Multifactorial genesis of enhanced platelet aggregability in patients with nephrotic syndrome.
Platelet aggregation, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF 4) release and thromboxane B2 (TxB2) formation in stimulated platelet-rich plasma were investigated in 13 patients with nephrotic syndrome who had normal serum creatinine levels (creatinine clearance greater than 70 ml/min/1.73 m2). In contrast to 13 sex- and age-matched controls, spontaneous platelet aggregation only occurred in patients with nephrotic syndrome with correlation to serum albumin and plasma fibrinogen levels. The EC50 (estimated concentration of aggregating agent to cause half maximum velocity of primary aggregation) for ADP and collagen and threshold concentration of arachidonic acid (threshold AA) were decreased in patients with nephrotic syndrome, reflecting a hyperaggregable state. In patients with nephrotic syndrome EC50 ADP values were significantly correlated to serum albumin, serum cholesterol and plasma fibrinogen, however, EC50 collagen or threshold AA did not correlate to these parameters. Plasma beta-TG levels were increased in patients, whereas plasma PF 4 levels were not significantly changed in patients compared to controls. In vitro TxB2 formation was elevated in patients only after stimulation with AA. Nevertheless, after stimulation with collagen and ADP, TxB2 formation was unchanged in patients compared to controls. Platelet hyperaggregability in nephrotic patients was confirmed in our study. However, unchanged thromboxane B2 formation after collagen stimulus as well as missing correlations between EC50 collagen or threshold AA and serum albumin were contradictory to the hypothesis that enhanced AA availability due to hypoalbuminemia is responsible for platelet hyperaggregability. Platelet hyperaggregability in terms of EC50 ADP being associated with serum albumin levels as well as to serum cholesterol and plasma fibrinogen indicate a multifactorial genesis.
Machleidt
C
C
Department of Nephrology, Robert-Bosch-Krankenhaus Stuttgart, Federal Republic of Germany.
Mettang
T
T
Stärz
E
E
Weber
J
J
Risler
T
T
Kuhlmann
U
U
D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000097:blood*; D010974:Platelet Aggregation; D010978:Platelet Factor 4 / Q000378:metabolism; D011863:Radioimmunoassay; D013929:Thromboxane B2 / Q000096:biosynthesis; D001620:beta-Thromboglobulin / Q000378:metabolism
D001620:beta-Thromboglobulin; D010978:Platelet Factor 4; D013929:Thromboxane B2