An ultrastructural morphometric analysis of platelet giant and fusion granules

Our purpose in this study was to establish ultrastructural morphometric criteria that can be used to define pathologic giant and fusion platelet granules and to determine whether patients with neoplastic myeloproliferative disorders (MPD) can be distinguished from other patients. We have morphometrically analyzed 2,391 giant and fusion granule profiles from 46 patients with neoplastic MPD, 127 other diseased control subjects, and 30 normal subjects using a computerized image analyzer. The largest granule profile observed in normal subjects had an area of 0.51 mu 2 and a perimeter of 3.21 mu. The most irregularly shaped of the large granule profiles photographed from normal subjects had a form factor (FF) value of 0.31. FF values indicate the degree of deviation of a given granule contour from a circle and is expressed by the formula 4 pi A/P2. A pathologic granule profile was then defined as a granule that exceeded any of these limits. Fifty-seven percent of the patients with neoplastic MPD were determined to have abnormal platelet granule profiles using the aforementioned morphometric criteria. It was determined, however, that morphometrically defined giant- and fusion-type granule profiles were nonspecific and were also found in 20% of the other diseased patients with no clinical evidence of an underlying neoplastic MPD. Morphometry has allowed us to define the upper limits of normal for the area and perimeter of individual platelet granules. Morphometrically defined giant fusion granules were determined to be more prevalent in the neoplastic MPD group, but because of their nonspecificity, may only have diagnostic significance for the individual patient in specific clinical settings. The pathogenesis of platelet fusion granules is discussed.