Transfusional hemosiderosis is the accumulation of iron in the liver and heart but also endocrine organs, in patients who receive or did receive frequent blood transfusions (such as those with thalassemia, sickle cell disease, leukemia, aplastic anemia or myelodysplastic syndrome).

Three main forms have been described: thalassemia major, thalassemia intermedia, and thalassemia minor. All people with thalassemia are susceptible to health complications that involve the spleen (which is often enlarged and frequently removed) and gallstones. These complications are mostly found in thalassemia major and intermedia patients. Individuals with beta thalassemia major usually present within the first two years of life with severe anemia, poor growth, and skeletal abnormalities during infancy. Untreated thalassemia major eventually leads to death, usually by heart failure; therefore, birth screening is very important.

Excess iron causes serious complications within the liver, heart, and endocrine glands. Severe symptoms include liver cirrhosis, liver fibrosis, and in extreme cases, liver cancer. Heart failure, growth impairment, diabetes and osteoporosis are life-threatening contributors brought upon by TM. The main cardiac abnormalities seen to have resulted from thalassemia and iron overload include left ventricular systolic and diastolic dysfunction, pulmonary hypertension, valveulopathies, arrhythmias, and pericarditis. Increased gastrointestinal iron absorption is seen in all grades of beta thalassemia and increased red blood cell destruction by the spleen due to ineffective erythropoiesis further releases additional iron into the bloodstream.

Hemosiderosis (AmE) or haemosiderosis (BrE) is a form of iron overload disorder resulting in the accumulation of hemosiderin.

Types include:

- Transfusion hemosiderosis

- Idiopathic pulmonary hemosiderosis

- Transfusional diabetes

Hemosiderin deposition in the lungs is often seen after diffuse alveolar hemorrhage, which occurs in diseases such as Goodpasture's syndrome, granulomatosis with polyangiitis, and idiopathic pulmonary hemosiderosis. Mitral stenosis can also lead to pulmonary hemosiderosis. Hemosiderin collects throughout the body in hemochromatosis. Hemosiderin deposition in the liver is a common feature of hemochromatosis and is the cause of liver failure in the disease. Selective iron deposition in the beta cells of pancreatic islets leads to diabetes due to distribution of transferrin receptor on the beta cells of islets and in the skin leads to hyperpigmentation. Hemosiderin deposition in the brain is seen after bleeds from any source, including chronic subdural hemorrhage, cerebral arteriovenous malformations, cavernous hemangiomata. Hemosiderin collects in the skin and is slowly removed after bruising; hemosiderin may remain in some conditions such as stasis dermatitis. Hemosiderin in the kidneys has been associated with marked hemolysis and a rare blood disorder called paroxysmal nocturnal hemoglobinuria.

Hemosiderin may deposit in diseases associated with iron overload. These diseases are typically diseases in which chronic blood loss requires frequent blood transfusions, such as sickle cell anemia and thalassemia, though beta thalassemia minor has been associated with hemosiderin deposits in the liver in those with non-alcoholic fatty liver disease independent of any transfusions.

The presentation of this disorder entails anemia, arthritis, hepatic anomalies, and recurrent infections are clinical signs of the disease. Iron overload occurs mainly in the liver, heart, pancreas, thyroid, and kidney

Ted DeVita died of transfusional iron overload from too many blood transfusions.

Atransferrinemia, also called familial hypotransferrinemia, is an autosomal recessive metabolic disorder in which there is an absence of transferrin, a plasma protein that transports iron through the blood.

Atransferrinemia is characterized by anemia and hemosiderosis in the heart and liver. The iron damage to the heart can lead to heart failure. The anemia is typically microcytic and hypochromic (the red blood cells are abnormally small and pale). Atransferrinemia was first described in 1961 and is extremely rare, with only ten documented cases worldwide.

Haemolytic crises are acute accelerated drops in haemoglobin level. The red blood cells break down at a faster rate. This is particularly common in patients with coexistent G6PD deficiency. Management is supportive, sometimes with blood transfusions.

Acute chest syndrome (ACS) is defined by at least two of the following signs or symptoms: chest pain, fever, pulmonary infiltrate or focal abnormality, respiratory symptoms, or hypoxemia. It is the second-most common complication and it accounts for about 25% of deaths in patients with SCD, majority of cases present with vaso-occlusive crises then they develop ACS. Nevertheless, about 80% of patients have vaso-occlusive crises during ACS.

Beta thalassemias (β thalassemias) are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to clinically asymptomatic individuals. Global annual incidence is estimated at one in 100,000. Beta thalassemias are caused by mutations in the "HBB" gene on chromosome 11, inherited in an autosomal recessive fashion. The severity of the disease depends on the nature of the mutation.

HBB blockage over time leads to decreased beta-chain synthesis. The body's inability to construct new beta-chains leads to the underproduction of HbA. Reductions in HbA available overall to fill the red blood cells in turn leads to microcytic anemia. Microcytic anemia ultimately develops in respect to inadequate HBB protein for sufficient red blood cell functioning. Due to this factor, the patient may require blood transfusions to make up for the blockage in the beta-chains. Repeated blood transfusions can lead to build-up of iron overload, ultimately resulting in iron toxicity. This iron toxicity can cause various problems, including myocardial siderosis and heart failure leading to the patient’s death.

There are several methods available for diagnosing and monitoring hemosiderosis including:

- Serum ferritin

- Liver biopsy

- MRI

Serum ferritin is a low cost, readily available, and minimally invasive method for assessing body iron stores. However, the major problem with using it as an indicator of hemosiderosis is that it can be elevated in a range of other medical conditions unrelated to iron levels including infection, inflammation, fever, liver disease, renal disease and cancer.

While liver biopsies provide a direct measure of liver iron concentration, the small sample size relative to the size of the liver can lead to sampling errors given the heterogeneity of iron concentration within the liver. Furthermore, the invasive nature of liver biopsy and the associated risks of complications (which can range from pain, haemorrhage, gallbladder perforation and other morbidities through to death in approx 1 in 10,000 cases) prevent it being used as a regular monitoring tool.

MRI is emerging as an alternative method for measuring liver iron loading because it is non-invasive, safer and generally cheaper to perform than liver biopsy; does not suffer from problems with sampling variability; and can be used more frequently than performing liver biopsies.

AIHA is classified as either warm autoimmune hemolytic anemia or cold autoimmune hemolytic anemia, which includes cold agglutinin disease and paroxysmal cold hemoglobinuria. These classifications are based on the characteristics of the autoantibodies involved in the pathogenesis of the disease. Each has a different underlying cause, management, and prognosis, making classification important when treating a patient with AIHA.

CDA type IV is characterized by mild to moderate splenomegaly. Hemoglobin is very low and patients are transfusion dependent. MCV is normal or mildly elevated. Erythropoiesis is normoblastic or mildly to moderately megaloblastic. Nonspecific erythroblast dysplasia is present.

Hemoglobin Barts, abbreviated Hb Barts, is an abnormal type of hemoglobin that consists of four gamma globins. It is moderately insoluble, and therefore accumulates in the red blood cells. It has an extremely high affinity for oxygen, resulting in almost no oxygen delivery to the tissues. As an embryo develops, it begins to produce alpha-globins at weeks 5-6 of development. When both HBA1 and HBA2, the two genes that code for alpha globins, are non-functional, only gamma globins are produced. These gamma globins bind to form hemoglobin Barts. It is produced in the disease alpha-thalassemia and in the most severe of cases, it is the only form of haemoglobin in circulation. In this situation, a fetus will develop hydrops fetalis and normally die before or shortly after birth, unless intrauterine blood transfusion is performed.

Since hemoglobin Barts is elevated in alpha thalassaemia, it can be measured, providing a useful screening test for this disease in some populations.

The ability to measure hemoglobin Barts makes it useful in newborn screening tests. If hemoglobin Barts is detected on a newborn screen, the patient is usually referred for further evaluation since detection of hemoglobin Barts can indicate either one alpha globin gene deletion, making the baby a silent alpha thalassemia carrier, two alpha globin gene deletions (alpha thalassemia), or hemoglobin H disease (three alpha globin gene deletions). Deletion of four alpha globin genes is not compatible with life.

This variant of hemoglobin is so called as it was discovered at St. Bartholomew's Hospital in London, also called St. Barts.

Hereditary stomatocytosis describes a number of inherited autosomal dominant human conditions which affect the red blood cell, in which the membrane or outer coating of the cell 'leaks' sodium and potassium ions.

Anemia of prematurity refers to a form of anemia affecting preterm infants with decreased hematocrit.

Autoimmune hemolytic anemia (or autoimmune haemolytic anaemia; AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases. The intracellular components of the RBCs are released into the circulating blood and into tissues, leading to some of the characteristic symptoms of this condition. The antibodies are usually directed against high-incidence antigens, therefore they also commonly act on allogenic RBCs (RBCs originating from outside the person themselves, e.g. in the case of a blood transfusion). AIHA is a relatively rare condition, affecting one to three people per 100,000 per year.

The terminology used in this disease is somewhat ambiguous. Although MeSH uses the term "autoimmune hemolytic anemia", some sources prefer the term "immunohemolytic anemia" so drug reactions can be included in this category. The National Cancer Institute considers "immunohemolytic anemia", "autoimmune hemolytic anemia", and "immune complex hemolytic anemia" to all be synonyms.

Congenital dyserythropoietic anemia type IV is an autosomal dominant inherited red blood cell disorder characterized by ineffective erythropoiesis and hemolysis resulting in anemia. Circulating erythroblasts and erythroblasts in the bone marrow show various morphologic abnormalities. Affected individuals with CDAN4 also have increased levels of fetal hemoglobin.

Reticulocytopenia, also known as an "aplastic crisis" or "marrow failure", is the medical term for an abnormal decrease of reticulocytes in the body. Reticulocytes are immature red blood cells. Reticulocytopenia may be a result of viral parvovirus B19 infection, which invades and destroys red blood cell precursors and halts the red cell production. If infection occurs in individuals with sickle cell anemia, spherocytosis, or Beta thalassemia that will lead to incorporation of two anemia-induced mechanisms: decreased red cell production and hemolysis. The result is a rapid and severe anemia (aplastic crisis) which may require blood transfusion.

Signs of hemolytic disease of the newborn include a positive direct Coombs test (also called direct agglutination test), elevated cord bilirubin, and hemolytic anemia. It is possible for a newborn with this disease to have neutropenia and neonatal alloimmune thrombocytopenia as well.Hemolysis leads to elevated bilirubin levels. After delivery bilirubin is no longer cleared (via the placenta) from the neonate's blood and the symptoms of jaundice (yellowish skin and yellow discoloration of the whites of the eyes) increase within 24 hours after birth. Like other severe neonatal jaundice, there is the possibility of acute or chronic kernicterus, however the risk of kernicterus is higher because of the rapid destruction of blood cells. It is important to note that isoimmunization is a risk factor for neurotoxicity and lowers the level at which kernicterus can occur. Untreated profound anemia can cause high-output heart failure, with pallor, enlarged liver and/or spleen, generalized swelling, and respiratory distress.

HDN can be the cause of hydrops fetalis, an often-severe form of prenatal heart failure that causes fetal edema.

Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis fetalis, is an alloimmune condition that develops in a fetus, when the IgG molecules (one of the five main types of antibodies) produced by the mother pass through the placenta. Among these antibodies are some which attack antigens on the red blood cells in the fetal circulation, breaking down and destroying the cells (hemolysis). The fetus can develop reticulocytosis and anemia. This fetal disease ranges from mild to very severe, and fetal death from heart failure (hydrops fetalis) can occur. When the disease is moderate or severe, many erythroblasts (immature red blood cells) are present in the fetal blood, and so these forms of the disease can be called "erythroblastosis fetalis" (or "erythroblastosis foetalis").

HDFN represents a breach of immune privilege for the fetus or some other form of impairment of the immune tolerance of pregnancy. Various types of HDFN are classified by which alloantigen provokes the response. In order of incidence, the types include ABO, anti-RhD, anti-RhE, anti-Rhc, anti-Rhe, anti-RhC, multiantigen combinations, and anti-Kell.

People with PCH, a polyclonal IgG anti-P autoantibody binds to red blood cell surface antigens in the cold. This can occur in a susceptible individual as blood passes through cold extremities in cold weather. When the blood returns to the warmer central circulation, the red blood cells are lysed with complement, causing intravascular hemolysis. Hemoglobinuria and anemia can then occur. The anemia may be mild or severe.

Pancytopenia is a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets.

If only two parameters from the full blood count are low, the term bicytopenia can be used. The diagnostic approach is the same as for pancytopenia.

Acute PCH tends to be transient and self-limited, particularly in children. Chronic PCH associated with syphilis resolves after the syphilis is treated with appropriate antibiotics. Chronic idiopathic PCH is usually mild.

Haematologists have identified a number of variants. These can be classified as below.

- Overhydrated hereditary stomatocytosis

- Dehydrated HSt (hereditary xerocytosis; hereditary hyperphosphatidylcholine haemolytic anaemia)

- Dehydrated with perinatal ascites

- Cryohydrocytosis

- 'Blackburn' variant.

- Familial pseudohyperkalaemia

There are other families that do not fall neatly into any of these classifications.

Stomatocytosis is also found as a hereditary disease in Alaskan malamute and miniature schnauzer dogs.

In ABO hemolytic disease of the newborn (also known as ABO HDN) maternal IgG antibodies with specificity for the ABO blood group system pass through the placenta to the fetal circulation where they can cause hemolysis of fetal red blood cells which can lead to fetal anemia and HDN. In contrast to Rh disease, about half of the cases of ABO HDN occur in a firstborn baby and ABO HDN does not become more severe after further pregnancies.

The ABO blood group system is the best known surface antigen system, expressed on a wide variety of human cells. For Caucasian populations about one fifth of all pregnancies have ABO incompatibility between the fetus and the mother, but only a very small minority develop symptomatic ABO HDN. The latter typically only occurs in mothers of blood group O, because they can produce enough IgG antibodies to cause hemolysis.

Although very uncommon, cases of ABO HDN have been reported in infants born to mothers with blood groups A and B.