Background: Emicizumab is an alternative non-factor approach for treating patients with hemophilia A. However, there is a potential risk of thrombotic events when emicizumab is concomitantly administered with pro-hemostatic therapies.
Objectives: To assess the hemostatic effect in vitro when a plasma-derived factor VIII concentrate containing von Willebrand factor (pdFVIII/VWF) was added to hemophilia A plasma (HAp) in combination with emicizumab.
Methods: HAp and HAp with FVIII inhibitors (HAp-i) samples with different concentrations of emicizumab (50 and 100 μg/mL) were combined with activated prothrombin complex concentrate at 0.5 to 1 U/mL, recombinant activated factor VII (rFVIIa) at 0.5 to 7 μg/mL, and pdFVIII/VWF at 0.1 to 4.5 IU/mL. Thrombin generation (TG; thrombin peak and endogenous thrombin potential) was determined using a Calibrated Automated Thrombogram assay.
Results: When activated prothrombin complex concentrate was added to HAp and HAp-i with emicizumab, TG dramatically increased (multiplier effect > 4.5×). Addition of rFVIIa to HAp or HAp-i with emicizumab moderately increased TG in a concentration-related manner compared with rFVIIa alone. Addition of pdFVIII/VWF to HAp or HAp-i with emicizumab induced a TG response equivalent to those samples without emicizumab. In an in vitro model of immune tolerance induction with bleeds (HAp-i 15 Bethesda units), combination of pdFVIII/VWF, emicizumab, and rFVIIa did not trigger a multiplying effect on TG.
Conclusions: pdFVIII/VWF showed a non-additive effect on TG when combined in vitro with emicizumab. This finding suggests that emicizumab has limited ability to promote factor X activation in the presence of pdFVIII/VWF, thus reducing the risk of thrombotic events.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1111/jth.14887 | DOI Listing |
Plant Genome
September 2024
Wheat Research Institute, Gansu Academy of Agricultural Sciences, Lanzhou, China.
BMC Genomics
July 2024
College of Agriculture, Ludong University, Yantai, 264000, China.
Background: Alfin-like proteins are a kind of plant-specific transcription factors, and play vital roles in plant growth, development and stress responses.
Results: In this study, a total of 27 Alfin-like transcription factors were identified in wheat. TaAL genes were unevenly distributed on chromosome.
Plant Genome
September 2024
State Key Laboratory of Aridland Crop Science, Gansu Agricultural University, Lanzhou, China.
Mol Genet Genomics
May 2024
National Center for Soybean Improvement, National Key Laboratory of Crop Genetics and Germplasm Enhancement and Utilization, Jiangsu Collaborative Innovation Center for Modern Crop Production, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
Soybean [Glycine max (L.) Merr.] is an important legume crop worldwide, which provides abundant plant protein and oil for human beings.
View Article and Find Full Text PDFBMC Plant Biol
April 2024
State Key Laboratory of Aridland Crop Science, Gansu Agricultural University, Lanzhou, 730070, China.
Background: Ubiquitination is an important regulatory step of selective protein degradation in the plant UPS (ubiquitin-proteasome system), which is involved in various biological processes in eukaryotes. Ubiquitin-conjugating enzymes play an intermediate role in the process of protein ubiquitination reactions and thus play an essential role in regulating plant growth and response to adverse environmental conditions. However, a genome-wide analysis of the UBC gene family in wheat (Triticum aestivum L.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!