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%.

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.

Certain gastrointestinal disorders can cause anemia. The mechanisms involved are multifactorial and not limited to malabsorption but mainly related to chronic intestinal inflammation, which causes dysregulation of hepcidin that leads to decreased access of iron to the circulation.

- "Helicobacter pylori" infection.

- Gluten-related disorders: untreated celiac disease and non-celiac gluten sensitivity. Anemia can be the only manifestation of celiac disease, in absence of gastrointestinal or any other symptoms.

- Inflammatory bowel disease.

Basically classified by causative mechanism, types of congenital hemolytic anemia include:

- Genetic conditions of RBC Membrane

- Hereditary spherocytosis

- Hereditary elliptocytosis

- Genetic conditions of RBC metabolism (enzyme defects). This group is sometimes called "congenital nonspherocytic (hemolytic) anemia", which is a term for a congenital hemolytic anemia without spherocytosis, and usually excluding hemoglobin abnormalities as well, but rather encompassing defects of glycolysis in the erythrocyte.

- Glucose-6-phosphate dehydrogenase deficiency (G6PD or favism)

- Pyruvate kinase deficiency

- Aldolase A deficiency

- Hemoglobinopathies/genetic conditions of hemoglobin

- Sickle cell anemia

- Congenital dyserythropoietic anemia

- Thalassemia

Fluid overload (hypervolemia) causes decreased hemoglobin concentration and apparent anemia:

- General causes of hypervolemia include excessive sodium or fluid intake, sodium or water retention and fluid shift into the intravascular space.

Typical causes of microcytic anemia include:

- Childhood

- Iron deficiency anemia, by far the most common cause of anemia in general and of microcytic anemia in particular

- Thalassemia

- Adulthood

- Iron deficiency anemia

- Sideroblastic anemia, In congenital sideroblastic anemia the MCV (mean corpuscular volume) is either low or normal. In contrast, the MCV is usually high in the much more common acquired sideroblastic anemia.

- Anemia of chronic disease, although this more typically causes normochromic, normocytic anemia. Microcytic anemia has been discussed by Weng et al.

- Lead poisoning

- Vitamin B (pyridoxine) deficiency

Other causes that are typically thought of as causing normocytic anemia or macrocytic anemia must also be considered, and the presence of two or more causes of anemia can distort the typical picture.

There are five main causes of microcytic anemia forming the acronym TAILS. Thalassemia, Anemia of chronic disease, Iron deficiency, Lead poisoning and Congenital sideroblastic anemia. Only the first three are common in most parts of the world. In theory, these three can be differentiated by their red blood cell (RBC) morphologies. Anemia of chronic disease shows unremarkable RBCs, iron deficiency shows anisocytosis, anisochromia and elliptocytosis, and thalessemias demonstrate target cells and coarse basophilic stippling. In practice though elliptocytes and anisocytosis are often seen in thalessemia and target cells occasionally in iron deficiency. All three may show unremarkable RBC morphology. Coarse basophlic stippling is one reliable morphologic finding of thalessemia which does not appear in iron deficiency or anemia of chronic disease. The patient should be in an ethnically at risk group and the diagnosis is not confirmed without a confirmatory method such as hemoglobin HPLC, H body staining, molecular testing or another reliable method. Course basophlic stippling occurs in other cases as seen in Table 1

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.

Aplastic anemia can be caused by exposure to certain chemicals, drugs, radiation, infection, immune disease; in about half the cases, yet a defintive cause is unknown. It is not a familial line hereditary condition, nor is it contagious. It can be acquired due to exposure to other conditions but if a person develops the condition, their offspring would not develop it by virtue of their gene connection.

Aplastic anemia is also sometimes associated with exposure to toxins such as benzene, or with the use of certain drugs, including chloramphenicol, carbamazepine, felbamate, phenytoin, quinine, and phenylbutazone. Many drugs are associated with aplasia mainly according to case reports, but at a very low probability. As an example, chloramphenicol treatment is followed by aplasia in less than one in 40,000 treatment courses, and carbamazepine aplasia is even rarer.

Exposure to ionizing radiation from radioactive materials or radiation-producing devices is also associated with the development of aplastic anemia. Marie Curie, famous for her pioneering work in the field of radioactivity, died of aplastic anemia after working unprotected with radioactive materials for a long period of time; the damaging effects of ionizing radiation were not then known.

Aplastic anemia is present in up to 2% of patients with acute viral hepatitis.

One known cause is an autoimmune disorder in which white blood cells attack the bone marrow.

Short-lived aplastic anemia can also be a result of parvovirus infection. In humans, the P antigen (also known as globoside), one of the many cellular receptors that contribute to a person's blood type, is the cellular receptor for parvovirus B19 virus that causes erythema infectiosum (fifth disease) in children. Because it infects red blood cells as a result of the affinity for the P antigen, Parvovirus causes complete cessation of red blood cell production. In most cases, this goes unnoticed, as red blood cells live on average 120 days, and the drop in production does not significantly affect the total number of circulating red blood cells. In people with conditions where the cells die early (such as sickle cell disease), however, parvovirus infection can lead to severe anemia.

More frequently parvovirus B19 is associated with aplastic crisis which involves only the red blood cells ( despite the name). Aplastic anemia involves all different cell lines.

In some animals, aplastic anemia may have other causes. For example, in the ferret ("Mustela putorius furo"), it is caused by estrogen toxicity, because female ferrets are induced ovulators, so mating is required to bring the female out of heat. Intact females, if not mated, will remain in heat, and after some time the high levels of estrogen will cause the bone marrow to stop producing red blood cells.

Blood contains iron within red blood cells, so blood loss leads to a loss of iron. There are several common causes of blood loss. Women with menorrhagia (heavy menstrual periods) are at risk of iron-deficiency anemia because they are at higher-than-normal risk of losing a larger amount blood during menstruation than is replaced in their diet. Slow, chronic blood loss within the body — such as from a peptic ulcer, angiodysplasia, a colon polyp or gastrointestinal cancer, or excessively heavy periods — can cause iron-deficiency anemia. Gastrointestinal bleeding can result from regular use of some groups of medication, such as NSAIDs (e.g. aspirin), as well as anticoagulants such as clopidogrel and warfarin; however, these are required in some patients, especially those with states causing thrombophilia.

The issue is thought of as representing any of the following:

- a decreased production of normal-sized red blood cells (e.g., anemia of chronic disease, aplastic anemia);

- an increased production of HbS as seen in sickle cell disease (not sickle cell trait);

- an increased destruction or loss of red blood cells (e.g., hemolysis, posthemorrhagic anemia);

- an uncompensated increase in plasma volume (e.g., pregnancy, fluid overload);

- a B2 (riboflavin) deficiency

- a B6 (pyridoxine) deficiency

- or a mixture of conditions producing microcytic and macrocytic anemia.

Blood loss, suppressed production of RBCs or hemolysis represent most cases of normocytic anemia. In blood loss, morphologic findings are generally unremarkable except after 12 to 24 hrs where polychromasia appears. For reduced production of RBCs, like with low erythropoietin, the RBC morphology is unremarkable. Patients with disordered RBC production, e.g. myelodysplastic syndrome, may have a dual population of elliptocytes, teardrop cells, or other poikilocytes as well as a nucleated RBCs. Hemolysis will often demonstrate poikilocytes specific to a cause or mechanism. E.g. Bite cells and/or blistor cells for oxidative hemolysis, Acanthocytes for pyruvate kinase deficiency or McLeod phenotype, Sickle cells for sickle cell anemia, Spherocytes for immune-mediated hemolysis or hereditary spherocytosis, Elliptocytosis for iron deficiency or hereditary elliptocytosis and schistocytes for intravascular hemolysis. Many hemolytic anemias show multiple poikilocytes such as G6PD deficiency which may show blister and bites cells as well as shistocytes. Neonatal hemolysis may not follow the classic patterns as in adults

A moderate degree of iron-deficiency anemia affects approximately 610 million people worldwide or 8.8% of the population. It is slightly more common in females (9.9%) than males (7.8%). Mild iron deficiency anemia affects another 375 million.

The prevalence of iron deficiency as a cause of anemia varies among countries; in the groups in which anemia is most common, including young children and a subset of non-pregnant women, iron deficiency accounts for a fraction of anemia cases in these groups ("25% and 37%, respectively"). Iron deficiency is a more common cause of anemia in other groups, including pregnant women.

Within the United States, iron-deficiency anemia affects about 2% of adult males, 10.5% of Caucasian women, and 20% of African-American and Mexican-American women.

Causes of sideroblastic anemia can be categorized into three groups: congenital sideroblastic anemia, acquired clonal sideroblastic anemia, and acquired reversible sideroblastic anemia. All cases involve dysfunctional heme synthesis or processing. This leads to granular deposition of iron in the mitochondria that form a ring around the nucleus of the developing red blood cell. Congenital forms often present with normocytic or microcytic anemia while acquired forms of sideroblastic anemia are often normocytic or macrocytic.

- Congenital sideroblastic anemia

- X-linked sideroblastic anemia: This is the most common congenital cause of sideroblastic anemia and involves a defect in ALAS2, which is involved in the first step of heme synthesis. Although X-linked, approximately one third of patients are women due to skewed X-inactivation (lyonizations).

- Autosomal recessive sideroblastic anemia involves mutations in the SLC25A38 gene. The function of this protein is not fully understood, but it is involved in mitochondrial transport of glycine. Glycine is a substrate for ALAS2 and necessary for heme synthesis. The autosomal recessive form is typically severe in presentation.

- Genetic syndromes: Rarely, sideroblastic anemia may be part of a congenital syndrome and present with associated findings, such as ataxia, myopathy, and pancreatic insufficiency.

- Acquired clonal sideroblastic anemia

- Clonal sideroblastic anemias fall under the broader category of myelodysplastic syndromes (MDS). Three forms exist and include refractory anemia with ringed sideroblasts (RARS), refractory anemia with ringed sideroblasts and thrombocytosis (RARS-T), and refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS). These anemias are associated with increased risk for leukemic evolution.

- Acquired reversible sideroblastic anemia

- Causes include excessive alcohol use (the most common cause of sideroblastic anemia), pyridoxine deficiency, lead poisoning, and copper deficiency. Excess zinc can indirectly cause sideroblastic anemia by decreasing absorption and increasing excretion of copper. Antimicrobials that may lead to sideroblastic anemia include isoniazid, chloramphenicol, cycloserine, and linezolid.

Sideroblastic anemias are often described as responsive or non-responsive in terms of increased hemoglobin levels to pharmacological doses of vitamin B.

1- Congenital: 80% are responsive, though the anemia does not completely resolve.

2- Acquired clonal: 40% are responsive, but the response may be minimal.

3- Acquired reversible: 60% are responsive, but course depends on treatment of the underlying cause.

Severe refractory sideroblastic anemias requiring regular transfusions and/or that undergo leukemic transformation (5-10%) significantly reduce life expectancy.

A normocytic anemia is defined as an anemia with a mean corpuscular volume (MCV) of 80–100 which is the normal range. However, the hematocrit and hemoglobin is decreased.

Mild macrocytosis is a common finding associated with rapid blood restoration or production, since in general, "fresh" or newly produced red cells (reticulocytes) are larger than the mean (average) size, due to slow shrinkage of normal cells over a normal red cell circulating lifetime. Thus, chronic obstructive pulmonary disease (COPD), in which red cells are rapidly produced in response to low oxygen levels in the blood, often produces mild macrocytosis. Also, rapid blood replacement from the marrow after a traumatic blood loss, or rapid red blood cell turnover from rapid hemolysis (G6PD deficiency), also often produces mild macrocytosis in the associated anemia.

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).

Round macrocytes which are not codocytes are produced in chronic alcoholism (which produces a mild macrocytosis even in the absence of vitamin deficiency), apparently as a direct toxic effect of alcohol specifically on the bone marrow.

Anisocytosis is identified by RDW and is classified according to the size of RBC measured by MCV. According to this, it can be divided into

- Anisocytosis with microcytosis – Iron deficiency, sickle cell anemia

- Anisocytosis with macrocytosis – Folate or vitamin B deficiency, autoimmune hemolytic anemia, cytotoxic chemotherapy, chronic liver disease, myelodysplastic syndrome

Increased RDW is seen in iron deficiency anemia and decreased or normal in thalassemia major (Cooley's anemia), thalassemia intermedia

- Anisocytosis with normal RBC size – Early iron, vit B12 or folate deficiency, dimorphic anemia, Sickle cell disease, chronic liver disease, Myelodysplastic syndrome

Runner’s macrocytosis is a phenomenon of increased red blood cell size as a compensatory mechanism for increased red blood cell turnover. The impact forces from running can lead to red blood cell hemolysis and accelerate red blood cell production. This can shift the ratio of red blood cells towards younger, larger cells. This shift may be reflected in higher than normal mean corpuscular volume (MCV) values, an indicator of red blood cell size.

This is not a pathological condition but may indicate a propensity toward iron deficiency anemia due to high red blood cell turnover.

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.

Microcytic anemia is not caused by reduced DNA synthesis.

Thalassemia can cause microcytosis. Depending upon how the terms are being defined, thalassemia can be considered a cause of microcytic anemia, or it can be considered a cause of microcytosis but not a cause of microcytic anemia.

There are many causes of microcytosis, which is essentially only a descriptor. Cells can be small because of mutations in the formation of blood cells (hereditary microcytosis) or because they are not filled with enough hemoglobin, as in iron-deficiency-associated microcytosis.

Red blood cells can be characterised by their haemoglobin content as well as by their size. The haemoglobin content is referred to as the cell's colour. Therefore, there are both "normochromic microcytotic red cells" and "hypochromic, microcytotic red cells". The normochromic cells have a normal concentration of haemoglobin, and are therefore 'red enough' while the hypochromic cells do not; thus the value of the mean corpuscular hemoglobin concentration.

Microcytic anaemia is any of several types of anaemia characterized by small red blood cells (called microcytes). The normal mean corpuscular volume (abbreviated to MCV on full blood count results) is 80-100 fL, with smaller cells (100 fL) as macrocytic (the latter occur in macrocytic anemia).The MCV is the average red blood cell size.

In microcytic anaemia, the red blood cells (erythrocytes) are usually also hypochromic, meaning that the red blood cells appear paler than usual. This is reflected by a lower-than-normal mean corpuscular hemoglobin concentration (MCHC), a measure representing the amount of hemoglobin per unit volume of fluid inside the cell; normally about 320-360 g/L or 32-36 g/dL. Typically, therefore, anemia of this category is described as "microcytic, hypochromic anaemia".

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.

Repetitive impacts to the body may cause mechanical trauma and bursting (hemolysis) of red blood cells. This has been documented to have occurred in the feet during running and hands from Conga or Candombe drumming. Defects in red blood cell membrane proteins have been identified in some of these patients. Free haemoglobin is released from lysed red blood cells and filtered into the urine.

A person with well-treated PA can live a healthy life. Failure to diagnose and treat in time, however, may result in permanent neurological damage, excessive fatigue, depression, memory loss, and other complications. In severe cases, the neurological complications of pernicious anemia can lead to death - hence the name, "", meaning deadly.

An association has been observed between pernicious anemia and certain types of gastric cancer, but a causal link has not been established.