Clinical experience using peripheral blood parameters to analyse the mutation type of thalassemia carriers in pregnant women

Thalassaemia is a typically monogenic disease caused by mutations or deletions in the globin gene and has a high prevalence in southern China. Prenatal screening for thalassaemia can be effective in reducing the incidence of thalassaemia. Haematologic parameters of pregnant thalassaemia carriers are diverse and potentially valuable for identifying different types of genotypes. By comparing and evaluating haematological parameters, formulas in the literature, we tried to reveal differences between pregnant women carrying different types of thalassaemia genes. The Mentzer formula (MCV/RBC) showed a strong ability to differentiate thalassaemia genotypes in pregnant women. In addition, combined with haemoglobin electrophoresis HbA2 can further distinguish the –α/αα, α^Tα/αα, –/αα, β⁺/N and β⁰/N groups. HbA2 divides them into two groups. Based on the Mentzer formula, we can further decide which type of thalassaemia to screen (α/β and the subgroups) for genotyping. Therefore, this simpler and more cost-effective workflow has great potential for application in screening pregnant women for thalassaemia carriers.Impact Statement<b>What is already known on this subject?</b> Currently, it is known that thalassaemia gene carriers have abnormal blood indicators. Many findings describe their important values in distinguishing thalassaemia and other blood diseases. They combined different metrics as an algorithm to distinguish thalassaemia and iron deficiency anaemia. Prenatal screening is an effective method to reduce the incidence of thalassaemia. The current main method is PCR. Due to technical and financial constraints, many backward places cannot use this technology. The necessity for prenatal screening for thalassaemia has been overlooked.<b>What</b><b>the results of this study add?</b> Among these algorithms, Mentzer formula revealed differences in haematological parameters during pregnancy between normal individuals and thalassaemia carriers. Combining the HbA2, thalassaemia carriers can be distinguished from normal individuals, including –α/αα, α^Tα/αα, –/αα, β⁰/N and β⁺/N.<b>What are the implications of these findings for clinical practice and/or further research?</b> We provide another tool for these hospitals that donot have Hb electrophoresis test and PCR. Then the clinical doctor can get some evidence and suggest women go to another big hospital for essential tests. It is an excellent suggestion. In the future, we will collect more specific gene types and further investigate their potential relationship using these formulas. <b>What is already known on this subject?</b> Currently, it is known that thalassaemia gene carriers have abnormal blood indicators. Many findings describe their important values in distinguishing thalassaemia and other blood diseases. They combined different metrics as an algorithm to distinguish thalassaemia and iron deficiency anaemia. Prenatal screening is an effective method to reduce the incidence of thalassaemia. The current main method is PCR. Due to technical and financial constraints, many backward places cannot use this technology. The necessity for prenatal screening for thalassaemia has been overlooked. <b>What</b><b>the results of this study add?</b> Among these algorithms, Mentzer formula revealed differences in haematological parameters during pregnancy between normal individuals and thalassaemia carriers. Combining the HbA2, thalassaemia carriers can be distinguished from normal individuals, including –α/αα, α^Tα/αα, –/αα, β⁰/N and β⁺/N. <b>What are the implications of these findings for clinical practice and/or further research?</b> We provide another tool for these hospitals that donot have Hb electrophoresis test and PCR. Then the clinical doctor can get some evidence and suggest women go to another big hospital for essential tests. It is an excellent suggestion. In the future, we will collect more specific gene types and further investigate their potential relationship using these formulas.

地中海贫血（Thalassaemia）是一类因珠蛋白基因发生突变或缺失引发的单基因遗传病，在我国南方地区具有较高的患病率。针对地中海贫血开展产前筛查可有效降低该疾病的新发患儿出生率。妊娠合并地中海贫血携带者的血液学参数呈现多样化特征，且对鉴别不同基因型具有潜在的临床应用价值。本研究通过比对与评估各类血液学参数及文献报道的计算公式，旨在揭示携带不同类型地中海贫血基因的孕妇之间的表型差异。其中，Mentzer公式（MCV/RBC）在区分孕妇地中海贫血基因型方面展现出较强的分辨能力。此外，联合血红蛋白电泳（haemoglobin electrophoresis）检测的HbA2指标，可进一步区分–α/αα、α^Tα/αα、–/αα、β⁺/N及β⁰/N这五类基因型群体。HbA2可将上述群体初步划分为两大类别，结合Mentzer公式即可进一步明确需开展基因分型筛查的地中海贫血类型（α型、β型及其亚型）。因此，这一操作简便且成本效益更优的筛查流程，在孕妇地中海贫血携带者筛查领域具备良好的应用潜力。研究影响声明<b>该主题已有哪些研究进展？</b>目前学界已明确，地中海贫血基因携带者存在血液学指标异常。多项研究证实此类指标在区分地中海贫血与其他血液疾病方面具有重要临床价值，已有研究通过整合不同检测指标构建算法，实现地中海贫血与缺铁性贫血的鉴别诊断。产前筛查是降低地中海贫血新发患儿出生率的有效手段，当前主流筛查方法为聚合酶链式反应（PCR），但受限于技术条件与资金成本，许多欠发达地区无法开展此项检测，地中海贫血产前筛查的必要性也因此被忽视。<b>本研究新增的研究成果？</b>在现有各类筛查算法中，Mentzer公式可清晰展现正常孕妇与地中海贫血携带者在妊娠期间的血液学参数差异。联合HbA2指标，可将地中海贫血携带者与正常个体进行有效区分，涵盖–α/αα、α^Tα/αα、–/αα、β⁰/N及β⁺/N等基因型群体。<b>本研究发现对临床实践及后续研究的启示？</b>本研究为未配备血红蛋白电泳及PCR检测设备的医疗机构提供了另一套筛查工具，临床医生可借此获取初步筛查依据，建议孕妇转诊至上级医院完成必要的确诊检测，该方案具备良好的实用性。未来我们将收集更多特定基因型样本，进一步探究此类血液学计算公式与不同基因型间的潜在关联。<b>该主题已有哪些研究进展？</b>目前学界已明确，地中海贫血基因携带者存在血液学指标异常。多项研究证实此类指标在区分地中海贫血与其他血液疾病方面具有重要临床价值，已有研究通过整合不同检测指标构建算法，实现地中海贫血与缺铁性贫血的鉴别诊断。产前筛查是降低地中海贫血新发患儿出生率的有效手段，当前主流筛查方法为聚合酶链式反应（PCR），但受限于技术条件与资金成本，许多欠发达地区无法开展此项检测，地中海贫血产前筛查的必要性也因此被忽视。<b>本研究新增的研究成果？</b>在现有各类筛查算法中，Mentzer公式可清晰展现正常孕妇与地中海贫血携带者在妊娠期间的血液学参数差异。联合HbA2指标，可将地中海贫血携带者与正常个体进行有效区分，涵盖–α/αα、α^Tα/αα、–/αα、β⁰/N及β⁺/N等基因型群体。<b>本研究发现对临床实践及后续研究的启示？</b>本研究为未配备血红蛋白电泳及PCR检测设备的医疗机构提供了另一套筛查工具，临床医生可借此获取初步筛查依据，建议孕妇转诊至上级医院完成必要的确诊检测，该方案具备良好的实用性。未来我们将收集更多特定基因型样本，进一步探究此类血液学计算公式与不同基因型间的潜在关联。