ristocetin and Nephrotic-Syndrome

In 22 children with steroid responsive nephrotic syndrome (SRNS), we examined platelets aggregability to ristocetin, and the data obtained wre compared with negative charge on platelet membrane based on the binding of cationic dye alcian blue 8GX (AB) or plasma levels of von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor (Rcof) activity. At the initial or relapse stage of SRNS, the enhanced platelet aggregation to ristocetin was observed, and correlated with the decreased alcian blue binding to platelets. Ristocetin-induced vWF:Ag binding to platelets by using 125I-vWF was significantly increased. In addition, ristocetin-induced platelets aggregation (RIPA) using washed nephrotic platelets still enhanced as found in the patient's platelets rich plasma (PRP), even when it was resuspended into normal plasma. These results suggest that the decrease of platelet surface negative charge play an important role of heighten RIPA found in children with SRNS.

Topics: Adolescent; Blood Platelets; Child; Child, Preschool; Female; Humans; Male; Nephrotic Syndrome; Platelet Aggregation; Ristocetin; von Willebrand Factor

To elucidate the mechanism of enhanced ristocetin-induced platelet aggregation (RIPA) in steroid-responsive nephrotic syndrome (SRNS), plasma levels of von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor (RCof) were examined in 6 patients and the amount of ristocetin-induced vWF binding to platelets was determined. At the initial or relapse stage, the plasma vWF:Ag level was 415 +/- 137% and the RCof level was 364 +/- 117%. The ratio of RCof/vWF:Ag was 0.90 +/- 0.15 and no abnormalities of vWF:Ag multimers were observed, indicating that neither functional nor structural abnormalities were present in patient's plasma. The amount of ristocetin-induced normal vWF binding to nephrotic washed platelets, when ristocetin was used at concentrations of 0.5, 0.75, and 1.0 mg/ml, was 152-163% above the binding to normal platelets. In addition, nephrotic washed platelets resuspended in either normal or nephrotic plasma aggregated at a low concentration of ristocetin (0.75 mg/ml) which did not induce aggregation of normal platelets. In accordance with these observations, the decrease of Alcian blue 8GX binding to platelets, reflecting diminished surface negative charge, was also observed. These results appear to indicate that the plasma vWF level and the altered surface-negative charge in platelets both contribute to heightened vWF binding to GPIb, thus lowering the ristocetin concentration required for RIPA in SRNS.

Topics: Adolescent; Adrenal Cortex Hormones; Alcian Blue; Antigens; Child; Child, Preschool; Female; Humans; Iodine Radioisotopes; Male; Nephrotic Syndrome; Platelet Aggregation; Platelet Membrane Glycoproteins; Protein Binding; Ristocetin; von Willebrand Factor

In 20 patients with nephrotic syndrome we confirm previous findings of in vitro platelet hyperaggregability to arachidonic acid, and describe similar hyperaggregability to ristocetin. As previously reported also, the addition of albumin to nephrotic platelet-rich plasmas corrected platelet hyperaggregability to arachidonic acid, but exerted little effect on ristocetin-induced aggregation, and there was no correlation between platelet aggregation thresholds to arachidonate and to ristocetin. Incubation with indomethacin abolished the generation of thromboxane B2 after stimulation with arachidonate, but had no effect on the stimulation with ristocetin, during which no TxB2 was produced. The nephrotic patients had elevated factor VIII-related antigen (Factor VIII R:Ag) concentrations in their plasma, but in addition both decreased serum IgG and platelet-associated IgG were found which were correlated. The hyperaggregability of nephrotic platelets to ristocetin may relate to the elevated factor VIII R:Ag levels, or to the low platelet-associated IgG, since platelet IgG Fc receptors and von Willebrand factor receptors are spatially close or identical.

Topics: Adult; Antigens; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Factor VIII; Humans; Immunoglobulin G; In Vitro Techniques; Indomethacin; Male; Middle Aged; Nephrotic Syndrome; Platelet Aggregation; Ristocetin; Serum Albumin; Thromboxane B2; von Willebrand Factor