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In healthy persons, a daily dose of 2,000 IU of vitamin E given for 10 days does not prolong the bleeding time and has no influence on collagen- and ADP-induced platelet aggregation nor on platelet prostaglandin synthesis. Therefore, even high doses of vitamin E have no place in platelet function suppressing therapy.

Cyclooxygenase activity in human platelets reappears after ingestion of aspirin as a function of the platelet production rate. In different studies the activity reappeared without delay or with an interval of at least 48 h after stopping the drug. Because inhibition of megakaryocyte cyclooxygenase is the sole likely explanation for a delay we determined thromboxane B2 in human megakaryocytes obtained under local anaesthesia. We found that aspirin does not inhibit human megakaryocytes in vivo but does so in vitro. Therefore, it does not seem likely that there is actually a delay in platelet cyclooxygenase resurgence after aspirin intake. In order to suppress platelet cyclooxygenase constantly, aspirin should be given once or twice a day and not once or twice a week.

3 commonly used parameters for platelet aggregability were tested for their dependence on citrate concentrations. Relatively minor changes in citrate concentrations markedly influenced ADP threshold values for secondary aggregation. Collagen induced platelet malondialdehyde (MDA) production was reduced by increasing the citrate level. This effect was still present in plasma which was also anticoagulated with EDTA. Thrombin induced MDA production was considerably higher in EDTA than in citrate plasma. Citrate appears to inhibit aggregation as well as MDA synthesis. The latter effect does not seem to be solely caused by the effect of citrate on ionized calcium levels.

In a group of 56 patients with acute leukaemia, the relation between leukaemic cell motility and peripheral leukaemic cell count, degree of organomegaly, maturation and FAB classification was investigated. Cell motility was studied by means of directly observed motility and scoring of handmirror cells and anti-HLA-capping. The percentage of moving cells in the peripheral blood was higher than in the bone marrow. A positive correlation was found between the percentage of moving cells in the peripheral blood and the peripheral leukaemic cell count. In acute myeloid leukaemia, the percentage of moving cells in the bone marrow and the degree of organomegaly were higher in the monoblastic groups than in the myeloblastic groups. No correlation was found between directly observed motility, handmirror cells and capping. Leukaemic cell motility can play a role in the egress of leukaemic cells from the bone marrow, resulting in a higher tumour mass, thereby influencing prognosis.

In acute myeloid leukaemia the peripheral leukocyte count is known to be a prognostic factor. The preserved capacity of leukaemic cells to mature has also been suggested to be one. In a series of 179 cases of adult acute myeloid leukaemia peripheral leukaemic cell count and degree of maturation were found to be inversely correlated. As the degree of maturation of leukaemic cells in peripheral blood was lower than that in bone marrow in the majority of cases, blast cells appear to be released more easily from the marrow than cells that have matured to some extent in the direction of the larger promyelocytic or promonocytic cell type. In a series of 35 cases we found peripheral blast cells to be smaller than those in bone marrow. Moreover, central blast cell diameter and peripheral leukaemic cell count were inversely correlated. Therefore, leukaemic cell size or some factor related to it may contribute to the preferential egress of small immature cells from the marrow. Differences in proliferative activity could not account for the inverse correlation between degree of maturation and leukaemic cell count.

In acute myeloid leukemia the leukemic cells are thought to be blocked in their normal differentiation. The stage of differentiation is the basis for the FAB classification. Induction of cell differentiation is a new and promising development in the treatment of some myeloproliferative diseases. The criteria for cell maturation and differentiation are almost all based on the morphology of the leukemic cells. In this study we tried to specify the maturation stage of the leukemic cells by quantitative enzyme analysis. In the HL60 (promyelocytic) cell line cells we determined the following enzymes: myeloperoxidase; alpha naphthyl acetate esterase; alpha naphthyl butyrate esterase and lactate dehydrogenase. The enzyme profiles obtained after culturing the cells in the presence of the differentiation inducing agents 1:25 dihydroxy vitamin D3 and DMSO were compared with several cytochemical and functional parameters. The results obtained in this study show that quantitative enzyme analysis is a useful tool in the study of myeloid or monocytic differentiation.

In normal males, platelet prostaglandin synthesis as measured by malondialdehyde (MDA) production is blocked by more than 90% after administration of 600 mg of calciumacetylsalicylic acid and by more than 50% after 100 mg. Repeated doses of 100 mg at 12 h intervals progressively decrease MDA production to below 10% of the basic value. Bleeding time increases from 3.38 +/- 0.36 min to 7.73 0.91 min (mean +/- SEM). The data indicate that 12 h 100 mg doses of calciumacetylsalicylic acid (equal to 80 mg of aspirin) adequately inhibit platelet function.