Photo-Optical Methods Can Lead to Clinically Relevant Overestimation of Fibrinogen Concentration in Plasma Diluted With Hydroxyethyl Starch

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Abstract
Background: Adequate fibrinogen concentration is a crucial component of sufficient perioperative/posttraumatic hemostasis. In major blood loss, large volumes of fluids are being administered, which have been shown to interfere with valid determination of fibrinogen concentration. This may lead to wrong treatment decisions. We studied the variables that cause the discrepancies between measured and true fibrinogen concentrations in samples diluted with volume replacement fluids. Methods: Citrated plasma samples of healthy volunteers were diluted by 30% and 50% with phosphate buffered saline (PBS), hydroxyethyl starch (HES) 10% (200/0.5), or gelatine (GEL). Fibrinogen concentrations of diluted samples were derived from the prothrombin time (PT) and the Clauss method (CLS) was applied. With the latter, several modifications and combinations of detection principles and thrombin reagents were investigated. Values were compared with ‘‘true,’’ that is, calculated values based on the results of undiluted samples for each method. Results: Photo-optical methods resulted in significant overestimation of the fibrinogen concentration in blood diluted with HES, depending on the thrombin reagent used. This was particularly true for modifications of the CLS aimed at measuring low fibrinogen concentrations. Use of another thrombin reagent gave satisfactory results for this modification. The validity of mechanical end point determination methods was considered sufficient and was not influenced by the use of different thrombin reagents. Conclusions: Fibrinogen determination methods used in situations of major blood loss need to be validated with samples containing significant amounts of volume replacement fluids, particularly colloids. Only some combinations of test principle, detection method, and reagents will give valid results.

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