Validation of Nijmegen-Bethesda assay modifications to allow inhibitor measurement during replacement therapy and facilitate inhibitor surveillance
Validation of Nijmegen-Bethesda assay modifications to allow inhibitor measurement during replacement therapy and facilitate inhibitor surveillance
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DOI：
10.1111/j.1538-7836.2012.04705.x
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发表时间：
2012-06-01
影响因子：
10.4
通讯作者：
Soucie, J. M.
中科院分区：
文献类型：
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作者：
Miller, C. H.;Platt, S. J.;Soucie, J. M.
背景：作为美国疾病控制和预防中心（CDC）于2006年启动的抑制剂监测试点项目的一部分，建立了集中的抑制剂测量。目的：验证一种适用于治疗和未治疗患者的抑制剂测定方法。方法/结果：共纳入710例A型血友病患者；122例有抑制剂（HI）病史。50份用冷包装和冷冻运输的分离标本的Nijmegen-Bethesda测定（NBA）结果相当（r = 0.998）。由于228个初始样品中55%具有因子(F) VIII活性（VIII: C），因此增加了热处理步骤。将标本加热至56摄氏度30分钟并离心去除FVIII，在最近接受治疗的患者中，VIII: C和FVIII抗原降低至< 1 U dL（-1）。加热前抑制剂阴性的159例HI阴性和30例HI阳性标本中5例加热后Nijmegen-Bethesda单位（NBU）升高至>= 0.5。加热和未加热抑制剂阳性标本的相关性为0.94 （P = 0.0001）。1 NBU阳性对照和阴性对照的变异系数（CV）分别为10.3%和9.8%。根据710例入组标本的结果，CDC抑制剂阳性定义为>= 0.5 NBU。纳入643例入组后标本时，结果相似。160名B型血友病患者中，2名患有HI。其他人都是NBU
Background: As part of a pilot U.S. inhibitor surveillance project initiated at the Centers for Disease Control and Prevention (CDC) in 2006, a centralized inhibitor measurement was instituted. Objective: To validate a modified method for inhibitor measurement suitable for surveillance of treated and untreated patients. Methods/Results: In all, 710 subjects with hemophilia A were enrolled; 122 had a history of inhibitor (HI). Nijmegen-Bethesda assay (NBA) results on 50 split specimens shipped on cold packs and frozen were equivalent (r = 0.998). Because 55% of 228 initial specimens had factor (F) VIII activity (VIII: C) present, a heat treatment step was added. Heating specimens to 56 degrees C for 30 min and centrifuging removed FVIII, as demonstrated by a reduction of VIII: C and FVIII antigen to < 1 U dL(-1) in recently treated patients. Among specimens inhibitor-negative before heating, one of 159 with negative HI and five of 30 with positive HI rose to >= 0.5 Nijmegen-Bethesda units (NBU) after heating. Correlation of heated and unheated inhibitor-positive specimens was 0.94 (P = 0.0001). The modified method had a coefficient of variation (CV) for a 1 NBU positive control of 10.3% and for the negative control of 9.8%. Based on results on 710 enrollment specimens, a positive CDC inhibitor was defined as >= 0.5 NBU. Results were similar when 643 post-enrollment specimens were included. Of 160 enrolled hemophilia B patients, two had HI. All others had NBU