Detection of Platelet Dense Granule Deficiency in Pediatric Patients by Quantitative Electron Microscopy

Abstract number: P1519

Ye^1,2 CC, Rand^1,2 ML, Kahr^1,2 WHA, Christensen¹ H, Rosenberg¹ HI, Edwards¹ VD, Leung¹ R, Blanchette^1,2 VS, Abdelhaleem^1,2 M

^{1,2 1,2 11}The Hospital for Sick Children, Toronto, Canada

Platelet dense granule (DG) deficiency comprises a group of heterogeneous disorders that are often associated with a bleeding diathesis; its precise diagnosis requires DG quantitation. We implemented a previously described quantitative method that employs whole mount transmission electron microscopy (TEM) on glutaraldehyde-fixed platelet-rich plasma in which dense granules (DGs) in 50–100 platelets are counted and averaged. A reference range of 3–7 DGs/platelet was established. Here we report our experience with this test. Peripheral blood specimens from 61 patients with a variable bleeding diathesis and/or a family history of bleeding were processed and examined during the period of July, 2001 to December, 2004. Of these, 42 cases (69%) had decreased DGs, ranging from 0.0 to 2.9 DGs/platelet (mean 1.9/platelet) and 19 cases (31%) had DGs of 3.0–10.6/platelet (mean 4.6/platelet). By standard TEM, the intracellular structures other than the storage granules were morphologically unremarkable in all the cases. Among those with decreased DGs were 23 pediatric cases (11 males, 12 females), with ages ranging from 2 months to 18 years (median 4 years) and platelet counts ranging from 121–406 × 10⁹/L (median 238 × 10⁹/L). Most of these patients had variable non-specific abnormalities in platelet aggregation testing. Except for one female infant with severe DG abnormality and a-granule deficiency, all the cases appeared to have isolated DG deficiency. No correlation was noted between DG counts and platelet counts. Twelve of the 23 pediatric cases with decreased DGs had their parents evaluated. In all but one of these families, one or both parents also had decreased DGs (<3.0/platelet). These 19 adults constituted the rest of our positive cases. In conclusion, many pediatric patients with DG deficiency may have inherited the disease from their parents. DG quantitation by whole-mount TEM is valuable in detecting DG deficiency.