title: Hemodilution modulates the time of onset and rate of fibrinolysis in human and rabbit plasma.
abstract: BACKGROUND
  Fibrinolysis has a critical role in the development of bleeding after insertion of a ventricular assist device (VAD). However, chronically, VAD-mediated fibrinolysis may also diminish thromboembolic events. Management of VADs involves fluid administration. It was hypothesized that the fluid administered could modulate fibrinolysis.
  
  
  METHODS
  Human plasma was diluted (0% to 30%) with 0.9% NaCl, 5% albumin or Voluven (6% hydroxyethyl-starch [HES], mean molecular weight 130 kD) and exposed to tissue-type plasminogen activator (tPA). Plasma obtained from rabbits just before and after 30% dilution with PentaLyte (6% HES, 220 kD), Voluven or Hextend (6% HES, 450 kD) were exposed to tPA. Thrombelastographic clot strength and onset/rate of fibrinolysis were determined.
  
  
  RESULTS
  In human plasma, 0.9% NaCl significantly decreased clot strength, but either prolonged or maintained the onset of fibrinolysis, with the rate of fibrinolysis significantly increased only at 30% dilution. Five percent albumin significantly decreased clot strength and did not affect the onset of fibrinolysis, but it did decrease the rate of fibrinolysis. Voluven significantly decreased clot strength to the greatest extent compared with the other fluids, and decreased the time of onset of fibrinolysis. Rabbit plasma after hemodilution demonstrated significantly decreased clot strength and decreased time of onset of fibrinolysis as compared with Voluven in human plasma.
  
  
  CONCLUSIONS
  Compared with crystalloid or albumin, HES solutions enhance fibrinolysis by decreasing clot strength and decreasing the time of onset of fibrinolysis. Further studies are warranted to determine whether the fluid administered to patients with VADs can impact hemorrhagic and thrombotic morbidity.
authors.affiliation: Division of Cardiothoracic Anesthesia, Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, Alabama 35249-6810, USA. vnielsen@uab.edu <vnielsen@uab.edu>
authors.forename: Vance G
authors.initials: VG
authors.lastname: Nielsen
mesh_terms: D000418:Albumins / Q000494:pharmacology; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D026122:Factor XIIIa / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology*; D006353:Heart-Assist Devices / Q000009:adverse effects; D006438:Hemodilution / Q000379:methods*; D006470:Hemorrhage / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010949:Plasma / Q000502:physiology*; D011817:Rabbits; D012965:Sodium Chloride / Q000494:pharmacology; D013927:Thrombosis / Q000503:physiopathology / Q000517:prevention & control; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000502:physiology; D000979:alpha-2-Antiplasmin / Q000378:metabolism
chemical_list: D000418:Albumins; C485123:HES 130-0.4; D006895:Hydroxyethyl Starch Derivatives; D000979:alpha-2-Antiplasmin; D012965:Sodium Chloride; D005337:Fibrin; D026122:Factor XIIIa; D010959:Tissue Plasminogen Activator