TABLE 2.
Summaries of most relevant TGA studies for thrombotic conditions. Testing for individual heritable thrombophilic defects with specific component assays reflects neither gene‐environment interaction nor the connectivity of the coagulation network components, i.e. it does not measure the composite phenotype. In this perspective, measurement of laboratory phenotypes for the stratification of thrombotic risk might be crucial. Measurement of the thrombin generating potential could provide a method for quantifying the composite effect of multiple risk factors 20 , 21 for thrombotic disorders which are usually related to an increased TG. Depending on the situation, different test features may have to be used
| Clinical situation | Preferred TGA parameter | Main findings | Reference | |
|---|---|---|---|---|
| Disease | Objective | |||
| Thrombophilia | Assess the risk of first and recurrent venous thrombotic event by the use of TGA | ETP | Individuals with an increased ETP had an increased risk of a first deep venous thrombosis. | 20 |
| Thrombophilia | Phenotyping of venous thrombosis | ETP | TGA is sensitive to genetic variation in hemostasis‐related genes, which makes it a promising tool to identify novel genetic risk factors of VTE. | 21 |
| Thrombophilia | Characterization of coagulation phenotype | Velocity index | Thrombin generation based upon the individual's blood composition is associated with the risk for thrombosis and may be useful as a predictive marker for evaluating thrombosis on an individual basis. | 23 |
| Thrombophilia | Determine the association between hypercoagulability and first and recurrent thrombosis by the use of TGA | Peak | Elevated peak was associated with an increased risk of thrombosis. | 24 |
| Thrombophilia | Investigate relationship between recurrence of VTE and TGA | Peak | Measurement of thrombin generation identifies patients at low risk for recurrent VTE. | 22 |
| Thrombophilia | Determine risk of venous thromboembolism | ETP | ETP measured in the presence of thrombomodulin may help to distinguish patients with different risk of VTE. | 29 |
| Antiphospholipid syndrome | Investigation of thrombotic events in patients with activated protein C resistance (aPC) | ETP | aPC resistance diagnosed with TGA in a majority of patients with lupus anticoagulant. A history of thrombotic events is associated with aPC resistance measured by change in ETP. | 33, 34 |
| Antiphospholipid syndrome | Assess the thrombotic risk in lupus anticoagulants‐positive patients | Peak /Lag time | Thrombin generation can detect the antiphospholipid syndrome with TGA as single test. | 37 |
| Atherothrombosis and stroke | Stent thrombosis | Velocity index | Stent thrombosis patients showed a hypercoagulable state detected by TGA. | 47 |
| Acute coronary syndrome | Search for predictors of cardiovascular death | ETP, Peak, Velocity index | ETP, peak thrombin and velocity index were significantly higher in patients who died compared to alive patients during 24‐month follow‐up. | 48 |
| Acute ischemic stroke (AIS) | Prediction of AIS | ETP | Increased thrombin generation is associated with AIS but not with coronary heart disease. Thrombin generation merges as an independent risk factor of AIS, especially in women. | 49 |
| Neonates undergoing cardiac surgery | Hypercoagulability testing and prediction of thrombosis | Peak | TGA is an independent risk factor for thrombosis and may help identify neonates at high risk for thrombosis following cardiac surgery. | 50 |
| Extracorporeal membrane oxygenation (ECMO) | Coagulation phenotyping | Peak, ETP | The increase in underlying peak TG and ETP observed in adult ECMO patients ap‐pears to be at least in part due to elevated Factor VIII levels, low antithrombin levels, and activated protein C resistance, which may contribute to hypercoagulability during ECMO. | |