血红蛋白A2在静止型和标准型α-地中海贫血筛查中的价值探讨

Screening Value of Hemoglobin A2 in Resting and Standard α-thalassemia

目的:探讨血红蛋白A2(HbA2)在静止型和标准型α-地中海贫血患者筛查中的应用价值。方法:回顾分析2013年5月-2017年12月在本院就诊疑为地中海贫血的患者(MCV、MCH同时降低)8 979例,采用全自动毛细管电泳方法进行血红蛋白电泳分析,同时应用跨越断裂点PCR(gap-PCR)技术和DNA反向点杂交芯片技术(reversedot blot,RDB)进行基因分型检测。探讨HbA2在静止型和标准型α-地中海贫血患者筛查中的应用价值,同时分析了患者基因突变类型与HbA2是否异常的相关性。结果:8 979例疑为地中海贫血患者中3 588例为静止型和标准型α-地中海贫血,阳性率为39.96%,其中HbA2正常参考范围内2 980例,占静止型和标准型α-地中海贫血83.05%(2 980/3 588),HbA2异常608例,占16.94%(608/3 588)。从基因突变的类型看,静止型和标准型α-地中海贫血中无论HbA2是否正常均以缺失型为主,分别为97.71%(3 506/3 588)、93.91%(571/608),两者间比较差异无统计学意义(P>0.05)。HbA2正常者占其相应突变类型的比例分别为:--SEA/αα型占81.17%(2 388/2 942);-α3.7/αα型占98.73%(389/394);-α4.2/αα型占92.86%(156/168);ααCS/αα突变型占51.11%(23/45);ααQS/αα突变型占45.45%(10/22);ααWS/αα突变型占80.0%(12/15)。在2 980例静止型和标准型α-地贫HbA2含量正常的患者中,检出1 379例血清铁蛋白降低。检测结果显示,血清铁蛋白<15 μg/L女性铁缺乏患者841例(地贫缺铁组)占60.98%(841/1 379),HbA2平均含量为(2.2±0.23)%,对照组530例为(2.4±0.24)%,两者差异无统计学意义(P>0.05);血清铁蛋白<30 μg/L男性铁缺乏患者538例(地贫缺铁组)占39.01%(538/1 379),HbA2平均含量为(2.39±0.25)%,而对照组310例含量为(2.5±0.24)%,两者差异亦无统计学意义(P>0.05)。结论:静止型和标准型α-地中海贫血采用MCV、MCH加上HbA2的筛查模式可导致很大部分被漏检,特别是HbA2在正常参考范围内时及缺铁状态下,漏检更为严重。缺铁患者HbA2含量对缺铁性地贫患者的诊断可出现干扰现象。提醒广大临床医生应当根据临床表现,在排除缺铁性贫血后,结合血细胞分析、血红蛋白电泳等多种指标综合判断,对可疑患者应注重基因检测,避免漏诊。

Objective:To explorer the value of hemoglobin A2 (HbA2) in screening patients with quiescent and standard α-thalassaemia.Method:Reviewed and analyzed the 8 979 suspected cases of the thalassemia (MCV,MCH decrease) in our hospital from May 2013 to December 2017,using automatic capillary electrophoresis method of hemoglobin electrophoresis analysis.At the same time,genotyping of the screened positive sample was performed by gap single polymerase chain reaction (gap-PCR) and reverse dot blot hybridization (RDB).To investigate the application value of HbA2 in screening patients with stationary and standard α-thalassaemia,and to analyze the correlation between the type of gene mutation in patients and whether HbA2 is abnormal or not.Result:A total of 3 588 in the 8 979 suspected thalassemia patients were found to be stationary and standard α-thalassemia,with a positive rate of 39.96%.Among them,2 980 cases of HbA2 within the normal reference range accounted for 83.05% (2 980/3 588),and 608 cases of HbA2 abnormality accounting for 16.94% (608/3 588).In terms of the types of gene mutations,no matter whether HbA2 was normal or not,the deletion type mainly accounted for 97.71% (3 506/3 588) and 93.91% (571/608) of the static and standard α-thalassaemia.There was no statistical significance between these two types (P>0.05).The proportions of normal HbA2 in the corresponding mutation types were:--SEA/αα 81.17% (2 388/2 942);-α3.7/αα 98.73% (389/394);-α4.2/αα 92.86% (156/168);αCS/αα accounted for 51.11% (23/45);αQS/αα accounted for 45.45% (10/22);αWS/αα accounted for 80.0% (12/15).Among 2 980 patients with normal HbA2 levels of both stationary type and standard type,1 379 patients with reduced serum ferritin were detected.Test results showed that serum ferritin <15 μg/L female with iron deficiency in 841 cases (group to lean iron deficiency) accounted for 60.98% (841/1 379),HbA2 average content was (2.2±0.23)%,the control group530 cases and (2.4±0.24)%,there was no statistically significant difference between the two groups (P>0.05).Serum ferritin <30 μg/L male patients with iron deficiency in 538 cases (group to lean iron deficiency) accounted for 39.01% (538/1 379),HbA2 average content was (2.39±0.25)%,while the control group,310 cases and (2.5±0.24)%,there was no significant difference between the two groups (P>0.05).Conclusion:The screening mode of MCV,MCH and HbA2 for stationary and standard α-thalassaemia can lead to a large number of missed detections,especially when HbA2 is normal and iron deficiency.The content of HbA2 in patients with iron deficiency may interfere with the diagnosis of patients with iron deficiency.Remind that the majority of clinicians should base on clinical manifestations,in the exclusion of iron deficiency anemia,combining with blood cell analysis,hemoglobin electrophoresis and other indicators to have comprehensive judgment.Suspicious patients should be paid attention on genetic testing in order to avoid missed diagnosis.