Department of Coagulation, Royal Hallamshire Hospital, Sheffield, UK.
The Royal London Hospital, Barts Health NHS Trust, London, UK.
Haemophilia. 2020 Nov;26(6):1181-1186. doi: 10.1111/hae.14162. Epub 2020 Sep 30.
Acquired haemophilia A (AHA) is a rare bleeding disorder caused by the development of autoantibodies to endogenous human factor VIII (hFVIII). If treatment of bleeding is required, one option is recombinant porcine FVIII (rpFVIII). Cross-reactivity between factor VIII inhibitors and rpFVIII has previously been described.
The aim of this study was to retrospectively assess the incidence of cross-reacting anti-porcine inhibitors in patients diagnosed with AHA in two UK centres.
The plasma of fifty-one patients diagnosed with AHA via reduced FVIII:C and positive FVIII inhibitor titre as detected with a Nijmegen-Bethesda assay (NBA) was also tested by a porcine Bethesda assay (PBA). The NBA was modified by replacement of human FVIII with rpFVIII in the PBA, with determination of residual FVIII by one-stage clotting assay.
The median FVIII inhibitor titre by NBA was 22.8 BU/mL (range: 0.8-1000 BU/mL). 37% of samples exhibited linear, type 1 kinetics in the NBA. Negative PBA was observed in 26 patients, and 25 were positive (median PBA: 3.5 BU/mL; range: 0.8-120 BU/mL). Type 1 kinetics were observed in 40% of PBA-positive patients. At NBA tires of greater than 100 BU/mL, the positive predictive value for the presence of porcine cross-reactivity was 100%. At NBA below 5 BU/mL, the negative predictive value for the presence of porcine cross-reactivity was 71%.
Cross-reactivity between FVIII inhibitors and rpFVIII was observed in 49% of patients. The presence of inhibitors to rpFVIII may influence the treatment choice for patients with acquired haemophilia A.
获得性血友病 A（AHA）是一种罕见的出血性疾病，由内源性人凝血因子 VIII（hFVIII）自身抗体的发展引起。如果需要治疗出血，一种选择是重组猪凝血因子 VIII（rpFVIII）。因子 VIII 抑制剂与 rpFVIII 之间的交叉反应性以前已有描述。
本研究旨在回顾性评估两个英国中心诊断为 AHA 的患者中交叉反应性抗猪抑制剂的发生率。
通过减少 FVIII:C 和阳性 FVIII 抑制剂滴度（如用 Nijmegen-Bethesda 测定法（NBA）检测到）诊断为 AHA 的五十一名患者的血浆也通过猪 Bethesda 测定法（PBA）进行了检测。NBA 通过在 PBA 中用人凝血因子 VIII 替换 rpFVIII 进行了修改，通过一步法凝血测定法确定残余 FVIII。
NBA 中的中位 FVIII 抑制剂滴度为 22.8 BU/mL（范围：0.8-1000 BU/mL）。37%的样本在 NBA 中表现出线性、1 型动力学。26 名患者的 PBA 为阴性，25 名患者为阳性（中位 PBA：3.5 BU/mL；范围：0.8-120 BU/mL）。40%的 PBA 阳性患者表现出 1 型动力学。在 NBA 轮胎大于 100 BU/mL 时，存在猪交叉反应的阳性预测值为 100%。在 NBA 低于 5 BU/mL 时，存在猪交叉反应的阴性预测值为 71%。
在 49%的患者中观察到 FVIII 抑制剂与 rpFVIII 之间的交叉反应性。猪凝血因子 VIII 抑制剂的存在可能会影响获得性血友病 A 患者的治疗选择。
