title: Abnormal platelet cytoskeletal assembly in hemodialyzed patients results in deficient tyrosine phosphorylation signaling.
abstract: BACKGROUND
  Uremic patients have a bleeding tendency associated with a platelet dysfunction. We evaluated the impact of a repeated hemodialysis procedure on primary hemostasis by analyzing different aspects of platelet activation 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 hemodialysis who were transferred to continuous ambulatory peritoneal dialysis. Studies included routine platelet aggregations and evaluation of platelet-subendothelium interactions under flow conditions. Contractile proteins and tyrosine 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 improved when patients were shifted from hemodialysis to continuous ambulatory peritoneal dialysis (P < 0.05 for both percentage of surface covered by platelets and aggregate formation). The association of cytoskeletal proteins in platelets from patients under hemodialysis treatment was statistically decreased with respect to the corresponding values in platelets from patients not 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-phosphorylated 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 stress during hemodialysis has a deleterious effect on the organization of platelet cytoskeleton, which seems to impair the translocation of signal transduction proteins within platelets compromising the platelet function in uremia.
authors.affiliation: Servicios de Hemoterapia-Hemostasia and Nefrología, Hospital Clínic, Fundació Clínic (IDIBAPS), Universitat de Barcelona, Spain. mdiaz@medicina.ub.es
authors.forename: M
authors.initials: M
authors.lastname: Díaz-Ricart
authors.forename: E
authors.initials: E
authors.lastname: Estebanell
authors.forename: A
authors.initials: A
authors.lastname: Cases
authors.forename: J
authors.initials: J
authors.lastname: Calls
authors.forename: J
authors.initials: J
authors.lastname: López-Pedret
authors.forename: M
authors.initials: M
authors.lastname: Carretero
authors.forename: R
authors.initials: R
authors.lastname: Castillo
authors.forename: A
authors.initials: A
authors.lastname: Ordinas
authors.forename: G
authors.initials: G
authors.lastname: Escolar
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D003599:Cytoskeleton / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010766:Phosphorylation; D010974:Platelet Aggregation; D010976:Platelet Count; D006435:Renal Dialysis; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism*; D014511:Uremia / Q000097:blood*
chemical_list: D014443:Tyrosine; D013917:Thrombin