title: Anticoagulation intensity sufficient for haemodialysis does not prevent activation of coagulation and platelets.
abstract: BACKGROUND
  A single bolus of dalteparin at the start of haemodialysis (HD) may prevent clot formation, but subclinical activation of platelets and coagulation may still occur. Consequently, the relationship between clinical clotting events and activation markers of platelets and coagulation before and during HD is of interest.
  
  
  METHODS
  The effect of tapered doses of dalteparin during 84 HD sessions (4-4.5 h) was prospectively examined in 12 patients. Six of the patients were treated with warfarin. The initial dalteparin dose was reduced to 50% if no clotting was observed. Clinical clotting was evaluated by inspection of the air trap every hour and by inspection of the dialyser after each session. Anti-FXa activity was measured for assessment of dalteparin activity. Markers of activated plasma coagulation, (thrombin-antithrombin (TAT) and prothrombin fragment 1+2 (PF1+2)) and a marker of platelet activation (beta-thromboglobulin, beta-TG), were measured before the start of and after 3 and 4 h of dialysis. Ten pre-dialytic patients with chronic renal failure served as a control group. A total of 230 measurements of each parameter were performed.
  
  
  RESULTS
  An anti-FXa activity above 0.4 IU/ml at the end of HD inhibits overt clot formation for 4 h. This was obtained by an intravenous dalteparin dose of about 5000 IU. TAT and PF1+2 correlated to clinical clotting episodes (r=0.50 and 0.47, P<0.001). beta-TG was not significantly correlated to clinical clotting. All parameters increased during the sessions (TAT, PF1+2, beta-TG, P<0.001). When measurements during clinical clotting episodes were disregarded, all parameters were still markedly increased. Warfarin-treated patients had lower TAT and PF1+2. Dialysis patients had higher beta-TG values than pre-dialytic patients.
  
  
  CONCLUSIONS
  Despite clinically effective anticoagulation, obtained by dalteparin administration, platelets and coagulation are activated by HD, resulting in a potentially thrombophilic state. Warfarin treatment reduces clinical clot formation and subclinical activation of coagulation.
authors.affiliation: Department of Internal Medicine, Research Institute for Internal Medicine, National Hospital, Oslo, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Sagedal
authors.forename: A
authors.initials: A
authors.lastname: Hartmann
authors.forename: K
authors.initials: K
authors.lastname: Sundstrøm
authors.forename: S
authors.initials: S
authors.lastname: Bjørnsen
authors.forename: F
authors.initials: F
authors.lastname: Brosstad
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000032:analysis; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D000990:Antithrombin III; D001777:Blood Coagulation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000097:blood; D017985:Dalteparin / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D015951:Factor Xa / Q000276:immunology; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D010940:Plant Proteins; D015539:Platelet Activation / Q000187:drug effects*; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D006435:Renal Dialysis; D014859:Warfarin / Q000627:therapeutic use; D001620:beta-Thromboglobulin / Q000032:analysis
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D004268:DNA-Binding Proteins; D010446:Peptide Fragments; D010940:Plant Proteins; D011498:Protein Precursors; C046193:antithrombin III-protease complex; D001620:beta-Thromboglobulin; C086710:positive element factor 1 protein, Oryza sativa; D014859:Warfarin; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D000990:Antithrombin III; D011516:Prothrombin; D010447:Peptide Hydrolases; D015951:Factor Xa; D017985:Dalteparin