Thrombin time

Principle

• A standard dilute thrombin solution is added to citrated plasma; the time for fibrinogen to be converted into a fibrin clot is measured.
• It bypasses all other factors and tests only the final step: fibrinogen quantity and function, and the presence of thrombin inhibitors.

Specimen

• 3.2% sodium citrate, 9:1 ratio; platelet-poor plasma; avoid heparin contamination.

Procedure

• Pre-warm plasma to 37 °C.
• Add thrombin reagent (bovine or human, low concentration per manufacturer) and time clot formation.
• Test a normal control plasma in parallel.

Results

• Typical reference interval is reagent dependent, commonly under about 20 s; often reported with the control time. Local ranges apply.

Interpretation

• Prolonged: unfractionated heparin (very sensitive), direct thrombin inhibitors such as dabigatran and argatroban (very sensitive; a normal TT makes significant dabigatran levels unlikely), hypofibrinogenaemia, dysfibrinogenaemia, high levels of fibrin(ogen) degradation products (DIC, thrombolysis), paraproteins (myeloma) and neonatal fibrinogen.
• Direct Xa inhibitors (rivaroxaban, apixaban) and LMWH have little effect at usual levels.
• Reptilase time (snake venom enzyme) is not affected by heparin: long TT with normal reptilase time points to heparin; both prolonged points to a fibrinogen problem or FDPs.

Quality control and pitfalls

• Heparin contamination from IV lines is a common cause of unexpected prolonged TT.
• Very high fibrinogen can occasionally prolong the TT.
• Clotted or under-filled samples and bovine thrombin antibodies (after exposure to topical bovine thrombin) cause errors.

Clinical use

• Investigation of prolonged PT and APTT, suspected heparin contamination, DIC, fibrinogen disorders and detection of dabigatran.