National Institute of Immunohaematology (ICMR), 13th floor, KEM Hospital, Parel, Mumbai 400 012, India.
Dept. of Haematology, Seth GS Medical College, KEM Hospital, Parel, Mumbai 400012, India.
Thromb Res. 2018 Dec;172:29-35. doi: 10.1016/j.thromres.2018.10.015. Epub 2018 Oct 18.
Presence of lupus anticoagulants (LA) in haemophilia and their interference in coagulation assays is well-known. Factor VIII (FVIII) inhibitors are generally time and temperature dependent whereas LAs are immediate acting inhibitors (IAIs). The present study reports the challenges in laboratory detection of both progressive and non-progressive, specific FVIII inhibitors in the presence of LA.
From 2012 through 2015, 4900 HA patients were screened for inhibitors. APTT based inhibitor screening tests and Nijmegen-modified Bethesda assay (NBA) were done in all samples. LA test and FVIII inhibitors by ELISA were done in patients with IAIs.
Out of 451 patients positive for inhibitors in the initial screening tests, classical and progressive FVIII inhibitors were observed in 398 patients while 53 had IAIs showing no/partial correction in 1:1 mixtures of NPP and patient plasma. In 27 patients, both FVIII and FIX activity levels were <1%, resulting in difficulty in diagnosis. In 48 HA patients with IAIs, 42 were LA positive. 4 patients were found to have only LA with false positive results in NBA while 38 had a combination of LA and FVIII inhibitors. Six patients were LA negative and had only FVIII IAIs. Five (62.5%) of 8 HA patients initiated on immune tolerance induction (ITI) also were positive for IAIs.
The findings emphasizes the presence of specific FVIII inhibitors in congenital HA with absence of time dependent inactivation kinetics in a small proportion of cases. ELISA or chromogenic assays along with LA testing can offer accurate laboratory diagnosis in patients with coexisting LA.
已知狼疮抗凝物（LA）存在于血友病患者中，并会干扰凝血检测。VIII 因子（FVIII）抑制剂通常具有时间和温度依赖性，而 LA 是即刻作用抑制剂（IAI）。本研究报告了在存在 LA 的情况下，实验室检测进展性和非进展性、特异性 FVIII 抑制剂的挑战。
2012 年至 2015 年，对 4900 名血友病患者进行了抑制剂筛查。所有样本均进行基于 APTT 的抑制剂筛选试验和尼姆斯改良贝塞斯达测定（NBA）。LA 试验和 ELISA 法检测 FVIII 抑制剂用于存在 IAI 的患者。
在初始筛选试验中，有 451 名患者呈抑制剂阳性，其中 398 名患者存在经典和进展性 FVIII 抑制剂，53 名患者存在 IAI，在 NPP 和患者血浆 1:1 混合液中无/部分纠正。在 27 名患者中，FVIII 和 FIX 活性水平均<1%，导致诊断困难。在 48 名存在 IAI 的血友病患者中，42 名 LA 阳性。在 NBA 中发现 4 名患者仅存在 LA，且结果为假阳性，而 38 名患者同时存在 LA 和 FVIII 抑制剂。6 名患者为 LA 阴性，且仅存在 FVIII IAI。5 名（62.5%）接受免疫耐受诱导（ITI）治疗的血友病患者也存在 IAI。
这些发现强调了在先天性血友病患者中存在特异性 FVIII 抑制剂，并且在一小部分病例中缺乏时间依赖性失活动力学。ELISA 或显色测定法结合 LA 检测可以为同时存在 LA 的患者提供准确的实验室诊断。
