Minimal interference of concizumab with standard clinical coagulation laboratory assays – An in vitro study

IF 3 2区 医学 Q2 HEMATOLOGY
Haemophilia Pub Date : 2024-06-25 DOI:10.1111/hae.15070
Cecilia Augustsson, Karin Strandberg, Marianne Kjalke
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引用次数: 0

Abstract

Introduction

Non-factor replacement therapies are emerging as prophylactic treatment options in haemophilia A or B (HA/HB) with and without inhibitors. Concizumab is an anti-tissue factor pathway inhibitor (TFPI) monoclonal antibody preventing factor (F)Xa inhibition and enhancing thrombin generation. Based on experience with other non-factor therapies and extended half-life products, there is a focus on potential interference with common clinical coagulation assays used to monitor patients treated with concizumab.

Aim

To evaluate the impact of concizumab on standard clinical coagulation assays.

Methods

Plasma samples (normal, HA/HB with/without inhibitors) in the presence/absence of added concizumab (250–16,000 ng/mL) were analysed in clinical assays including activated partial thromboplastin time (aPTT), prothrombin time (PT), FVIII and FIX one-stage clot and chromogenic substrate assay, assays for detecting FVIII or FIX inhibitors and other assays for coagulation factors.

Results

Concizumab did not impact PT assays, but resulted in a small shortening of aPTT (up to 5 s in haemophilia plasma and 0.4 s in normal plasma). Concizumab had no, or only a minor impact on FVIII and FIX activity assays or Bethesda inhibitor assays. FXI and FXII activity in normal plasma, as measured by single factor aPTT-based assay, was significantly increased in the presence of concizumab (+11% each). This was also the case for FVII and FX measured by PT-based assays using plasma with 25% of FVII or FX (+64% and +22%, respectively).

Conclusion

The presence of concizumab did not, or only slightly, influence the outcome of standard clinical coagulation assays relevant for HA and HB.

Abstract Image

康利珠单抗对标准临床凝血实验室检测的干扰最小--一项体外研究。
导言:非因子替代疗法正在成为血友病 A 或 B(HA/HB)患者的预防性治疗选择,无论患者是否患有抑制剂。康妥珠单抗是一种抗组织因子通路抑制剂(TFPI)单克隆抗体,可防止因子(F)Xa受抑制并增强凝血酶的生成。根据其他非因子疗法和延长半衰期产品的经验,人们关注用于监测接受康利珠单抗治疗的患者的常用临床凝血测定的潜在干扰:方法:对添加/不添加康利珠单抗(250-16,000 纳克/毫升)的血浆样本(正常、HA/HB(含/不含抑制剂))进行临床检测分析,包括活化部分凝血活酶时间(aPTT)、凝血酶原时间(PT)、FVIII 和 FIX 一阶段凝血和显色底物检测、FVIII 或 FIX 抑制剂检测以及其他凝血因子检测:结果:康西珠单抗对 PT 检测没有影响,但会导致 aPTT 略有缩短(血友病血浆中可达 5 秒,正常血浆中为 0.4 秒)。康舒单抗对 FVIII 和 FIX 活性测定或 Bethesda 抑制剂测定没有影响或仅有轻微影响。用基于单因子 aPTT 的检测法测量正常血浆中的 FXI 和 FXII 活性,发现在使用康妥珠单抗的情况下,这两种活性显著增加(各增加 11%)。使用含 25% FVII 或 FX 的血浆进行基于 PT 的检测所测得的 FVII 和 FX 也是如此(分别为 +64% 和 +22%):结论:康珠单抗的存在不会或仅会轻微影响与 HA 和 HB 相关的标准临床凝血测定的结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Haemophilia
Haemophilia 医学-血液学
CiteScore
6.50
自引率
28.20%
发文量
226
审稿时长
3-6 weeks
期刊介绍: Haemophilia is an international journal dedicated to the exchange of information regarding the comprehensive care of haemophilia. The Journal contains review articles, original scientific papers and case reports related to haemophilia care, with frequent supplements. Subjects covered include: clotting factor deficiencies, both inherited and acquired: haemophilia A, B, von Willebrand''s disease, deficiencies of factor V, VII, X and XI replacement therapy for clotting factor deficiencies component therapy in the developing world transfusion transmitted disease haemophilia care and paediatrics, orthopaedics, gynaecology and obstetrics nursing laboratory diagnosis carrier detection psycho-social concerns economic issues audit inherited platelet disorders.
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