Characteristics of hemophilia patients with factor VIII inhibitors detected by prospective screening.
Characteristics of hemophilia patients with factor VIII inhibitors detected by prospective screening.
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DOI：
10.1002/ajh.24104
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发表时间：
2015-10
影响因子：
12.8
通讯作者：
Hemophilia Inhibitor Research Study Investigators
中科院分区：
文献类型：
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作者：
Miller CH;Rice AS;Boylan B;Payne AB;Kelly FM;Escobar MA;Gill J;Leissinger C;Soucie JM;Hemophilia Inhibitor Research Study Investigators
通过前瞻性筛选确定的抑制剂特征可能与临床检测到的抑制剂特征不同。在一项在17家血友病中心进行的前瞻性研究中，通过Nijmegen-Bethesda试验测量了中心抑制物，824例血友病A患者中有23例（2.8%）检测到新的抑制物：9例高滴度抑制物（HTI：7例≥5.0 NBU，免疫耐受诱导开始时2例为2.6和3.4 NBU）和14例低滴度抑制物（LTI：0.5-1.9 NBU）。HTI发生在较早的年龄（中位数2岁，范围1-18，与中位数11岁，范围2-61，P = 0.016）。HTI（22%）和LTI（43%）均发生在非重度患者中。所有HTI，但只有64%的LTI，被发现是FVIII特异性显色Bethesda测定或荧光免疫测定（FLI），表明假阳性率高LTI。重复标本证实了所有HTI、7/9例LTI和7/7例FVIII特异性LTI。HTI和FVIII特异性LTI之间的FLI结果相似;均包括IgG 1和IgG 4亚类。1975年至1979年在美国13个中心进行的一项可比的前瞻性研究在1,306名患者中发现了31种（2.4%）新的抑制剂。在这两项研究中，三分之一的抑制物发生在非重度患者中，四分之一发生在150个暴露日（艾德）后。在抑制物发生的年龄（旧研究中位年龄为16岁，目前为5岁，P = 0.024）和抑制物发生前的艾德中观察到显著差异，旧研究中10%和当前研究中43%的患者在20艾德内发生，表明抑制物发生的时间变化。前瞻性筛查可检测所有严重程度、年龄和ED患者的抑制物。然而，一些LTI是假阳性。
Characteristics of inhibitors identified by prospective screening may differ from those detected clinically. In a prospective study at 17 hemophilia centers with central inhibitor measurement by Nijmegen-Bethesda assay, 23 (2.8%) of 824 hemophilia A patients had new inhibitors detected: nine high-titer inhibitors (HTI: 7 ≥5.0 NBU plus 2 of 2.6 and 3.4 NBU at immune tolerance induction initiation) and 14 low-titer inhibitors (LTI: 0.5–1.9 NBU). HTI occurred at an earlier age (median 2 years, range 1–18, vs. median 11 years, range 2–61, P = 0.016). Both HTI (22%) and LTI (43%) occurred in non-severe patients. All HTI, but only 64% of LTI, were found to be FVIII-specific by chromogenic Bethesda assay or fluorescence immunoassay (FLI), indicating a high rate of false-positive LTI. Repeat specimens confirmed all HTI, 7/9 LTI, and 7/7 FVIII-specific LTI. FLI results were similar between HTI and FVIII-specific LTI; all included IgG1 and IgG4 subclasses. A comparable prospective study conducted from 1975 to 1979 at 13 U.S. centers found 31 (2.4%) new inhibitors among 1,306 patients. In both studies, one-third of inhibitors occurred in non-severe patients and one-quarter after 150 exposure days (ED). Significant differences were seen in the age at which inhibitors occurred (median 16 years in the older study vs. 5 years currently, P = 0.024) and in ED before inhibitor development, 10% in the older study and 43% currently study occurring within 20 ED, suggesting a temporal change in inhibitor development. Prospective screening detects inhibitors in patients of all severities, ages, and ED. Some LTI, however, are false positives.