IMPAIRED PLATELET BINDING OF FIBRINOGEN DUE TO A LOWER NUMBER OF GPIIB IIIA RECEPTORS IN POLYCYTHEMIA-VERA/

We have previously described a stimulus-specific defect in platelet ag gregation in polycythaemia vera (PV) after stimulation with surface re ceptor dependent agonists such as platelet activating factor (PAF), In contrast, responses to phorbol myristate acetate (PMA) were normal. W e now report that after PAF stimulation, using flow cytometry, the amo unt of fibrinogen bound to its receptor was significantly lower in PV platelets with a median MFI of 6.0 (range 4.1-17.3) compared to contro ls, 12.8 (range 8-21.3; n=11; p<0.01), We found no evidence of preacti vation of PV platelets. Quantitative analysis of GPIIIa gave a signifi cantly lower number of GPIIIa on resting PV platelets, 14300 subunits of GPIIIa (range 8500-15500) vs. 19800 for controls (range 13400-26800 ; n=12; p<0.01). Both patients and controls increased their number of receptors on the cell surface after stimulation with PAF and PMA, but the significant difference in the number of receptors per cell remaine d. Indirect evaluation of PAF receptor function showed that activation of CD 62 did not differ in PV and controls after PAF stimulation. Add itionally, although the basal level of serotonin in platelet-rich plas ma was significantly lower in PV, there was a threefold increase of th e basal level after stimulation with PAF for both PV and control plate lets, also indicating a normal interaction of PAF with its receptor. A lthough our results indicate both an impaired PAF induced aggregation in PV and a lower number of GPIIb/IIIa complexes on single platelets, whether these phenomena are related remains uncertain. (C) 1998 Elsevi er Science Ltd.