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Modified clot waveform analysis to measure plasma coagulation potential in the presence of the anti-factor IXa/factor X bispecific antibody emicizumab.
J Thromb Haemost. 2018 06; 16(6):1078-1088.JT

Abstract

Essentials The activated partial prothrombin time (aPTT) cannot predict the activity of emicizumab (Emi). Adjusted clot waveform analyses using a prothrombin time (PT)/aPTT initiator were developed. Activity of Emi in the co-presence of factor VIII or bypassing agents was quantified. This assay is useful for assessing coagulation potential in Emi-treated hemophilia A.

SUMMARY

Background Emicizumab is an anti-activated factor IX/FX bispecific antibody that mimics activated FVIII cofactor function. Emicizumab does not require activation by thrombin, and its effect on shortening the activated partial thromboplastin time (APTT) is much greater than that of FVIII. Therefore, the APTT has limited utility in hemophilia A (HA) patients treated with emicizumab. Aim To evaluate the global coagulation potential of emicizumab. Methods Clot waveform analysis (CWA) with prothrombin time (PT)/APTT mixed reagents was used to define hemostatic monitoring protocols in HA patients. A modified parameter, adjusted-|min1| (Ad|min1|), was developed. Maximum and minimum percentage transmittance were defined as 100% and 0% in the precoagulation and postcoagulation phases, respectively. Ad|min1| was calculated as an index of the maximum velocity of the coagulation process. Results Ad|min1| obtained with mixed-trigger reagent (PT/APTT/buffer, 1 : 15 : 135) in the presence of emicizumab optimally corresponded to the conversion rate estimated in animals; 0.2-0.4 IU dL-1 equivalent FVIII per 1 μg mL-1 emicizumab). Ex vivo addition of emicizumab to HA plasma with or without inhibitors resulted in concentration-dependent increases in Ad|min1|, with some individual variations. The addition of various concentrations of FVIII to HA plasma mixed with emicizumab resulted in dose-dependent increases in Ad|min1|. Similarly, mixtures of activated prothrombin complex concentrate and emicizumab added to HA plasma resulted in dose-dependent increases in Ad|min1|. In contrast, enhanced coagulation potential appeared to be better defined by the clot time than by Ad|min1| in experiments using recombinant activated FVII. Conclusion The PT/APTT reagent-triggered adjusted CWA could provide a useful means of assessing global coagulation potential in emicizumab-treated HA patients, with enhanced activity neither masking nor being masked by FVIII or bypassing agents.

Authors+Show Affiliations

Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan.Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan. Course of Hemophilia Treatment & Pathology, Nara Medical University, Kashihara, Nara, Japan.Engineering Division, Sysmex Corporation, Kobe, Japan.Chugai Pharmaceutical Co., Gotenba, Japan.Engineering Division, Sysmex Corporation, Kobe, Japan.Chugai Pharmaceutical Co., Gotenba, Japan.Department of Pediatrics, Nara Medical University, Kashihara, Nara, Japan. Course of Hemophilia Treatment & Pathology, Nara Medical University, Kashihara, Nara, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29645406

Citation

Nogami, K, et al. "Modified Clot Waveform Analysis to Measure Plasma Coagulation Potential in the Presence of the Anti-factor IXa/factor X Bispecific Antibody Emicizumab." Journal of Thrombosis and Haemostasis : JTH, vol. 16, no. 6, 2018, pp. 1078-1088.
Nogami K, Matsumoto T, Tabuchi Y, et al. Modified clot waveform analysis to measure plasma coagulation potential in the presence of the anti-factor IXa/factor X bispecific antibody emicizumab. J Thromb Haemost. 2018;16(6):1078-1088.
Nogami, K., Matsumoto, T., Tabuchi, Y., Soeda, T., Arai, N., Kitazawa, T., & Shima, M. (2018). Modified clot waveform analysis to measure plasma coagulation potential in the presence of the anti-factor IXa/factor X bispecific antibody emicizumab. Journal of Thrombosis and Haemostasis : JTH, 16(6), 1078-1088. https://doi.org/10.1111/jth.14022
Nogami K, et al. Modified Clot Waveform Analysis to Measure Plasma Coagulation Potential in the Presence of the Anti-factor IXa/factor X Bispecific Antibody Emicizumab. J Thromb Haemost. 2018;16(6):1078-1088. PubMed PMID: 29645406.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modified clot waveform analysis to measure plasma coagulation potential in the presence of the anti-factor IXa/factor X bispecific antibody emicizumab. AU - Nogami,K, AU - Matsumoto,T, AU - Tabuchi,Y, AU - Soeda,T, AU - Arai,N, AU - Kitazawa,T, AU - Shima,M, Y1 - 2018/05/13/ PY - 2017/10/15/received PY - 2018/4/13/pubmed PY - 2019/9/17/medline PY - 2018/4/13/entrez KW - FVIII KW - PT/APTT KW - bypassing agents KW - clot waveform analysis KW - emicizumab SP - 1078 EP - 1088 JF - Journal of thrombosis and haemostasis : JTH JO - J Thromb Haemost VL - 16 IS - 6 N2 - : Essentials The activated partial prothrombin time (aPTT) cannot predict the activity of emicizumab (Emi). Adjusted clot waveform analyses using a prothrombin time (PT)/aPTT initiator were developed. Activity of Emi in the co-presence of factor VIII or bypassing agents was quantified. This assay is useful for assessing coagulation potential in Emi-treated hemophilia A. SUMMARY: Background Emicizumab is an anti-activated factor IX/FX bispecific antibody that mimics activated FVIII cofactor function. Emicizumab does not require activation by thrombin, and its effect on shortening the activated partial thromboplastin time (APTT) is much greater than that of FVIII. Therefore, the APTT has limited utility in hemophilia A (HA) patients treated with emicizumab. Aim To evaluate the global coagulation potential of emicizumab. Methods Clot waveform analysis (CWA) with prothrombin time (PT)/APTT mixed reagents was used to define hemostatic monitoring protocols in HA patients. A modified parameter, adjusted-|min1| (Ad|min1|), was developed. Maximum and minimum percentage transmittance were defined as 100% and 0% in the precoagulation and postcoagulation phases, respectively. Ad|min1| was calculated as an index of the maximum velocity of the coagulation process. Results Ad|min1| obtained with mixed-trigger reagent (PT/APTT/buffer, 1 : 15 : 135) in the presence of emicizumab optimally corresponded to the conversion rate estimated in animals; 0.2-0.4 IU dL-1 equivalent FVIII per 1 μg mL-1 emicizumab). Ex vivo addition of emicizumab to HA plasma with or without inhibitors resulted in concentration-dependent increases in Ad|min1|, with some individual variations. The addition of various concentrations of FVIII to HA plasma mixed with emicizumab resulted in dose-dependent increases in Ad|min1|. Similarly, mixtures of activated prothrombin complex concentrate and emicizumab added to HA plasma resulted in dose-dependent increases in Ad|min1|. In contrast, enhanced coagulation potential appeared to be better defined by the clot time than by Ad|min1| in experiments using recombinant activated FVII. Conclusion The PT/APTT reagent-triggered adjusted CWA could provide a useful means of assessing global coagulation potential in emicizumab-treated HA patients, with enhanced activity neither masking nor being masked by FVIII or bypassing agents. SN - 1538-7836 UR - https://www.unboundmedicine.com/medline/citation/29645406/Modified_clot_waveform_analysis_to_measure_plasma_coagulation_potential_in_the_presence_of_the_anti_factor_IXa/factor_X_bispecific_antibody_emicizumab_ L2 - https://doi.org/10.1111/jth.14022 DB - PRIME DP - Unbound Medicine ER -