Hypochromic anemia is a generic term for any type ofanemia in which thered blood cells are paler than normal. (Hypo- refers toless, andchromic meanscolour.) 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 cellhemoglobin (the pigment that imparts the red color) in proportion to the volume of the cell. Clinically the color can be evaluated by themean corpuscular hemoglobin (MCH) ormean corpuscular hemoglobin concentration (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.[1] 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.[2]
Red blood cells will also be small (microcytic), leading to substantial overlap with the category ofmicrocytic anemia. The most common causes of this kind of anemia areiron deficiency andthalassemia.
Hypochromic anemia was historically known aschlorosis orgreen 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,headaches, a capricious or scantyappetite andamenorrhea.
- Pandar
- Now, the pox upon her green-sickness for me!
- Bawd
- 'Faith, there's no way to be rid on't but by the way to the pox. Here comes the Lord Lysimachus disguised.
- Shakespeare (attrib).Pericles Prince of Tyre[3]
In 1554, German physicianJohannes Lange described a condition, which he called "the disease of virgins" because, he said, it was "peculiar tovirgins". 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.[4] He prescribed that those affected should "live with men andcopulate. 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.[5] 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 byMontpellier professor of medicineJean Varandal from the ancient Greek word "chloros" meaning "greenish-yellow", "pale green", "pale", "pallid" or "fresh". Both Lange and Varandal claimedHippocrates as a reference, but their lists of symptoms do not match that in the HippocraticDisease of Virgins, a treatise that was translated into Latin in the 1520s and thus became available to early modern Europe.[4]
In addition to "green sickness", the condition was known asmorbus virgineus ("virgin's disease") orfebris amatoria ("lover's fever").Francis Grose's 1811Dictionary of the Vulgar Tongue defined "green sickness" as: "The disease of maids occasioned bycelibacy."[6]
In 1681, English physicianThomas Sydenham classified chlorosis as ahysterical disease affecting not only adolescent girls but also "slender and weakly women that seemconsumptive." He advocatediron 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 themenstrual Purgation, or from a Congestion of crude Humours in theViscera, vitiating the Ferments of the Bowels, especially those of Concoction, and placing therein a depraved Appetite of Things directly preternatural, asChalk, 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.[7]
Chlorosis is briefly mentioned inCasanova'sHistoire de ma vie: "I do not know, but we have some physicians who say that chlorosis in girls is the result of that pleasureonanism indulged in to excess".
In 1841, the Bohemian doctor and pharmacistAlbert Popper published a treatment for Chlorosis containingVitriolum martis (sulfuric acid andiron) andSal tartari (potassium carbonate) inÖsterreichische medicinische Wochenschrift which was republished and refined in the following years.[8][9][10][11][12]
In 1845, the French writerAuguste Saint-Arroman gave a recipe for a treatment by medicinal chocolate that included iron filings in hisDe 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[13] and in 1872, French physicianArmand Trousseau also advocated treatment with iron, although he still classified chlorosis as a "nervous disease".[14][15][16]
In 1887, physicianSir Andrew Clark ofLondon Hospital proposed a physiological cause for chlorosis, tying its onset to the demands placed on the bodies of adolescent girls by growth andmenarche. In 1891,Frank Wedekind's playSpring Awakening referenced the disease. In 1895,University of Edinburgh pathologist ProfRalph Stockman built upon experiments demonstrating that inorganic iron contributed tohemoglobin 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 inT. C. Boyle'sThe Road to Wellville has chlorosis, and the narrator describes her green skin and black lips.
In 1936, Arthur J. Patek and Clark W. Heath ofHarvard Medical School concluded that chlorosis was identical to hypochromic anemia.[17] More recently, some people have suggested that it may have been endometriosis, but the historical descriptions cannot easily be mapped on to this condition.[18]
Hypochromic anemia may be caused byvitamin B6 deficiency from a low iron intake, diminished iron absorption, or excessive iron loss. It can also be caused byinfections (e.g.hookworms) or otherdiseases (i.e.anemia of chronic disease), therapeuticdrugs, copper toxicity, andlead poisoning. One acquired form of anemia is also known asFaber's syndrome. It may also occur from severe stomach or intestinal bleeding caused byulcers or medications such asaspirin or bleeding fromhemorrhoids.[19][20]
Hypochromic anemia occurs in patients with hypochromic microcytic anemia with iron overload. The condition isautosomal recessive and is caused by mutations in theSLC11A2 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.[21]
It also occurs in patients with hereditary iron refractoryiron-deficiency anemia (IRIDA). Patients with IRIDA have very low serum iron andtransferrin saturation, but their serumferritin is normal or high. The anemia is usually moderate in severity and presents later in childhood.[22]
Hypochromic anemia is also caused bythalassemia and congenital disorders likeBenjamin anemia.[23]
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