The platelet defect in leukemia. Platelet ultrastructure, adenine nucleotide metabolism, and the release reaction.

Abstract

A B S T R A C T The ultrastructure and adenine nucleotide metabolism of platelets from patients with acute leukemia were studied to elucidate possible mechanisms for the platelet dysfunction observed in this clinical setting. Nonstimulated (resting) platelets from leukemic patients varied greatly in size; exhibited marked variation in the number of alpha granules present per cell; had poorly delineated circumferential bands of microtubules; and often grossly dilated open channel systems or cytoplasmic vacuolization. The intracellular concentrations of ATP and ADP were significantly below normal, and the specific radioactivity of ATP and ADP of nonstimulated platelets in leukemia was equivalent to or exceeded that seen in stimulated normal platelets. Addition of ADP or collagen to platelets from leukemic patients was followed by retarded and incomplete shape change, delayed and incomplete centripetal migration of subcellular organelles, impaired degranulation, and the formation of loose aggregates composed of relatively few platelets. Stimulation of "leukemic" platelets with collagen led to the release of significantly subnormal amounts of ATP and ADP and no significant change in the specific radioactivity of the intracellular nucleotides. In contrast to the results in normal platelets, the conversion of ATP to inosine monophosphate and hypoxanthine in platelets in leukemia failed to increase significantly with collagen stimulation. The results indicate that abnormalities exist in the storage pool of adePortions of this work were presented to the 46th Annual

Effect of platelet count on secretion capacity: formulization and use of the formulae for evaluation of platelet secretion in thrombocytopenic patients

“…Bleeding may occur even when platelet count exceeds 50 000 ml À1 in hypoproliferative thrombocytopenias, especially in hematologic neoplasms [4][5][6]. In ITP, significant hemorrhage frequently does not occur even in very low platelet counts [7].…”

“…These observations suggest that platelet functional capacity may also play a role in bleeding complications during thrombocytopenia. In acute leukemia and ITP patients, platelet function disorders (mostly secretion defects) have been described in various studies [4,14,15]. However, these studies have been done only in patients with relatively mild thrombocytopenia (especially acute megakaryoblastic leukemia) as platelet functional evaluations could not be performed during prominent thrombocytopenia.…”

“…Clinical data suggest that platelet functional capacity and consequently bleeding risk are heterogeneous in various causes of thrombocytopenia [4][5][6][7]. Bleeding manifestations are relatively rare in patients with idiopathic thrombocytopenic purpura (ITP) as compared with equally thrombocytopenic patients with megakaryocyte deficiency.…”

“…Bleeding manifestations are relatively rare in patients with idiopathic thrombocytopenic purpura (ITP) as compared with equally thrombocytopenic patients with megakaryocyte deficiency. Hemorrhage may occur at apparently acceptable platelet levels in various thrombocytopenic patients, probably due to associated platelet dysfunction [4][5][6][8][9][10][11][12]. It is difficult to evaluate platelet functions in patients with thrombocytopenia and no routine method has been described for this purpose.…”

Increased Collagen Synthesis of Bone Marrow Fibroblasts by Materials Released from Platelets of Chronic Granulocytic Leukemia and Polycythemia vera

“…These platelet abnormalities in patients with CGL and PV are considered to be intrinsic. Cowan et al [4] have reported that there was no significant decrease of granules in platelets of the patients with myelofi brosis compared to that of normals. Weinfeld et al [ 17] have shown that the size of platelets from patients with myelofibrosis is larger than that from normals.…”