Abstract
We have studied a family with a previously undescribed familial platelet abnormality. 5 year old twins were evaluated because of excessive bruising and bleeding since infancy. Their mother also had a moderate bleeding tendency. All three had slightly decreased numbers of platelets (P) of variable size, abnormally low prothrombin consumption (which corrected with a P substitute), and abnormal P factor 3 availability (which corrected with disruption of P by repeated freezing and thawing). P aggregation was normal with ADP, epinephrine and ristocetin, but absent upon addition of collagen. SEM revealed abnormal surface activation upon contact, with the multi-podded giant P showing little evidence of spreading capability. In all 3 subjects P morphometry confirmed the impression of giant P. Whereas only 10% of normal control P had a maximum diameter (D max) of >3um, 77-82% of the twins
β
P had a D max of >3um, while 40% of the mother’s P did as well. Whereas only 5% of normal P had a surface area (SA) of>4.5 um
2
, 55 and 93% of the twins' P and 50% of their mother’s P had>4.5 um
2
SA. Morphologically a number of P profiles had extensively vacuolated interiors (twins had 5-6 X normal). Other P sections contained only a few organelles. We applied quantitative morphometry to P sections. When organelles were counted per um
2
of P, all 3 family members had mitochondria and ∝ granules in the normal range, whereas all 3 had a slight reduction in dense bodies. (These findings rule out a diagnosis of gray platelet syndrome). The ∝ granule compartment, although of normal numbers, displayed a higher than normal proportion of mixed type granules (dense component, bulls eye configurations in a lower density homogeneous matrix). Multiple defects (20% or more vacuolated P, reduced dense bodies, abnormal surface membrane) appear to be responsible for ineffective platelet plug formation.