Platelet activation markers in patients with nephrotic syndrome. A comparative study of different platelet function tests.
OBJECTIVE
Enhanced platelet reactivity may play a significant role in the genesis of the hypercoagulable state of nephrotic syndrome. However, the role of platelet function testing in nephrosis is controversial, partly because the methods used to assess platelet function (platelet aggregation and immunoassays of plasma beta-thromboglobulin and platelet factor 4) have such marked methodological problems. In the present study, we evaluated several tests assessing platelet function in 18 adult patients with idiopathic nephrotic syndrome and normal renal function.


METHODS
Platelet function was assessed by measurement of plasma beta-thromboglobulin (enzyme-linked immunosorbent assay, ELISA), plasma P-selectin (ELISA), circulating platelets exposing the activation-dependent antigens P-selectin (CD62P) and lysosomal GP53 (CD63) (flow cytometry), and by aggregation response to agonists such as ADP and collagen. Results were compared to those obtained in a group of 16 age- and gender-matched healthy subjects.


RESULTS
Levels of plasma beta-thromboglobulin (p = 0.001), plasma P-selectin (p < 0.001), and CD62P/CD63-positive platelets (p < 0.001 for both) were increased in nephrotic patients as compared to healthy controls. Platelet hyperaggregability in vitro was found in 13/18 patients. The reproducibility of platelet activation markers, as assessed by blood sample collection a week later from all patients, was found to be higher for plasma P-selectin (Spearman correlation coefficient, R = 0.99) and circulating activated platelets (CD62P: R = 0.97; CD63: R = 0.96) than for plasma beta-thromboglobulin (R = 0.78).


CONCLUSIONS
Pronounced platelet activation takes place in nephrotic syndrome and may contribute to the hypercoagulability of nephrosis. Whole blood flow cytometry assay of platelet activation and plasma P-selectin assay may represent useful tests to assess the hypercoagulable state in nephrotic patients.
Institute of Nephrology, Department of Medicine, G. D'Annunzio University, SS Annunziata Hospital, Via dei Vestini, I-66013 Chieti, Italy.
Vittorio
V
Sirolli
Enzo
E
Ballone
Donato
D
Garofalo
Gabriele
G
Merciaro
Nicola
N
Settefrati
Rocco
R
Di Mascio
Patrizia
P
Di Gregorio
Mario
M
Bonomini
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000097:blood*; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D060149:Tetraspanin 30; D001620:beta-Thromboglobulin / Q000378:metabolism
D015703:Antigens, CD; D015415:Biomarkers; C554586:CD63 protein, human; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D001620:beta-Thromboglobulin