Highlights & Basics
- There are at least four different and distinct alpha-thalassemias: silent carrier (1 affected alpha-globin gene), alpha-thalassemia trait (2 affected alpha-globin genes), hemoglobin H (Hb H) disease (typically 3 affected alpha-globin genes), and alpha-thalassemia major (also known as Hb Bart hydrops fetalis syndrome; typically deletion of all 4 alpha-globin genes).
- The severity of the clinical manifestations of anemia and hemolysis correspond with the genetic defect and the degree of impairment in alpha-globin synthesis.
- Alpha-thalassemia is found in malarial regions of the world (sub-Saharan Africa, the Mediterranean basin, the Middle East, South Asia, and Southeast Asia) and should be suspected in patients with these ethnic backgrounds and with microcytosis and/or anemia.
- The vast majority of alpha-thalassemia patients are clinically well and most are asymptomatic. Many patients with Hb H are also clinically well, but are at risk for acute hemolytic episodes, aplastic crises, iron overload (even in the absence of chronic transfusions), hypersplenism, and endocrine disease.
- Education is an important part of management and should cover the risks of acute events and, in genetic counseling, the risks of conceiving a child with Hb H disease or the potentially devastating alpha-thalassemia major.
- Acquired Hb H disease is rare and occurs in association with hematologic disorders, most commonly in male patients with myelodysplastic syndrome.
Quick Reference
History & Exam
Key Factors
symptoms of anemia
splenomegaly
Other Factors
childhood or young adulthood
family history of alpha-thalassemia
symptoms of gallstones
growth retardation
history of prior iron supplementation
jaundice
mild dysmorphic facial features
extramedullary hematopoiesis
Diagnostics Tests
1st Tests to Order
hemoglobin (Hb)
mean corpuscular volume (MCV)
mean corpuscular hemoglobin (MCH)
red blood cell count
peripheral smear
reticulocyte percentage
serum iron
serum ferritin
Other Tests to consider
brilliant cresyl blue staining of red blood cells
Hb electrophoresis
Hb fractionation by high-performance liquid chromatography (HPLC)
gap-polymerase chain reaction (gap-PCR)
multiplex ligation-dependent probe amplification
direct sequencing/reverse dot blot
MRI (hepatic or cardiac)
superconducting quantum interference devices (SQUID)
liver biopsy
Treatment Options
acute
acute hemolytic episodes: pregnant or nonpregnant
identification of cause + monitoring + folic acid supplementation
red blood cell transfusion
transient aplastic crisis: pregnant or nonpregnant
red blood cell transfusion
Definition
Classifications
Types and variants
Genotypic and phenotypic classification
- Silent carrier state occurs when only 1 of the 4 alpha-globin genes is affected.
- Patients are likely to be asymptomatic and hematologically normal.
- Alpha-thalassemia silent carrier is also known as alpha-thalassemia silent trait, alpha-thalassemia-2 trait, heterozygosity for alpha(+) thalassemia, and alpha-thalassemia minor.
- Alpha-thalassemia trait occurs when 2 of the 4 alpha-globin genes are affected: for example, either heterozygosity for alpha(0) thalassemia (that is, 2 alpha-globin genes on the same chromosome, in cis, are deleted) or homozygosity for alpha(+) thalassemia (that is, 1 alpha-globin gene on each chromosome, in trans, is deleted or mutated).
- Patients with alpha-thalassemia trait may have a mild asymptomatic anemia, and physicians often mistakenly diagnose these patients as having iron-deficiency anemia.
- Importantly, patients who are homozygous for nondeletional alpha(+) thalassemia may have more severe manifestations of the disease. This is the case with Hemoglobin Constant Spring, which is caused by a mutation in the alpha-2 globin gene. Patients who are homozygous for this mutation (that is, both alpha-2 globin genes are affected) have a more serious clinical phenotype than those who are homozygous for deletional alpha(+) thalassemia. They have a mild anemia with a normal mean corpuscular volume (MCV) and slightly low mean corpuscular hemoglobin (MCH), and frequently have jaundice and splenomegaly.[6]
- Hb H disease typically affects 3 alpha-globin genes (beta4 tetramers). Image It is most commonly caused by deletion of 3 alpha-globin genes, but can also be caused by deletion of 2 alpha-globin genes with an inactivating point mutation of a third gene.
- Atypical Hb H disease (or even hydrops fetalis) can also be caused by homozygous nondeletion mutations such as polyadenylation signal mutations in the alpha-2 globin gene.[7]
- Hb H may be detected in the peripheral blood on routine Hb electrophoresis. Hb H inclusion bodies may also be demonstrated on supravital staining.
- Typically caused when all 4 alpha-globin genes are deleted.
- It is also known as hemoglobin Bart hydrops fetalis syndrome or homozygous alpha(0) thalassemia.
Vignette
Common Vignette 1
Common Vignette 2
Other Presentations
Epidemiology
Etiology
Pathophysiology
Images
Diagnostic Approach
History
- Presence and duration of symptoms related to anemia (fatigue, shortness of breath, dizziness)
- Presence and duration of symptoms related to jaundice (yellow discoloration of the sclerae, skin, and mucous membranes)
- Presence and duration of symptoms related to gallstones (nausea, gas, bloating, and abdominal pain)
- Prior history of iron supplementation or red cell transfusion (although most patients with Hb H disease do not require chronic transfusions, in one study up to one third of those with nondeletional Hb H did require regular transfusions)[8]
- Ethnic origin of the patient (sub-Saharan Africa, the Mediterranean basin, the Middle East, South Asia, and Southeast Asia)
- History of other affected family members
- Age of the patient (because alpha-thalassemia can have such wide variability in clinical manifestations, patients may present anywhere from in utero, with hydrops fetalis, to any point during adulthood, with an asymptomatic microcytosis; however, those with more severe manifestations will generally present in childhood or young adulthood).
Physical exam
Initial laboratory evaluation
Subsequent laboratory evaluation
Risk Factors
History & Exam
Tests
Differential Diagnosis
Iron-deficiency anemia
Differentiating Signs/Symptoms
- Symptoms associated with severe iron deficiency and not seen in alpha-thalassemia include pica (the craving for nonfood items).
Differentiating Tests
- With iron-deficiency anemia, iron indices will show low serum iron, high transferrin, low transferrin saturation, and low ferritin, whereas iron studies are usually normal in alpha-thalassemia. Iron deficiency will also present as a microcytic, hypochromic anemia; however, it will typically present as an acquired rather than a congenital disorder.
- Red blood cell count will be high in alpha-thalassemia and tend to be low or normal in iron-deficiency anemia.
- If the diagnosis is in question, a short well-monitored trial of iron repletion will frequently confirm the diagnosis.
Beta-thalassemia
Differentiating Signs/Symptoms
- Beta-thalassemia major often presents at a few months of age with progressive pallor and abdominal distension; perinatal history is most often uneventful.
Differentiating Tests
- Beta-thalassemia, with impaired beta-globin chain synthesis, will also present as a microcytic, hypochromic anemia.
- Hb electrophoresis/high-performance liquid chromatography (HPLC) will reveal an increased Hb A2 in most forms of beta-thalassemia. Beta-globin gene sequencing will detect most but not all underlying molecular defects in beta-thalassemia. Sequencing will not detect deletional beta-thalassemias.
Differentiating Signs/Symptoms
- Patients with variant hemoglobin disorders have clinical manifestations of variable severity. When inherited in combination with beta(0)-thalassemia, patients can present as beta-thalassemia major.
Differentiating Tests
- Variant hemoglobins, either alone or in combination with other globin diseases, can present as a microcytic, hypochromic anemia.
- Many of these will be detected by Hb electrophoresis/HPLC; however, DNA-based globin gene testing may be required to confirm the diagnosis.
Anemia of chronic disease
Differentiating Signs/Symptoms
- Clinical history is crucial in differentiating anemia of chronic disease from thalassemia. History includes age of onset, family history, ethnicity of patient, prior hemoglobin and red cell indices, history of acute and chronic infections, autoimmune disorders, malignant disease, major trauma and surgery, and critical illness, with physical findings of the underlying disorder.
Differentiating Tests
- Degree of anemia is typically mild to moderate and normocytic. Anemia of chronic disease can uncommonly present as a microcytic, hypochromic anemia.
- Iron studies may show low serum iron and transferrin saturation with normal or elevated ferritin.
- WBC and differential and platelet count may be elevated due to associated infection or inflammation.
Lead poisoning
Differentiating Signs/Symptoms
- Appropriate history of exposure to lead; irritability, aggressive behavior, low appetite, difficulty sleeping, headaches, reduced sensations, loss of previous developmental skills, constipation; rarely, vomiting, muscle weakness, seizures, or coma.
Differentiating Tests
- Lead poisoning interferes with delta-aminolevulinic acid dehydratase (ALAD) and thus with heme synthesis, and can lead to a microcytic anemia.
- Peripheral smear will show basophilic stippling in lead poisoning, and the reticulocyte count will be depressed, in contrast to an elevated reticulocyte count in alpha-thalassemia. Diagnosis can be confirmed by serum lead levels.
Differentiating Signs/Symptoms
- Sideroblastic anemias are due to defective heme synthesis and can be congenital (i.e., X-linked) or acquired (lead, ethanol).
- History appropriate to acquired SA, including nutritional imbalances and prolonged exposure to toxins and drugs.
- History of myelodysplastic syndrome.
Differentiating Tests
- Two populations of red cells may be seen on peripheral smear in SA. Diagnosis is confirmed by bone marrow aspiration and biopsy.
B12 deficiency anemia
Differentiating Signs/Symptoms
- Although anemia due to B12 deficiency is classically easily distinguishable from thalassemia by the high mean corpuscular volume (MCV) and peripheral smear findings, B12 deficiency can also present as a normocytic or a microcytic disorder, often in the presence of coexisting iron deficiency.[55]
- B12 deficiency may also lead to neurologic deficits: classically, a symmetric neuropathy with ataxia associated with loss of position and vibration sense.[56] Other neurologic findings include memory loss, irritability, and dementia.
Differentiating Tests
- The peripheral smear classically reveals hypersegmented neutrophils and macrocytosis. Serum B12 level is low, and serum homocysteine and methylmalonic acid levels are elevated.
- Bone marrow exam, if performed, will reveal hypercellularity and megaloblastic changes. The anemia will correct with vitamin B12 repletion.
Folate deficiency
Differentiating Signs/Symptoms
- Anemia due to folate deficiency will typically be macrocytic.
Differentiating Tests
- The MCV will be high, and serum homocysteine (but not methylmalonic acid) will be elevated. Serum and red blood cell folate levels will be low.
Other hemolytic anemias
Differentiating Signs/Symptoms
- The patient who presents with anemia must always receive a full diagnostic evaluation. The differential diagnosis includes other causes of hemolytic anemia.
Differentiating Tests
- Active hemolysis will lead to an elevated LDH, low haptoglobin, indirect bilirubinemia, and an elevated reticulocyte count. The evaluation must include investigation for both intracorpuscular (enzyme and membrane defects) and extracorpuscular (autoimmune-mediated hemolytic anemia, drug-induced hemolysis, or microangiopathic causes) etiologies of hemolysis.
Differentiating Signs/Symptoms
- The differential diagnosis of anemia also includes hematologic malignancies. Clues to the presence of an underlying malignancy include systemic symptoms (fever, weight loss), lymphadenopathy, and abnormalities in other cell lines with associated symptoms (i.e., thrombocytopenia and bleeding).
Differentiating Tests
- The white cell and platelet counts will frequently be abnormal. The peripheral smear may reveal evidence of the underlying disorder: for example, dysplasia in myelodysplastic syndrome and circulating blasts in acute myeloid or lymphoid leukemia. An urgent bone marrow aspirate and biopsy are required to confirm the diagnosis.
Screening
Carrier screening
Prenatal diagnosis
Newborn screening
Asymptomatic patient with microcytosis
Treatment Approach
Alpha-thalassemia silent carrier and alpha-thalassemia trait
Hb H disease
Alpha-thalassemia major
Treatment Options
acute hemolytic episodes: pregnant or nonpregnant
identification of cause + monitoring + folic acid supplementation
Primary Options
folic acid (vitamin B9)
children and adults: 1 mg orally once daily until response, then 0.4 mg orally once daily
Comments
- Treatment for acute hemolytic episodes includes investigation as to the cause of the hemolytic event (including evaluation for coexisting G6PD deficiency), monitoring (for severe anemia, assessment of cardiovascular status, and transfusions, depending on the severity of anemia and tolerance to transfusions), and folic acid supplementation.
red blood cell transfusion
Comments
- Depending on the severity and tolerance of anemia, a patient with severe anemia may be hospitalized to have red blood cell transfusion. There is no absolute threshold at which transfusion should be initiated, with the exception of patients with very severe anemia (hemoglobin level <5 g/dL).[73] In general, patients with a hemoglobin <7 g/dL may require transfusion.[50]
transient aplastic crisis: pregnant or nonpregnant
red blood cell transfusion
Comments
- Transient aplastic crises are most commonly due to infection with parvovirus B19 infection, which infects erythroid progenitor cells.[103] The resultant reticulocytopenia may lead to a severe anemia, particularly in patients with chronic hemolysis. Transient aplastic crises are self-limited (1-2 weeks), and treatment is supportive, with bridging red blood cell transfusions until erythroid recovery.
nonpregnant
alpha-thalassemia silent carrier
avoidance of unnecessary iron supplementation + supportive care
Comments
- Alpha-thalassemia silent carrier (1 affected alpha-globin gene) status is generally associated with normal Hb levels; patients with alpha-thalassemia trait (2 affected alpha-globin genes) may have a mild asymptomatic anemia. It is important to avoid unnecessary and potentially harmful iron supplementation in this population and to provide education, particularly with regard to genetic counseling.[104]
alpha-thalassemia trait
avoidance of unnecessary iron supplementation + supportive care
Comments
- Alpha-thalassemia silent carrier (1 affected alpha-globin gene) status is generally associated with normal Hb levels; patients with alpha-thalassemia trait (2 affected alpha-globin genes) may have a mild asymptomatic anemia. It is important to avoid unnecessary and potentially harmful iron supplementation in this population and to provide education, particularly with regard to genetic counseling.[104]
- Patients who are homozygous for Hb Constant Spring (Hb CS/CS; a subtype of alpha-thalassemia trait) have a more serious clinical phenotype than those who are homozygous for deletional alpha(+) thalassemia. They have a mild anemia and frequently have jaundice and splenomegaly with a normal mean corpuscular volume (MCV) and slightly low mean corpuscular hemoglobin (MCH).[6] Patients should be followed regularly for assessment of degree of anemia and hemolysis as well as for assessment of the development or worsening of splenomegaly.
Hb H disease
folic acid supplementation + supportive care
Primary Options
folic acid (vitamin B9)
children and adults: 1 mg orally once daily
Comments
- Education is an important part of management and should cover the risks of acute events and, in genetic counseling, the risks of conceiving a child with hemoglobin H (Hb H) disease or the potentially devastating alpha-thalassemia major.
- Patients with Hb H disease are at risk for complications, including transient episodes of severe anemia (secondary to increased oxidant stress from medication or illness), aplastic crisis due to parvovirus B19 or other viral infections, cholelithiasis, leg ulcers, splenomegaly, calcium and vitamin D deficiency, osteopenia, and growth retardation.[5] [43] [66] [67] See Complications .
- Patients and their families must be informed of the need to seek medical attention if they notice symptoms such as increased fatigue, shortness of breath, jaundice, or dark urine.
- Hb H disease refers to both the more common deletional and the less common nondeletional Hb H disease. Patients with nondeletional Hb H disease tend to have a more severe clinical course, with younger age at diagnosis, more symptoms, and greater degrees of splenomegaly, and are more likely to require transfusion than are patients with deletional Hb H disease.[5] In one report, one third of patients with nondeletional Hb H disease required regular transfusions.[8]
- All patients ≥10 years of age with non-transfusion-dependent thalassemia syndromes (≥15 years in patients with deletional Hb H disease) should undergo magnetic resonance evaluation for iron overload status at 1- to 2-year intervals; serum ferritin levels should be measured every 3 months.[73] Serum ferritin levels may underestimate iron concentration.[52]
red blood cell transfusion
Comments
- Patients with nondeletional Hb H, such as Hb H/Constant Spring, are more likely to require both acute and chronic transfusions than patients with deletional Hb H disease.[5] [52] The decision to provide either acute or chronic transfusions depends on age, severity of anemia, and the patient's ability to tolerate anemia. Tolerance of anemia will be influenced by the presence or absence of comorbidities such as cardiovascular disease.
- The small proportion of patients who may need chronic transfusion therapy should be carefully evaluated and managed in a thalassemia center with appropriate expertise.[50] The decision to initiate a chronic transfusion program should take into account multiple variables including the severity of anemia, the patient's comorbid conditions (including cardiovascular status, which, if impaired, can lead to intolerance of even moderate anemia), and associated complications. Prior to transfusion, red cell antigen phenotyping should be performed, and patients should be transfused with appropriately matched blood to minimize the risk of alloimmunization.[90]
- Patients must be carefully monitored for iron overload. Cardiac, endocrine, and hepatic function must also be carefully monitored.[73]
iron chelation therapy
Primary Options
- deferasirox
consult specialist for guidance on dose
- deferasirox
- deferoxamine
consult specialist for guidance on dose
- deferoxamine
Secondary Options
- deferiprone
consult specialist for guidance on dose
- deferiprone
Comments
- Iron status can be followed by serum ferritin, and quantification of liver iron by MRI, superconducting quantum interference devices, or liver biopsy.[51] Although data are limited for alpha-thalassemia, liver iron concentrations of ≥5 mg Fe/g dry weight in non-transfusion-dependent beta-thalassemia intermedia patients are associated with increased risk of vascular events, hypothyroidism, osteoporosis, and hypogonadism.[73] [74] Serum ferritin levels of ≥800 nanograms/mL appear to correlate with liver iron concentrations of ≥5 mg Fe/g dry weight.[73] [105] In patients with the more severe forms of alpha-thalassemia at risk of iron overload, such as those with Hb H disease, iron levels should be evaluated regularly. All patients ages ≥10 years with non-transfusion-dependent thalassemia syndromes (≥15 years in patients with deletional Hb H disease) should have magnetic resonance evaluation for iron overload status at 1- to 2-year intervals; serum ferritin levels should be measured every 3 months.[73] Serum ferritin levels may underestimate iron concentration.[52]
- Guidelines recommend that iron chelation therapy should be initiated in non-transfusion-dependent thalassemia patients ages ≥10 years (≥15 years in patients with deletional Hb H disease) if liver iron concentration is ≥5 mg Fe/g dry weight (or serum ferritin level is ≥800 nanograms/mL when liver iron concentration measurement is unavailable).[73]
- Two oral iron chelators, deferasirox and deferiprone, and one parenteral iron chelator, deferoxamine, are available in the US and Europe. One meta-analysis of randomized controlled trials that evaluated these three agents in patients with severe thalassemia failed to identify one iron chelator that was consistently superior to the others.[75] Adverse effects and intensive demands of iron chelation therapy may contribute to reduced adherence in transfusion-dependent patients with thalassemia.[92]
- Deferasirox is approved by the US Food and Drug Administration (FDA) for use in transfusion-dependent patients ≥2 years, and in non-transfusion-dependent thalassemia patients ages ≥10 years with liver iron concentrations ≥5 mg Fe/g dry weight and serum ferritin levels >300 nanograms/mL. In Europe, deferasirox is approved for patients ≥2 years with transfusion-dependent thalassemia and patients ≥10 years with non-transfusion-dependent thalassemia where deferoxamine cannot be used or is inadequate. Deferasirox carries a warning related to the risk of renal failure, hepatic failure, and gastrointestinal hemorrhage.[78] Additional adverse effects include auditory and ocular impairment, rash, and bone marrow suppression. Serum creatinine, liver function, and auditory and ophthalmic function should be monitored before initiation of and during therapy.[79]
- Deferiprone is approved by the FDA for treatment of iron overload due to blood transfusions in patients ages ≥3 years with thalassemia and other anemias. In Europe, deferiprone is licensed for use in patients with thalassemia major when current chelation therapy is contraindicated or inadequate. Deferiprone increases risk for agranulocytosis; complete blood count (CBC) with differential must be monitored regularly while undergoing treatment.[81] [82] Deferiprone can cause gastrointestinal and joint adverse effects.
- Deferoxamine has a very short half-life and is administered as a slow subcutaneous or intravenous infusion. This limits acceptability to patients and can impede adherence. Deferoxamine effectively reduces both liver and cardiac iron.[83] [84] It is renally and hepatically cleared, and carries a risk of auditory and ophthalmic toxicity, requiring regular monitoring.
splenectomy + preoperative vaccination + postoperative penicillin-VK and antiplatelet agents
Primary Options
penicillin V potassium
children <5 years of age: 125 mg orally twice daily; children ≥5 years of age: 250 mg orally twice daily
and/or
- aspirin
adults: 81 mg orally once daily
Comments
- Splenectomy is often considered if a patient develops painful splenomegaly, hypersplenism with associated pancytopenia, an increase in transfusion requirement, poor growth and development due to worsening anemia, or lack of availability of transfusion or iron chelation therapy.[73] [85] It may be particularly effective in raising the hemoglobin level and avoiding transfusions in patients with Hb H CS.[52] However, the potential for serious complications, including infection, thrombosis, and pulmonary hypertension, requires careful consideration before proceeding.[86] [87]
- Patients must be educated regarding the risks of post-splenectomy sepsis and the need for immediate medical evaluation in the case of febrile illness. Patients undergoing splenectomy may undergo concomitant cholecystectomy if there is evidence of cholelithiasis.[73]
hematopoietic stem cell transplant for severe transfusion-dependent disease
pregnant
alpha-thalassemia silent carrier
routine prenatal supplementation if not iron overloaded and close follow-up
Comments
- In alpha-thalassemia silent carrier, the Hb does not usually decline below 9 g/dL and intervention is not typically required.[65] Routine prenatal supplementation with prenatal vitamins (if not iron overloaded) and close follow-up are usually sufficient.
alpha-thalassemia trait
routine prenatal supplementation if not iron overloaded and close follow-up
Comments
- In alpha-thalassemia trait, the Hb does not usually decline below 9 g/dL and intervention is not typically required.[65] Routine prenatal supplementation with prenatal vitamins (if not iron overloaded) and close follow-up are usually sufficient.
with Hb H disease
routine prenatal supplementation + close follow-up + supportive care
Comments
- Pregnancy leads to a relative increase in plasma volume greater than red cell mass, which results in a decrease in Hb.
- Pregnant women with Hb H disease who are not iron overloaded should receive the same prenatal supplementation as pregnant women without thalassemia; however, they should be followed closely and transfusion may be required, particularly if the Hb declines below 8 g/dL.
- Iron chelation therapy is avoided during pregnancy to minimize potential teratogenicity and iron deficiency in the fetus.[107]
- It is important to avoid medications associated with oxidant injury in G6PD deficiency, such as sulfonamides and nitrofurantoin, and to provide education, particularly with regard to genetic counseling.
red blood cell transfusion
Comments
- Transfusion may be required, particularly if the Hb declines below 8 g/dL. Red cell transfusion may be given, even if there is a concern for iron overload.[107]
fetus with alpha-thalassemia major
intrauterine red blood cell transfusion
Comments
- Following diagnosis of alpha-thalassemia major, the mother may choose to terminate the pregnancy. Counseling should, however, recognize that intrauterine transfusion (IUT) is an option for expectant parents who receive a prenatal diagnosis of alpha-thalassemia major.[97] Fetuses (diagnosed prenatally) with homozygous alpha(0) variants that spare the zeta-globin gene, or (--(FIL)/--(SEA) or --(THAI)/--(SEA)) genotypes, will survive into the second or third trimester, or, occasionally, to birth.
- The American Society of Hematology recommends offering IUT to all families who wish to pursue fetal intervention for alpha-thalassemia major. If desired, IUT should begin as soon as technically possible, generally at 18 weeks' gestation, to mitigate the long-term impact of fetal hypoxia. A similar protocol to standard protocols for alloimmunization should be followed.[37]
- A review of data from the alpha-thalassemia registry (International Registry of Patients With Alpha Thalassemia) indicates that fetuses with alpha-thalassemia major who received at least two IUTs had delivery near term, resolution of hydrops, normal neurodevelopmental outcomes, and excellent survival.[97] Case reports and case series report similar outcomes.[98] [99]
- Patients who survive alpha-thalassemia major in utero will require lifelong transfusion (with the attendant requirement for iron chelation), or hematopoietic stem cell transplantation.[37]
Emerging Tx
Betibeglogene autotemcel
In utero hematopoietic stem cell (HSC) transplantation
Pyruvate kinase activators
Luspatercept
Prevention
Primary Prevention
Follow-Up Overview
Prognosis
Alpha-thalassemia major
Monitoring
Complications
Citations
Northern California Comprehensive Thalassemia Center. Standards of care guidelines for thalassemia. 2012 [internet publication].[Full Text]
Thalassaemia International Federation. 2021 guidelines for the management of transfusion dependent thalassaemia (TDT). 4th ed. Version 2.01. 2021 [internet publication].[Full Text]
Thalassaemia International Federation. Guidelines for the management of non transfusion dependent thalassaemia (NTDT). 2nd edition. 2017 [internet publication].[Full Text]
Northern California Comprehensive Thalassemia Center. Standards of care guidelines for thalassemia. 2012 [internet publication].[Full Text]
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Key Articles
Referenced Articles
Guidelines
Diagnostic
Summary
Recommends offering universal hemoglobinopathy testing to persons planning pregnancy or at the initial prenatal visit.Published by
American College of Obstetricians and Gynecologists
Published
2022
Summary
Recommendations regarding screening of hemoglobinopathies in pregnancy.Published by
American College of Obstetricians and Gynecologists
Published
2007 (reaffirmed 2018)
Summary
Evidence-based recommendations for the evaluation of nonimmune hydrops fetalis.Published by
Society for Maternal-Fetal Medicine
Published
2015
Summary
Explores current hemoglobinopathy screening and diagnostic methodologies.Published by
Association of Public Health Laboratories; Centers for Disease Control and Prevention
Published
2015
Summary
Expert overview of diagnosis of thalassemia major.Published by
Northern California Comprehensive Thalassemia Center
Published
2012
Summary
Recommendations regarding the diagnosis of alpha-thalassemia.Published by
Thalassaemia International Federation
Published
2021
Summary
Recommendations for carrier identification and prenatal diagnosis of hemoglobinopathies.Published by
European Molecular Genetics Quality Network
Published
2015
Treatment
Summary
Recommendations for prenatal screening, perinatal management, and postnatal care in alpha-thalassemia major.Published by
American Society of Hematology
Published
2021
Summary
Recommendations for the care and management of patients with thalassemia in Canada. A guideline for patients and their families, and clinicians.Published by
Thalassemia Foundation of Canada
Published
2016
Summary
Evidence-based recommendations for the management of nonimmune hydrops fetalis.Published by
Society for Maternal-Fetal Medicine
Published
2015
Summary
Overview of management of thalassemia major.Published by
Northern California Comprehensive Thalassemia Center
Published
2012
Summary
Consensus-based guidelines for the management of transfusion-dependent thalassemia.Published by
Thalassaemia International Federation
Published
2021
Summary
Consensus-based guidelines for the management of non-transfusion-dependent thalassemia.Published by
Thalassaemia International Federation
Published
2017