Anemia

Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin available for oxygen transport, or abnormalities in hemoglobin that impair its function. When anemia comes on slowly, the symptoms are often vague, such as tiredness, weakness, shortness of breath, headaches, and a reduced ability to exercise. When anemia is acute, symptoms may include confusion, feeling like one is going to pass out, loss of consciousness, and increased thirst. Anemia must be significant before a person becomes noticeably pale. Additional symptoms may occur depending on the underlying cause. Anemia can be temporary or long-term and can range from mild to severe. Anemia can be caused by blood loss, decreased red blood cell production, and increased red blood cell breakdown. Causes of blood loss include menstruation, bleeding due to inflammation of the stomach or intestines, bleeding from surgery, serious injury, or blood donation. Causes of decreased production include iron deficiency, folate deficiency, vitamin B 12 deficiency, thalassemia and a number of bone marrow tumors.…

Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin available for oxygen transport, or abnormalities in hemoglobin that impair its function. When anemia comes on slowly, the symptoms are often vague, such as tiredness, weakness, shortness of breath, headaches, and a reduced ability to exercise. When anemia is acute, symptoms may include confusion, feeling like one is going to pass out, loss of consciousness, and increased thirst. Anemia must be significant before a person becomes noticeably pale. Additional symptoms may occur depending on the underlying cause. Anemia can be temporary or long-term and can range from mild to severe. Anemia can be caused by blood loss, decreased red blood cell production, and increased red blood cell breakdown. Causes of blood loss include menstruation, bleeding due to inflammation of the stomach or intestines, bleeding from surgery, serious injury, or blood donation. Causes of decreased production include iron deficiency, folate deficiency, vitamin B 12 deficiency, thalassemia and a number of bone marrow tumors. Causes of increased breakdown include genetic disorders such as sickle cell anemia, infections such as malaria, and certain autoimmune diseases like autoimmune hemolytic anemia. Anemia can also be classified based on the size of the red blood cells and amount of hemoglobin in each cell. If the cells are small, it is called microcytic anemia; if they are large, it is called macrocytic anemia; and if they are normal sized, it is called normocytic anemia. The diagnosis of anemia in men is based on a hemoglobin of less than 130 g/L; in non-pregnant women, it is less than 120 g/L, while in pregnant women it is less than 105–110. Further testing is then required to determine the cause. Treatment depends on the specific cause. Certain groups of individuals, such as pregnant women, can benefit from the use of iron pills for prevention. Dietary supplementation, without determining the specific cause, is not recommended. The use of blood transfusions is typically based on a person's signs and symptoms. In those without symptoms, they are not recommended unless hemoglobin levels are less than 60 to 80 g/L (6 to 8 g/dL). These recommendations may also apply to some people with acute bleeding. Erythropoiesis-stimulating agents are only recommended in those with severe anemia. Anemia is the most common blood disorder, affecting about a fifth to a third of the global population. Iron-deficiency anemia is the most common cause of anemia worldwide, and affects nearly one billion people. In 2013, anemia due to iron deficiency resulted in about 183,000 deaths – down from 213,000 deaths in 1990. This condition is most prevalent in children with also an above average prevalence in elderly and women of reproductive age (especially during pregnancy). Women aged 15 to 49 years experienced an increase in the global prevalence from 27.6% to 30.7% between 2012 to 2023 with either no improvement or an increase in prevalence in nearly all regions. In 2025, the WHO noted a rate of 35.5% in pregnant women, compared with 30.5% in non-pregnant women, along with a rate of almost 40% in children aged under 5 years. Anemia is one of the six WHO global nutrition targets for 2025 and for diet-related global targets endorsed by World Health Assembly in 2012 and 2013. Efforts to reach global targets contribute to reaching Sustainable Development Goals (SDGs), with anemia as one of the targets in SDG 2 for achieving zero world hunger.

Signs and symptoms

Symptoms of anemia can come on quickly or slowly. If the anemia develops slowly (chronic), the body may adapt and compensate for this change up to a point. In this case, no symptoms may appear until the anemia becomes more severe. General symptoms of mild anemia can include feeling tired, weak, dizziness, headaches, shortness of breath, and pale or yellowish skin. Acute anemia, often caused by blood loss (hemorrhagic shock) has more severe symptoms, including rapid heartbeat, low blood pressure,and confusion. The body may compensate for the lack of oxygen-carrying capability of the blood by increasing cardiac output. Symptoms may include palpitations, angina (if pre-existing heart disease is present), difficulty walking, and symptoms of heart failure. In severe anemia, there may be signs of a hyperdynamic circulation: tachycardia (a fast heart rate), bounding pulse, flow murmurs, and cardiac ventricular hypertrophy (enlargement). Pallor resulting from severe anemia may be visible in the hand palms and fingernails beds, although it may be difficult to detect in dark toned skin. Other locations to detect pallor are the inner lining of the lower eyelid and the tongue. Other symptoms associated with anemia depend on the underlying cause of the disorder; for example - Chronic iron-deficiency anemia may be associated with symptoms that can include spoon-shaped nails, sore or abnormally smooth tongue, hair loss, or pica (the desire to eat things which are not food, such as ice or earth). Anemia caused by vitamin B 12 deficiency may be associated with psychological problems such as anxiety and confusion, memory loss, and depression.

Diagnosis

|alt=Microscopic view with H&E stain of a blood smear with abnormally small, pale red blood cells

Definitions

There are several definitions of anemia. A strict but broad definition is an absolute decrease in red blood cell mass, however, a broader definition is a lowered ability of the blood to carry oxygen. An operational definition is a decrease in whole-blood hemoglobin concentration of more than 2 standard deviations below the mean of an age- and sex-matched reference range.

Testing

Anemia is typically diagnosed on a complete blood count from a blood sample. An automated hematology analyzer measures the hemoglobin level, hematocrit (% volume of RBCs in the blood), the size of the RBCs, and counts of white blood cells and platelets. Further tests will be needed to determine the underlying cause; these may include (not a complete list): A count of reticulocytes (immature RBCs), which measures the capacity of the bone marrow to produce new RBCs. Iron profile, to establish if there is underlying iron deficiency (the most common cause of anemia). Family history and genetic testing, to establish if there is an inherited disorder (the second most common cause). Peripheral blood smear - a small blood sample is examined under a microscope to check the size and shape of RBCs. Among other things, this should detect malaria parasites, which are globally the third most common cause. Serum creatinine, to check if poor kidney function underlies the anemia.

Causes

In humans, mature red blood cells (RBCs) are flexible biconcave disks, lacking cell nucleus and organelles. The process by which new RBCs are produced is termed erythropoiesis; committed stem cells in the red bone marrow of large bones take 7 days to mature into red blood cells. Between 2 and 3 million new RBCs are produced per second in human adults. The functional lifetime of a RBC is about 100–120 days, during which time the cells are continually moving within the blood circulation. The aging RBC undergoes changes in its plasma membrane, making it susceptible to recognition by macrophages and subsequent breakdown in the spleen, thus removing old and defective cells and continually purging the blood. This process is termed eryptosis; much of the resulting breakdown products are recirculated in the body. RBC breakdown by eryptosis normally occurs at the same rate as production by erythropoiesis, thus maintaining a balanced RBC population in the circulation. The causes of anemia may be classified as impaired red blood cell (RBC) production, increased RBC destruction (hemolytic anemia), blood loss, and fluid overload (hypervolemia). Globally, the most common underlying cause of anemia is dietary iron deficiency, followed by the inherited conditions thalassaemia and sickle cell trait, and infectious disease (principally malaria).

Impaired production

Disturbance of proliferation and differentiation of stem cells Pure red cell aplasia Aplastic anemia affects all kinds of blood cells. Fanconi anemia is a hereditary disorder or defect featuring aplastic anemia and various other abnormalities, including malformation of the extremities. Anemia of kidney failure due to insufficient production of the hormone erythropoietin Anemia of endocrine disease Disturbance of proliferation and maturation of erythroblasts Pernicious anemia is a form of megaloblastic anemia due to vitamin B 12 deficiency. Anemia of folate deficiency, as with vitamin B 12 , causes megaloblastic anemia. Anemia of prematurity, by diminished erythropoietin response to declining hematocrit levels, combined with blood loss from laboratory testing, generally occurs in premature infants at two to six weeks of age. Iron-deficiency anemia, resulting in deficient heme synthesis. Globally, this is the most common type of anemia; it may be caused by poor diet (common in poor communities), blood loss, or poor absorption of iron from food. Sources of blood loss can include heavy periods, childbirth, uterine fibroids, stomach ulcers, colon cancer, and urinary tract bleeding. Poor absorption of iron from food may occur as a result of an intestinal disorder such as inflammatory bowel disease or celiac disease, or surgery such as a gastric bypass. In low income communities with poor diet, parasitic worms, malaria, and HIV/AIDS increase the risk of iron deficiency anemia. Thalassemias, causing deficient globin synthesis Congenital dyserythropoietic anemias, causing ineffective erythropoiesis. Anemia of kidney failure. Other mechanisms of impaired RBC production Myelophthisic anemia or myelophthisis is a severe type of anemia resulting from the replacement of bone marrow by other materials, such as malignant tumors, fibrosis, or granulomas. The term Leukoerythroblastic is applied to a typical blood smear showing immature and abnormal erythrocytes. Myelodysplastic syndrome Anemia of chronic disease. Chronic inflammation can disrupt iron handling, limiting its availability for red blood cell formation. In chronic inflammation, the liver produces high levels of hepcidin, a hormone which regulates iron metabolism. This leads to high ferritin levels and low transferrin saturation, a pattern known as "functional iron deficiency." In this condition, iron availability is restricted even when total body iron stores are adequate, contributing to anemia common in inflammatory bowel diseases and chronic infections. This mechanism is commonly seen in older hospitalized patients with long-standing illnesses such as infections, heart failure or autoimmune conditions. Intestinal inflammation, which may be caused by: Helicobacter pylori infection. , gluten-related disorders such as untreated celiac disease and non-celiac gluten sensitivity; or Inflammatory bowel disease.

Increased destruction

Anemias of increased red blood cell destruction are generally classified as hemolytic anemias. These types generally feature jaundice, and elevated levels of lactate dehydrogenase. Intrinsic (intracorpuscular) abnormalities cause premature destruction. All of these, except paroxysmal nocturnal hemoglobinuria, are hereditary genetic disorders. Hereditary spherocytosis is a hereditary defect that results in defects in the RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by the spleen. Hereditary elliptocytosis is another defect in membrane skeleton proteins. Abetalipoproteinemia, causing defects in membrane lipids. Enzyme deficiencies Pyruvate kinase and hexokinase deficiencies, causing defect glycolysis. Glucose-6-phosphate dehydrogenase deficiency (G6PDD) and glutathione synthetase deficiency, causing increased oxidative stress. Hemoglobinopathies Sickle cell anemia Hemoglobinopathies causing unstable hemoglobins Paroxysmal nocturnal hemoglobinuria Extrinsic (extracorpuscular) abnormalities Antibody-mediated Warm autoimmune hemolytic anemia is caused by an autoimmune attack against red blood cells, primarily by IgG. It is the most common of the autoimmune hemolytic diseases. It can be idiopathic, that is, without any known cause, drug-associated or secondary to another disease such as systemic lupus erythematosus, or a malignancy, such as chronic lymphocytic leukemia. Cold agglutinin hemolytic anemia is primarily mediated by IgM. It can be idiopathic or result from an underlying condition. Rh disease, one of the causes of hemolytic disease of the newborn Transfusion reaction to blood transfusions Mechanical trauma to red blood cells Microangiopathic hemolytic anemias, including thrombotic thrombocytopenic purpura and disseminated intravascular coagulation Mechanical heart valves and blood pumps. Parasitic Trypanosoma congolense causes the disease nagana in cattle and other domesticated animals. Infection with the malaria parasite is a common cause of anemia across many tropical and subtropical regions. Breakdown of hemoglobin Heinz body anemia, which may be caused by G6PD deficiency, or through oxidative damage by administered drugs.

Blood loss

Trauma Gastrointestinal blood loss: Lesions, leading to either acute bleeds (e.g. variceal lesions, peptic ulcers, hemorrhoids ) or chronic blood loss (e.g. angiodysplasia). Chronic bleeding due to infection by intestinal nematodes feeding on blood, such as hookworms and the whipworm Trichuris trichiura Gynecologic disturbances: From abnormally heavy menstruation Repeated pregnancies and short birth intervals. Many types of cancers, such as leukemia and multiple myeloma, may cause acute or chronic blood loss. Anemia caused by medical interventions (Iatrogenic anemia): acute blood loss from repeated blood draws, surgical procedures, or as a side effect of chemotherapy.

Fluid overload

Fluid overload (hypervolemia) causes decreased hemoglobin concentration and apparent anemia: General causes of hypervolemia include excessive sodium or fluid intake, sodium or water retention. During early pregnancy, hormonal changes trigger an increase in blood plasma volume, while red cell mass increases more slowly. This physiological change dilutes existing RBCs and may trigger a diagnosis of anemia.

Treatment

Epidemiology

Anemia affects 24% of the world's population, with iron-deficiency anemia accounting for the majority of cases.

History

Signs of severe anemia in human bones from 4000 years ago have been uncovered in Thailand. The first discovery and discussion of blood was in 1674 when Antoni van Leeuwenhoek described red blood cells (RBCs) as "small round globules." RBCs counterpart, hemoglobin, wasn't discovered until much later by FL Hünefeld in 1840. In 1746, Vincenzo Menghini showed that iron was concentrated in the red blood cells using a magnetic knife. Between 1877-1885, many key tools emerged like hemocytometer (RBC count), hemoglobin measurement, and hematocrit measurement that allowed for quantitative diagnosis of blood. By the 1920s it was confirmed by multiple different studies that iron existed in plasma. McCance and Widdowson showed that iron is not excreted from the body in 1938, and it was later confirmed that iron absorption is the main way the body regulates iron levels. Ancient cultures like Assyria and Mediterranean societies used iron for medical treatments, however this occurred before iron's biological role was understood. In the 1500s, Nicholas Monarde used iron's "healing powers" to treat gout, acne and hair loss. Anemia was recognized as a clinical entity in 1807. Early diagnosis of anemia in the early 1800s were based solely on physical examinations such as fatigue, paleness, sweating, difficulty breathing, and dizziness. It wasn't until the late 1800s that new technologies allowed for a more in depth, lab-based diagnosis of anemia. In 1939, anemia was officially defined as "a deficiency of blood not due to hemorrhage".

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