ArticleThrombosis and haemostasis2023
Sensitive Measurement of Clinically Relevant Factor VIII Levels in Thrombin Generation Assays Requires Presence of Factor XIa.
Article in Thrombosis and haemostasis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 3 citations in OpenAlex.
- Laboratory Challenges in the Era of Novel Haemophilia Therapies.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2026Review
- Intrinsic activated thrombin generation for treatment efficacy and monitoring of octocog alfa and emicizumab in severe hemophilia A.Research and practice in thrombosis and haemostasis · 2026Article
- Thrombin generation to predict breakthrough bleeding in patients with acquired hemophilia A under emicizumab prophylaxis.Haematologica · 2026Article
- Tissue Factor/Factor XIa Dual-activated Thrombin Generation is Able to Reliably Measure Thrombin Generation at All Hemophilia A Disease Severities.TH open : companion journal to thrombosis and haemostasis · 2026Article
- Comparative Thrombin Generation in Animal Plasma: Sensitivity to Human Factor XIa and Tissue Factor.International journal of molecular sciences · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHemophilia A (HA) is characterized by decreased or absent factor VIII (FVIII) activity. Current FVIII assays are based on clotting time and thus only provide information about the initiation of coagulation. In contrast, thrombin generation assays (TGAs) can be used to measure the full coagulation spectrum of initiation, propagation, and termination that provide information on the whole course of thrombin generation and inhibition. However, the 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 clinically low levels of FVIII.
aimsOptimization of the TGA for measurements of low FVIII levels in severe HA patients.
methodsTGA measurements were performed in severe HA pooled plasma (
resultsTGA 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.
conclusionWe propose a critical optimization for the setup of the TGA 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, prediction of interventions, and follow-up.
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