Experimental gene therapy exists to treat hereditary spherocytosis in lab mice; however, this treatment has not yet been tried on humans due to all of the risks involved in human gene therapy.

Hereditary spherocytosis is the most common disorder of the red cell membrane and affects 1 in 2,000 people of Northern European ancestry. According to Harrison's Principles of Internal Medicine, the frequency is at least 1 in 5,000.

The protective effect of sickle-cell trait does not apply to people with sickle cell disease; in fact, they are more vulnerable to malaria, since the most common cause of painful crises in malarial countries is infection with malaria. It has therefore been recommended that people with sickle-cell disease living in malarial countries should receive anti-malarial chemoprophylaxis for life.

From birth to five years of age, penicillin daily, due to the immature immune system that makes them more prone to early childhood illnesses is recommended. Dietary supplementation of folic acid had been previously recommended by the WHO. A 2016 Cochrane review of its use found "the effect of supplementation on anaemia and any symptoms of anaemia remains unclear" due to a lack of medical evidence.

The ideal treatment for anemia of chronic disease is to treat the chronic disease successfully, but this is rarely possible.

Parenteral iron is increasingly used for anemia in chronic renal disease and inflammatory bowel disease.

Erythropoietin can be helpful, but this is costly and may be dangerous. Erythropoietin is advised either in conjunction with adequate iron replacement which in practice is intravenous, or when IV iron has proved ineffective.

The most important measure is prevention – avoidance of the drugs and foods that cause hemolysis. Vaccination against some common pathogens (e.g. hepatitis A and hepatitis B) may prevent infection-induced attacks.

In the acute phase of hemolysis, blood transfusions might be necessary, or even dialysis in acute kidney failure. Blood transfusion is an important symptomatic measure, as the transfused red cells are generally not G6PD deficient and will live a normal lifespan in the recipient's circulation. Those affected should avoid drugs such as aspirin.

Some patients may benefit from removal of the spleen (splenectomy), as this is an important site of red cell destruction. Folic acid should be used in any disorder featuring a high red cell turnover. Although vitamin E and selenium have antioxidant properties, their use does not decrease the severity of G6PD deficiency.

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.

PRCA is considered an autoimmune disease as it will respond to immunosuppressant treatment such as ciclosporin in many patients, though this approach is not without risk.

It has also been shown to respond to treatments with Rituximab and Tacrolimus.

Iron overload is an unavoidable consequence of chronic transfusion therapy, necessary for patients with beta thalassemia. Iron chelation is a medical therapy that avoids the complications of iron overload. The iron overload can be removed by Deferasirox, an oral iron chelator, which has a dose- dependent effect on iron burden. Every unit of transfused blood contains 200–250 mg of iron and the body has no natural mechanism to remove excess iron. Deferasirox is a vital part in the patients health after blood transfusions. During normal iron homeostasis the circulating iron is bound to transferrin, but with an iron overload, the ability for transferrin to bind iron is exceeded and non-transferrin bound iron is formed. It represents a potentially toxic iron form due to its high propensity to induce oxygen species and is responsible for cellular damage. The prevention of iron overload protects patients from morbidity and mortality. The primary aim is to bind to and remove iron from the body and a rate equal to the rate of transfusional iron input or greater than iron input. During clinical trails patients that received Deferasirox experienced no drug-related neutropenia or agranulocytosis, which was present with other iron chelators. Its long half life requires it to be taken once daily and provides constant chelation. Cardiac failure is a main cause of illness from transfusional iron overload but deferasirox demonstrated the ability to remove iron from iron-loaded myocardial cells protecting beta thalassemia patients from effects of required blood transfusions.

In general, AIHA in children has a good prognosis and is self-limiting. However, if it presents within the first two years of life or in the teenage years, the disease often follows a more chronic course, requiring long-term immunosuppression, with serious developmental consequences. The aim of therapy may sometimes be to lower the use of steroids in the control of the disease. In this case, splenectomy may be considered, as well as other immunosuppressive drugs. Infection is a serious concern in patients on long-term immunosuppressant therapy, especially in very young children (less than two years).

Patients may require episodic blood transfusions. Transfusion-dependent patients develop iron overload and require chelation therapy to remove the excess iron. Transmission is autosomal recessive; however, dominant mutations and compound heterozygotes have been reported. Genetic counseling is recommended and prenatal diagnosis may be offered. Alleles without a mutation that reduces function are characterized as (β).

Mutations are characterized as (βo) if they prevent any formation of β chains,

mutations are characterized as (β+) if they allow some β chain formation to occur.

G6PD-deficient individuals do not appear to acquire any illnesses more frequently than other people, and may have less risk than other people for acquiring ischemic heart disease and cerebrovascular disease.

Treatments for anemia depend on cause and severity. Vitamin supplements given orally (folic acid or vitamin B) or intramuscularly (vitamin B) will replace specific deficiencies.

Hemolytic anemia affects nonhuman species as well as humans. It has been found, in a number of animal species, to result from specific triggers.

Some notable cases include hemolytic anemia found in black rhinos kept in captivity, with the disease, in one instance, affecting 20% of captive rhinos at a specific facility. The disease is also found in wild rhinos.

Dogs and cats differ slightly from humans in some details of their RBC composition and have altered susceptibility to damage, notably, increased susceptibility to oxidative damage from consumption of onion. Garlic is less toxic to dogs than onion.

Nutritional iron deficiency is common in developing nations. An estimated two-thirds of children and of women of childbearing age in most developing nations are estimated to suffer from iron

deficiency; one-third of them have the more severe form of the disorder, anemia. Iron deficiency from nutritional causes is rare in men and postmenopausal women. The diagnosis of iron deficiency mandates a search for potential sources of loss, such as gastrointestinal bleeding from ulcers or colon cancer. Mild to moderate iron-deficiency anemia is treated by oral iron supplementation with ferrous sulfate, ferrous fumarate, or ferrous gluconate. When taking iron supplements, stomach upset or darkening of the feces are commonly experienced. The stomach upset can be alleviated by taking the iron with food; however, this decreases the amount of iron absorbed. Vitamin C aids in the body's ability to absorb iron, so taking oral iron supplements with orange juice is of benefit. In anemias of chronic disease, associated with chemotherapy, or associated with renal disease, some clinicians prescribe recombinant erythropoietin or epoetin alfa, to stimulate RBC production, although since there is also concurrent iron deficiency and inflammation present, parenteral iron is advised to be taken concurrently.

Overall, hemoglobin C disease is one of the more benign hemoglobinopathies. Mild-to-moderate reduction in RBC lifespan may accompany from mild hemolytic anemia. Individuals with hemoglobin C disease have sporadic episodes of musculoskeletal (joint) pain. People with hemoglobin C disease can expect to lead a normal life.

Much literature exists regarding the treatment of AIHA. Efficacy of treatment depends on the correct diagnosis of either warm- or cold-type AIHA.

Warm-type AIHA is usually a more insidious disease, not treatable by simply removing the underlying cause. Corticosteroids are first-line therapy. For those who fail to respond or have recurrent disease, splenectomy may be considered. Other options for recurrent or relapsed disease include immunosuppressants such as rituximab, danazol, cyclophosphamide, azathioprine, or cyclosporine.

Cold agglutinin disease is treated with avoidance of cold exposure. Patients with more severe disease (symptomatic anemia, transfusion dependence) may be treated with rituximab. Steroids and splenectomy are less efficacious in cold agglutinin disease.

Paroxysmal cold hemoglobinuria is treated by removing the underlying cause, such as infection.

Corticosteroids and immunoglobulins are two commonly used treatments for warm antibody AIHA. Initial medical treatment consists of prednisone. If ineffective, splenectomy should be considered.

If refractory to both these therapies, other options include rituximab, danazol, cyclosphosphamide, azathioprine, or ciclosporin.

High-dose intravenous immune globulin may be effective in controlling hemolysis, but the benefit is short lived (1–4 weeks), and the therapy is very expensive.

Usually no treatment is needed. Folic acid supplementation may help produce normal red blood cells and improve the symptoms of anemia

Genetic testing for the presence of mutations in protein molecules is considered to be a confirmatory testing technique. It is important to know the risks regarding the transmission and dangers of HPP.

Definitive therapy depends on the cause:

- Symptomatic treatment can be given by blood transfusion, if there is marked anemia. A positive Coombs test is a relative contraindication to transfuse the patient. In cold hemolytic anemia there is advantage in transfuse warmed blood

- In severe immune-related hemolytic anemia, steroid therapy is sometimes necessary.

- In steroid resistant cases, consideration can be given to rituximab or addition of an immunosuppressant ( azathioprine, cyclophosphamide)

- Association of methylprednisolone and intravenous immunoglobulin can control hemolysis in acute severe cases

- Sometimes splenectomy can be helpful where extravascular hemolysis, or hereditary spherocytosis, is predominant (i.e., most of the red blood cells are being removed by the spleen).

Untreated, severe aplastic anemia has a high risk of death. Modern treatment, by drugs or stem cell transplant, has a five-year survival rate that exceeds 85%, with younger age associated with higher survival.

Survival rates for stem cell transplant vary depending on age and availability of a well-matched donor. Five-year survival rates for patients who receive transplants have been shown to be 82% for patients under age 20, 72% for those 20–40 years old, and closer to 50% for patients over age 40. Success rates are better for patients who have donors that are matched siblings and worse for patients who receive their marrow from unrelated donors.

Older people (who are generally too frail to undergo bone marrow transplants), and people who are unable to find a good bone marrow match, undergoing immune suppression have five-year survival rates of up to 75%.

Relapses are common. Relapse following ATG/ciclosporin use can sometimes be treated with a repeated course of therapy. In addition, 10-15% of severe aplastic anemia cases evolve into MDS and leukemia. According to a study, for children who underwent immunosuppressive therapy, about 15.9% of children who responded to immunosuppressive therapy encountered relapse.

Milder disease can resolve on its own.

Treating immune-mediated aplastic anemia involves suppression of the immune system, an effect achieved by daily medicine intake, or, in more severe cases, a bone marrow transplant, a potential cure. The transplanted bone marrow replaces the failing bone marrow cells with new ones from a matching donor. The multipotent stem cells in the bone marrow reconstitute all three blood cell lines, giving the patient a new immune system, red blood cells, and platelets. However, besides the risk of graft failure, there is also a risk that the newly created white blood cells may attack the rest of the body ("graft-versus-host disease"). In young patients with an HLA matched sibling donor, bone marrow transplant can be considered as first-line treatment, patients lacking a matched sibling donor typically pursue immunosuppression as a first-line treatment, and matched unrelated donor transplants are considered a second-line therapy.

Medical therapy of aplastic anemia often includes a course of antithymocyte globulin (ATG) and several months of treatment with ciclosporin to modulate the immune system. Chemotherapy with agents such as cyclophosphamide may also be effective but has more toxicity than ATG. Antibody therapy, such as ATG, targets T-cells, which are believed to attack the bone marrow. Corticosteroids are generally ineffective, though they are used to ameliorate serum sickness caused by ATG. Normally, success is judged by bone marrow biopsy 6 months after initial treatment with ATG.

One prospective study involving cyclophosphamide was terminated early due to a high incidence of mortality, due to severe infections as a result of prolonged neutropenia.

In the past, before the above treatments became available, patients with low leukocyte counts were often confined to a sterile room or bubble (to reduce risk of infections), as in the case of Ted DeVita.

In all cases, the treatment of poikilocytosis depends on its cause. For example, poikilocytosis can be caused by a vitamin deficiency (e.g. vitamin B or folic acid), in which case the treatment is to replenish the deficient vitamin. It can be caused by a digestive disease, such as celiac disease, in which case the solution may lie in treating the underlying celiac disease so that nutrients can be properly absorbed.

In 2007, the drug eculizumab was approved for the treatment of PNH. It improves quality of life and decreases the need for blood transfusions but does not appear to affect the risk of death. It does not appear to change the risk of blood clots, myelodysplastic syndrome, acute myelogenous leukemia, or aplastic anemia.

Eculizumab is controversial due to its high cost, as it is among the most expensive pharmaceuticals in the world, with a price of US$440,000 per person per year. Eculizumab is a humanized monoclonal antibody that acts as a terminal complement inhibitor. The U.S. Food and Drug Administration (FDA) has issued a black-box warning for eculizumab whose recipients have a 1,000 to 2,000-fold greater risk of invasive meningococcal disease compared to the general U.S. population. Patients for whom eculizumab is prescribed are strongly advised by the FDA to receive meningococcal vaccination at least two weeks prior to starting therapy and to consider antimicrobial prophylaxis for the duration of treatment with eculizumab.