Comparison of clot-based, chromogenic and fluorescence assays for measurement of factor VIII inhibitors in the US Hemophilia Inhibitor Research Study.
Comparison of clot-based, chromogenic and fluorescence assays for measurement of factor VIII inhibitors in the US Hemophilia Inhibitor Research Study.
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DOI：
10.1111/jth.12259
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发表时间：
2013-07
期刊：
影响因子：
--
通讯作者：
Hemophilia Inhibitor Research Study Investigators
中科院分区：
文献类型：
--
作者：
Miller CH;Rice AS;Boylan B;Shapiro AD;Lentz SR;Wicklund BM;Kelly FM;Soucie JM;Hemophilia Inhibitor Research Study Investigators
血友病治疗产品抑制剂（抗体）的检测和验证对于临床护理、产品安全性评估和人群趋势评估非常重要。使用先前报道的改良奈梅亨-贝塞斯达凝血测定 (NBA)、显色贝塞斯达测定 (CBA) 和新型荧光免疫测定 (FLI)，对血友病抑制剂研究中的患者进行了因子 VIII (FVIII) 抑制剂的集中监测。 NBA 和 CBA 对 1005 个样本进行了测试，FLI 对 272 个样本进行了测试。奈梅亨-贝塞斯达单位 (NBU) <0.5 的 880/883 份标本 (99.7%) 呈阴性，NBU ≥ 2.0 的 42/42 份标本 (100%) 和 NBU 0.5-1.9 的 43/80 份标本 (53.8%) 呈阳性。在 NBA 阳性和 CBA 阴性的标本中，58.1% 为 FLI 阴性，12.9% 有狼疮抗凝证据，35.5% 有非时间依赖性抑制。 1.0-1.9 NBU 标本中 CBA 和 FLI 呈阳性，分别为 72.4% 和 100%，0.5-0.9 NBU 标本中 CBA 和 FLI 呈阳性，分别为 43.1% 和 50.0%。 FLI 在 98.0% 的 CBA 阳性样本和 81.6% 的 NBA 阳性样本中检测到抗体（P=0.004）。 NBA检测到的21种新抑制剂中，5种（23.8%）0.7-1.3 NBU在CBA或FLI中没有反应。在先前呈 0.5–1.9 NBU 阳性的患者中，7/25 (28%) 的 CBA 或 FLI 不呈阳性。 FLI 在 36/169 NBU 阴性样本 (21.3%) 中呈阳性。对于 26% 0.5-1.9 NBU 的抑制剂，CBA 或 FLI 无法证明 FVIII 特异性；必须谨慎解释此类结果。应始终重复在基于凝块的测定中检测到的低滴度抑制剂，并考虑使用更具体的测定来评估其与 FVIII 的反应性。
Detection and validation of inhibitors (antibodies) to hemophilia treatment products are important for clinical care, evaluation of product safety, and assessment of population trends. Centralized monitoring for factor VIII (FVIII) inhibitors was conducted for patients in the Hemophilia Inhibitor Research Study using a previously reported modified Nijmegen-Bethesda clotting assay (NBA), a chromogenic Bethesda assay (CBA), and a novel fluorescence immunoassay (FLI). NBA and CBA were performed on 1005 specimens and FLI on 272 specimens. CBA was negative on 880/883 specimens (99.7%) with Nijmegen-Bethesda units (NBU)<0.5 and positive on 42/42 specimens (100%) with NBU≥2.0 and 43/80 specimens (53.8%) with NBU 0.5–1.9. Among specimens with positive NBA and negative CBA, 58.1% were FLI-negative, 12.9% had evidence of lupus anticoagulant, and 35.5% had non-time-dependent inhibition. CBA and FLI were positive on 72.4% and 100% of 1.0–1.9 NBU specimens and 43.1% and 50.0% of 0.5–0.9 NBU specimens. FLI detected antibodies in 98.0% of CBA-positive and 81.6% of NBA-positive specimens (P=0.004). Among 21 new inhibitors detected by NBA, 5 (23.8%) with 0.7–1.3 NBU did not react in CBA or FLI. Among previously positive patients with 0.5–1.9 NBU, 7/25 (28%) were not CBA or FLI positive. FLI was positive on 36/169 NBU-negative specimens (21.3%). FVIII specificity could not be demonstrated by CBA or FLI for 26% of inhibitors of 0.5–1.9 NBU; such results must be interpreted with caution. Low titer inhibitors detected in clot-based assays should always be repeated, with consideration given to evaluating their reactivity with FVIII using more specific assays.
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作者：
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DOI：
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