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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Platelet abnormalities in idiopathic myelofibrosis: functional, biochemical and immunomorphological correlations.

BACKGROUND: An extensive study of platelet function was performed on 18 consecutive patients affected by idiopathic myelofibrosis (IM). MATERIALS AND METHODS: Clinical hematological and morphofunctional parameters were studied in IM patients and control subjects. Platelet tests, ultrastructural data, immunocytochemical von Willebrand factor detection, freeze fracturing results and free cytosolic calcium level were evaluated. RESULTS: Bleeding time was frequently found to be prolonged, but it never reached levels which could give any cause for concern. Aggregation by ADP, collagen and epinephrine was always altered, sometimes profoundly; on the contrary, agglutination by ristocetin was almost always normal, albeit occasionally increased. Plasma beta-TG and PF4 levels were found to be elevated in 11 and 12 patients, respectively. This indicated an abnormal release from platelet alpha-granules. Depletion of alpha-granules was also confirmed by the intraplatelet von Willebrand factor (vWF) labelling with colloidal gold particles bound to polyclonal antibodies against human vWF. In fact: 1) the number of positive alpha-granules/microm2 and per single platelet was reduced; 2) the intensity of the immunocytochemical reaction for single positive alpha-granules and for each platelet was significantly reduced. Freeze-fracturing studies showed an increase in the number of intra-membrane particles (IMP) on the P face of the platelet membrane with respect to normal platelets preincubated with ADP. However, no differences in their distribution or diameter were observed. High concentrations of free cytosolic calcium were always found and Ca++ ATPase activity was increased. Conversely, Na+/K+ ATPase activity was always reduced. CONCLUSIONS: We can hypothesize that the platelet membrane is altered in IM, resulting in facilitated activation, even by subliminal stimuli, and that this continuous platelet activation ultimately leads to alpha-granule depletion.[1]


  1. Platelet abnormalities in idiopathic myelofibrosis: functional, biochemical and immunomorphological correlations. Leoni, P., Rupoli, S., Lai, G., Brunelli, M.A., Belmonte, M.M., Pugnaloni, A., Rabini, R.A., Mazzanti, L., Biagini, G. Haematologica (1994) [Pubmed]
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