Cite this page: Crookston K, Rosenbaum LS, Gober-Wilcox J. Factor I (fibrinogen) assay. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/coagulationfibrinogen.html. Accessed November 28th, 2024.
Definition / general
- Major plasma protein that is synthesized by the liver and is converted to fibrin by thrombin
- Levels can be reduced in disseminated intravascular coagulation (DIC), liver disease, inherited and acquired fibrinogen disorders, thrombolytic therapy, dilutional coagulopathy following massive transfusion and in L-asparaginase therapy
- Levels can be increased in an acute phase reaction, malignancy, females (particularly post-menopausal), pregnancy, oral contraceptive use
- Reference range is usually 1.5 - 4.0 g/L
- Purpose of fibrinogen assay: Fibrinogen assays are typically used to investigate the following:
- Investigation of abnormal coagulation tests (e.g. PT / PTT)
- Investigation of unexplained bleeding
- Investigation of suspected inherited or acquired disorders of fibrinogen (afibrinogenemia, hypofibrinogenemia and dysfibrinogenemia)
- Evaluation of DIC
- Establishment and monitoring of thrombolytic therapy
- Assessment of cardiovascular risk
- Types of fibrinogen assays:
- There are different assays that measure fibrinogen levels and are selected based upon the clinical scenario
- Clauss assay: A functional assay which is based upon the time for fibrin clot formation
- Diluted patient plasma is clotted using a high concentration of thrombin and then the clotting time is measured
- The high concentration of thrombin ensures that the clotting times are independent of the amount of thrombin present
- A calibration curve is generated by clotting times of dilutions of reference plasma samples of known fibrinogen concentrations
- The clotting time is inversely proportional to the amount of fibrinogen in the sample
- Most laboratories use an automated method based on optical density in which fibrin formation decreases light transmission and increases scattered light
- Values can be affected by turbid specimens (e.g. hyperbilirubinemia, hyperlipidemia)
- Values are falsely decreased by heparin > 0.6 units/mL or fibrin degradation products
- The most widely used laboratory method
- Typically used in investigation of bleeding diathesis, congenital and acquired fibrinogen abnormalities, DIC or thrombolytic therapy
- Immunological assays: An immunological method based on measuring fibrinogen antigen rather than functional fibrinogen
- Uses antibodies directed against fibrinogen
- Techniques include enzyme linked immunoabsorbent assays (ELISA), radial immunodiffusion or electrophoresis
- Typically used in investigation of congenital fibrinogen disorders where there is a discrepancy between functional activity and antigen level
- Clottable protein assay: Method based upon clot weight
- Thrombin is added to patient plasma in the absence of calcium ions and then the clot is washed and dissolved by alkaline urea or other reagents
- Spectrophotometry is performed, and since the majority of the protein present in the clot is fibrin, the protein concentration will be equivalent to the fibrinogen concentration
- Very labor intensive and time consuming to perform
- Occasionally used in evaluation of congenital fibrinogen disorders
- PT-based assay: Fibrinogen levels are indirectly measured (derived) and are calculated based on the prothrombin time (PT)
- A calibration curve is generated using prothrombin times and changes in optical density of a series of plasma dilutions of known fibrinogen concentration
- A PT is performed on the patient sample and the fibrinogen level is calculated based on the change in optical density
- Simple and inexpensive test
- Not recommended for routine laboratory use since values can vary based on type of reagents and analyzers used and therefore results are not interchangeable between laboratories or hospitals. Also, when compared to results given by the Clauss assay, the PT-based method has been shown to produce higher values in certain conditions such as liver disease, DIC, renal disease, dysfibrinogenemia, and in those receiving anticoagulants or thrombolytic therapy
- Note: Assays should not be performed on samples collected within 4 hours of heparin administration or on samples collected from heparin-contaminated arterial or venous lines, as heparin may lead to falsely low fibrinogen levels
- There are different assays that measure fibrinogen levels and are selected based upon the clinical scenario
Additional references