Thrombin time (TT): a specialist clotting test explained

Clotting involves a cascade of factors that ends with thrombin converting soluble fibrinogen into insoluble fibrin strands that form the clot. The thrombin time bypasses the earlier steps by adding thrombin directly to the patient's plasma. Sheffield Laboratory Medicine describes it as assessing the functionality of the fibrinogen to fibrin conversion step in the common pathway, in which thrombin cleaves fibrinopeptides A and B, leading to fibrin monomers and later polymers.

The time to form a clot depends on how much fibrinogen is present, its structure and the action of any inhibitors in the sample. A normal thrombin time therefore shows that the end of the cascade is working; an abnormal one raises questions about fibrinogen or drugs that block thrombin.

Thrombin time is not part of a standard coagulation screen. It is added when the PT or aPTT is unexpectedly prolonged, in suspected disseminated intravascular coagulation or liver disease, to check for heparin contamination, and to look at fibrinogen function. Newcastle Hospitals Laboratories note it is used with the protamine time to detect heparin in a sample (the thrombin time is prolonged and the protamine time is normal), and with a reptilase time to determine the cause of a prolonged aPTT.

Lab Tests Online UK lists the usual coagulation screen as PT and aPTT, often with fibrinogen, requested for unexplained bleeding or bruising and before surgery, with thrombin time as a second-line investigation.

No patient preparation is needed. The sample is taken from a vein into a light blue sodium citrate tube, which must be filled to the line to give the correct blood to anticoagulant ratio, and mixed well. Newcastle quote a minimum adult volume of 2.7 mL and sample stability of 24 hours, and Sheffield reject samples that are underfilled, haemolysed, clotted or activated, asking for a repeat. Lipaemia (fatty blood) and haemolysis can interfere, as can sampling from a line containing heparin.

Tell staff about every anticoagulant you take, including tablets such as dabigatran, and any recent heparin.

Sheffield Laboratory Medicine lists causes of a prolonged thrombin time: reduced fibrinogen concentration (particularly below 1.0 g/L), congenital or acquired dysfibrinogenaemia, the presence of heparin, hirudin, lepirudin or direct oral anticoagulants, and high concentrations of D-dimers (fibrin degradation products). Newcastle add that it can also be prolonged by fibrinogen deficiency or dysfunction and fibrin degradation products, and that it is particularly sensitive to the direct thrombin inhibitor dabigatran, giving very long times even at sub-therapeutic levels.

Other situations include liver failure, which affects fibrinogen production and function, and paraproteins that interfere with fibrin formation. A thrombin time with protamine sulphate can confirm heparin as the cause, since protamine corrects the effect of heparin.

Lab Tests Online UK describes the PT as a measure of the extrinsic pathway and the aPTT as the intrinsic and common pathways, with fibrinogen and platelet count as companions. The thrombin time adds a specific look at the last step. D-dimer, a fibrin degradation product, can both lengthen the thrombin time and, separately, be used to rule out venous clots when negative in low-risk patients.

Together with a fibrinogen assay, the thrombin time helps decide whether a low fibrinogen, a faulty fibrinogen or an inhibitor is responsible for a prolonged clotting screen.

Further tests may include fibrinogen, reptilase time, mixing studies and specific drug assays. Treatment depends on the cause: stopping heparin or adjusting an anticoagulant, replacing fibrinogen, or managing liver disease or DIC. Seek urgent help for heavy bleeding, black stools, vomiting blood or a head injury while on anticoagulants; call 999 or attend A&E.