Abnormal distribution of organelles in mouse Myh9^−/−and human MYH9-RD platelets. (A) Wide-field electron micrographs of mouse platelets showing the heterogeneous content of Myh9^−/− platelets (right) as compared with WT cells (left). Arrows point to low-content platelets and the arrowhead to a high-content platelet. (B) Quantification of the total number of organelles (α and δ granules, lysosomes, and mitochondria) per platelet as observed by TEM. The number of organelles is plotted as a function of the platelet size, and 215 and 190 platelets were analyzed for WT and Myh9^−/− mice, respectively. P < .0001 for comparison of variances in the point distribution between WT and Myh9^−/− mice. (C) 3D reconstructions from an FIB/SEM analysis showing the face and profile views of 1 WT (left) and 2 Myh9^−/− platelets (right). Note the strong heterogeneity in the organelle contents of the Myh9^−/− platelets as compared with the WT one. (D) Ultrastructure of human platelets from a control individual (i) as compared with a MYH9-RD patient (ii-iii). (E) Quantification of the number of organelles (α and δ granules, lysosomes, and mitochondria) per platelet as a function of the platelet size, for the MYH9-RD patient (right) and a normal donor (left). Organelles were counted in 178 and 170 platelets for the control and patient, respectively. P < .0001 for comparison of variances in the point distribution.