南方医科大学学报

南方医科大学学报 ›› 2016, Vol. 36 ›› Issue (04): 592-.

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改良Bethesda方法、改良Nijmegen方法和空白法检测凝血因子Ⅷ抑制物及其影响因素

冯厚梅，李强，许伟珊，陈东妙，郑磊   

  • 出版日期:2016-04-20 发布日期:2016-04-20

Modified Bethesda, modified Nijmegen and blank assays for coagulation factor VIII inhibitor detection and factors affecting the results

  • Online:2016-04-20 Published:2016-04-20

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摘要： 目的评价改良Bethesda方法、改良Nijmegen方法和空白法检测血友病A患者凝血因子Ⅷ抑制物的临床应用价值，并探 讨凝血因子Ⅷ抑制物检测的影响因素。方法采用改良Bethesda方法、改良Nijmegen方法和以去离子水替代缓冲液或乏Ⅷ因 子血浆的空白法，分别检测257例血友病A患者的抑制物水平，以抑制物滴度≥0.60 BU/mL判为阳性结果，并对3种方法检测结 果的阳性率及抑制物滴度水平进行分析。结果改良Bethesda 方法、改良Nijmegen 方法和空白法的阳性率分别为79.38%、 85.21%和72.37%。改良Bethesda方法与改良Nijmegen方法之间相关系数为0.996（P<0.001），两种方法的抑制物滴度水平之间 有显著的统计学差异（P<0.001），阳性率无显著的统计学差异（P=0.105）；改良Bethesda方法与空白法之间相关系数为0.994（P< 0.001），抑制物滴度水平之间有显著的统计学差异（P<0.001），阳性率无显著的统计学差异（P=0.079）；改良Nijmegen方法与空 白法之间相关系数为0.994（P<0.001），抑制物滴度水平之间有显著的统计学差异（P<0.001），阳性率有显著的统计学差异（P= 0.001）。结论改良Nijmegen方法具有较高的灵敏度，改良Bethesda方法次之，空白法最差。反应体系中各凝血因子活性水平 的一致性是影响凝血因子Ⅷ抑制物检测的主要因素，而稳定的缓冲体系也是影响检测结果稳定性、灵敏度及特异性不可忽视的 因素。

Abstract: Objective To evaluate the clinical value of modified Bethesda assay, modified Nijmegen assay and blank assay for detection of coagulation factor VIII (FVIII) inhibitors in patients with hemophilia A and analyze the factors that affect FVIII inhibitor detection. Methods The levels of FVIII inhibitors in 257 patients with hemophilia A were detected using modified Bethesda assay, modified Nijmegen assay and blank assay (in which the buffer or FVIII-deficient plasma in the control mixture was replaced by deionized water). The 3 methods were compared for positivity rates and FVIII inhibitor titers based on the positive cut-off value of FVIII inhibitors ≥0.60 BU/mL. Results The positive rates of modified Bethesda assay, modified Nijmegen assay and blank assay were 79.38%, 85.21% and 72.37%, respectively. A strong correlation was found between the results by modified Bethesda assay and modified Nijmegen assay (r=0.996, P<0.001), and FVIII inhibitor titers (P<0.001) but not the positive rates (P=0.105) detected by the two methods differed significantly. The correlation coefficients between modified Nijmegen assay and blank assay was 0.994 (P<0.001), and a significant difference was found in FVIII inhibitor titers (P<0.001) but not the positivity rates (P=0.079) detected by the two methods. The correlation coefficient between modified Nijmegen assay and blank assay was 0.994 (r=0.994), and the two methods yielded significantly different FVIII inhibitor titers and positivity rates (P=0.001). Conclusion The modified Bethesda assay has a lower sensitivity than modified Nijmegen assay but has a higher sensitivity than blank assay. The consistency level of coagulation factors in the reaction system and stable buffer system are important factors that affect FVIII-inhibitor detection.