HbA1c是一种具有特定六肽结构的血红蛋白分子,拥有血液浓度相对稳定的优点,临床常用其代表总的糖化血红蛋白水平。在实际的检测中,除血糖浓度外,还有一些因素也可以影响糖化血红蛋白的值,如果出现糖化结果与临床不符,不妨考虑是否为以下因素引起的。
因素一 红细胞因素
红细胞的寿命是影响GHb的一个重要因素。GHb在红细胞内的合成是缓慢、连续进行的,一些慢性肝病、肾病会使红细胞寿命的缩短,减少GHb形成的时间,使结果偏低;反之,脾切除术后、再生障碍性贫血等导致红细胞寿命延长的疾病会使检测结果偏高。
因素二 血红蛋白因素
Hb出现变异体可使相应的分子空间构象和等电点等发生改变,影响HbA1c的测量。美国(NGSP)网站公布了一些检测系统受Hb变异体或衍生物干扰与否的数据(见表1)。
@在缺乏具体方法数据的情况下,通常可以假定免疫分析方法在临床检测中不会受到HbE和HbD的显著干扰,因为E和D替换距离血红蛋白β链的n端较远(16)。
$ 在缺乏特定方法数据的情况下,一般可以认为当HbF水平大于10-15%,免疫分析法和硼酸亲和法会受到干扰 (20,43)。
# 当区分出HbE变异体时,结果不受明显的干扰。在未区分出HbE变异体的情况下,HbA1c结果偏低。
↑ 表示干扰导致结果偏高
↓ 表示干扰导致结果偏低
表1 NGSP总结的各种Hb变异体或衍生物对糖化血红蛋白检测的影响,另外,由平均血红蛋白量减低造成的低色素贫血,如缺铁性贫血,也可影响HbA1c的测定,使其结果偏高。
因素三 血液环境因素
尿毒症患者常伴高尿素血症,尿素在体内可自发地分离形成氨和氰酸盐,氰酸盐经质子化作用后形成异氰酸,异氰酸与蛋白质的α和ε氨基基团反应即形成氨基甲酰。Hbβ链N端的缬氨酸可与异氰酸发生特异性的结合反应,形成稳定的氨基甲酰Hb。对于离子交换法测定的GHb,氨基甲酰化的Hb浓度超过5.4%时就会使其结果出现极大的假性偏高。不过,对于免疫法和亲和色谱法,其结果不受氨基甲酰Hb的影响。
因素四 饮食及药物因素
大量服用含有维生素C和维生素E的食物或药物可抑制Hb糖基化,使测定结果假性降低。一些抗感染的药物,如,可通过降低血浆中肿瘤转移因子-α水平,增强胰岛素抵抗,从而降低HbA1c水平。
因素五 妊娠
妊娠是育龄期妇女经历的一个特殊时期。妊娠期的血容量较妊娠前会有明显增加,Hb出现生理性降低,导致HbA1c的测定结果要低于非妊娠期妇女。部分妊娠中晚期的妇女会有贫血的困扰,在检测时也要考虑贫血对检测的影响。
因素六 标本储存因素
样本的储存时间及温度都对GHb的结果有一定的影响。用于测量GHb的血在长时间存放后,其测定结果会随着存放时间的延长而逐渐升高。与免疫法相比,离子交换色谱法和硼酸盐亲和色谱法测量受到温度的影响较小。大多数检测方法的样本都可在-70℃低温冻干条件下保存1年,检测结果不受影响。全血样本可在4℃保存1周。在37℃条件下,未经任何处理的全血样本保存时间应小于1天。在室温条件下,全血样本可保存数天。
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