Comparison of the Clauss and Prothrombin Time-Derived Fibrinogen Methods in Patients with Dysfibrinogenemia, and Verification of their Reference Interval

Abstract

Introduction: Dysfibrinogenemia is a coagulation disorder caused by abnormal fibrinogen functions, with ever-growing concern in medical field. Therefore, it is critical to establish and optimise effective methods, both in terms of efficient and accurate clinical diagnosis and cost effectiveness. Methods: Fibrinogen assays; PT-derived and Clauss quantification are such method. This study, compared fibrinogen concentrations determined by the Clauss and PT-derived methods in 80 patients (diseased clinical group) and in 20 and 120 healthy patients (pilot and main study respectively). Reference interval verification was done following the Clinical and Laboratory Standards Institute guidelines. Results: There was a significant difference between Clauss fibrinogen and PT-derived fibrinogen irrespective of sample clinical groups, although, the discrepancy between these two assays appeared to correlate. Normal patients (mean PT-Fib 4.50 vs Clauss 3.07g/l, p <0.0001), r = 0.7567. Liver/renal dysfunction (mean PT-Fib 2.20 vs Clauss 1.75g/l, p = 0.0003), r = 0.8622. Critically-ill (mean PT-Fib 2.7 vs Clauss 2.17g/l, p <0.0001), r = 0.9553 and OAC (mean PT-Fib 3.49 vs Clauss 2.49g/l, p = 0.0004), r = 0.8158. 70% of PT-derived and 95% of Clauss fibrinogen results were within the reference interval 1.5 – 4.5 g/L. Verification of the published reference interval failed as >10% of the PT-derived results were outside the reference interval. Conclusion: Performing both PT-derived and Clauss methods on all clotting screen requests will prevent missed diagnosis, although, it will provide extra cost of £10,825. Thus, it is necessary to determine fibrinogen reference intervals for both the PT-derived and Clauss methods. Until further studies verify a reference interval for PT-Fib at the IH, the Clauss assay is a preferable diagnostic tool when treating patients with low fibrinogen concentrations. The PT-derived may erroneously report patients’ plasma fibrinogen concentration as normal.