Characterization of Thrombin Generation Curve Shape in Presence of Platelets from Acute Venous Thromboembolism Patients

Lagrange, Jérémy; Wagner, Bianca; Nagler, Markus; Cate, Vincent ten; Robles, Alejandro Pallares; Koeck, Thomas; Rapp, Steffen; Prochaska, Jürgen H.; Spronk, Henri M. H.; Wenzel, Philip; Ruf, Wolfram; Cate, Hugo Ten; Wild, Philipp S.; Panova‐Noeva, Marina

doi:10.3390/jcm9092892

Cited by 1 publication

(2 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We consider the shape of TGA curves to be essential for correct data interpretation, although this is a vastly overlooked aspect of the assay. 12 Due to low amounts of thrombin formed in HA plasma, especially when using regular low TF-only activated TGA, a proper coagulation pattern consisting of initiation, propagation, and inhibition might not occur, which is reflected in an aberrant curve shape. However, the Thrombinoscope will still provide its calculated parameters like peak height and ETP.…”

Section: Discussionmentioning

confidence: 99%

“…During the setup of the assay we specifically looked at the quality of the resulting TGA curves in each of the development stages. We consider the shape of TGA curves to be essential for correct data interpretation, although this is a vastly overlooked aspect of the assay 12 . Due to low amounts of thrombin formed in hemophilia A plasma, especially when using regular low TF-only activated TGA, a proper coagulation pattern consisting of initiation, propagation and inhibition might not occur, which is reflected in an aberrant curve shape.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

See 1 more Smart Citation

Sensitive Measurement of Clinically Relevant Factor VIII Levels in Thrombin Generation Assays Requires Presence of Factor XIa

et al. 2023

View full text Add to dashboard Cite

Background: Hemophilia A (HA) is characterized by decreased or absent FVIII. Current FVIII assays are based on clotting time and only provide information about the initiation of coagulation. In contrast, thrombin generation assays (TGA) can be used to measure the full coagulation spectrum of initiation, propagation and termination that provide information on the course of thrombin generation and inhibition. However, commercially available TG kits lack sensitivity for measurements of hemophilia plasma within lower FVIII ranges, which is essential for explaining differences in bleeding phenotypes in hemophiliacs at clinical low levels of FVIII. Aims: Optimization of thrombin generation for measurements of low FVIII levels in severe HA patients. Methods: TGA measurements were performed in severe HA pooled plasma (n=10). Investigation of several pre-analytical and analytical variables were performed in a stepwise process and adjusted based on sensitivity towards intrinsic coagulation activation. Results: TGA initiated by tissue factor (TF) alone at varying concentrations was unable to significantly differentiate between FVIII levels below 20%. In contrast, TGA activation with low concentrations of TF in presence of FXIa appeared to be highly sensitive for FVIII changes both in high and low ranges. In addition, a representative TGA-curve at trough levels could only be produced using the dual TF/FXIa TGA. Conclusion: We propose a critical optimization for the setup of the thrombin generation assay for measurements in severe HA plasma. The dual TF/FXIa TGA shows increased sensitivity, especially in lower FVIII ranges, which allows for better individual characterization at baseline, predictions of interventions and follow-up.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%