What is Clauss fibrinogen (coagulation test)?

What is Clauss Fibrinogen?

The Clauss fibrinogen assay is a quantitative, clot-based functional test that measures plasma fibrinogen concentration by adding excess thrombin to diluted plasma and measuring the time to clot formation, with results interpolated from a standard curve. 1, 2

Test Methodology

The Clauss method is the most frequently recommended laboratory method for measuring fibrinogen and is recommended by the WHO as the standard approach. 1, 3 The test works through the following mechanism:

• Excess thrombin is added to diluted plasma samples, which converts fibrinogen to fibrin 1, 2
• The clotting time is measured mechanically or using a photo-optical method and compared against a calibration curve 1
• Pre-dilution of plasma samples minimizes interference from substances like heparin and fibrinogen degradation products 2
• Results are expressed in g/L, with a normal reference range of 1.8-3.5 g/L or 2.0-4.0 g/L depending on the reagent used 1

Clinical Significance

The Clauss assay measures functional fibrinogen activity rather than total fibrinogen protein. 1 This distinction is critical because:

• Fibrinogen is the first coagulation factor to critically decrease during massive blood loss replacement 1
• In trauma patients, fibrinogen levels <2 g/L are associated with significant bleeding risk, with postpartum hemorrhage studies showing <2 g/L having 100% positive predictive value for progression to severe bleeding 1
• The Clauss method correlates with functional coagulation parameters such as Reptilase Time, Thrombin Time, and Prothrombin Time 4

Important Limitations and Pitfalls

The Clauss method can significantly overestimate actual fibrinogen concentration in the presence of artificial colloids such as hydroxyethyl starch (HES). 1 Additional limitations include:

• Reproducibility is significantly impaired in patients after thrombolytic therapy or with disseminated intravascular coagulation 1
• The test cannot distinguish between quantitative defects (low fibrinogen amount) and qualitative defects (dysfunctional fibrinogen) without additional testing 5
• In dysfibrinogenemia, the Clauss assay underestimates fibrinogen by approximately five-fold compared to PT-derived methods, which can erroneously report normal levels 4

Comparison with Alternative Methods

PT-derived fibrinogen methods should not be used interchangeably with the Clauss method. 6 Key differences include:

• PT-derived methods overestimate fibrinogen in dysfibrinogenemia and correlate with fibrinogen antigen rather than functional activity 4
• Immunological assays measure total fibrinogen antigen concentration rather than the amount contributing to clotting 1
• Viscoelastic point-of-care methods (FibTEM) may be preferable for guiding fibrinogen administration in acute bleeding scenarios, though they can be affected by residual platelet function 1

Clinical Application

The Clauss assay is the diagnostic tool of choice when diagnosing or treating patients with low fibrinogen levels, particularly in bleeding scenarios. 4 In cardiac surgery and trauma:

• Hypofibrinogenemia is defined as plasma fibrinogen <2.0 g/L by the Clauss method 7
• Treatment with fibrinogen concentrate or cryoprecipitate is recommended when fibrinogen falls below 1.5-2.0 g/L in the setting of significant bleeding 1
• The use of PT-derived methods may pose greater risk to patients as plasma concentration may be erroneously reported as normal when functional fibrinogen is critically low 4