited platelet disorders in our cohort had platelet dense granule deficiency. We examined both bleeding and laboratory findings of the patients with platelet dense granule deficiency and failed to demonstrate a strong correlation with the severity of bleeding symptoms or a specific laboratory feature. <b>What is the impact?</b>Platelet dense granule deficiency is common in pediatric patients with suspected inherited platelet disorders.Patients may present with a wide range of bleeding symptoms, and dense granule deficiency can be challenging to diagnose using standard platelet function tests available in most clinical laboratories. Platelet dense granule deficiency is common in pediatric patients with suspected inherited platelet disorders. Patients may present with a wide range of bleeding symptoms, and dense granule deficiency can be challenging to diagnose using standard platelet function tests available in most clinical laboratories.