A thrombin generation assay (TGA) or thrombin generation test (TGT) is a global coagulation assay (GCA) and type of coagulation test which can be used to assess

coagulation Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanis ...

and

thrombotic Thrombosis (from Ancient Greek "clotting") is the formation of a Thrombus, blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses plate ...

risk. It is based on the potential of a plasma to generate

thrombin Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma- ...

over time, following activation of coagulation via addition of

phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids ty ...

tissue factor Tissue factor, also called platelet tissue factor, factor III, or CD142, is a protein encoded by the ''F3'' gene, present in subendothelial tissue and leukocytes. Its role in the clotting process is the initiation of thrombin formation from the ...

, and

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

. The results of the TGA can be output as a thrombogram or thrombin generation curve using computer software with calculation of thrombogram parameters. TGAs can be performed with methods like the semi-automated

calibrated automated thrombogram The calibrated automated thrombogram (CAT or CT) is a thrombin generation assay (TGA) and global coagulation assay (GCA) which can be used as a coagulation test to assess thrombotic risk. It is the most widely used TGA. The CAT is a semi-automat ...

(CAT) (2003) or the fully-automated ST Genesia system (2018). TGAs were first used as manual assays in the 1950s and have since become increasingly automated.

Parameters

Thrombogram parameters for the TGA include: * Lag time (minutes; time until thrombin first generated/thrombin concentration first increased) * Time to peak or ttPeak (minutes; time to maximum concentration of thrombin generated) * Start tail (minutes; time at which thrombin generation ends and all generated thrombin has been inhibited) * Peak height or peak thrombin (molar concentration (e.g., nM) of thrombin; peak or maximum concentration of thrombin generated) * Velocity index (slope of thrombin generation between lag time/first thrombin generation and time to peak; corresponds to first derivative of this part of curve) * Endogenous thrombin potential (ETP; area under the curve of the thrombin generation curve)

ETP-based APC resistance test

The addition of

activated protein C Protein C, also known as autoprothrombin IIA and blood coagulation factor XIX, is a zymogen, that is, an inactive enzyme. The activated form plays an important role in regulating anticoagulation, inflammation, and apoptosis, cell death and ...

(APC) to a TGA results in an inhibition of thrombin generation as measured by reduction of the endogenous thrombin potential (ETP; area under the thrombin generation curve). This can be used to assess APC resistance and is termed the ETP-based APC resistance test. Results may be expressed as normalized APC sensitivity ratio (nAPCsr), which corresponds to the ratio of the ETP measured in the presence and absence of APC divided by the same ratio in reference plasma. The higher the nAPCsr value, the greater the APC resistance of the person. The ETP-based APC resistance test was developed in 1997.

References

{{Hematology blood tests Blood tests Coagulation system Medical signs