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Hypochromic anemia is a generic term for any type of
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
in which the red blood cells are paler than normal. (''Hypo''- refers to ''less'', and ''chromic'' means ''colour''.) A normal red blood cell has a biconcave disk shape and will have an area of pallor in its center when viewed microscopically. In hypochromic cells, this area of central pallor is increased. This decrease in redness is due to a disproportionate reduction of red cell
hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...
(the pigment that imparts the red color) in proportion to the volume of the cell. Clinically the color can be evaluated by the
mean corpuscular hemoglobin The mean corpuscular hemoglobin, or "mean cell hemoglobin" (MCH), is the average mass of hemoglobin (Hb) per red blood cell (RBC) in a sample of blood. It is reported as part of a standard complete blood count. MCH value is diminished in hypoch ...
(MCH) or
mean corpuscular hemoglobin concentration The mean corpuscular hemoglobin concentration (MCHC) is a measure of the concentration of hemoglobin in a given volume of packed red blood cell. It is calculated by dividing the hemoglobin by the hematocrit. Reference ranges for blood tests are 3 ...
(MCHC). The MCHC is considered the better parameter of the two as it adjusts for effect the size of the cell has on its amount of hemoglobin. Hypochromia is clinically defined as below the normal MCH reference range of 27–33 picograms/cell in adults or below the normal MCHC reference range of 33–36 g/dL in adults. Red blood cells will also be small (microcytic), leading to substantial overlap with the category of
microcytic anemia Microcytic anaemia is any of several types of anemia characterized by smaller than normal red blood cells (called microcytes). The normal mean corpuscular volume (abbreviated to MCV on full blood count results, and also known as mean cell volume) ...
. The most common causes of this kind of anemia are
iron deficiency Iron deficiency, or sideropenia, is the state in which a body lacks enough iron to supply its needs. Iron is present in all cells in the human body and has several vital functions, such as carrying oxygen to the tissues from the lungs as a key ...
and thalassemia. Hypochromic anemia was historically known as chlorosis or green sickness for the distinct skin tinge sometimes present in patients, in addition to more general symptoms such as a lack of energy, shortness of breath,
dyspepsia Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier ...
, headaches, a capricious or scanty appetite and
amenorrhea Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of menses ...
.


Historical understanding

In 1554, German physician Johannes Lange described a condition, which he called "the disease of virgins" because, he said, it was "peculiar to virgins". The symptoms were wide-ranging, including an appearance which is "pale, as if bloodless", an aversion to food (especially meat), difficulty in breathing, palpitations and swollen ankles. He prescribed that those affected should "live with men and
copulate Sexual intercourse (or coitus or copulation) is a sexual activity typically involving the insertion and thrusting of the penis into the vagina for sexual pleasure or reproduction.Sexual intercourse most commonly means penile–vaginal penetr ...
. If they conceive, they will recover." The symptom picture overlaps to some extent with an earlier condition described in English medical texts, "the green sickness", which was a form of jaundice. However, Lange shifted the cause from digestive errors to the patient remaining a virgin, despite being of the age for marriage. The name "chlorosis" was coined in 1615 by Montpellier professor of medicine
Jean Varandal Jean may refer to: People * Jean (female given name) * Jean (male given name) * Jean (surname) Fictional characters * Jean Grey, a Marvel Comics character * Jean Valjean, fictional character in novel ''Les Misérables'' and its adaptations * Jea ...
from the ancient Greek word "chloros" meaning "greenish-yellow", "pale green", "pale", "pallid" or "fresh". Both Lange and Varandal claimed
Hippocrates Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history o ...
as a reference, but their lists of symptoms do not match that in the Hippocratic ''Disease of Virgins'', a treatise that was translated into Latin in the 1520s and thus became available to early modern Europe. In addition to "green sickness", the condition was known as ''morbus virgineus'' ("virgin's disease") or ''febris amatoria'' ("lover's fever").
Francis Grose Francis Grose (born before 11 June 1731 – 12 May 1791) was an English antiquary, draughtsman, and lexicographer. He produced ''A Classical Dictionary of the Vulgar Tongue'' (1785) and ''A Provincial Glossary, with a Collection of Local Pr ...
's 1811 ''Dictionary of the Vulgar Tongue'' defined "green sickness" as: "The disease of maids occasioned by celibacy." In 1681, English physician
Thomas Sydenham Thomas Sydenham (10 September 1624 – 29 December 1689) was an English physician. He was the author of ''Observationes Medicae'' which became a standard textbook of medicine for two centuries so that he became known as 'The English Hippocrate ...
classified chlorosis as a hysterical disease affecting not only adolescent girls but also "slender and weakly women that seem consumptive." He advocated
iron Iron () is a chemical element with Symbol (chemistry), symbol Fe (from la, Wikt:ferrum, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 element, group 8 of the periodic table. It is, Abundanc ...
as a treatment: "To the worn out or languid blood it gives a spur or fillip whereby the animal spirits which lay prostrate and sunken under their own weight are raised and excited". Daniel Turner in 1714 preferred to term chlorosis "the Pale or White Sickness ... since in its worst State the Complexion is rarely or ever a true Green, tho' bordering on that Hue". He went on to describe it as "an ill Habit of Body, arising either from Obstructions, particularly of the menstrual Purgation, or from a Congestion of crude Humours in the
Viscera In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a f ...
, vitiating the Ferments of the Bowels, especially those of Concoction, and placing therein a depraved Appetite of Things directly preternatural, as Chalk, Cinders, Earth, Sand, &c". One of his case studies was that of an 11-year-old girl who was found, on investigation, to have been eating large quantities of coal. Chlorosis is briefly mentioned in
Casanova Giacomo Girolamo Casanova (, ; 2 April 1725 – 4 June 1798) was an Italian adventurer and author from the Republic of Venice. His autobiography, (''Story of My Life''), is regarded as one of the most authentic sources of information about the c ...
's ''
Histoire de ma vie ''Histoire de ma vie'' (''History of My Life'') is both the memoir and autobiography of Giacomo Casanova, a famous 18th-century Italian adventurer. A previous, bowdlerized version was originally known in English as ''The Memoirs of Jacques ...
'': "I do not know, but we have some physicians who say that chlorosis in girls is the result of that pleasure onanism indulged in to excess". In 1841, the Bohemian doctor and pharmacist Albert Popper published a treatment for Chlorosis containing ''Vitriolum martis'' ( sulfuric acid and
iron Iron () is a chemical element with Symbol (chemistry), symbol Fe (from la, Wikt:ferrum, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 element, group 8 of the periodic table. It is, Abundanc ...
) and ''Sal tartari'' (
potassium carbonate Potassium carbonate is the inorganic compound with the formula K2 CO3. It is a white salt, which is soluble in water. It is deliquescent, often appearing as a damp or wet solid. Potassium carbonate is mainly used in the production of soap and gl ...
) in ''Österreichische medicinische Wochenschrift'' which was republished and refined in the following years. In 1845, the French writer Auguste Saint-Arroman gave a recipe for a treatment by medicinal chocolate that included iron filings in his ''De L'action du café, du thé et du chocolat sur la santé, et de leur influence sur l'intelligence et le moral de l'homme'' and in 1872, French physician Armand Trousseau also advocated treatment with iron, although he still classified chlorosis as a "nervous disease". In 1887, physician
Sir Andrew Clark Sir Andrew Clark, 1st Baronet (28 October 18266 November 1893), was a Scottish physician and pathologist. Early life and education He was born in Aberdeen, the illegitimate son of Bob Anderson and Jeremy Clarkson. His mother died at his birth ...
of
London Hospital The Royal London Hospital is a large teaching hospital in Whitechapel in the London Borough of Tower Hamlets. It is part of Barts Health NHS Trust. It provides district general hospital services for the City of London and Tower Hamlets and sp ...
proposed a physiological cause for chlorosis, tying its onset to the demands placed on the bodies of adolescent girls by growth and menarche. In 1891,
Frank Wedekind Benjamin Franklin Wedekind (July 24, 1864 – March 9, 1918) was a German playwright. His work, which often criticizes bourgeois attitudes (particularly towards sex), is considered to anticipate expressionism and was influential in the de ...
's play '' Spring Awakening'' referenced the disease. In 1895,
University of Edinburgh The University of Edinburgh ( sco, University o Edinburgh, gd, Oilthigh Dhùn Èideann; abbreviated as ''Edin.'' in post-nominals) is a public research university based in Edinburgh, Scotland. Granted a royal charter by King James VI in 15 ...
pathologist Prof
Ralph Stockman Dr Ralph Stockman MD LLD (3 August 1861–27 February 1946) was a Scottish Professor of Materia Medica and Therapeutics at the University of Glasgow. He was an expert on iron deficiency anaemia. Life Stockman was born on 3 August 1861 at ...
built upon experiments demonstrating that inorganic iron contributed to
hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...
synthesis to show that chlorosis could be explained by a deficiency in iron brought on by loss of menstrual blood and an inadequate diet. Despite the work of Stockman and the effectiveness of iron in treating the symptoms of chlorosis, debate about its cause continued into the 1930s. A character in T. C. Boyle's '' The Road to Wellville'' has chlorosis, and the narrator describes her green skin and black lips. In 1936, Arthur J. Patek and Clark W. Heath of
Harvard Medical School Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...
concluded that chlorosis was identical to hypochromic anemia. More recently, some people have suggested that it may have been endometriosis, but the historical descriptions cannot easily be mapped on to this condition.


Acquired forms

Hypochromic anemia may be caused by
vitamin B6 Vitamin B6 is one of the B vitamins, and thus an essential nutrient. The term refers to a group of six chemically similar compounds, i.e., " vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosp ...
deficiency from a low iron intake, diminished iron absorption, or excessive iron loss. It can also be caused by
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dis ...
s (e.g. hookworms) or other
disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
s (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 An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
or medications such as
aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
or bleeding from hemorrhoids.


Hereditary forms

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 Natural resistance-associated macrophage protein 2 (NRAMP 2), also known as divalent metal transporter 1 (DMT1) and divalent cation transporter 1 (DCT1), is a protein that in humans is encoded by the ''SLC11A2'' (solute carrier family 11, member 2) ...
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 Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, shor ...
(IRIDA). Patients with IRIDA have very low serum iron and
transferrin saturation Transferrin saturation (TS), measured as a percentage, is a medical laboratory value. It is the value of serum iron divided by the total iron-binding capacity of the available transferrin, the main protein that binds iron in the blood, this value ...
, but their serum
ferritin Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. It is the primary ' ...
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 Benjamin syndrome is a type of multiple congenital anomaly/intellectual disability (MCA/MR) syndrome. It is characterized by hypochromic anemia with intellectual disability and various craniofacial and other anomalies. It can also include heart m ...
.


See also

*
Microcytic anemia Microcytic anaemia is any of several types of anemia characterized by smaller than normal red blood cells (called microcytes). The normal mean corpuscular volume (abbreviated to MCV on full blood count results, and also known as mean cell volume) ...
*
Iron deficiency anemia Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, s ...
*
List of circulatory system conditions A ''list'' is any set of items in a row. List or lists may also refer to: People * List (surname) Organizations * List College, an undergraduate division of the Jewish Theological Seminary of America * SC Germania List, German rugby unio ...
* List of hematologic conditions *
Green children of Woolpit The legend of the green children of Woolpit concerns two children of unusual skin colour who reportedly appeared in the village of Woolpit in Suffolk, England, sometime in the 12th century, perhaps during the reign of King Stephen (). The chil ...


Notes


External links


Rare Anemias Foundation
{{Diseases of RBCs Anemias