Correlation of GP53 and P-selectin expression in myeloproliferative disorders and normal controls

Platelet degranulation occurs when platelets are activated Alpha degranulation releases P-selectin whereas lysosomal degranulation releases GP53. A correlation between these two markers might therefore be expected. We studied the correlation between P-selectin and GP53 in 50 patients with myeloproliferative disorders (MPD), 35 normal controls and 105 disease controls (patients with inflammatory bowel disease [IBD, n=52], rheumatoid arthritis [RA, n=26] and coronary artery disease [CAD, n=27]) by flow cytometry before and after stimulation with thrombin ex vivo. There was no significant correlation between percentage expression of P-selectin and GP53 in unstimulated samples in normal individuals; r=0.13, P=0.3, n=34. Mild thrombin stimulation (10 mU/ml) led to both alpha and lysosomal degranulation with a strong correlation (r=0.62, P<0.001, n=35). Disease controls (IBD, RA and CAD) showed similar trends. In patients with MPD, in contrast, a strong correlation between the expression of these platelet activation markers was demonstrable in unstimulated samples (r=0.37, P=0.007, n=50). P-selectin and GP53 expression in stimulated samples also correlated well. The data support the existence of different control pathways for the steady state expression of P-selectin and GP53. Heterogeneous steady state responses of P-selectin and GP53 may be physiological and loss of this heterogeneity may be a hitherto unreported and pathologically important feature of MPD. This lack of correlation appears to be specific to MPD and is not simply a function of increased in vivo platelet activation.