Owaidah Tarek, Almomen Abdulakareem, Tarawah Ahmed, Warsi Ashraf, Alkasim Fawaz, Alzahrani Hazzaa, Saleh Mahassen, Kashari Ohoud, Jastaniah Wasil
Hematology and Transfusion Medicine, Department of Pathology and Laboratory Medicine (MBC 10), King Faisal Specialist Hospital and Research Center Alfaisal University Riyadh, Saudi Arabia.
Medicine-Hematology, King Saud University Medical City and Blood and Cancer Center Riyadh, Saudi Arabia.
Am J Blood Res. 2022 Jun 20;12(3):82-87. eCollection 2022.
Emicizumab is a bispecific monoclonal antibody with the ability to bridge FIXa and FX, mimic FVIII, and restore normal hemostasis in patients with hemophilia A. Moreover, substantial evidence has shown that emicizumab-treated patients do not require monitoring, except before surgery or invasive procedures. However, introducing this novel drug to the market poses some challenges to physicians and clinical laboratories due to its interaction with conventional coagulation tests.
Given the challenges and laboratory interactions posed by this novel drug, there is an unmet clinical need to develop clear recommendations for emicizumab laboratory monitoring to highlight which laboratory tests should be used, which tests should be avoided, and when these tests should be performed. These expert recommendations are essential to prevent inappropriate testing or misleading interpretations and reduce the extra costs of unnecessary monitoring.
A consensus meeting was conducted in December 2019, including top experts on hemophilia from Saudi Arabia, to discuss this issue.
The experts agreed that, aPTT (activated Partial Thromboplastin Time)-based tests are not suitable for laboratory monitoring patients treated with emicizumab. Only FVIII chromogenic assays based on bovine FIX and FX proteins can be used to measure FVIII levels. They reviewed and recommended the type and time of testing for anti-factor VIII antibodies. Drug levels should be measured using the recommended test only when the anti-drug antibody (ADA) is clinically suspected and after excluding other causes (such as patient non-compliance).
依美珠单抗是一种双特异性单克隆抗体,能够连接FIXa和FX,模拟FVIII,并恢复A型血友病患者的正常止血功能。此外,大量证据表明,接受依美珠单抗治疗的患者除手术或侵入性操作前外无需监测。然而,由于其与传统凝血试验的相互作用,将这种新型药物推向市场给医生和临床实验室带来了一些挑战。
鉴于这种新型药物带来的挑战和实验室相互作用,临床上迫切需要制定关于依美珠单抗实验室监测的明确建议,以突出应使用哪些实验室检测、应避免哪些检测以及何时进行这些检测。这些专家建议对于防止不适当的检测或误导性解释以及减少不必要监测的额外成本至关重要。
2019年12月召开了一次共识会议,与会专家包括来自沙特阿拉伯的血友病顶级专家,以讨论该问题。
专家们一致认为,基于活化部分凝血活酶时间(aPTT)的检测不适用于依美珠单抗治疗患者的实验室监测。只有基于牛FIX和FX蛋白的FVIII显色测定可用于测量FVIII水平。他们审查并推荐了抗FVIII抗体检测的类型和时间。仅在临床怀疑存在抗药物抗体(ADA)且排除其他原因(如患者不依从)后,才应使用推荐检测方法测量药物水平。