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.

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.

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.

Sickle cell trait provides a survival advantage over people with normal hemoglobin in regions where malaria is endemic. The trait is known to cause significantly fewer deaths due to malaria, especially when "Plasmodium falciparum" is the causative organism. This is a prime example of natural selection, evidenced by the fact that the geographical distribution of the gene for hemoglobin S and the distribution of malaria in Africa virtually overlap. Because of the unique survival advantage, people with the trait become increasingly numerous as the number of malaria-infected people increases. Conversely, people who have normal hemoglobin tend to succumb to the complications of malaria.

Although the precise mechanism for this phenomenon is not known, a several factors are believed to be responsible.

- Infected erythrocytes (red blood cells) tend to have lower oxygen tension, because it is significantly reduced by the parasite. This causes sickling of that particular erythrocyte, signalling the phagocytes to get rid of the cell and hence the parasite within.

- Since the sickling of parasite-infected cells is higher, these selectively get removed by the reticulo-endothelial system, thus sparing the normal erythrocytes.

- Excessive vacuole formation occurs in those parasites infecting sickle cells.

- Sickle trait erythrocytes produce higher levels of the superoxide anion and hydrogen peroxide than normal erythrocytes do, both are toxic to malarial parasites.

The sickle cell trait was found to be 50% protective against mild clinical malaria, 75% protective against admission to the hospital for malaria, and almost 90% protective against severe or complicated malaria.

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.

PNH is rare, with an annual rate of 1-2 cases per million. The prognosis without disease-modifying treatment is 10–20 years. Many cases develop in people who have previously been diagnosed with aplastic anemia or myelodysplastic syndrome. The fact that PNH develops in MDS also explains why there appears to be a higher rate of leukemia in PNH, as MDS can sometimes transform into leukemia.

25% of female cases of PNH are discovered during pregnancy. This group has a high rate of thrombosis, and the risk of death of both mother and child are significantly increased (20% and 8% respectively).

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.

About 90% of people survive to age 20, and close to 50% survive beyond the fifth decade. In 2001, according to one study performed in Jamaica, the estimated mean survival for people with sickle-cell was 53 years old for men and 58 years old for women with homozygous SCD. The specific life expectancy in much of the developing world is unknown.

The thalassemia trait may confer a degree of protection against malaria, which is or was prevalent in the regions where the trait is common, thus conferring a selective survival advantage on carriers (known as heterozygous advantage), thus perpetuating the mutation. In that respect, the various thalassemias resemble another genetic disorder affecting hemoglobin, sickle-cell disease.

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.

Sickle-cell anaemia can lead to various complications, including:

- Increased risk of severe bacterial infections due to loss of functioning spleen tissue (and comparable to the risk of infections after having the spleen removed surgically). These infections are typically caused by encapsulated organisms such as "Streptococcus pneumoniae" and "Haemophilus influenzae". Daily penicillin prophylaxis is the most commonly used treatment during childhood, with some haematologists continuing treatment indefinitely. Patients benefit today from routine vaccination for "S. pneumoniae".

- Stroke, which can result from a progressive narrowing of blood vessels, prevents oxygen from reaching the brain. Cerebral infarction occurs in children and cerebral haemorrhage in adults.

- Silent stroke causes no immediate symptoms, but is associated with damage to the brain. Silent stroke is probably five times as common as symptomatic stroke. About 10–15% of children with SCD suffer strokes, with silent strokes predominating in the younger patients.

- Cholelithiasis (gallstones) and cholecystitis may result from excessive bilirubin production and precipitation due to prolonged haemolysis.

- Avascular necrosis (aseptic bone necrosis) of the hip and other major joints may occur as a result of ischaemia.

- Decreased immune reactions due to hyposplenism (malfunctioning of the spleen)

- Priapism and infarction of the penis

- Osteomyelitis (bacterial bone infection), the most common cause of osteomyelitis in SCD is "Salmonella" (especially the atypical serotypes "Salmonella typhimurium, Salmonella enteritidis, Salmonella choleraesuis" and "Salmonella paratyphi" B), followed by "Staphylococcus aureus" and Gram-negative enteric bacilli perhaps because intravascular sickling of the bowel leads to patchy ischaemic infarction.

- Acute papillary necrosis in the kidneys

- Leg ulcers

- In eyes, background retinopathy, proliferative retinopathy, vitreous haemorrhages, and retinal detachments can result in blindness. Regular annual eye checks are recommended.

- During pregnancy, intrauterine growth retardation, spontaneous abortion, and pre-eclampsia

- Chronic pain: Even in the absence of acute vaso-occlusive pain, many patients have unreported chronic pain.

- Pulmonary hypertension (increased pressure on the pulmonary artery) can lead to strain on the right ventricle and a risk of heart failure; typical symptoms are shortness of breath, decreased exercise tolerance, and episodes of syncope. 21% of children and 30% of adults have evidence of pulmonary hypertension when tested; this is associated with reduced walking distance and increased mortality.

- Chronic kidney failure due to sickle-cell nephropathy manifests itself with hypertension, protein loss in the urine, loss of red blood cells in urine and worsened anaemia. If it progresses to end-stage renal failure, it carries a poor prognosis.

The disorder affects all genders but is more prevalent in certain ethnicities and age groups. 20 people die per year causing thalassemia to be listed as a “rare disease”. In the United States, thalassemia’s prevalence is approximately 1 in 272,000 or 1,000 people. There have been 4,000 hospitalized cases in England in 2002 and 9,233 consultant episodes for thalassemia. Men accounted for 53% of hospital consultant episodes and women accounted for 47%. The mean patient age is 23 with only 1% of consultants the patient is older than 75 and 69% were 15-59 year olds. The Children’s Hospital Oakland formed an international network to combat thalassemia. “It is the world’s most common genetic blood disorder and is rapidly increasing”. 7% of the world’s population are carriers and 400,000 babies are born with the trait annually. It is usually fatal in infancy if blood transfusion are not initiated immediately.

Acquired hemolytic anemia can be divided into immune and non-immune mediated forms of hemolytic anemia.

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.

Acquired hemolytic anemia may be caused by immune-mediated causes, drugs and other miscellaneous causes.

- Immune-mediated causes could include transient factors as in "Mycoplasma pneumoniae" infection (cold agglutinin disease) or permanent factors as in autoimmune diseases like autoimmune hemolytic anemia (itself more common in diseases such as systemic lupus erythematosus, rheumatoid arthritis, Hodgkin's lymphoma, and chronic lymphocytic leukemia).

- Spur cell hemolytic anemia

- Any of the causes of hypersplenism (increased activity of the spleen), such as portal hypertension.

- Acquired hemolytic anemia is also encountered in burns and as a result of certain infections (e.g. malaria).

- Lead poisoning resulting from the environment causes non-immune hemolytic anemia.

- Runners can suffer hemolytic anemia due to "footstrike hemolysis", owing to the destruction of red blood cells in feet at foot impact.

- Low-grade hemolytic anemia occurs in 70% of prosthetic heart valve recipients, and severe hemolytic anemia occurs in 3%.

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.

Absence of effective splenic function or absence of the whole spleen (asplenia) is associated with increased risks of overwhelming post splenectomy infection, especially from polysaccharide encapsulated bacteria and organisms that invade erythrocytes. People without a spleen have a weakened immune system, although other immune organs compensate for the missing spleen. Vaccination against encapsulated bacteria and prophylactic antibiotics can be used to counteract lowered immunity in asplenic patients. Specifically, people without a spleen are recommended to be vaccinated against pneumonia, influenza, Haemophilus influenza type b and meningococci.

Hypochromic anemia occurs in patients with hypochromic microcytic anemia with iron overload. The condition is autosomal recessive and is caused by mutations in the SLC11A2 gene. The condition prevents red blood cells from accessing iron in the blood, which causes anemia that is apparent at birth. It can lead to pallor, fatigue, and slow growth. The iron overload aspect of the disorder means that the iron accumulates in the liver and can cause liver impairment in adolescence or early adulthood.

It also occurs in patients with hereditary iron refractory iron-deficiency anemia (IRIDA). Patients with IRIDA have very low serum iron and transferrin saturation, but their serum ferritin is normal or high. The anemia is usually moderate in severity and presents later in childhood.

Hypochromic anemia is also caused by thalassemia and congenital disorders like Benjamin anemia.

Pneumococcal septicemia, or whole-body infection caused by the "Streptococcus pneumoniae" bacteria, has been reported to cause autosplenectomy but is a very rare and poorly understood complication of the infection.

Limiting some microbes' access to iron can reduce their virulence, thereby potentially reducing the severity of infection. Blood transfusion to patients with anemia of chronic disease is associated with a higher mortality, supporting the concept.

Many substances are potentially harmful to people with G6PD deficiency. Variation in response to these substances makes individual predictions difficult. Antimalarial drugs that can cause acute hemolysis in people with G6PD deficiency include primaquine, pamaquine, and chloroquine. There is evidence that other antimalarials may also exacerbate G6PD deficiency, but only at higher doses. Sulfonamides (such as sulfanilamide, sulfamethoxazole, and mafenide), thiazolesulfone, methylene blue, and naphthalene should also be avoided by people with G6PD deficiency as they antagonize folate synthesis, as should certain analgesics (such as phenazopyridine and acetanilide) and a few non-sulfa antibiotics (nalidixic acid, nitrofurantoin, isoniazid, dapsone, and furazolidone). Henna has been known to cause hemolytic crisis in G6PD-deficient infants. Rasburicase is also contraindicated in G6PD deficiency. High dose intravenous vitamin C has also been known to cause haemolysis in G6PD deficiency carriers, thus G6PD deficiency testing is routine before infusion of doses of 25g or more.

Hypochromic anemia may be caused by vitamin B6 deficiency from a low iron intake, diminished iron absorption, or excessive iron loss. It can also be caused by infections (e.g. hookworms) or other diseases (i.e. anemia of chronic disease), therapeutic drugs, copper toxicity, and lead poisoning. One acquired form of anemia is also known as Faber's syndrome. It may also occur from severe stomach or intestinal bleeding caused by ulcers or medications such as aspirin or bleeding from hemorrhoids.

Hemoglobin C gene is found in 2-3% of US African-Americans while 8% of US African \-Americans have hemoglobin S (Sickle) gene. Thus Hemoglobin SC disease is significantly more common than Hemoglobin CC disease. Hemoglobin C is found in areas of West Africa, such as Nigeria, where Yorubas live.

About 1 out of every 40 African-Americans has hemoglobin C trait. The trait also affects people whose ancestors came from Italy, Greece, Africa, Latin America, and the Caribbean region. However, it is possible for a person of any race or nationality to have hemoglobin C trait. In terms of geographic distribution, the hemoglobin C allele is found at the highest frequencies in West Africa, where it has been associated with protection against malaria. Hemoglobin C disease is present at birth, though some cases may not be diagnosed until adulthood. Both sexes, male and female, are affected equally.

In 2003, the incidence of Rh(D) sensitization in the United States was 6.8 per 1000 live births; 0.27% of women with an Rh incompatible fetus experience alloimmunization.

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).