2023/05/26 by Tom W. van de Berg, Erik A.M. Beckers, Erik A. M. Beckers +7 · 1 citation
Medicine · #Blood Coagulation and Thrombosis Mechanisms #Coagulation, Bradykinin, Polyphosphates, and Angioedema #Hemophilia Treatment and Research
paper · pdf · doi:10.1055/a-2101-7961
openalex publication_date 2023/05/26 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/11
BACKGROUND: Hemophilia 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. AIMS: Optimization of the TGA for measurements of low FVIII levels in severe HA patients. METHODS: = 10). Investigations of several preanalytical and analytical variables of the assay were performed in a stepwise process and adjusted based on sensitivity toward 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 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.