The inherited diseases of haemoglobin are an emerging global health burden

Abstract

Thalasseamia is one of the common genetic disorders. A genetic defect causes reduction of the globin chains leading to chronic haemolytic anaemia from birth. The mainstay of treatment is blood transfusion to maintain adequate levels of the haemoglobin. Secondary iron overload in β-thalassaemia patients is secondary to multiple blood transfusions and increased iron absorption. Excesses iron potentially catalyses free-radicals generation and impairment in cellular function and integrity. Extensive iron-induced injury develops in the heart, liver, pancreas and endocrine system. In regularly transfused patients, in the absence of iron-chelation therapy, death from iron-induced heart failure occurs by the mid-teenage years. Conventional treatment with the parenteral iron chelator desferrioxamine improves mortality but it is too expensive for middle and lowincome countries. Oral iron chelators, such as deferiprone (L1) and deferasirox, appear to be promising, however, they are still too expensive or need special monitoring. Serum ferritin has been used for many years as a guide for chelation therapy. However, recent studies demonstrated that using serum ferritin or liver iron measurements as a monitor of iron-chelation intensive therapy would have been discontinued long before the iron had cleared from the heart. There is evidence of the value of myocardial T2* measurements by MRI for the detection of early cardiac iron overload which cannot be predicted by liver iron or serum ferritin and for the monitoring of iron-chelation therapy. The major problem is the expensiveness of MRI measurement. In conclusion, the problem of iron chelation in low-income countries may be summarized as follows: i) drugs, are not available in every countries that need the medicine, ii) the cost of drugs is too high for most low income countries, iii) there is poor education of doctor, parents/ patients and local government about the benefit of iron chelation, iv) there is need for monitoring of its toxicity and adverse drug reaction. In the TIF conference in Dubai, in 2006, a group of experts had agreed to send a document to the D-G of the WHO with a strong request that all chelators (currently available and those that will be available in the future) be designated essential for the treatment of transfusion dependent anaemias. 地中海贫血是一种常见的遗传病。 某种遗传缺陷会引起球蛋白链减少，使患者自出生时就引发慢性溶血性贫血。 主要治疗方法是通过输血将血红蛋白维持在适当水平。 Β型地贫患者再次铁过载不如多次输血和增加铁吸收的效果好。 过量的铁对于自由基生成具有潜在的催化作用，并且对于细胞功能和完整性也有所伤害。 大量输入铁会对心脏、肝脏、胰腺、内分泌系统都造成伤害。 在定时接受输血的患者中，几岁的儿童会因缺乏铁螯合疗法，输入铁而引发的心力衰竭造成死亡。 注射铁螯合剂去铁胺这种常规疗法能降低死亡率，但是对于中低收入国家来说这种疗法价格非常昂贵。 口服螯合剂，例如去铁酮（L1）和口服除铁药等，看似不错，但价格仍然昂贵，有些服药还需特别监测。 一直以来，铁蛋白都用作螯合疗法的引导剂。 然而，近年的研究表明，在去除心脏中的铁之前，利用铁蛋白或肝脏含铁量测量来监控大量使用铁的螯合疗法就中断了。 有证据表明，为了发现无法以肝脏铁或铁蛋白来预测的早期心脏铁过载以及为了监控铁螯合疗法而使用核磁共振成像（MRI）来测定心肌衰竭T2*值。 主要问题是核磁共振成像（MRI）价格昂贵。 总而言之，在低收入国家使用铁螯合疗法可总结如下： 1）并非每个有需要用药的国家都能提供药；2）对大多数低收入国家来说，药的价格都过于昂贵；3）医生、患儿父母、患者、当地政府在铁螯合疗法的优点方面所受教育程度不足；4）需要监控其毒性以及药物不良反应。 在2006年迪拜举行的地中海贫血国际联盟（TIF）大会上，一批专家赞同将资料提交给世界卫生组织（WTO）D-G，并强烈要求所有的螯合剂（目前可找到的以及未来可使用的）都应指定给需依靠输血来维持生命的贫血性疾病的疗法

Keywords

• global health burden hemoglobin disorders.