地中海贫血预防与诊治科普知识 Brochure of Thalassemia Prevention, Diagnosis, and Treatment

(一)什么是地中海贫血? What is Thalassemia?

地中海贫血是一种遗传性溶血性疾病，是由于珠蛋白基因的缺陷所致。临床上表现为慢性溶血性贫血。地中海贫血广泛流行于地中海沿洋国家和亚洲国家。

Thalassemia is a genetic hemolytic disease caused by defects in the globin genes. Clinically, it manifests as chronic hemolytic anemia. Thalassemia is widespread in Mediterranean and Asian countries.

(二)地中海贫血的分类? Classification of Thalassemia

1.根据基因缺陷不同，可将地中海贫血分为α、β、δ、和δβ地中海贫血，其中以α和β地中海贫血最常见。

2.根据病情轻重，α地申海贫血:分为静止型、轻型、中间型(Hb H病)和重型(Hb Bart's 胎儿水肿综合征) ; β地中海贫血:分为轻型、中间型和重型。

1. Based on the gene defects, it can be categorized into α-, ß-, δ-, and δβ-thalassemia. Among these，α- and ß- thalassemia are the most common.

2. Based on the severity，α-thalassemia can be divided into silent carrier，α-Thalassaemia trait, HbH disease, and Hb Bart's Hydrops Foetalis Syndrome. ß-thalassemia can be c1assified into mild, intermediate, and severe types.

(三)地中海贫血如何由父母遗传给下一代?

How is Thalassemia Inherited from Parents to Offspring?

如果夫妇双方携带地中海贫血基因，则有可能生育中间型、重型地中海贫血患儿，或静止型、轻型地中海贫血基因携带者。

If both parents carry the thalassemia gene, there is a possibility of giving birth to children with intermediate or severe thalassemia or silent/mild carriers of the thalassemia gene.

(四)地中海贫血有哪些症状?

What are the Symptoms of Thalassemia?

1. 静止型和轻型α和ß地中海贫血没有临床症状，少部份人有轻微贫血。

2. 重型α地中海贫血胎儿于妊娠晚期在宫内死亡，同时可给孕妇带来妊娠高血压综合征、产后大出血等严重后果。

3. 重型ß地中海贫血病人于生后3-6个月出现慢性进行性贫血，生长发育缓慢，有肝脾肿大、心力衰竭等合并症，需每月定期输血，使用祛铁剂。

4. 中间型α地中海贫血(Hb H病)有轻度至中度贫血，部分可有重度贫血，黄疸，肝脾肿大等。

1. Silent and mild types of α and ß thalassemia have no clinical symptoms, with a small portion of individuals experiencing slight anemia.

2. Severe α-thalassemia fetuses may die in utero in the late stages of pregnancy, posing risks of preeclampsia and postpartum hemorrhage to the pregnant mother.

3. Patients with severe ß-thalassemia show signs of chronic progressive anemia 3-6 months post-birth, exhibit slow growth and development, hepatosplenomegaly, heart failure, and require regular blood transfusions and iron chelation therapy.

4. Intermediate α-thalassemia (Hb H disease) patients can have mild to moderate anemia, while some might experience severe anemia, jaundice, and hepatosplenomegaly.

(五)如何诊断地中海贫血? How to Diagnose Thalassemia?

以下检测可筛查和诊断地中海贫血:血常规检查，血红蛋白分析，基因分析等。

需要注意的是，部分α地中海贫血和ß地中海贫血的血常规，血红蛋白分析检测结果可以正常，要做基因分析才能确诊。

Tests like complete blood count, hemoglobin analysis, and genetic analysis can be used to screen and diagnose thalassemia. lt's important to note that some α and ß thalassemias might show normal results in routine blood tests and hemoglobin analysis; a definitive diagnosis requires genetic testing.

(六)如何避免生育重型地中海贫血患儿

How to Prevent Giving Birth to a Child with Severe Thalassemia?

1.避免生育重型地中海贫血患儿的措施

1.Measures to prevent the birth of a child with severe thalassemia:

公众教育，人群筛查，遗传咨询和高危夫妇产前诊断是避免重型地中海贫血胎儿出生的唯一有效途径。

Public education, population screening, genetic counseling, and prenatal diagnosis for high-risk couples.

2. 什么情况需要做胎儿地中海贫血产前诊断?

2. When should prenatal diagnosis for fetal thalassemia be performed?

1.夫妇双方于婚前、孕前或怀孕旱期进行血常规检查，血红蛋白分析，基因分析等检查，明确夫妇双方是否携带有相同类型的地中海贫血基因。

2.如夫妇携带有相同类型的地中海贫血基因，有可能生育重型地中海贫血胎儿，则需要对胎儿进行产前基因诊断。当诊断胎儿为重型或中间型地中海贫血，建议终止妊娠。

1. Both partners should undergo routine blood tests, hemoglobin analysis, and genetic testing before marriage, before pregnancy, or in the early stages of pregnancy to determine if they both carry the same type of thalassemia gene.

2. If both partners carry the same type of thalassemia gene and there's a risk of giving birth to a child with severe thalassemia, then prenatal genetic diagnosis is recommended. If the fetus is diagnosed with severe or intermediate thalassemia, termination of the pregnancy is advised.

3.什么时候做胎儿产前诊断?

3. When to undergo prenatal diagnosis?

怀孕后做产前诊断的最佳时间

1.妊娠10-13周取绒毛;

2.妊娠18-25周取羊水或胎儿脐带血。

Optimal times post-conception for prenatal diagnosis include:

1. 10-13 weeks for chorionic villus sampling.

2. 18-25 weeks for amniocentesis or fetal cord blood sampling.

(七)地中海贫血的治疗Treatment of Thalassemia

1.轻型地中海贫血

1. Mild Thalassemia:

静止型和轻型地中海贫血(地中海贫血基因携带者)不需要治疗，但婚育时应做遗传咨询。

Silent and mild thalassemias (thalassemia gene carriers) don't require treatment, but genetic counseling is advised when considering marriage and having children.

2.中间型地中海贫血

2. Intermediate Thalassemia:

预防感染，避免服用一些药物，以免加重溶血。血红蛋白<90g/L时要输血治疗。

Prevent infections, avoid certain drugs to prevent exacerbation of hemolysis. Blood transfusion is recommended when hemoglobin is <90g/L.

3.重型地中海贫血

3. Severe Thalassemia:

·需要定期输血，保持血红蛋白>100g/L。

·祛铁治疗:当输血10次后，测定血清铁蛋白>1000ng/ml，开始使用祛铁药，维持血清铁蛋白不超过2000ng/ml。

·继发性铁过载评估:年龄大于5 岁可行核磁共振评估心脏、肝脏铁沉积情况。

·造血干细胞移植治疗:符合条件的患者可接受干细胞移植治疗，达到治愈。但也有失败的风险。

• Regular blood transfusions are necessary to maintain hemoglobin levels >100g/L.

• Start chelation therapy after 10 transfusions when serum ferritin >1000ng/ml and keep it below 2000ng/m1.

• Secondary iron overload assessment is possible with MRI for cardiac and Iiver iron deposition in patients over 5 years old.

• Hematopoietic stem cell transplantation can be curative for eligible patients, but there's also a risk offailure.

4.造血干细胞移植：目前临床根治地中海贫血唯一方法

4. Hematopoietic Stem Cell Transplantation: the only definitive treatment for thalassemia currently.

·移植配型:患者本人、供者(同胞或父母亲) 注意事项:患者输血2周后方可抽血，以免影响结果;

.移植前准备:①患者、供者体检;②服用移植前用药(羟基脲治疗3个月) ;

·移植阶段:①进入移植仓，移植约需要住院1-2个月时间;②移植经历:预处理期、骨髓空虚期、造血重建期;

·移植后随访:①移植后3个月每周随访1-2次;②移植后3-6个月每2周随访1次 ; ③移植后6-12个月每月随访1次。

·移植费用:①同胞全相合10 - 15万元人民币(1. 5 - 2.5万美元) ;②非亲缘或单倍体移植20-25万元(3-4万美元)。

• Transplant matching: the patient, the donor (siblings or parents). Note: The patient can have blood drawn only 2 weeks after a transfusion to avoid affecting the results.

• Pre-transplant preparations: ①physical examinations for both the patient and the donor; ②pre-transplant medication intake (hydroxyurea therapy for 3 months).

• Transplant stages: ①hospitalization required for about 1-2 months; ②undergoing stages like preconditioning, bone marrow suppression , and hematopoietic reconstruction.

• Post-transplant follow-ups: ①once to twice weekly for the first 3 months posttransplant; ② once every two weeks from the 3rd to 6th month post-transplant; ③ once a month from the 6th to 12th month post-transplant.

• Transplant costs: ① for a full match with a sibling: 100-150 thousand RMB (approximately 15-25 thousand USD); ② For non-relative or haploidentical transplantation: 200-250 thousand RMB (approximately 30-40 thousand USD).

5.基因治疗：未来地中海贫血治疗发展趋势

5. Gene Therapy: the future trend in the treatment ofthalassemia

·筛选评估:1周;

·干细胞动员、采集及制备:过程约1个月;

·基因治疗过程:进入移植仓，移植约需要住院1个月时间;移植经历:预处理期、回输自体造血干细胞、造血重建期

• Screening and evaluation: 1 week.

• Stem cell mobilization, collection, and preparation: The process takes about 1 month.

• Gene therapy procedure:①admission to the transplantation ward, hospitalization required for approximately 1 month. ② transplantation stages: preconditioning, reinfusion of autologous hematopoietic stem cells, and hematopoietic reconstruction period.

6.新药治疗：罗特西普（晚期红细胞成熟剂）

6. New Medicine: Luspatercept (a late-stage erythroid maturation agent).

·用法用量:注射用罗特西普治疗。地中海贫血的推荐起始剂量为1. 0mg/kg，每3周一次。根据治疗反应调整剂量，最大治疗剂量不应超过每3周1. 25 mg/kg。

·不良反应:最常报告的药物不良反应(至少15%的患者)为头痛、骨痛和关节痛。

• Dosage: The recommended starting dose for treating ß-thalassemia with luspatercept is 1.0 mg/kg every 3 weeks. The dose can be adjusted based on the therapeutic response, but it should not exceed 1.25 mg/kg every 3 weeks.

• Adverse reactions: The most commonly reported adverse reactions (in at least 15% of patients) include headaches, bone pain, and joint pain.