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Thrombin Time (TT)

SI UNITS (recommended)

CONVENTIONAL UNITS

(Final-Pathway Coagulation Assay - Measures Conversion of Fibrinogen → Fibrin)

Synonyms

  • TT
  • Thrombin clotting time (TCT)
  • Thrombin assay
  • Plasma thrombin time
  • Fibrinogen-to-fibrin conversion test

Units of Measurement

  • seconds (s)
  • sec

(No other unit types; always reported in time.)

Description

Thrombin Time (TT) is a clot-based coagulation test that measures the time taken for thrombin to convert fibrinogen → fibrin after adding a standardized amount of thrombin to plasma.

It evaluates:

  • Fibrinogen quantity or function
  • Presence of inhibitors to thrombin or fibrin formation

It is NOT affected by deficiencies in clotting factors of the intrinsic or extrinsic pathways (e.g., factors VIII, IX, XI, VII).

What TT Detects Well

  • Hypofibrinogenemia
  • Dysfibrinogenemia
  • Direct thrombin inhibitors (DTIs)
  • Heparin contamination
  • Fibrin degradation products (FDPs)
  • Severe liver dysfunction (low fibrinogen)

Physiological Role of Pathway Measured

TT assesses the final step of coagulation:

Fibrinogen → (Thrombin) → Fibrin → Clot

Any defect in fibrinogen or its conversion will prolong TT.

Reference Intervals

(Tietz 8E + ISTH + Mayo + ARUP)

Normal Thrombin Time

  • 14 – 19 seconds

(Exact upper limit depends on reagent; many labs use 15–21 sec.)

Critical Interpretation

  • > 25 sec → abnormal (possible heparin or fibrinogen issues)
  • > 30 sec → strongly abnormal; evaluate fibrinogen or DTI exposure
  • < 14 sec → rarely clinically significant

Causes of Prolonged Thrombin Time

1. Anticoagulant Drugs

Heparin

TT is extremely sensitive - even tiny amounts prolong TT.

Direct Thrombin Inhibitors

  • Dabigatran
  • Argatroban
  • Bivalirudin

DOAC interference

Dabigatran prolongs TT markedly (often >100 sec).

2. Fibrinogen Abnormalities

Low fibrinogen

  • Severe liver disease
  • Disseminated intravascular coagulation (DIC)
  • Major bleeding
  • Massive transfusion

Qualitative defects

Congenital or acquired.

3. Presence of Fibrin Degradation Products

Seen in:

  • DIC
  • Severe thrombosis
  • Fibrinolysis

FDPs block fibrin polymerization → prolonged TT.

4. Paraproteinemia

IgM/IgA interference:

  • Multiple myeloma
  • Waldenström macroglobulinemia

5. Lupus Anticoagulant

Rarely prolongs TT unless fibrinogen is also low.

6. Heparin Contamination

Common during sample collection from heparinized central lines.

Causes of Normal TT

TT is normal in:

  • Factor VIII, IX, XI, XII deficiency
  • Vitamin K deficiency
  • Warfarin therapy
  • Liver disease without fibrinogen impairment
  • Hemophilia (all types)

This makes TT valuable for investigating prolonged PT/aPTT with normal TT, narrowing down the cause.

Diagnostic Uses

1. Evaluate Suspected Heparin Contamination

TT is the most sensitive test for heparin.

2. Detect Direct Thrombin Inhibitors

Dabigatran, argatroban → markedly prolonged TT.

3. Diagnose Fibrinogen Disorders

  • Low fibrinogen
  • Dysfibrinogenemia
  • Afibrinogenemia

4. Workup for DIC

Prolonged TT + low fibrinogen = suggestive.

5. Distinguishing Causes of Abnormal aPTT

Useful in evaluating unexplained coagulation abnormalities.

Analytical Notes

  • Uses reptilase time as a comparative test:
    • Reptilase unaffected by heparin and DTI.
    • TT prolonged + reptilase normal = heparin/DTI effect
    • Both prolonged = fibrinogen defect or FDP excess
  • Avoid heparin-contaminated samples.
  • Process quickly; fibrinogen degrades at room temperature.

Clinical Pearls

  • TT is not influenced by factor deficiencies except fibrinogen-related ones.
  • If aPTT is prolonged but TT normal → suspect intrinsic pathway defect (hemophilia).
  • Dabigatran causes dramatic TT prolongation - often >100 seconds.
  • TT is one of the best screening tools for dysfibrinogenemia.
  • Reptilase time helps differentiate heparin effect from fibrinogen abnormalities.

Interesting Fact

Thrombin time was one of the earliest clotting assays developed and remains the most sensitive routine test for detecting even minute amounts of heparin.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Coagulation Tests
  2. ISTH (International Society on Thrombosis and Haemostasis) Guidelines
  3. Mayo Clinic Laboratories - Thrombin Time
  4. ARUP Consult - Coagulation Evaluation
  5. British Society for Haematology - Coagulation Testing Standards

Last updated: January 27, 2026

Reviewed by : Medical Review Board

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