Structural-functional relationships in platelets in acute leukemia and related disorders

Platelet ultrastructure and adenine nucleotide metabolism were studied in acute leukemia in order to elucidate mechanisms for the functional defects of platelets in this clinical setting. A number of structural defects were observed: (1) giant platelets, (2) marked variability in the number and size of cytoplasmic granules, (3) dilatation of the open channel system, (4) cytoplasmic vacuolization, and (5) poorly delineated microtubular system. Metabolic defects included reduced cellular concentrations of ATP and ADP and selective reduction of the storage pool (non-metabolic) nucleotides. Stimulation of platelets was associated with delayed and incomplete granule migration, reduced degranulation, subnormal release of ATP and ADP, and poor platelet aggregate formation. The structural and metabolic defects observed indicate abnormalities exist in the contractile mechanism and the release reaction of platelets in acute leukemia which partly explain the functional defects reported previously. Platelets from patients with pre-leukemic states share some of the structural and metabolic defects seen in acute leukemia. The defects are less uniform consistent with a lesser degree of functional impairment than seen in acute leukemia. Studies of megakaryocytic ultrastructure suggest that the structural defects seen in acute leukemia and pre-leukemia may arise in the late stages of megakaryocyte maturation.