title: Coagulation activation, depletion of platelet granules and endothelial integrity in case of uraemia and haemodialysis treatment.
abstract: BACKGROUND
  During haemodialysis (HD) treatment, increase of platelet (PLT) activation and induction of procoagulant activity is demonstrated. Although the role of the endothelium and its direct interaction with coagulation and homeostasis is known, it is not elucidated how PLT activation markers and activation of coagulation coincide with markers of endothelial integrity during HD treatment. In the present study uraemia and HD induced changes, with particular emphasis on PLT granules depletion, activation of coagulation and endothelial integrity were investigated.
  
  
  METHODS
  To detect depletion of PLT granules, peripheral blood slide smears were screened by light microscopy for qualitative evaluation of PLT granule containing cytoplasm, as indicated by its granules staining density. Activation of coagulation was investigated by establishement of thrombin-antithrombin (TAT) and fibrinogen concentrations. To evaluate endothelial integrity proendothelin (proET-1) plasma concentrations were established.
  
  
  RESULTS
  Results of our study demonstrate that proET-1 plasma concentrations were obviously increased in the subjects' group with end-stage chronic kidney disease (CKD) and renal failure if compared with a group of apparently healthy subjects. The amount of depleted PLT granules was obviously increased in the subjects' group with end-stage CKD if compared with the group with renal failure. Mean plasma concentrations of TAT and fibrinogen revealed results within the reference range.
  
  
  CONCLUSIONS
  It is demonstrated that uraemia is associated with endothelial damage and aberrations in PLT granules morphology in subjects with HD treatment. We hypothesize that increased proET-1 concentrations reflect ongoing stress on endothelial cells amongst others due to uraemia. Biomarkers like proET-1 and aberrations in PLT granules morphology assist in the early detection of procoagulant activity of the endothelium.
authors.affiliation: Department of Clinical Chemistry, Haematology & Immunology, Medical Center Alkmaar, Alkmaar, The Netherlands. m.i.schoorl@mca.nl
authors.forename: Marianne
authors.initials: M
authors.lastname: Schoorl
authors.forename: Margreet
authors.initials: M
authors.lastname: Schoorl
authors.forename: Menso J
authors.initials: MJ
authors.lastname: Nubé
authors.forename: Piet C M
authors.initials: PC
authors.lastname: Bartels
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D016896:Treatment Outcome; D014511:Uremia / Q000097:blood* / Q000473:pathology / Q000628:therapy
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