title: Management of heparin resistance during cardiopulmonary bypass: the effect of five different anticoagulation strategies on hemostatic activation.
abstract: OBJECTIVE
  Attenuation of hemostatic activation is a central goal during CPB. However, this poses a problem in patients insensitive to heparin. The present investigation was performed to assess different strategies of managing patients with heparin resistance during CPB.
  
  
  METHODS
  A randomized, prospective clinical investigation.
  
  
  METHODS
  A major European heart center.
  
  
  METHODS
  Five groups with 20 patients each were investigated.
  
  
  METHODS
  The groups were handled as follows: (1). maintenance of a target ACT, (2). maintenance of the target unfractionated heparin (UFH) level and supplementation of a UFH level-based strategy with (3). AT III, (4). the direct thrombin inhibitor r-hirudin, or (5). the short-acting platelet glycoprotein (GP) IIb/IIIa antagonist tirofiban. Platelet count and generation of contact factor XIIa, thrombin, and soluble fibrin were assessed. Samples were obtained before CPB and after CPB before protamine infusion.
  
  
  RESULTS
  There were no differences observed in the generation of factor XIIa. The UFH-based strategy and supplementation with AT III, r-hirudin, and tirofiban resulted in significantly reduced (p < 0.05) thrombin generation compared with ACT management. A significant reduction of fibrin formation was seen only in patients who received AT III, r-hirudin, or tirofiban supplementation to the UFH. The administration of tirofiban resulted in a significant preservation of the platelet count compared with the other groups. There were no significant differences in the postoperative blood loss.
  
  
  CONCLUSIONS
  Activation of hemostasis during CPB in heparin-resistant patients most likely has to be attributed to stimulation of the tissue factor pathway. Even the sole use of high concentrations of UFH does not effectively inhibit this activation. Therefore, in these patients anticoagulation during CPB with UFH should be supplemented with either AT III, a short-acting direct thrombin inhibitor, or a short-acting platelet glycoprotein IIb/IIIa antagonist.
authors.affiliation: Department of Anesthesia, Deutsches Herzzentrum Berlin, Germany. Koster@dhzb.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Koster
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischer
authors.forename: Marcus
authors.initials: M
authors.lastname: Gruendel
authors.forename: Andreas
authors.initials: A
authors.lastname: Mappes
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Kuebler
authors.forename: Matthias
authors.initials: M
authors.lastname: Bauer
authors.forename: Herman
authors.initials: H
authors.lastname: Kuppe
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D000991:Antithrombins / Q000627:therapeutic use; D001779:Blood Coagulation Factors / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D004351:Drug Resistance / Q000502:physiology*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006487:Hemostasis / Q000187:drug effects*; D006493:Heparin / Q000627:therapeutic use*; D024764:Hirudin Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011446:Prospective Studies; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001779:Blood Coagulation Factors; D005343:Fibrinolytic Agents; D014443:Tyrosine; D006493:Heparin; D000077466:Tirofiban