The American College of Obstetricians and Gynecologists recommends all people thinking of becoming pregnant be tested to see if they have thalassemia. Genetic counseling and genetic testing are recommended for families who carry a thalassemia trait.

A screening policy exists in Cyprus to reduce the rate of thalassemia, which, since the program's implementation in the 1970s (which also includes prenatal screening and abortion), has reduced the number of children born with the disease from one of every 158 births to almost zero.

In Iran as a premarital screening, the man's red cell indices are checked first, if he has microcytosis (mean cell hemoglobin < 27 pg or mean red cell volume < 80 fl), the woman is tested. When both are microcytic, their hemoglobin A2 concentrations are measured. If both have a concentration above 3.5% (diagnostic of thalassemia trait) they are referred to the local designated health post for genetic counseling.

Large scale awareness campaigns are being organized in India both by government and non-government organizations in favor of voluntary premarital screening to detect carriers of thalassemia and marriage between both carriers are strongly discouraged.

The diagnosis of delta-beta thalassemia is done via hypochromic microcytic red cell indices. This test is a part of a CBC, and could be employed to diagnose the reason the individual might have anemia, in this case due to thalassemia.

All beta thalassemias may exhibit abnormal red blood cells, a family history is followed by DNA analysis. This test is used to investigate deletions and mutations in the alpha- and beta-globin-producing genes. Family studies can be done to evaluate carrier status and the types of mutations present in other family members. DNA testing is not routine, but can help diagnose thalassemia and determine carrier status. In most cases the treating physician uses a clinical prediagnosis assessing anemia symptoms: fatigue, breathlessness and poor exercise tolerance. Further genetic analysis may include HPLC should routine electrophoresis prove difficult.

Physical examination may show an enlarged spleen. Tests that may be done include: Complete Blood Count (CBC), Hemoglobin electrophoresis, Peripheral blood smear, and Blood hemoglobin.

Genetic counseling may be appropriate for high-risk couples who wish to have a baby.

Abdominal pain due to hypersplenism and splenic infarction and right-upper quadrant pain caused by gallstones are major clinical manifestations. However, diagnosing thalassemiæ from symptoms alone is inadequate. Physicians note these signs as associative due to this disease's complexity. The following associative signs can attest to the severity of the phenotype: pallor, poor growth, inadequate food intake, splenomegaly, jaundice, maxillary hyperplasia, dental malocclusion, cholelithiasis, systolic ejection murmur in the presence of severe anemia and pathologic fractures. Based on symptoms, tests are ordered for a differential diagnosis. These tests include complete blood count; hemoglobin electrophoresis; serum transferrin, ferritin, total iron-binding capacity; urine urobilin and urobilogen; peripheral blood smear, which may show codocytes, or target cells; hematocrit; and serum bilirubin.

Those homozygous (Hb LeporeLepore; a very rare situation) or compound heterozygous (Hb Lepore-Β-thalassaemia) might suffer from a severe anaemia. They should be managed in a comprehensive multi-disciplinary program of care. Management includes a regular course of blood transfusions, although the clinical severity in compound (double) heterozygotes can range from minor to major, depending on the combination of genes that have caused the condition.

A potential complication that may occur in children that suffer acute anemia with a hemoglobin count below 5.5 g/dl is silent stroke A silent stroke is a type of stroke that does not have any outward symptoms (asymptomatic), and the patient is typically unaware they have suffered a stroke. Despite not causing identifiable symptoms a silent stroke still causes damage to the brain, and places the patient at increased risk for both transient ischemic attack and major stroke in the future.

Patient may present with symptomatic anemia or with sickle crises. In the United States and other countries with new-born screening programs, the disease may be identified in neonates.

Diagnostic tests include DNA sequencing, hemoglobin electrophoresis, and high-performance liquid chromatography.

In terms of treatment for delta-beta thalassemia one possible concern would be anemia, where, therefore, blood transfusions would be given to the affected individual (though blood transfusions might introduce complications, as well).

Stem cell transplant is another option, but the donor and the individual who will receive the bone marrow transplant must be compatible, the risks involved should be evaluated, as well

Thalassemia can coexist with other hemoglobinopathies. The most common of these are:

- Hemoglobin E/thalassemia: common in Cambodia, Thailand, and parts of India, it is clinically similar to β thalassemia major or thalassemia intermedia.

- Hemoglobin S/thalassemia: common in African and Mediterranean populations, is clinically similar to sickle-cell anemia, with the additional feature of splenomegaly.

- Hemoglobin C/thalassemia: common in Mediterranean and African populations, hemoglobin C/β thalassemia causes a moderately severe hemolytic anemia with splenomegaly; hemoglobin C/β thalassemia produces a milder disease.

- Hemoglobin D/thalassemia: common in the northwestern parts of India and Pakistan (Punjab region).

There have been reports of pulmonary venous thromboembolism in pregnant women with sickle cell trait, or men during prolonged airflight, and mild strokes and abnormalities on PET scans in children with the trait.

Sickle cell trait appears to worsen the complications seen in diabetes mellitus type 2 (retinopathy, nephropathy and proteinuria) and provoke hyperosmolar diabetic coma nephropathy, especially in male patients.

Treatment is the same as for patients with sickle cell disease. Patients may receive hydroxyurea to induce the protective effects of increased fetal hemoglobin production. They may also benefit from blood transfusions especially during vaso-occlusive crises. Patients may be offered chemoprophylaxis with penicillin. They may have splenic dysfunction and splenectomy is frequently performed. Vaccination against encapsulated bacteria including Streptococcus pneumoniae is recommended.

In general on acid electrophoresis in order of increasing mobility are hemoglobins F, A=D=G=E=O=Lepore, S, and C.

This is how abnormal hemoglobin variants are isolated and identified using these two methods. For example, a Hgb G-Philadelphia would migrate with S on alkaline electrophoresis and would migrate with A on acid electrophoresis, respectively

use of iso electric focusing to determine quantitative differences in globin chain synthesis and high performance liquid chromatography that separates hemoglobins based on their various affinities for the column

There was a study on a three year old that was a carrier of the hemoglobin variant of Hopkins-2. The child had mild anemia and reticulocytosis, which is commonly seen in anemia. There were, however, no sickled cells found in the blood and they had no symptoms relating to sickle cell. There was also a reduced mean corpuscular volume (MCV), which is the average volume of red blood cell count.

In general on alkaline electrophoresis in order of increasing mobility are hemoglobins A2, E=O=C, G=D=S=Lepore, F, A, K, J, Bart's, N, I, and H.

In general a sickling test (sodium bisulfite) is performed on abnormal hemoglobins migrating in the S location to see if the red cells precipitate in solution.

Because of the microcirculatory distress, a telltale sign or symptom of a potential sickling collapse is cramping. Specifically to sickle cell trait, cramping occurs in the lower extremities and back in athletes undergoing intense physical activity or exertion. In comparison to heat cramps, sickling cramps are less intense in terms of pain and have a weakness and fatigue associated with them, as opposed to tightly contracted muscles that lock up during heat cramps.

A sickling collapse comes on slowly, following cramps, weakness, general body aches and fatigue. Individuals with known positive sickle cell trait status experiencing significant muscle weakness or fatigue during exercise should take extra time to recover and hydrate before returning to activity in order to prevent further symptoms.

A collapse can be prevented by taking steps to ensure sufficient oxygen levels in the blood. Among these preventative measures are proper hydration and gradual acclimation to conditions such as heat, humidity, and decreased air pressure due to higher altitude. Gradual progression of exertion levels also helps athletes' bodies adjust and compensate, gaining fitness slowly over the course of several weeks.

People who have hemoglobin E/β-thalassemia have inherited one gene for hemoglobin E from one parent and one gene for β-thalassemia from the other parent. Hemoglobin E/β-thalassemia is a severe disease, and it still has no universal cure. It affects more than a million people in the world. The consequences of hemoglobin E/β-thalassemia when it is not treated can be heart failure, enlargement of the liver, problems in the bones, etc.

There is a variety of genotypes depending on the interaction of HbE and α-thalassemia. The presence of the α-thalassemia reduces the amount of HbE usually found in HbE heterozygotes. In other cases, in combination with certain thalassemia mutations, it provides an increased resistance to malaria ("P. falciparum").

The gold standard for the diagnosis of Vitamin B deficiency is a low blood level of Vitamin B. A low level of blood Vitamin B is a finding that normally can and should be treated by injections, supplementation, or dietary or lifestyle advice, but it is not a diagnosis. Hypovitaminosis B can result from a number of mechanisms, including those listed above. For determination of cause, further patient history, testing, and empirical therapy may be clinically indicated.

A measurement of methylmalonic acid (methylmalonate) can provide an indirect method for partially differentiating Vitamin B and folate deficiencies. The level of methylmalonic acid is not elevated in folic acid deficiency. Direct measurement of blood cobalamin remains the gold standard because the test for elevated methylmalonic acid is not specific enough. Vitamin B is one necessary prosthetic group to the enzyme methylmalonyl-coenzyme A mutase. Vitamin B deficiency is but one among the conditions that can lead to dysfunction of this enzyme and a buildup of its substrate, methylmalonic acid, the elevated level of which can be detected in the urine and blood.

Due to the lack of available radioactive Vitamin B, the Schilling test is now largely a historical artifact. The Schilling test was performed in the past to help determine the nature of the vitamin B deficiency. An advantage of the Schilling test was that it often included Vitamin B with intrinsic factor.

Treatment of individuals with CDA usually consist of frequent blood transfusions, but this can vary depending on the type that the individual has. Patients report going every 2–3 weeks for blood transfusions. In addition, they must undertake chelation therapy to survive; either deferoxamine, deferasirox, or deferiprone to eliminate the excess iron that accumulates. Removal of the spleen and gallbladder are common. Hemoglobin levels can run anywhere between 8.0 g/dl and 11.0 g/dl in untransfused patients, the amount of blood received by the patient is not as important as their baseline pre-transfusion hemoglobin level. This is true for ferritin levels and iron levels in the organs as well, it is important for patients to go regularly for transfusions in order to maximize good health, normal ferritin levels run anywhere between 24 and 336 ng/ml, hematologists generally do not begin chelation therapy until ferritin levels reach at least 1000 ng/ml. It is more important to check iron levels in the organs through MRI scans, however, than to simply get regular blood tests to check ferritin levels, which only show a trend, and do not reflect actual organ iron content.

Gene therapy, as well as, bone marrow transplant are also possible treatments for the disorder, but each have their own risks at this point in time. Bone marrow transplantation is the more used method between the two, whereas researchers are still trying to definitively establish the results of gene therapy treatment. It generally requires a 10/10 HLA matched donor, however, who is usually a sibling. As most patients do not have this, they must rely on gene therapy research to potentially provide them with an alternative. CDA at both clinical and genetic aspects are part of a heterogeneous group of genetic conditions. Gene therapy is still experimental and has largely only been tested in animal models until now. This type of therapy has promise, however, as it allows for the autologous transplantation of the patient's own healthy stem cells rather than requiring an outside donor, thereby bypassing any potential for graft vs. host disease (GVHD).

In the United States, the FDA approved clinical trials on Beta thalassemia patients in 2012. The first study, which took place in July 2012, recruited human subjects with thalassemia major, and ended in 2014.

Hemoglobin E is most prevalent in mainland Southeast Asia (Thailand, Myanmar, Cambodia, Laos, Vietnam), where its prevalence can reach 30 or 40%, and Northeast India, where in certain areas carrier rates reach 60% of the population. In Thailand the mutation can reach 50 or 70%, and it is higher in the northeast of the country. In Sri Lanka, it can reach up to 40% and affects those of Sinhalese and Vedda descent. It is also found at high frequencies in Bangladesh and Indonesia. The trait can also appear in people of Turkish, Chinese and Filipino descent. The mutation is estimated to have arisen within the last 5,000 years. In Europe there have been found cases of families with hemoglobin E, but in these cases, the mutation differs from the one found in South-East Asia. This means that there may be different origins of the βE mutation.

There were five carriers of Hemoglobin Hopkins 2 in the Fuller-Carr family and ten double heterozygotes of Ho-2 and Hemoglobin S. All the carriers were in good health and had normal hematology test results. Out of those carrying hemoglobin S and Ho-2, none were anemic; but, a few of those studied displayed elevated reticulocyte counts. This is measured through a blood test that analyzes the speed of production of red blood cells by bone marrow and its release into the blood. There was no suggestion of symptomatic sickle cell anemia in the family.

While no single test is reliable to distinguish iron deficiency anemia from the anemia of chronic inflammation, there are sometimes some suggestive data:

- In anemia of chronic inflammation without iron deficiency, ferritin is normal or high, reflecting the fact that iron is sequestered within cells, and ferritin is being produced as an acute phase reactant. In iron deficiency anemia ferritin is low.

- Total iron-binding capacity (TIBC) is high in iron deficiency, reflecting production of more transferrin to increase iron binding; TIBC is low or normal in anemia of chronic inflammation.

Anemia of chronic disease is usually mild but can be severe. It is usually normocytic, but can be microcytic. The presence of both anemia of chronic disease and dietary iron deficiency in the same patient results in a more severe anemia.