title: Effect of high- and low-molecular-weight low-substituted hydroxyethyl starch on blood coagulation during acute normovolemic hemodilution in pigs.
abstract: BACKGROUND
  Hydroxyethyl starches (HES) with lower impact on blood coagulation but longer intravascular persistence are of clinical interest. The current study aimed to investigate in vivo the isolated effect of molecular weight on blood coagulation during progressive acute normovolemic hemodilution.
  
  
  METHODS
  Twenty-four pigs were normovolemically hemodiluted up to a total exchange of 50 ml . kg . body weight of HES 650/0.42 or HES 130/0.42. Serial blood sampling was performed to measure HES plasma concentration and to assess blood coagulation. Concentration-effect relations were analyzed by linear regression, followed by the Student t test on regression parameters.
  
  
  RESULTS
  Blood coagulation was increasingly compromised toward hypocoagulability by acute normovolemic hemodilution with both treatments (P < 0.01). Significantly greater impact on activated partial thromboplastin time (P = 0.04) and significantly stronger decrease of maximal amplitude (P = 0.04), angle alpha (P = 0.02), and coagulation index (P = 0.02) was seen after acute normovolemic hemodilution with HES 650/0.42 as compared with HES 130/0.42. Except for factor VIII (P = 0.04), no significant differences between both treatments were observed when relating antihemostatic effects to HES plasma concentrations (P > 0.05). A significantly lesser decrease of hemoglobin concentration has been found with HES 650/0.42 as compared with HES 130/0.42 (P < 0.01) in relation to HES plasma concentrations.
  
  
  CONCLUSIONS
  High-molecular-weight HES (650/0.42) shows a moderately greater antihemostatic effect than low-molecular-weight HES (130/0.42) during acute normovolemic hemodilution. However, similar effects on hemostasis were observed with both treatments when observed antihemostatic effects were related to measured HES plasma concentrations. In addition, HES 650/0.42 may have a lower efficacy in immediately restoring plasma volume.
authors.affiliation: Department of Anesthesiology, Division of Clinical Pharmacology and Toxicology, University Hospital Lausanne, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Thyes
authors.forename: Caveh
authors.initials: C
authors.lastname: Madjdpour
authors.forename: Philippe
authors.initials: P
authors.lastname: Frascarolo
authors.forename: Thierry
authors.initials: T
authors.lastname: Buclin
authors.forename: Marco
authors.initials: M
authors.lastname: Bürki
authors.forename: Andreas
authors.initials: A
authors.lastname: Fisch
authors.forename: Marc-Alexander
authors.initials: MA
authors.lastname: Burmeister
authors.forename: Lars
authors.initials: L
authors.lastname: Asmis
authors.forename: Donat R
authors.initials: DR
authors.lastname: Spahn
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D001809:Blood Viscosity; D006438:Hemodilution; D006895:Hydroxyethyl Starch Derivatives / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D008970:Molecular Weight; D010314:Partial Thromboplastin Time; D010952:Plasma Substitutes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011517:Prothrombin Time; D012121:Respiration, Artificial; D013552:Swine; D013916:Thrombelastography
chemical_list: D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes