Thrombin Mixing Study

Thrombin time will be extended when functional fibrinogen levels are <100 mg/dL.^6,7 This can occur due to congenital conditions including afibrinogenemia (complete lack of fibrinogen), hypofibrinogenemia, and in dysfibrinogenemia, a condition characterized by the presence of dysfunctional fibrinogen. Acquired conditions which can lead to diminished fibrinogen levels and extended thrombin times include liver disease, renal disease, disseminated intravascular coagulation (DIC), amyloidosis, malignancy, and thrombolytic therapy.⁶ Thrombin inhibitors including heparin, argatroban, and hirudin will cause and extended thrombin time.⁷

If the TT on the 1:1 mixture is corrected to normal or near normal, fibrinogen deficiency or dysfunction may be confirmed by the combination of the clot-based fibrinogen activity assay and the fibrinogen antigen immunoassay.⁶ Failure of the 1:1 mix to correct suggests the presence of an inhibitor. Heparin can be ruled out through the addition of a heparin neutralizer. If no heparin is present, a fibrinogen activity and fibrinogen antigen may be used to confirm and quantitate afibrinogenemia, hypofibrinogenemia, and dysfibrinogenemia. If disseminated intravascular coagulation (DIC) is suspected, D-dimer and/or FDP assays may be used.⁶ If a bovine thrombin (anti-IIa) inhibitor is suspected, a thrombin time using human-derived thrombin as the reagent should be performed.⁶ If a paraprotein disorder is suspected, a serum protein electrophoresis may be performed.⁶