Dingli David, De Castro Iii Carlos, Koprivnikar Jamie, Kulasekararaj Austin, Maciejewski Jaroslaw, Mulherin Brian, Panse Jens, Pullarkat Vinod, Röth Alexander, Shammo Jamile, Terriou Louis, Weitz Ilene, Yermilov Irina, Gibbs Sarah, Broder Michael, Beenhouwer David, Kuter David
Mayo Clinic, Rochester, MN, USA.
Duke University Medical Center, Duke Cancer Institute, Durham, NC, USA.
Hematology. 2024 Dec;29(1):2329030. doi: 10.1080/16078454.2024.2329030. Epub 2024 Mar 21.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, non-malignant hematologic disease characterized by complement-mediated hemolysis (with or without hemoglobinuria), fatigue, increased susceptibility to thrombosis, and bone marrow dysfunction. The development of complement inhibitors has transformed outcomes for patients with PNH, but patients may still experience pharmacodynamic breakthrough hemolysis (BTH), which can be caused by exposure to a complement amplifying condition (CAC), such as vaccination, infection, or surgery.
A 13-member expert panel used a validated methodology (a RAND/UCLA modified Delphi panel) to develop consensus on how to classify pharmacodynamic BTH in patients with complement-inhibitor treated PNH. Physicians reviewed literature, rated the appropriateness of over 400 scenarios, and discussed the ratings at an in-person meeting.
After the meeting, the panel agreed on 77% of scenarios. Here, we present the group's agreed-upon recommendations on how to manage BTH caused by a CAC, as well as provide a severity classification system for BTH and strategies to mitigate risk of BTH in special circumstances (e.g. vaccination, planned or unplanned surgery, and pregnancy).
In general, as severity of BTH increased, experts agreed more interventions to manage the BTH were appropriate. These recommendations are based on clinical experience and opinion. Without clear data from randomized trials to guide the management of BTH, expert opinion can be useful to support patient care.
阵发性睡眠性血红蛋白尿（PNH）是一种罕见的获得性非恶性血液病，其特征为补体介导的溶血（伴或不伴血红蛋白尿）、疲劳、血栓形成易感性增加及骨髓功能障碍。补体抑制剂的出现改变了PNH患者的治疗结局，但患者仍可能经历药效学突破性溶血（BTH），这可能由暴露于补体放大条件（CAC）引起，如接种疫苗、感染或手术。
一个由13名专家组成的小组采用经过验证的方法（兰德/加州大学洛杉矶分校改良德尔菲小组），就如何对接受补体抑制剂治疗的PNH患者的药效学BTH进行分类达成共识。医生查阅文献，对400多个病例的适宜性进行评分，并在一次面对面会议上讨论评分结果。
会议结束后，小组对77%的病例达成了一致意见。在此，我们展示该小组就如何处理由CAC引起的BTH达成的一致建议，并提供BTH的严重程度分类系统以及在特殊情况下（如接种疫苗、计划内或计划外手术及妊娠）降低BTH风险的策略。
总体而言，随着BTH严重程度的增加，专家们一致认为采取更多干预措施来处理BTH是合适的。这些建议基于临床经验和观点。在缺乏来自随机试验的明确数据来指导BTH的管理时，专家意见有助于支持患者护理。
