Thrombin Generation Assay: Are We Ready for Prime Time?

Pagano, Monica B.; Chandler, Wayne L.

doi:10.1373/jalm.2017.024083

Cited by 3 publications

(1 citation statement)

References 13 publications

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“…There is increasing awareness that thrombin generation (TG) provides a global coagulation profile of the complex interplay between proand anticoagulant drivers, whereas conventional clotting time tests only provide limited information about the initiation of coagulation. [1][2][3] Modern TG assays, such as the calibrated automated thrombinography (CAT), allow continuous and high-throughput TG measurements in plasma samples by using a thrombin-specific fluorogenic substrate. 4,5 TG assays have shown great potential in elucidating the mechanisms behind coagulation disorders, predicting bleeding/ thrombotic risk, and managing hemophilia/thrombosis treatment.…”

Section: Introductionmentioning

confidence: 99%

A novel assay for studying the involvement of blood cells in whole blood thrombin generation

Wan

Konings

Yan

et al. 2020

Journal of Thrombosis and Haemostasis

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Background Fluorogenic thrombin generation (TG) assays are commonly used to determine global coagulation phenotype in plasma. Whole blood (WB)‐TG assays reach one step closer to physiology by involving the intrinsic blood cells, but erythrocytes cause variable quenching of the fluorescence signals, hampering its routine application. Objective To develop a new assay for continuous WB‐TG measurement. Methods In the new WB‐TG assay, the erythrocyte‐caused distortion of signal was solved by continuously mixing the sample during the measurement. The assay was validated by evaluating the reproducibility and comparing with the paper‐based WB‐TG assay. Reconstituted human blood and WB from 119 healthy donors was tested to explore the influences of hematocrit and platelet count on TG. Results This novel WB‐TG assay showed good reproducibility while being less affected by contact activation compared with the previous paper‐based assay. Reconstitution experiments showed that the lag time of TG was shortened by the addition of platelets but not erythrocytes. Increasing hematocrit strongly augmented the peak thrombin, even in the presence of high platelet counts. The lag time and peak of WB‐TG of 119 healthy donors were positively related to erythrocyte count after adjusting for age, sex, and oral contraceptive use with multiple linear regression analyses. The reference range and interindividual variation of WB‐TG were determined in the healthy cohort. Conclusions A novel WB‐TG assay was developed, which is a straightforward tool to measure the involvement of platelets and erythrocytes in TG and may assist the research of blood cell‐associated coagulation disorders.

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Section: Introductionmentioning

confidence: 99%

A novel assay for studying the involvement of blood cells in whole blood thrombin generation

Wan

Konings

Yan

et al. 2020

Journal of Thrombosis and Haemostasis

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Thrombin Generation in Trauma Patients: How Do we Navigate Through Scylla and Charybdis?

Mitrophanov

Vandyck

Tanaka

2022

Curr Anesthesiol Rep

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Purpose of Review Coagulopathy is a complex pathological condition manifested through the insufficient or excessive tendency to form blood thrombi, which can be caused by trauma and surgery. A promising strategy to mitigate coagulopathy is the balanced restoration of the generation of thrombin — the main enzyme in the blood-coagulation system. We review studies focusing on thrombin, traumatic coagulopathy, and hemostatic balance — a concept aimed to avoid abnormally weak or excessively strong coagulation responses. Recent Findings Thrombin generation is impacted by coagulopathic conditions described by complex patterns, possibly depending on various factors. New methodologies of thrombin-generation measurement and analysis are emerging. Combinations of pro- and anticoagulant proteins can restore thrombin generation in coagulopathy. Balanced therapeutic strategies to improve thrombin generation may lead to favorable clinical outcomes. Summary Thrombin generation is an essential target of pharmacological intervention in traumatic and surgical coagulopathy. Graphic Abstract

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Correlation between Thrombin Generation, Standard Coagulation Assays, and Viscoelastic Assays for Hemostatic Assessment in Critically Ill Children

Thomas

Shea

Saini

et al. 2022

The Journal of Applied Laboratory Medicine

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Background Accurate assessment of hemostatic function is essential to guide care in critically ill children with acute and acquired coagulopathies. Thrombin generation (TG) provides a global assessment of procoagulant and anticoagulant factors and is commonly used in hemostasis research laboratories. Our objective was to determine the correlation of clinically available hemostasis assays with TG in critically ill children. Methods Children (<18 years old, >3 kg in weight) in the intensive care unit were enrolled from March 2016 to December 2019 in a prospective 2-center study. Coagulation tests were prothrombin time, activated thromboplastin time, anti-Xa assay, viscoelastic assays (thromboelastography [TEG], rotational thromboelastometry [ROTEM]), and TG (induced by 20 pM tissue factor in platelet poor plasma and reported as endogenous thrombin potential [ETP; nM*min]). Data are reported as median (interquartile range) or Spearman coefficient (ρ). Results Patients (n = 106, age 10.2 years [3.8–15.3]) were divided into 3 groups: (a) no anticoagulation (n = 46), (b) anticoagulation (unfractionated heparin) without extracorporeal life support (n = 34), or (c) with extracorporeal life support (n = 26). ETP was decreased in anticoagulated compared to non-anticoagulated patients (group 1: 902.4 [560.8–1234], group 2: 315.6 [0.0–962.2], group 3: 258.5 [0.0–716.6]; P < 0.0001). Across all patients, ETP correlated best with TEG kinetic time (TEG-K), in min (ρ = −0.639), followed by TEG reaction time, in min (ρ = −0.596). By group, ETP correlated best with international normalized ratio for group 1 (ρ = −0.469), TEG-K time for group 2 (ρ = −0.640), and anti-Xa for group 3 (ρ = −0.793). Conclusions Standard and viscoelastic assays have varying correlation with TG in critically ill children. TEG-K time had the most consistent moderate correlation with ETP across all groups.

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Thrombin Generation Assay: Are We Ready for Prime Time?

Cited by 3 publications

References 13 publications

A novel assay for studying the involvement of blood cells in whole blood thrombin generation

A novel assay for studying the involvement of blood cells in whole blood thrombin generation

Thrombin Generation in Trauma Patients: How Do we Navigate Through Scylla and Charybdis?

Correlation between Thrombin Generation, Standard Coagulation Assays, and Viscoelastic Assays for Hemostatic Assessment in Critically Ill Children

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