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Polychromasia is a disorder where there is an abnormally high number of immature
red blood cells Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek language, Greek ''erythros'' for "red" and ''k ...
found in the bloodstream as a result of being prematurely released from the
bone marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...
during blood formation (''poly''- refers to ''many'', and ''-chromasia'' means ''color''.) These cells are often shades of grayish-blue. Polychromasia is usually a sign of bone marrow stress as well as immature red blood cells. 3 types are recognized, with types 1 and 2 being referred to as 'young red blood cells' and type 3 as 'old red blood cells'.
Giemsa stain Giemsa stain (), named after German chemist and bacteriologist Gustav Giemsa, is a nucleic acid stain used in cytogenetics and for the histopathological diagnosis of malaria and other parasites. Uses It is specific for the phosphate groups of ...
is used to distinguish all three types of blood smears. The young cells will generally stain gray or blue in the cytoplasm. These young red blood cells are commonly called
reticulocytes Reticulocytes are immature red blood cells (RBCs). In the process of erythropoiesis (red blood cell formation), reticulocytes develop and mature in the bone marrow and then circulate for about a day in the blood stream before developing into mat ...
. All polychromatophilic cells are reticulocytes, however, not all reticulocytes are polychromatophilic. In the old blood cells, the cytoplasm either stains a light orange or does not stain at all.


Causes

Red blood cells can be released prematurely by a number of mechanisms. Premature release of red blood cells is usually caused due to damage of the bone marrow due to underlying causes as well as in response to the stimulation of hormones in strong association with
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, th ...
.
Erythropoetin Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the b ...
, a hormone made by the kidneys, controls the production of red blood cells as well as the rate at which they are released from the bone marrow. When these levels of erythropoetin rise, they signal the release of immature red blood cells into the bloodstream and is linked to anemia. Damaged bone marrow can also lead to polychromasia. The most common cause of bone marrow damage is penetration by
cancer cells Cancer cells are cells that divide continually, forming solid tumors or flooding the blood with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to form two daughter cells, and these d ...
, either from the bone marrow itself or as a consequence of
metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
from another part of the body.


Association with anemia

Normocytic anemia Normocytic anemia is a type of anemia and is a common issue that occurs for men and women typically over 85 years old. Its prevalence increases with age, reaching 44 percent in men older than 85 years. The most common type of normocytic anemia is a ...
is the most commonly seen type of anemia. This type of anemia is usually caused by the underproduction of blood cells as well as
hemolysis Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo o ...
. Anemia can be caused by either overproduction or underproduction of red blood cells, as well as the production of defective blood cells. Because there are more red blood cells needed in the body at that moment, they are released prematurely, leading to polychromasia.


Association with reticulocytosis

There is a slight correlation between polychromasia and reticulocytosis. It is much easier to test for polychromasia in blood cells than to perform special staining for reticulocytosis. If polychromasia is found in the blood cells, the reticulocyte count is taken to detect further disease or stress. If a low count of reticulocytes is found, it usually indicates bone marrow stress. If a high reticulocyte count is found, it is usually linked to hemolysis, but a
Coombs test A Coombs test, also known as antiglobulin test (AGT), is either of two blood tests used in immunohematology. They are the direct and indirect Coombs tests. The direct Coombs test detects antibodies that are stuck to the surface of the red blood ce ...
may be performed in this case to rule out immune-mediated hemolysis. Polychromasia can also be seen in blood smears when there is a normal reticulocyte count. This can be caused by infiltration of the bone marrow due to tumors as well as
fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...
, or scarring, of the marrow.


Embryology

The formation of red blood cells is commonly known as
hematopoiesis Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. ...
. Up to the first 60 days of life, the
yolk sac The yolk sac is a membranous sac attached to an embryo, formed by cells of the hypoblast layer of the bilaminar embryonic disc. This is alternatively called the umbilical vesicle by the Terminologia Embryologica (TE), though ''yolk sac'' is far ...
is the main source of hematopoiesis. The liver is then used as the main hematopoietic organ of the embryo until near birth, where it is then taken over by the bone marrow. Most red blood cells are released into the blood as reticulocytes. Polychromasia occurs when the immature reticulocytes of the bone marrow are released, resulting in a grayish blue color of the cells. This color is seen because of the ribosomes still left on the immature blood cells, which are not found on mature red blood cells. These cells still contain a nucleus as well due to the early release, which is not needed in mature blood cells because their only function is to carry oxygen in the blood. The life span of a typical red blood cell is acknowledged to be approximately 120 days, and the time period of a reticulocyte found in the blood to be one day. The percentage of reticulocytes calculated to be in the blood at any given time indicates the rapidity of the red blood cell turnover in a healthy patient. The number of reticulocytes, however, reflects the amount of erythropoiesis that has occurred on any certain day. The absolute number of reticulocytes is referred to as the
reticulocyte index The reticulocyte production index (RPI), also called a corrected reticulocyte count (CRC), is a calculated value used in the diagnosis of anemia. This calculation is necessary because the raw reticulocyte count is misleading in anemic patients. T ...
and is calculated by adjusting the reticulocyte percentage by the ratio of observed
hematocrit The hematocrit () (Ht or HCT), also known by several other names, is the volume percentage (vol%) of red blood cells (RBCs) in blood, measured as part of a blood test. The measurement depends on the number and size of red blood cells. It is norm ...
to expected hematocrit to get the 'corrected' reticulocyte count.


Diagnosis

Polychromasia can be detected through the use of stains that will change the color of the red blood cells that are affected. Under certain conditions, these red blood cells are shown to have an affinity for basic stains, contrary to the usual acid stains used. Polychromatic cells usually stain dark blue or gray and are distinguishable from normal blood cells mostly by a slight change in color.


History

In 1890, research done by
William Henry Howell William Henry Howell (February 20, 1860 – February 6, 1945) was an American physiologist. He pioneered the use of heparin as a blood anti-coagulant. Early life William Henry Howell was born on February 20, 1860, in Baltimore, Maryland. He gra ...
indicated that certain red blood cells found both in fetal circulation and bone marrow (of a cat) had unusual granulation. These granules are also called Grawitz granules. In most instances, he found that these granules were connected by a network of sorts. The cells that had this granulation were found in blood and tissues that had been freshly stained without undergoing fixation. Howell was the first to describe these blood cells as being of the prototype ''stippling'', which meant granular degeneration of the red blood cells. In 1893,
Max Askanazy Max Askanazy (24 February 1865, Stallupönen, East Prussia – 23 October 1940, Geneva, Switzerland) was a German-Swiss pathologist. In 1890 he received his medical doctorate from the University of Königsberg, where he worked for several years ...
, who was studying the blood of an anemic patient, discovered granulation in the blood cells that were polychromatic. Later studies were done by other scientists also showed the same results in other forms of anemia. This pattern of granulation was also seen in several types of toxic poisoning, especially
lead poisoning Lead poisoning, also known as plumbism and saturnism, is a type of metal poisoning caused by lead in the body. The brain is the most sensitive. Symptoms may include abdominal pain, constipation, headaches, irritability, memory problems, inferti ...
. However, other research has shown that there has been stippling found in normal blood cells as well. Stippling is supposed to be one of the earliest symptoms of lead poisoning, although most scientists now regard it as a degenerative condition, along with polychromasia.


References


External links

{{Medical resources , DiseasesDB = , ICD10 = , ICD9 = , ICDO = , OMIM = , MedlinePlus = 001318 , eMedicineSubj = , eMedicineTopic = , MeSH = , GeneReviewsName = Red blood cell disorders