Anemia

Anemia 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.

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.[3][4]

When anemia comes on slowly, the symptoms are often vague, such as tiredness, weakness, shortness of breath, headaches, and a reduced ability to exercise.[1] When anemia is acute, symptoms may include confusion, feeling like one is going to pass out, loss of consciousness, and increased thirst.[1] Anemia must be significant before a person becomes noticeably pale.[1] Additional symptoms may occur depending on the underlying cause.[1] Anemia can be temporary or long-term and can range from mild to severe.[5]

Anemia can be caused by blood loss, decreased red blood cell production, and increased red blood cell breakdown.[1] Causes of blood loss include menstruation, bleeding due to inflammation of the stomach or intestines, bleeding from surgery, serious injury, or blood donation.[1] Causes of decreased production include iron deficiency, folate deficiency, vitamin B12 deficiency, thalassemia and a number of bone marrow tumors.[1] Causes of increased breakdown include genetic disorders such as sickle cell anemia, infections such as malaria, and certain autoimmune diseases like autoimmune hemolytic anemia.[1]

Anemia can also be classified based on the size of the red blood cells and amount of hemoglobin in each cell.[1] 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.[1] 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.[6][7] Further testing is then required to determine the cause.[1][8]

Treatment depends on the specific cause. Certain groups of individuals, such as pregnant women, can benefit from the use of iron pills for prevention.[1][9] Dietary supplementation, without determining the specific cause, is not recommended.[1] The use of blood transfusions is typically based on a person's signs and symptoms.[1] In those without symptoms, they are not recommended unless hemoglobin levels are less than 60 to 80 g/L (6 to 8 g/dL).[1][10] These recommendations may also apply to some people with acute bleeding.[1] Erythropoiesis-stimulating agents are only recommended in those with severe anemia.[10]

Anemia is the most common blood disorder, affecting about a fifth to a third of the global population.[1][11][12] Iron-deficiency anemia is the most common cause of anemia worldwide, and affects nearly one billion people.[13] In 2013, anemia due to iron deficiency resulted in about 183,000 deaths – down from 213,000 deaths in 1990.[14] This condition is most prevalent in children[15][16] with also an above average prevalence in elderly[1] and women of reproductive age (especially during pregnancy).[13] 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.[17] 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),[18] with anemia as one of the targets in SDG 2 for achieving zero world hunger.[19]

Signs and symptoms

Symptoms of anemia can come on quickly or slowly.[21] 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.[20][22] General symptoms of mild anemia can include feeling tired, weak, dizziness, headaches, shortness of breath, and pale or yellowish skin.[22][23]

Acute anemia, often caused by blood loss (hemorrhagic shock) has more severe symptoms, including rapid heartbeat, low blood pressure,and confusion.[24]

The body may compensate for the lack of oxygen-carrying capability of the blood by increasing cardiac output. Symptoms related to this may include palpitations, angina (if pre-existing heart disease is present), difficulty walking, and symptoms of heart failure.[25] 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).[24]

Chronic anemia in infants may result in poor growth and impaired neurological development.[26]

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.[27][28][29]

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).[30]
• Anemia caused by vitamin B12 deficiency may be associated with psychological problems such as anxiety and confusion, memory loss, and depression.[31]

Diagnosis

Definitions

There are several definitions of anemia.[32] A strict but broad definition is an absolute decrease in red blood cell mass,[33] however, a broader definition is a lowered ability of the blood to carry oxygen.[34] 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.[35]

The name is derived from Ancient Greek ἀν- (an-) 'not' and "αἷμᾰ" (haîmă) 'blood'.[37] A related word, ischemia, derives from the Greek from ῐ̓́σχω (ĭ́skhō, "stop") and αἷμᾰ (haîmă, "blood"); the roots of the both words refer to the basic idea of "lack of blood", but the meaning is significantly different. Anemia implies widespread effects from blood that either is too scarce (e.g., blood loss) or is dysfunctional in its oxygen-supplying ability (due to whatever type of hemoglobin or erythrocyte problem). Ischemia is a restriction in blood supply to any tissue, muscle, or organ of the body, causing a shortage of oxygen that is needed to keep tissues alive, as may occur for example in a stroke.[38][39][40]

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,[41] 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):[42][43]

• A count of reticulocytes (immature RBCs), which measures the capacity of the bone marrow to produce new RBCs.[44]
• Iron profile, to establish if there is underlying iron deficiency (the most common cause of anemia).[45]
• Family history and genetic testing, to establish if there is an inherited disorder (the second most common cause).[45]
• 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.[46][47]
• Serum creatinine, to check if poor kidney function underlies the anemia.[48]

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.[50] The functional lifetime of a RBC is about 100–120 days, during which time the cells are continually moving within the blood circulation.[51] 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.[52] This process is termed eryptosis; much of the resulting breakdown products are recirculated in the body.[53] RBC breakdown by eryptosis normally occurs at the same rate as production by erythropoiesis, thus maintaining a balanced RBC population in the circulation.[54]

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).[55] 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).[28]