Thrombin generation assays are versatile tools in blood coagulation analysis: A review of technical features, and applications from research to laboratory routine

Depasse, François; Binder, Nikolaus B.; Müeller, Julia; Wissel, Thomas; Schwers, Stephan; Germer, Matthias; Hermes, Björn; Turecek, Peter L.

doi:10.1111/jth.15529

Cited by 44 publications

(54 citation statements)

References 68 publications

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“…This resulted in a significantly reduced interlaboratory variability 96 . For further information on the technical limitations in standardization issues of TGA see Depasse 2021 97 . However, TGA may still benefit from standardization across different systems.…”

Section: Discussionmentioning

confidence: 99%

“…96 For further information on the technical limitations in standardization issues of TGA see Depasse 2021 . 97 However, TGA may still benefit from standardization across different systems. One should keep in mind that, in contrast to TGA, some very common routine assays such as aPTT which are considered to give reliable readouts equally lack standardization.…”

Section: Discussionmentioning

confidence: 99%

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Clinical use of thrombin generation assays

Binder

Depasse

Müeller

et al. 2021

Journal of Thrombosis and Haemostasis

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Determining patient's coagulation profile, i.e. detecting a bleeding tendency or the opposite, a thrombotic risk, is crucial for clinicians in many situations. Routine coagulation assays and even more specialized tests may not allow a relevant characterization of the hemostatic balance. In contrast, thrombin generation assay (TGA) is a global assay allowing the dynamic continuous and simultaneous recording of the combined effects of both thrombin generation and thrombin inactivation. TGA thus reflects the result of procoagulant and anticoagulant activities in blood and plasma. Because of this unique feature, TGA has been widely used in a wide array of settings from both research, clinical and pharmaceutical perspectives. This includes diagnosis, prognosis, prophylaxis, and treatment of inherited and acquired bleeding and thrombotic disorders. In addition, TGA has been shown to provide relevant information for the diagnosis of coagulopathies induced by infectious diseases, comprising also disturbance of the coagulation system in COVID‐19, or for the assessment of early recurrence in breast cancer. This review article aims to document most clinical applications of TGA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinical use of thrombin generation assays

Binder

Depasse

Müeller

et al. 2021

Journal of Thrombosis and Haemostasis

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“…TGAs measure thrombin formation in plasma after addition of tissue factor and phospholipids. Contrarily to classical coagulation assays, both procoagulant and anticoagulant processes are dynamically investigated, resulting in a thrombogram with multiple derivate parameters reported [108]. TGAs can be used to assess hypo-and hypercoagulability, including APS [109,110].…”

Section: Alternative Assays For Lac Measurementmentioning

confidence: 99%

“…Recently, automated systems were introduced on the market with higher potential of use in routine practice because of reduced laboratory technician hands-on time, and decrease in inter-laboratory variation. Automated TGAs may provide more information based on phospholipid-dependent testing in one assay, compared to the multitude of assays needed for LAC detection today [108].…”

Section: Alternative Assays For Lac Measurementmentioning

confidence: 99%

Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances

Vandevelde

Devreese

2022

JCM

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Diagnosis of antiphospholipid syndrome (APS) requires the presence of a clinical criterion (thrombosis and/or pregnancy morbidity), combined with persistently circulating antiphospholipid antibodies (aPL). Currently, laboratory criteria aPL consist of lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) IgG/IgM, and anti-β2 glycoprotein I antibodies (aβ2GPI) IgG/IgM. Diagnosis and risk stratification of APS are complex and efforts to standardize and optimize laboratory tests have been ongoing since the initial description of the syndrome. LAC detection is based on functional coagulation assays, while aCL and aβ2GPI are measured with immunological solid-phase assays. LAC assays are especially prone to interference by anticoagulation therapy, but strategies to circumvent this interference are promising. Alternative techniques such as thrombin generation for LAC detection and to estimate LAC pathogenicity have been suggested, but are not applicable yet in routine setting. For aCL and aβ2GPI, a lot of different assays and detection techniques such as enzyme-linked immunosorbent and chemiluminescent assays are available. Furthermore, a lack of universal calibrators or standards results in high variability between the different solid-phase assays. Other non-criteria aPL such as anti-domain I β2 glycoprotein I and antiphosphatidylserine/prothrombin antibodies have been suggested for risk stratification purposes in APS, while their added value to diagnostic criteria seems limited. In this review, we will describe laboratory assays for diagnostic and risk evaluation in APS, integrating applicable guidelines and classification criteria. Current insights and hindrances are addressed with respect to both laboratory and clinical implications.

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“…The risk of bleeding or thrombosis can be assessed based on TGA testing. Based on an analysis of the literature, Tripodi et al concluded that TGA is a promising laboratory tool for investigating bleeding coagulopathies and predicting the risk of recurrent venous thromboembolism [ 69 , 70 ]. Similarly, Binder et al document in their review article most of the clinical applications of TGA for the prediction of thrombosis [ 71 ].…”

Section: Methodsmentioning

confidence: 99%

Determination of Thrombogenicity Levels of Various Antiphospholipid Antibodies by a Modified Thrombin Generation Assay in Patients with Suspected Antiphospholipid Syndrome

Bradacova

Slavík²,

Skoumalová³

et al. 2022

IJMS

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Antiphospholipid syndrome (APS) is a hypercoagulable state accompanied by the presence of heterogeneous antiphospholipid antibodies (aPL), which nonspecifically affect hemostasis by the presence of lupus anticoagulans (LA), anticardiolipin antibodies (aCL), antibodies against β2-glycoprotein-I (anti-β2GPI), but also non-criteria antibodies such as antibodies against β2-glycoprotein-I domain I (anti-DI), anti-phosphatidylserine/prothrombin (anti-PS/PT), anti-annexin V, and many others. The main target of the antibodies is the activated protein C (APC) system, the elimination of which can manifest itself as a thrombotic complication. The aim of this study was to determine the thrombogenicity of antibodies using a modified protein C-activated thrombin generation assay (TGA) on a group of 175 samples suspected of APS. TGA was measured with/without APC and the ratio of both measurements was evaluated (as for APC resistance), where a cut-off was calculated ≤4.5 (90th percentile) using 21 patients with heterozygous factor V Leiden mutation (FV Leiden heterozygous). Our study demonstrates the well-known fact that multiple positivity of different aPLs is a more severe risk for thrombosis than single positivity. Of the single antibody positivity, LA antibodies are the most serious (p value < 0.01), followed by aCL and their subgroup anti-DI (p value < 0.05). Non-criteria antibodies anti-annexin V and anti-PT/PS has a similar frequency occurrence of thrombogenicity as LA antibodies but without statistical significance or anti-β2GPI1 positivity. The modified TGA test can help us identify patients in all groups who are also at risk for recurrent thrombotic and pregnancy complications; thus, long-term prophylactic treatment is appropriate. For this reason, it is proving increasingly beneficial to include the determination antibodies in combination with modified TGA test.

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Thrombin generation assays are versatile tools in blood coagulation analysis: A review of technical features, and applications from research to laboratory routine

Cited by 44 publications

References 68 publications

Clinical use of thrombin generation assays

Clinical use of thrombin generation assays

Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances

Determination of Thrombogenicity Levels of Various Antiphospholipid Antibodies by a Modified Thrombin Generation Assay in Patients with Suspected Antiphospholipid Syndrome

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