Thrombin generation assay

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Thrombin generation assay
Synonyms TGA; Thrombin generation test; TGT
Test of Thrombin generation, coagulation, hypercoagulability

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 and thrombotic risk. [1] [2] [3] It is based on the potential of a plasma to generate thrombin over time, following activation of coagulation via addition of phospholipids, tissue factor, and calcium. [4] The results of the TGA can be output as a thrombogram or thrombin generation curve using computer software with calculation of thrombogram parameters. [5] [1]

Contents

TGAs can be performed with methods like the semi-automated calibrated automated thrombogram (CAT) (2003) or the fully-automated ST Genesia system (2018). [6] [1] [7] TGAs were first used as manual assays in the 1950s and have since become increasingly automated. [1]

Parameters

TGA thrombogram (thrombin generation curve) parameters. ETP is the endogenous thrombin potential or area under the curve. Thrombin generation assay thrombogram parameters.png
TGA thrombogram (thrombin generation curve) parameters. ETP is the endogenous thrombin potential or area under the curve.

Thrombogram parameters for the TGA include: [1]

ETP-based APC resistance test

The addition of activated protein C (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). [4] This can be used to assess APC resistance and is termed the ETP-based APC resistance test. [4] 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. [4] The higher the nAPCsr value, the greater the APC resistance of the person. [4] The ETP-based APC resistance test was developed in 1997. [4]

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Coagulation activation markers are biomarkers of net activation of coagulation and fibrinolysis. Examples include prothrombin fragment 1+2 (F1+2), thrombin–antithrombin complex (TAT), fibrinopeptide A (FpA), fibrin monomers (FMs), plasmin-α2-antiplasmin complex (PAP), activated protein C–protein C inhibitor (APC-PCI), and D-dimer (DD). These compounds are markers of thrombin generation, fibrin generation, and fibrinolysis. Coagulation activation markers, particularly D-dimer, are useful in the diagnosis of acute venous thromboembolism. They may also be useful in the assessment of hypercoagulability and venous thromboembolism risk.

Activated protein C–protein C inhibitor (APC-PCI) is a complex of activated protein C (APC) and protein C inhibitor (PCI). It has been measured in coagulation testing to evaluate coagulation, thrombosis, and other cardiovascular complications. It is a marker of thrombin generation and indicates hypercoagulability. The half-life of APC-PCI is either 40 minutes or 140 minutes.

References

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