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A modified thrombin generation assay to evaluate the plasma coagulation potential in the presence of emicizumab, the bispecific antibody to factors IXa/X.
Int J Hematol. 2020 Nov; 112(5):621-630.IJ

Abstract

Emicizumab shortens activated partial thromboplastin time (aPTT) greater than Factor (F)VIII. Clot waveform analysis triggered by ellagic acid and tissue factor trigger (Elg/TF) provided a useful means of assessing emicizumab activity. Thrombin generation assays (TGA) using this trigger reagent might also overcome the difficulties associated with aPTT by emicizumab. To compare TGA triggered by Elg/TF and other reagents (FXIa, TF) for evaluating emicizumab activity. Emicizumab, FVIII, or FVIII-bypassing agents (BPAs) were incubated with FVIII-deficient plasmas prior to TGA initiated by Elg/TF (0.2 μM/0.5 pM), FXIa (5.21 pM), or TF (PPP-Reagent LOW®). Emicizumab, FVIII, or BPAs increased peak thrombin generation (peak-Th) dose-dependently using Elg/TF-trigger and the other triggers. Low responses were evident with FXIa-trigger and the enhanced effects remained below normal levels with Elg/TF-trigger. Experiments using FVIII with emicizumab demonstrated an additive effect on peak-Th using Elg/TF-trigger, and this effect appeared to be less at FVIII ≥ 40 IU/dl. BPAs with emicizumab appeared to mediate additive effects, although its effects were variable. Parameters of thrombin generation from BPAs and emicizumab with Elg/TF-trigger were improved to normal level compared to low TF-trigger. Elg/TF-TGA could evaluate global coagulation potential during emicizumab prophylaxis including concomitant therapy with FVIII or BPAs.

Authors+Show Affiliations

Department of Pediatrics, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.Department of Pediatrics, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan. roc-noga@naramed-u.ac.jp.Chugai Pharmaceutical Co., Ltd, Kamakura, Kanagawa, Japan.Chugai Pharmaceutical Co., Ltd, Kamakura, Kanagawa, Japan.Chugai Pharmaceutical Co., Ltd, Kamakura, Kanagawa, Japan.Chugai Pharmaceutical Co., Ltd, Kamakura, Kanagawa, Japan.Department of Pediatrics, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32748217

Citation

Ogiwara, Kenichi, et al. "A Modified Thrombin Generation Assay to Evaluate the Plasma Coagulation Potential in the Presence of Emicizumab, the Bispecific Antibody to Factors IXa/X." International Journal of Hematology, vol. 112, no. 5, 2020, pp. 621-630.
Ogiwara K, Nogami K, Matsumoto N, et al. A modified thrombin generation assay to evaluate the plasma coagulation potential in the presence of emicizumab, the bispecific antibody to factors IXa/X. Int J Hematol. 2020;112(5):621-630.
Ogiwara, K., Nogami, K., Matsumoto, N., Noguchi-Sasaki, M., Hirata, M., Soeda, T., & Shima, M. (2020). A modified thrombin generation assay to evaluate the plasma coagulation potential in the presence of emicizumab, the bispecific antibody to factors IXa/X. International Journal of Hematology, 112(5), 621-630. https://doi.org/10.1007/s12185-020-02959-x
Ogiwara K, et al. A Modified Thrombin Generation Assay to Evaluate the Plasma Coagulation Potential in the Presence of Emicizumab, the Bispecific Antibody to Factors IXa/X. Int J Hematol. 2020;112(5):621-630. PubMed PMID: 32748217.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A modified thrombin generation assay to evaluate the plasma coagulation potential in the presence of emicizumab, the bispecific antibody to factors IXa/X. AU - Ogiwara,Kenichi, AU - Nogami,Keiji, AU - Matsumoto,Naoki, AU - Noguchi-Sasaki,Mariko, AU - Hirata,Michinori, AU - Soeda,Tetsuhiro, AU - Shima,Midori, Y1 - 2020/08/03/ PY - 2020/04/03/received PY - 2020/07/21/accepted PY - 2020/06/18/revised PY - 2020/8/5/pubmed PY - 2020/11/25/medline PY - 2020/8/5/entrez KW - Bispecific antibodies KW - Blood coagulation tests KW - Factor VIII KW - Hemophilia A KW - Treatment SP - 621 EP - 630 JF - International journal of hematology JO - Int J Hematol VL - 112 IS - 5 N2 - Emicizumab shortens activated partial thromboplastin time (aPTT) greater than Factor (F)VIII. Clot waveform analysis triggered by ellagic acid and tissue factor trigger (Elg/TF) provided a useful means of assessing emicizumab activity. Thrombin generation assays (TGA) using this trigger reagent might also overcome the difficulties associated with aPTT by emicizumab. To compare TGA triggered by Elg/TF and other reagents (FXIa, TF) for evaluating emicizumab activity. Emicizumab, FVIII, or FVIII-bypassing agents (BPAs) were incubated with FVIII-deficient plasmas prior to TGA initiated by Elg/TF (0.2 μM/0.5 pM), FXIa (5.21 pM), or TF (PPP-Reagent LOW®). Emicizumab, FVIII, or BPAs increased peak thrombin generation (peak-Th) dose-dependently using Elg/TF-trigger and the other triggers. Low responses were evident with FXIa-trigger and the enhanced effects remained below normal levels with Elg/TF-trigger. Experiments using FVIII with emicizumab demonstrated an additive effect on peak-Th using Elg/TF-trigger, and this effect appeared to be less at FVIII ≥ 40 IU/dl. BPAs with emicizumab appeared to mediate additive effects, although its effects were variable. Parameters of thrombin generation from BPAs and emicizumab with Elg/TF-trigger were improved to normal level compared to low TF-trigger. Elg/TF-TGA could evaluate global coagulation potential during emicizumab prophylaxis including concomitant therapy with FVIII or BPAs. SN - 1865-3774 UR - https://www.unboundmedicine.com/medline/citation/32748217/A_modified_thrombin_generation_assay_to_evaluate_the_plasma_coagulation_potential_in_the_presence_of_emicizumab_the_bispecific_antibody_to_factors_IXa/X_ L2 - https://dx.doi.org/10.1007/s12185-020-02959-x DB - PRIME DP - Unbound Medicine ER -