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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 adenine nucleotides and the release mechanism of platelets in acute leukemia. These defects appear to contribute to an impairment in the release reaction in these platelets. Many of the ultrastructural and metabolic defects seen in acute leukemia occur in platelets in preleukemia.
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PMID:The platelet defect in leukemia. Platelet ultrastructure, adenine nucleotide metabolism, and the release reaction. 4 18

Abnormalities in platelet dense granules, small intracellular organelles containing ATP, ADP, calcium, serotonin, and pyrophosphate, have frequently been reported in patients with leukemia and myeloproliferative disorders, particularly acute and chronic myelogenous leukemia. Recent studies of a family which includes several members with an autosomal dominant dense granule deficiency condition show an association between the presence of this form of dense granule deficiency and the development of acute myelogenous leukemia. Studies in two additional patients, one with the Monosomy 7 syndrome and the second with a myelodysplastic syndrome, revealed a defect in platelet dense granules. This defect appears to be due to an abnormality in the formation of these granules rather than the presence of empty vesicular structures or decreased contents due to activation associated secretion. The results suggest that the defect in platelet dense granules associated with leukemia or myelodysplastic syndromes may result from a chromosome alteration in the megakaryocyte cell line leading to decreased formation of dense granules. Studies in the family with an inherited bleeding disorder suggest that a gene coding for a protein important for the formation of dense granules is located adjacent to a gene which, when abnormal, may predispose to the development of leukemia.
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PMID:Platelet storage pool deficiency, leukemia, and myelodysplastic syndromes. 129 Sep 57

Platelet function and morphologic characteristics were evaluated in 43 patients with myeloproliferative disease (MPD), 5 patients with myelodysplastic syndrome (MDS), and 7 patients with secondary thrombocytosis (ST). Platelet Factor IV (PF4) and B-thromboglobulin (BTG) showed slight elevation in ST but significant elevation in all MPDs. They were either normal or slightly elevated in MDS. Defective platelet aggregation with one or more inducers was seen in 62% of all patients. An epinephrine-induced defect was the most consistent aggregation abnormality. Hyperaggregation and spontaneous aggregation were seen in 15% of patients. Of the eight patients who showed increased bleeding tendency, all eight showed defective aggregation with two or more inducers, five showed decreased surface activation response, as well as decreased or abnormal granules and dense tubular disarray in the transmission electron microscope (TEM) study. Seven patients had clinical evidence of recurrent arterial and venous thromboses. Five of these patients showed hyperaggregation response to adenosine diphosphate and collagen and abnormal Wu and Hoak platelet aggregate ratio. Four patients showed spontaneous aggregation on aggregometer. Surface activation response was significantly increased in five patients, and an increase in platelet granules by TEM study was seen in four patients. Primary thrombocythemia could be differentiated from secondary thrombocytosis (ST) by the presence of abnormal aggregation response and significantly increased PF4 and BTG in the former, and greatly elevated plasma fibrinogen and Factor VIII, as part of acute phase reactant response, in the latter.
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PMID:Platelet function and structure in myeloproliferative disease, myelodysplastic syndrome, and secondary thrombocytosis. 252 65

Because qualitative neutrophil and platelet dysfunction is an important concomitant of the myelodysplastic syndrome, functional studies were performed prospectively of cells from eight patients with myelodysplastic syndrome undergoing treatment with recombinant alpha 2 interferon. Neutrophil studies performed included myeloperoxidase release and superoxide anion generation, measured spectrophotometrically, in response to stimulation by phorbol-12-myristate-13-acetate, opsonized zymosan, and the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP), respectively. The most consistently abnormal of these tests was the fMLP-stimulated superoxide anion generation, which was low in six of seven patients tested. Mean results with this test were significantly lower than controls (mean +/- SD = 5.11 +/- 2.41 nmol/10(6) patient cells vs. 10.14 +/- 3.02 with normal cells, p less than 0.001). No significant change was noted following 2 or 8 weeks of interferon therapy. Because of the severe thrombocytopenia prevalent in myelodysplastic syndrome, fewer platelet studies were feasible. One patient, however, exhibited normal platelet numbers but markedly decreased aggregation in response to arachidonic acid, epinephrine, and collagen. After 4 weeks of treatment, this patient's platelet aggregation was noted to be normal. Platelets from two patients were purified by gel filtration, and the ATP/ADP ratios were determined by HPLC. Pretreatment ATP/ADP ratio of one patient was 4.85 (normal = 1.85 +/- 0.28) which declined to 3.27 on treatment and then returned to 4.80 following a 14-day period off treatment. Another patient, also with elevated ATP/ADP, exhibited a smaller decline during a treatment cycle. From these studies it was concluded that fMLP-stimulated superoxide generation may be a sensitive marker for neutrophil dysfunction in the myelodysplastic syndrome. No evidence was found for improvement of neutrophil dysfunction following alpha 2 interferon treatment. alpha 2 interferon, however, may sometimes have beneficial effects upon platelet dysfunction.
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PMID:A trial of recombinant alpha 2 interferon in the myelodysplastic syndrome: II. Characterization and response of granulocyte and platelet dysfunction. 282 14

Nine patients with myelodysplasia or myeloproliferative syndrome were studied with respect to platelet count and volume, 51Cr and 14C-serotonin platelet kinetics, bleeding time, and platelet dense and alpha-granule contents. Platelet counts ranged from 45,000 to 293,000 platelets/microliters. The bleeding time was significantly longer (greater than 4 minutes) than the predicted value in seven of nine patients. All patients had significant dense granule storage pool depletion (thrombin-releasable ADP was 0.59 +/- 0.30 vs. 2.41 +/- 0.20 mumol per 10(11) platelets in patients compared with normal volunteers; total platelet ADP was 0.97 +/- 0.29 vs. 2.72 +/- 0.15, and total platelet ATP/ADP was 4.77 +/- 1.89 vs. 1.65 +/- 0.11). The prolongation in bleeding time correlated inversely with thrombin-releasable ADP (r = -0.637, p less than 0.01) and with total ADP (r = -0.832, p less than 0.005), and directly with the ATP/ADP ratio (r = 0.781, p less than 0.005). When autologous platelets were doubly labeled with 14C-serotonin and 51Cr to test for loss of dense granule contents, marked preferential shortening of the 14C-serotonin platelet disappearance curve with relation to 51Cr platelet survival was observed in five of the six patients (six normal participants uniformly showed 14C-serotonin platelet disappearance patterns that were 15% to 20% longer than 51Cr platelet survivals). Reduction in alpha-granule contents was less striking and occurred less frequently than dense granule depletion (two of nine values were significantly reduced for platelet factor 4 content, whereas all patients had significantly reduced dense granule ADP levels). Mean plasma levels of both platelet factor 4 and beta-thromboglobulin were elevated in patients compared with normal participants (4.1 +/- 3.2 and 26.6 +/- 12.3 vs. 1.8 +/- 1.0 and 6.0 +/- 3.6 ng/ml; p less than 0.01 and p less than 0.01, respectively). Two patients had elevated urinary platelet factor 4. There was no correlation between platelet factor 4 content and thrombin-releasable platelet ADP levels (r = 0.167, p greater than 0.1). These patients had acquired storage pool deficiency of platelet dense granule ADP that correlated directly with platelet dysfunction, as measured by prolongation of bleeding time. The reduction in dense granule constituents appears to be the consequence of an ongoing loss of dense granule contents from circulating platelets.
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PMID:Correlation between prolonged bleeding time and depletion of platelet dense granule ADP in patients with myelodysplastic and myeloproliferative disorders. 623 83

Platelet function was studied in 17 patients with preleukaemia and the results were compared with those of 28 patients with other chronic myeloproliferative disorders. The test pattern included bleeding time (Ivy), platelet retention (Hellem II), PF-3 activity and availability after exposure to ADP and kaolin, and ADP-, epinephrine-, collagen- and ristocetin-induced aggregations. Platelet function was frequently impaired in patients with preleukemia. The defects were similar to those found in other myeloproliferative disorders. The most consistent finding was defective aggregation. Patients with thrombocytosis and/or with increased amounts of megakaryocytes in the bone marrow had fewer defects in platelet function. Retention defect was more common in patients with hypolobulated megakaryocytes, especially in those having a specific marker, the 5q- chromosome, in their bone marrow cells.
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PMID:Platelet function in preleukaemia. 746 20

Bleeding in myelodysplastic syndromes (MDS) is often related to thrombocytopenia. However, because MDS is a stem cell disorder, it is conceivable that platelet function (PF) abnormalities may play a role as well. A few studies have been reported, mainly with platelet aggregation (PA). A summary of the information discloses that about 68 MDS patients have been studied. Despite some conflicting data, it can be concluded that PA defects are quite common in MDS. About 75% of MDS patients demonstrated reduced PA with epinephrine, followed by decreased PA with arachidonic acid (54%), ADP (46%), collagen (43%), and ristocetin (22%). Several other PFs were studied, but the data require caution in interpretation. Despite the relatively high incidence of platelet dysfunction, bleeding in MDS patients is uncommon, with episodes tending to be mild, although recurrent. Nevertheless, some correlation between PA abnormalities and the tendency to bleed has been suggested. As patients demonstrate more PA defects, they tend to bleed more. Some authors suggest that PF studies may assist in diagnosing tough cases of MDS, as well as serving as prognostic markers. A large-scale study testing PF in a large number of MDS patients is required and is expected.
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PMID:Platelet function in the myelodysplastic syndromes. 1074 19

Platelet aggregation was decreased under action of ADP and collagen in patients with myelodysplastic syndrome. The decrease in aggregation started from 3-rd minutes and decreased in 4 and 5 minutes after action of ADP. The study of Ca(2+)-ATPase and Na+, K(+)-ATPase membrane activities showed the decrease in Ca(2+)-ATPase and increase in Na+, K(+)-ATPase activity in the patients with myelodysplastic syndrome.
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PMID:[Platelet membrane Ca(2+) and Na(+), K(+)-ATPase activity and aggregation in myelodysplastic syndrome]. 1291 63

The current study was aimed at investigating platelet function in MDS and its clinical significance. There were 23 patients with untreated MDS at presentation, including refractory anemia (RA), RA with ringed sideroblasts, RA and excess blasts and chronic myelomonocytic leukemia RAEBt. The mean platelet count was 167.9 x 109/L. Patients with a platelet count less than 70 x 109/l were excluded. The mean bleeding time (BT) was 2.7 min. Only four MDS patients had BT longer than the normal 1-4 min range. Platelet aggregation (PA) was studied with epinephrine (Epi), ADP, arachidonic acid (AA), ristocetin and collagen. Overall, 16 (70%) patients had PA abnormality, 65% had impaired Epi-induced PA, 57% demonstrated reduced ADP-induced PA. AA, ristocetin and collagen was decreased PA in 48, 22 and 17%, respectively. Five patients (22%) demonstrated spontaneous PA. Only seven patients (30%) were found to have normal PA with all five inducers. Six (26%) patients had spontaneous mild bleeding and all six bleeding MDS patients demonstrated at least one abnormal platelet function. The only bleeding patient with all five PA tests normal demonstrated prolonged BT. In the present study of 23 newly diagnosed MDS patients, PA abnormalities were relatively common, the BTs were usually normal, and bleedings were relatively uncommon and mild at platelet count between 70 and 397 x 109/l.
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PMID:Platelet function and its clinical significance in the myelodysplastic syndromes. 1516 10

The occurrence of a thrombocytopathy concomitantly to the development of a malignant haemopathy has been reported for some time, but little is known about the mechanism(s) involved in the platelet dysfunction. Platelet glycoprotein VI (GPVI) has now been identified as a principal platelet receptor for collagen. In this paper, we report the cases of two patients with a myelodysplasia and a B lymphopathy, respectively, who presented with thrombocytopathy in relation to a defective GPVI-mediated platelet reactivity to collagen. Thus, with regard to the different steps of adhesion, activation secretion or aggregation, patients' platelet responses to collagen and to the GPVI specific agonists, collagen related peptide (CRP) or convulxin were null or dramatically impaired. Platelet responses to other agonists ADP, TRAP, Arachidonic acid were normal or showed only a moderate decrease. GPVI content was repeatedly normal, and binding of specific ligands, such as convulxin, satisfactory. Nevertheless, specific activating monoclonal antibodies and convulxin failed to induce platelet secretion; collagen, CRP or convulxin were unable to provoke calcium mobilisation. Furthermore, using a perfusion chamber model, we showed that ex vivo collagen-induced thrombi formation was very impaired. Taken together, these data provide evidence, for the first time, of an acquired defect in GPVI-mediated platelet reactivity to collagen, which reflects data observed in constitutional GPVI deficiencies, in two patients with malignant haemopathies.
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PMID:Defective collagen-induced platelet activation in two patients with malignant haemopathies is related to a defect in the GPVI-coupled signalling pathway. 1563 May 3


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