The body normally gets the iron it requires from foods. If a person consumes too little iron, or iron that is poorly absorbed (non-heme iron), they can become iron deficient over time. Examples of iron-rich foods include meat, eggs, leafy green vegetables and iron-fortified foods. For proper growth and development, infants and children need iron from their diet. A high intake of cow’s milk is associated with an increased risk of iron-deficiency anemia. Other risk factors for iron-deficiency anemia include low meat intake and low intake of iron-fortified products.

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.

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.

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.

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.

There are many studies about LID and the frequency varies according to country of origin, diet, pregnancy status age, gender, etc. Depending on these previous conditions, the frequency can change from 11% in male athletes (Poland) to 44.7% in children less than 1 year old (China):

Frequency of LID in different countries and populations:

- Poland: 14 of LID (11%) in 131 male athletes and 31 of ID (26%) in 121 female athletes

- India: 27.5% of LID amongst student nurses

- Spain: 14.7% of LID in 211 women of child-bearing age in Barcelona

- China: In 3591 pregnant women and 3721 premenopausal from 15 provinces. It was found: LID 42.6% in pregnant women (urban first-trimester 41.9%) (rural 36.1%) while 34.4% of LID in premenopausal non-pregnant women (urban 35.6%)(rural 32.4%). Pediatric samples: In 9118 children from 31 provinces aged 7 months to 7 years, the global incidence of LID in children was 32.5%. Sub-classifying the cases according to age and origin (global/countryside): less than 1 y (7m to 12m) LID 44.7% (35.8% in countryside), 1 – 3 years LID 35.9% (31% in countryside), 4 to 7 years (LID 26.5%) (30.1% in countryside).

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

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.

PA is estimated to affect 0.1% of the general population and 1.9% of those over 60, accounting for 20–50% of B deficiency in adults. A review of literature shows that the prevalence of PA is higher in Northern Europe, especially in Scandinavian countries, and among people of African descent, and that increased awareness of the disease and better diagnostic tools might play a role in apparently higher rates of incidence.

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

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.

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.

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.

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

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.

Congenital hemolytic anemia (or hereditary hemolytic anemia) refers to hemolytic anemia which is primarily due to congenital disorders.

There is no consensus on how to treat LID but one of the options is to treat it as an iron-deficiency anemia with ferrous sulfate (Iron(II) sulfate) at a dose of 100 mg x day in two doses (one at breakfast and the other at dinner) or 3 mg x Kg x day in children (also in two doses) during two or three months. The ideal would be to increase the deposits of body iron, measured as levels of ferritin in serum, trying to achieve a ferritin value between 30 and 100 ng/mL. Another clinical study has shown an increase of ferritin levels in those taking iron compared with others receiving a placebo from persons with LID. With ferritin levels higher than 100 ng/mL an increase in infections, etc. has been reported. Another way to treat LID is with an iron rich diet and in addition ascorbic acid or Vitamin C, contained in many types of fruits as oranges, kiwifruits, etc. that will increase 2 to 5-fold iron absorption.

Iron is needed for bacterial growth making its bioavailability an important factor in controlling infection. Blood plasma as a result carries iron tightly bound to transferrin, which is taken up by cells by endocytosing transferrin, thus preventing its access to bacteria. Between 15 and 20 percent of the protein content in human milk consists of lactoferrin that binds iron. As a comparison, in cow's milk, this is only 2 percent. As a result, breast fed babies have fewer infections. Lactoferrin is also concentrated in tears, saliva and at wounds to bind iron to limit bacterial growth. Egg white contains 12% conalbumin to withhold it from bacteria that get through the egg shell (for this reason, prior to antibiotics, egg white was used to treat infections).

To reduce bacterial growth, plasma concentrations of iron are lowered in a variety of systemic inflammatory states due to increased production of hepcidin which is mainly released by the liver in response to increased production of pro-inflammatory cytokines such as Interleukin-6. This functional iron deficiency will resolve once the source of inflammation is rectified; however, if not resolved, it can progress to Anaemia of Chronic Inflammation. The underlying inflammation can be caused by fever, inflammatory bowel disease, infections, Chronic Heart Failure (CHF), carcinomas, or following surgery.

Reflecting this link between iron bioavailability and bacterial growth, the taking of oral iron supplements in excess of 200 mg/day causes a relative overabundance of iron that can alter the types of bacteria that are present within the gut. There have been concerns regarding parenteral iron being administered whilst bacteremia is present, although this has not been borne out in clinical practice. A moderate iron deficiency, in contrast, can provide protection against acute infection, especially against organisms that reside within hepatocytes and macrophages, such as malaria and tuberculosis. This is mainly beneficial in regions with a high prevalence of these diseases and where standard treatment is unavailable.

Megaloblastic anemia (or megaloblastic anaemia) is an anemia (of macrocytic classification) that results from inhibition of DNA synthesis during red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing cell growth without division, which presents as macrocytosis.

Megaloblastic anemia has a rather slow onset, especially when compared to that of other anemias.

The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically a deficiency of vitamin B and/or folic acid. Vitamin B deficiency alone will not cause the syndrome in the presence of sufficient folate, as the mechanism is loss of B dependent folate recycling, followed by folate-deficiency loss of nucleic acid synthesis (specifically thymine), leading to defects in DNA synthesis. Folic acid supplementation in the absence of vitamin B prevents this type of anemia (although other vitamin B-specific pathologies may be present). Loss of micronutrients may also be a cause. Copper deficiency resulting from an excess of zinc from unusually high oral consumption of zinc-containing denture-fixation creams has been found to be a cause.

Megaloblastic anemia not due to hypovitaminosis may be caused by antimetabolites that poison DNA production directly, such as some chemotherapeutic or antimicrobial agents (for example azathioprine or trimethoprim).

The pathological state of megaloblastosis is characterized by many large immature and dysfunctional red blood cells (megaloblasts) in the bone marrow and also by hypersegmented neutrophils (those exhibiting five or more nuclear lobes ("segments"), with up to four lobes being normal). These hypersegmented neutrophils can be detected in the peripheral blood (using a diagnostic smear of a blood sample).

Though genetic defects causing iron deficiency have been studied in rodents, there are no known genetic disorders of human iron metabolism that directly cause iron deficiency.

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.

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.

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.

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.