title: Hemostasis and hemodilution: a quantitative mathematical guide for clinical practice.
abstract: Quantitative changes of hemostasis during hemodilution remain unclear. With the increasing popularity of artificial blood substitutes (ABS), which solely provide oxygen-transport capacity, this issue becomes even more complex. We developed a mathematical model to quantitatively analyze hemostasis during hemodilution and validated it by recalculating patient data. We calculated and compared maximal allowable blood losses (MABL) related to minimal acceptable hematocrit, platelet concentration, and plasma fibrinogen concentration. MABL is the maximal blood loss that can be tolerated without any additional blood products. The variable with the smallest MABL thus limits hemodilution foremost. Hemodilution included isovolemic replacement of blood loss with colloid or acute normovolemic hemodilution (ANH) followed by isovolemic replacement of blood loss with colloid and ABS. We also related our findings to preoperative patient data (n = 204). The decline in platelet concentrations rarely (<2% of all patients) limits hemodilution. By contrast, critical plasma fibrinogen (< or =100 mg/dL) concentrations can often (< or =20% of all patients) limit hemodilution if their initial concentrations are within the lower normal range (<300 mg/dL). These findings become more frequent if ANH is combined with ABS. Under those circumstances ANH blood products are solely required for stabilization of hemostasis, thereby defeating the original purpose of combining ANH with ABS.
  
  
  CONCLUSIONS
  The causes of quantitative changes of hemostasis during hemodilution, as well as their clinical effect and relevance, remain unclear. Using a validated, realistic mathematical model, we demonstrate that hemostasis, especially plasma fibrinogen, can limit the extent of hemodilution. This phenomenon is particularly prominent when acute normovolemic hemodilution is combined with artificial blood substitutes.
authors.affiliation: *Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Münster, Münster, Germany; †Klinik für Anästhesiologie und Intensivmedizin, Leopold Franzens-Universität Innsbruck, Innsbruck, Austria; ‡Institut für Biomedizinische Technologien, Rheinisch-Westfälische Technische Hochschule Aachen, Germany; and §Klinik für Anästhesie, Krankenhaus Bethanien, Moers, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Singbartl
authors.forename: Petra
authors.initials: P
authors.lastname: Innerhofer
authors.forename: Jens
authors.initials: J
authors.lastname: Radvan
authors.forename: Birgit
authors.initials: B
authors.lastname: Westphalen
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fries
authors.forename: Raimund
authors.initials: R
authors.lastname: Stögbauer
authors.forename: Hugo
authors.initials: H
authors.lastname: Van Aken
mesh_terms: D016063:Blood Loss, Surgical / Q000503:physiopathology; D001802:Blood Substitutes / Q000008:administration & dosage / Q000627:therapeutic use; D001810:Blood Volume / Q000502:physiology; D004906:Erythrocyte Count; D005340:Fibrinogen / Q000032:analysis; D006400:Hematocrit; D006438:Hemodilution / Q000706:statistics & numerical data*; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D007432:Intraoperative Period; D015233:Models, Statistical; D010976:Platelet Count; D011446:Prospective Studies; D015203:Reproducibility of Results
chemical_list: D001802:Blood Substitutes; D005340:Fibrinogen