Influence of Different Hydroxyethyl Starch (HES) Formulations on Fibrinogen Measurement in HES-Diluted Plasma

Background: Fibrinogen is the first coagulation factor becoming critical in dilution coagulopathy. Volume replacement in major blood loss is performed with large volumes of crystalloid and colloid solutions. The latter has been shown to compromise accurate photo-optical measurement of fibrinogen. This study determined the influence of different hydroxyethyl starch (HES) formulations. Methods: Citrated plasma samples of 8 healthy volunteers were diluted by 30% or 50% with either HES 10% (200/0.5; HES-200), HES 6% (70/0.5; HES-70), or HES 6% (450/0.7; HES-450). Fibrinogen concentrations were determined by photo-optical measurement (Behring coagulation system [BCS]: derived fibrinogen, or Clauss fibrinogen, calibrated for high [CLS] or low fibrinogen concentrations [CLS-low]) as well as mechanical end point determinations (KC4: CLS-KC4). Measured values were compared with calculated values. Results: On average and across all photo-optical methods, fibrinogen concentrations were overestimated, particularly with HES-200. Hydroxyethyl starch-70 and HES-450 did not differ much from each other. Overestimation was relatively greater for 50% dilutions with all HES formulations. Surprisingly, overestimation was most prominent with CLS-low, the method supposed to most reliably measure low fibrinogen concentrations; overestimation amounted to 92% and 120% with HES-200, 54% and 73% with HES-70, and 51% and 79% with HES-450, for 30% and 50% dilutions, respectively. In contrast, CLS-KC4 always yielded sufficiently accurate results. Conclusions: The study showed that all HES solutions more or less impaired the fibrinogen measurement with the photo-optical method. In particular, overestimation with CLS-low may prevent timely fibrinogen replacement in major blood loss. Hydroxyethyl starch concentration appears to be more relevant for this effect than its molecular size.