Determination of Fibrinogen Ratio Cutoff Limits Using Indirect Reference Interval Methodology

Area of Science:

• Clinical Chemistry
• Hematology

Background:

• Discordant fibrinogen antigen-to-activity ratios are key indicators for diagnosing dysfibrinogenemia.
• Current laboratory cutoffs for these ratios are often based on limited validation studies.
• There is a need for more robust methods to establish accurate diagnostic criteria.

Purpose of the Study:

• To apply indirect reference interval (RI) methodology using large clinical datasets to determine reliable fibrinogen ratio cutoffs.
• To evaluate the efficacy of the RefineR algorithm in establishing these diagnostic parameters.
• To compare algorithm-derived cutoffs with existing validated laboratory standards.

Main Methods:

• Analysis of two large datasets (n=3693 and n=2192) of patient results including fibrinogen antigen and activity measurements.
• Utilized radial immunodiffusion (RID) and turbidimetry immunoassay for antigen quantification.
• Applied the RefineR algorithm to estimate reference intervals and ratio cutoffs for fibrinogen.

Main Results:

• Estimated fibrinogen antigen/activity ratio cutoffs closely approximated validated laboratory cutoffs (within 8% difference).
• The RefineR algorithm significantly overestimated upper reference interval limits for both fibrinogen antigen and activity (38.4%-57.2%).
• Estimated reference intervals were substantially wider than validated limits (41.8%-80%).

Conclusions:

• The RefineR algorithm offers a viable method for determining fibrinogen ratio cutoffs using extensive clinical data.
• The algorithm's inability to distinguish acute-phase reactants and its overestimation of RI limits require further refinement.
• This approach enhances the potential for more accurate dysfibrinogenemia detection through large-scale data analysis.