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.
Implications: 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.