Discrepancy between fibrinogen concentrations determined by clotting rate and clottability assays during the...

Assays based on clotting rate are commonly used as a routine method for determining the fibrinogen concentration in plasma. However, little is known about the influence of the acute-phase reaction on this assay. In order to disclose discrepancies between the fibrinogen concentrations obtained by a clotting rate assay (as described by Clauss) and a reference assay for total clottable protein (according to Jacobsson), we compared the fibrinogen concentrations determined by these two methods in plasma-samples collected preoperatively and on postoperative days 1, 3, and 5 in patients undergoing major elective surgery. The HMW (High Molecular Weight)-, LMW- and LMW'-fibrinogen fractions of the patient samples were also determined. In preoperative samples, good agreement between the two assays was found. In samples collected on postoperative days 1 and 3, the fibrinogen concentrations measured with the clotting rate assay were significantly higher than the concentrations measured with the total clottable protein assay (p=0.015 on both days). SDS-gel electrophoresis showed an increase in the median HMW-fraction from 69.7% (range 64.3-70.4) in preoperative samples to 85.8% (80.7-87.6) in samples drawn on day 3. The difference between fibrinogen concentrations obtained by the two methods was significantly correlated to the HMW-fraction of the samples. We conclude that during an acute-phase reaction, fibrinogen concentrations obtained by a clotting rate assay (as described by Clauss) are significantly higher than those measured by a total clottable protein assay (according to Jacobsson). The difference between the two methods correlates well with the relative HMW-fraction, indicating that the increase in HMW-fibrinogen is the main contributor to the observed discrepancy.