Abnormal platelet cytoskeletal assembly in hemodialyzed patients results in deficient tyrosine phosphorylation signaling

Background. Uremic patients have a bleeding tendency associated with a plat elet dysfunction. We evaluated the impact of a repeated hemodialysis proced ure on primary hemostasis by analyzing different aspects of platelet activa tion in uremic patients. Methods. Studies were performed in (1) eight patients with end-stage renal disease before the hemodialysis program was initiated and after initiating hemodialysis treatment, and in (2) eight patients on maintenance hemodialys is who were transferred to continuous ambulatory peritoneal dialysis. Studi es included routine platelet aggregations and evaluation of platelet-subend othelium interactions under flow conditions. Contractile proteins and tyros ine phosphorylation associated with the cytoskeleton were analyzed, before and after thrombin activation of platelets, by electrophoresis after Triton X-100 extraction. Results. No changes in the clinical parameters analyzed were observed among the different study groups. Aggregation and platelet adhesion only improve d when patients were shifted from hemodialysis to continuous ambulatory per itoneal dialysis (P < 0.05 for both percentage of surface covered by platel ets and aggregate formation). The association of cytoskeletal proteins in p latelets from patients under hemodialysis treatment was statistically decre ased with respect to the corresponding values in platelets from patients no t subjected to dialysis (P < 0.01 for actin). However, after two months on peritoneal dialysis, these values increased to almost control values (P < 0 .001 for actin, vs. hemodialysis). Similarly, translocation of tyrosine-pho sphorylated proteins to the cytoskeletal fraction was impaired in platelets from hemodialyzed patients, and it recovered partially after the patients transferred to continuous ambulatory peritoneal dialysis. Conclusions. Our present data support the concept that repeated platelet st ress during hemodialysis has a deleterious effect on the organization of pl atelet cytoskeleton, which seems to impair the translocation of signal tran sduction proteins within platelets compromising the platelet function in ur emia.