Table 1. Summary of the management of... | American Society of Hematology

Table 1.

Summary of the management of patients with Hb Bart’s hydrops fetalis/ATM

Recommendations	Comments
Screening and prenatal diagnosis
Carrier screening is recommended for couples with genetic ancestry from populations with high prevalence of α⁰-thal deletions.	Definitive genetic testing should be offered if both parents exhibit microcytosis and/or hypochromia on initial screening.
Prenatal diagnosis should be offered to all at-risk pregnancies.	Conventional approach involves obtaining fetal DNA or blood for molecular and/or Hb analysis. Noninvasive approach entails regular fetal US starting from 12-wk gestation. US can also aid in detecting some associated congenital abnormalities.
Prenatal care of affected pregnancies
Couples with affected pregnancies should receive detailed and nondirective counseling regarding all aspects of prenatal and long-term outcomes, as well as available therapeutic options.	Therapeutic options include fetal therapy with IUT, terminating the affected pregnancy, or continuing the pregnancy without IUT. The latter is generally not recommended because of a low chance of fetal/neonatal survival and a high risk of maternal complications.
Couples with affected pregnancies should be referred to centers with expertise in prenatal care for BHFS.	Care should be coordinated between obstetrics, neonatology, and hematology.
IUT should be initiated as soon as technically possible.	Most centers with available expertise can initiate IUT at 18-wk gestation. Initial IUT can be performed while awaiting the diagnosis.
The goal of IUT is to resolve hydrops and/or prevent development of hydrops, allowing for normal growth and development of the fetus, and preventing maternal complications.	In BHFS, the fetal Hb concentration does not represent functional Hb. The optimal transfusion volume or frequency for treating affected fetuses has not been established.
Delivery and neonatal care
Delivery should be planned at a tertiary care center.	Centers should have expertise in neonatal resuscitation, access to blood products, and clinical laboratories. Early delivery may be indicated if the fetus remains hydropic.
Resuscitation and management of acute illness should be initiated immediately after birth.	Depending on the effectiveness of IUT, the neonatal course may be complicated by varying degrees of respiratory distress, pulmonary hypertension, ascites, and hyperbilirubinemia. Neonates may be small for gestation age, or have complications associated with prematurity.
Transfusions should be started as soon as possible.	Upon delivery, functional Hb concentration (total Hb minus Hb Bart’s and HbH fractions) should be calculated and guide transfusions. The goal of transfusions is to keep functional Hb of >90 g/L; exchange transfusion can help with hyperbilirubinemia. Depending on the clinical status, as well as timing and effectiveness of IUT, most neonates may benefit from exchange transfusions for the first few transfusions.
Assessments and management for associated congenital anomalies and neurological evaluation should be offered.	Consider brain MRI, GU ultrasound, cardiac ECHO, and bone survey. Initiate appropriate management or consultation with relevant subspecialty.
Long-term management of patients with ATM
Infants should be referred to a comprehensive thalassemia clinic for regular transfusion therapy.	Hb analysis should be performed before each transfusion and functional Hb should be calculated. Transfusion should be aimed to keep a functional Hb of >90 g/L and nonfunctional Hb (HbH + Hb Bart’s) at <15%.
Monitoring and treatment of iron overload should be initiated after 1 y of age, balancing their benefit and side effects.	Children with ATM will develop iron overload at an earlier age than those with TDT-β. Iron chelation should not be started before first year of life and aggressive iron chelation is not recommended before age 2. Ferritin may underestimate the degree of hepatic iron overload; assessment of liver and cardiac iron concentration through MRI is strongly recommended. Depending on the degree of iron overload, patients may require high doses of chelation, or combination chelation therapy.
Patients should be closely monitored for complications of anemia, ineffective erythropoiesis, chronic hemolysis, regular transfusion, and chelation therapy.	Regular monitoring for growth and development, bone health, endocrinopathies, fertility, progressive splenomegaly, symptomatic cholelithiasis, and features associated with extramedullary hematopoiesis, as per published guidelines.
Management of congenital abnormalities	Early consultation with appropriate surgical teams (eg, plastic surgery or urology).
Management of neurocognitive compromise	All children should be referred to a developmental specialist for specialized intervention and appropriate support.
Curative therapy should be considered at an early age.	Although the pathophysiology of ATM differs from TDT-β, until further data, protocols similar to those used for TDT-β should be used for stem cell transplantation.

Recommendations	Comments
Screening and prenatal diagnosis
Carrier screening is recommended for couples with genetic ancestry from populations with high prevalence of α⁰-thal deletions.	Definitive genetic testing should be offered if both parents exhibit microcytosis and/or hypochromia on initial screening.
Prenatal diagnosis should be offered to all at-risk pregnancies.	Conventional approach involves obtaining fetal DNA or blood for molecular and/or Hb analysis. Noninvasive approach entails regular fetal US starting from 12-wk gestation. US can also aid in detecting some associated congenital abnormalities.
Prenatal care of affected pregnancies
Couples with affected pregnancies should receive detailed and nondirective counseling regarding all aspects of prenatal and long-term outcomes, as well as available therapeutic options.	Therapeutic options include fetal therapy with IUT, terminating the affected pregnancy, or continuing the pregnancy without IUT. The latter is generally not recommended because of a low chance of fetal/neonatal survival and a high risk of maternal complications.
Couples with affected pregnancies should be referred to centers with expertise in prenatal care for BHFS.	Care should be coordinated between obstetrics, neonatology, and hematology.
IUT should be initiated as soon as technically possible.	Most centers with available expertise can initiate IUT at 18-wk gestation. Initial IUT can be performed while awaiting the diagnosis.
The goal of IUT is to resolve hydrops and/or prevent development of hydrops, allowing for normal growth and development of the fetus, and preventing maternal complications.	In BHFS, the fetal Hb concentration does not represent functional Hb. The optimal transfusion volume or frequency for treating affected fetuses has not been established.
Delivery and neonatal care
Delivery should be planned at a tertiary care center.	Centers should have expertise in neonatal resuscitation, access to blood products, and clinical laboratories. Early delivery may be indicated if the fetus remains hydropic.
Resuscitation and management of acute illness should be initiated immediately after birth.	Depending on the effectiveness of IUT, the neonatal course may be complicated by varying degrees of respiratory distress, pulmonary hypertension, ascites, and hyperbilirubinemia. Neonates may be small for gestation age, or have complications associated with prematurity.
Transfusions should be started as soon as possible.	Upon delivery, functional Hb concentration (total Hb minus Hb Bart’s and HbH fractions) should be calculated and guide transfusions. The goal of transfusions is to keep functional Hb of >90 g/L; exchange transfusion can help with hyperbilirubinemia. Depending on the clinical status, as well as timing and effectiveness of IUT, most neonates may benefit from exchange transfusions for the first few transfusions.
Assessments and management for associated congenital anomalies and neurological evaluation should be offered.	Consider brain MRI, GU ultrasound, cardiac ECHO, and bone survey. Initiate appropriate management or consultation with relevant subspecialty.
Long-term management of patients with ATM
Infants should be referred to a comprehensive thalassemia clinic for regular transfusion therapy.	Hb analysis should be performed before each transfusion and functional Hb should be calculated. Transfusion should be aimed to keep a functional Hb of >90 g/L and nonfunctional Hb (HbH + Hb Bart’s) at <15%.
Monitoring and treatment of iron overload should be initiated after 1 y of age, balancing their benefit and side effects.	Children with ATM will develop iron overload at an earlier age than those with TDT-β. Iron chelation should not be started before first year of life and aggressive iron chelation is not recommended before age 2. Ferritin may underestimate the degree of hepatic iron overload; assessment of liver and cardiac iron concentration through MRI is strongly recommended. Depending on the degree of iron overload, patients may require high doses of chelation, or combination chelation therapy.
Patients should be closely monitored for complications of anemia, ineffective erythropoiesis, chronic hemolysis, regular transfusion, and chelation therapy.	Regular monitoring for growth and development, bone health, endocrinopathies, fertility, progressive splenomegaly, symptomatic cholelithiasis, and features associated with extramedullary hematopoiesis, as per published guidelines.
Management of congenital abnormalities	Early consultation with appropriate surgical teams (eg, plastic surgery or urology).
Management of neurocognitive compromise	All children should be referred to a developmental specialist for specialized intervention and appropriate support.
Curative therapy should be considered at an early age.	Although the pathophysiology of ATM differs from TDT-β, until further data, protocols similar to those used for TDT-β should be used for stem cell transplantation.

For more details, please refer to Amid et al.⁴⁸

ECHO, echocardiography; GU, genitourinary system; IUT, intrauterine transfusions; MRI, magnetic resonance imaging; US, ultrasound.

View Large

This Feature Is Available To Subscribers Only