Objective To evaluate the clinical application of Hb-A2 detection of thalassemia including-alpha-thalassemia and beta-thalassemia. Methods There were 70 Southeast Asia type alpha-thalassemia heterozygosity and 43 normal gene type resulted from Gap-PCR, and 33 beta-thalassemia heterozygosity and 36 normal gene type diagnosed by reverse dot blot (RDB). Cutoff value of Hb-A2 in finding of alpha-thalassemia and beta-thalassemia was present.The sensitivity, specificity, positive and negative likelihood ratio, and receiver operator characteristic curve (ROC) were used to evaluate the significance of Hb-A2 level in screening thalassemia in adults. Results The borderline values between normal and pathological range of Hb-A2 were ≤2.6% in alpha-thalassemia and ≥3.8% available in beta-thalassemia. Sensitivity and specificity were 59% and 54% in alpha-thalassemia, 76% and 83% in beta-thalassemia, respectively. ROC showed that the area covered beneath the curve of beta-thalassemia was more than that of alpha-thalassemia. Conclusions The cutoff between normal and pathological range of Hb-A2 is ≤2.3% in alpha-thalassemia and ≥3.8% in beta-thalassemia. Hb-A2 detection has higher sensitive and specific in beta-thalassemia diagnosis, but lower in alpha-thalassemia diagnosis.
目的：评价BIO-RAD D-10血红蛋白(Hb)检测仪在地中海贫血筛查中的应用。方法:对BIO-RAD D-10血红蛋白检测仪进行性能评价，并测定我院门诊及住院病人HbA2及HbF含量，同时采用法国Sebia全自动电泳仪进行血红蛋白琼脂糖电泳，比较两种方法对HbA2及HbF含量的检测结果。结果：BIORAＤ D-10血红蛋白检测仪检测HbA2及HbF批内精密度为4.8％、2.77％和1.42％、1.7％，批间精密度为491％、3.97％和2.87％、2.3％。共检测了1026例临床标本，并通过全自动琼脂糖凝胶电泳进行定量扫描，得出BIO-RAD D-10测定灵敏度为HbF 88.3％、HbA297.７％，特异性为HbF 96.7％、HbA2为95.6％,阳性预测值为HbF 97.4％、HbA2 96.9％,阴性预测值为HbF 85.4％、HbA2 96.6％。但如果有其他异常血红蛋白条带或血红蛋白H、Bart’s,D-10血红蛋白检测仪不能识别，只能分辨出未知峰。结论：BIO-RAD D-10血红蛋白检测仪能够分辨出HbA2及HbF异常增高者，为β地中海贫血的初筛提供快速的诊断依据。
Objective To determine the best threshold value of hemoglobin A2 (HbA2) for diagnosis of β-thalassemia (β-thal) carriers by using high performance liquid chromatography (HPLC), and to improve the application value of HbA2 as a diagnostic index for β-thal carriers to reduce the rates of missed diagnosis and misdiagnosis. Methods Using reverse dot blot (RDB) as a gold standard method, HbA2 results of 1 007 β-thal carriers and 606 normal controls in the past two years determined by HPLC were divided into true positive, false positive, true negative, and false negative based on the different threshold values of HbA2 results. Then, the evaluation indexes such as sensitivity, specificity, positive and negative likelihood ratio, and Youden’s index were evaluated. Next, the receiver operator characteristic (ROC) curve was drawn to determine the best threshold value of HbA2 for diagnosis of β-thal carriers by HPLC. Results If ≥4.0% was taken as the threshold value of HbA2 for diagnosis of β-thal carriers by HPLC, the evaluation indexes values were shown as follows: sensitivity 99.21%, specificity 99.34%, positive likelihood ratio 150.30, negative likelihood ratio 0.008, and Youden’s index 0.99. The Youden’s index was better than the other threshold values, and the corresponding tangent point was the peak point of the ROC curve. Conclusion When ≥4.0% serves as the best threshold value of HbA2 for diagnosis of β-thal carriers using HPLC, integrated evaluation performance of the corresponding sensitivity and specificity is the most ideal, and the authenticity of the diagnostic test is the best.
High performance liquid chromatography (HPLC) is currently the mainstream technology for detecting hemoglobin. Glycated hemoglobin (HbA1c) is a gold indicator for diagnosing diabetes, however, the accuracy of HbA1c test is affected by thalassemia factor hemoglobin F (HbF)/hemoglobin A2 (HbA2) and variant hemoglobin during HPLC analysis. In this study, a new anti-interference hemoglobin analysis system of HPLC is proposed. In this system, the high-pressure three-gradient elution method was improved, and the particle size and sieve plate aperture in the high-pressure chromatography column and the structure of the double-plunger reciprocating series high-pressure pump were optimized. The system could diagnose both HbA1c and thalassemia factor HbF/HbA2 and variant hemoglobin, and the performance of the system was anti-interference and stable. It is expected to achieve industrialization. In this study, the HbA1c and thalassemia factor HbF/HbA2 detection performance was compared between this system and the world’s first-line brand products such as Tosoh G8, Bio-Rad Ⅶ and D10 glycosylated hemoglobin analysis system. The results showed that the linear correlation between this system and the world-class system was good. The system is the first domestic hemoglobin analysis system by HPLC for screening of HbA1c and thalassemia factor HbF/HbA2 rapidly and accurately.
Objective To systematically review the survival outcome and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for β-thalassemia. Methods The PubMed, EMbase, CNKI, WanFang Data and CBM databases were electronically searched to collect studies on haplo-HSCT for β-thalassemia from January 1, 2017 to December 31, 2021. Two reviewers independently screened the literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.4.1 software and Stata 16.0 software. Results A total of 6 case-series studies involving 286 patients were included. The results of meta-analysis indicated that overall survival (OS) and thalassemia-free survival (TFS) for β-thalassemia patients undergoing haplo-HSCT were 92.5% (95%CI 86.1% to 96.1%) and 88.5% (95%CI 74.6% to 95.3%), the incidence of Ⅲ-Ⅳ degree acute graft versus host disease (Ⅲ-Ⅳ aGvHD) and chronic graft versus host disease (cGvHD) were 11.5% (95%CI 6.5% to 20.0%) and 23.1% (95%CI 12.3% to 39.8%), and the transplantation related mortality was 6.5% (95%CI 3.8% to 10.7%). Conclusion Relevant clinical studies published in the past 5 years provide the latest information and progress of haplo-HSCT for β-thalassemia. At present, great efficacy has been shown in NF-14-TM therapeutic regimen, but the long-term efficacy remains unclear. Due to the limited quality and quantity of the included studies, more high-quality evidence from long-term comparative studies is still needed.
β thalassemia is a hereditary hemolytic disease caused by the defect of β globin gene. Transfusion-dependent β thalassemia patients need long-term blood transfusion to survive, and a series of systemic and ocular complications will occur in the disease itself and long-term blood transfusion. Retinal blood vessel density decreases, retinal thickness thinned and elastic pseudoxanthoxanoma syndrome are found in fundus due to long-term anemia and side effects of iron chelating agent. At present, there are few reports about eye changes in thalassemia patients, and the cognition is relatively scarce. Therefore, it is necessary to be vigilant for physicians, deeply explore the cause and symptomatic treatment, combined with individual disease characteristics, to provide a more scientific and accurate plan for clinical treatment.