Anemia or anaemia (
British English
British English (BrE, en-GB, or BE) is, according to Lexico, Oxford Dictionaries, "English language, English as used in Great Britain, as distinct from that used elsewhere". More narrowly, it can refer specifically to the English language in ...
) is a
blood disorder
Hematologic diseases are disorders which primarily affect the blood & blood-forming organs. Hematologic diseases include rare genetic disorders, anemia, HIV, sickle cell disease & complications from chemotherapy or transfusions.
Myeloid
* Hemog ...
in which the
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
has a reduced ability to carry
oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...
due to a lower than normal number of
red blood cell
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 ''erythros'' for "red" and ''kytos'' for "holl ...
s, or a reduction in the amount of
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 ...
.
When anemia comes on slowly, the symptoms are often vague, such as
tiredness,
weakness
Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...
,
shortness of breath
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...
,
headaches, and a
reduced ability to exercise.
When anemia is acute, symptoms may include
confusion
In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion" ,
feeling like one is going to pass out,
loss of consciousness
Loss may refer to:
Arts, entertainment, and media Music
* ''Loss'' (Bass Communion album) (2006)
* ''Loss'' (Mull Historical Society album) (2001)
*"Loss", a song by God Is an Astronaut from their self-titled album (2008)
* Losses "(Lil Tjay son ...
, and
increased thirst.
Anemia must be significant before a person becomes noticeably
pale.
Symptoms of anemia depend on how quickly hemoglobin decreases.
Additional symptoms may occur depending on the underlying cause.
[ Preoperative anemia can increase the risk of needing a ]blood transfusion
Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
following surgery. Anemia can be temporary or long term and can range from mild to severe.
Anemia can be caused by blood loss
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, v ...
, decreased red blood cell production, and increased red blood cell breakdown. Causes of bleeding include trauma
Trauma most often refers to:
* Major trauma, in physical medicine, severe physical injury caused by an external source
* Psychological trauma, a type of damage to the psyche that occurs as a result of a severely distressing event
*Traumatic i ...
and gastrointestinal bleeding
Gastrointestinal bleeding (GI bleed), also called gastrointestinal hemorrhage (GIB), is all forms of bleeding in the gastrointestinal tract, from the mouth to the rectum. When there is significant blood loss over a short time, symptoms may include ...
. Causes of decreased production include 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 ...
, vitamin B12 deficiency
Vitamin B12 deficiency, also known as cobalamin deficiency, is the medical condition in which the blood and tissue have a lower than normal level of vitamin B12. Symptoms can vary from none to severe. Mild deficiency may have few or absent symp ...
, thalassemia and a number of bone marrow tumors. Causes of increased breakdown include genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
s such as sickle cell anemia
Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red bl ...
, infections such as malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
, and certain autoimmune diseases. 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
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) ...
; if they are large, it is called macrocytic anemia
The term ''macrocytic'' is from Greek words meaning "large cell". A macrocytic class of anemia is an ''anemia'' (defined as blood with an insufficient concentration of hemoglobin) in which the red blood cells (erythrocytes) are larger than their ...
; and if they are normal sized, it is called 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 ...
. The diagnosis of anemia in men is based on a hemoglobin of less than 130 to 140 g/L (13 to 14 g/dL); in women, it is less than 120 to 130 g/L (12 to 13 g/dL). Further testing is then required to determine the cause.
A large number of patients diagnosed with anemia of chronic disease
Anemia of chronic disease (ACD) or anemia of chronic inflammation is a form of anemia seen in chronic infection, chronic immune activation, and malignancy. These conditions all produce elevation of interleukin-6, which stimulates hepcidin product ...
present with no active inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
or dietary issues. These include many with reduced limb loading, such as spinal cord injured patients, astronauts, elderly people with limited mobility, bed-bound and experimental bed-rest subjects.
Certain groups of individuals, such as pregnant women, benefit from the use of iron pills for prevention.[ Dietary supplementation, without determining the specific cause, is not recommended.][ The use of ]blood transfusion
Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
s is typically based on a person's signs and symptoms.[ Symptoms of anemia depend on how quickly hemoglobin decreases.] 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 agent
Erythropoiesis-stimulating agents (ESA) are medications which stimulate the bone marrow to make red blood cells. They are used to treat anemia due to end stage kidney disease, chemotherapy, major surgery, or certain treatments in HIV/AIDS. In ...
s are only recommended in those with severe anemia.
Anemia is the most common blood disorder, affecting about a third of the global population. 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 ...
affects nearly 1 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). The name is derived from grc, ἀναιμία ', meaning "lack of blood", from ἀν- ''an-'', "not" and αἷμα ''haima'', "blood".
Anemia is one of the six WHO
Who or WHO may refer to:
* Who (pronoun), an interrogative or relative pronoun
* Who?, one of the Five Ws in journalism
* World Health Organization
Arts and entertainment Fictional characters
* Who, a creature in the Dr. Seuss book '' Horton He ...
global nutrition targets for 2025 and for diet-related global targets endorsed by World Health Assembly
The World Health Assembly (WHA) is the forum through which the World Health Organization (WHO) is governed by its 194 member states. It is the world's highest health policy setting body and is composed of health ministers from member states.
Th ...
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
Sustainable Development Goal 2 (SDG 2 or Global Goal 2) aims to achieve "zero hunger". It is one of the 17 Sustainable Development Goals established by the United Nations in 2015. The official wording is: "End hunger, achieve food security and im ...
for achieving zero world hunger.
Signs and symptoms
Anemia is considered to be the most common blood disorder. A person with anemia may not have any symptoms depending on the underlying cause, and no symptoms may be noticed, as the anemia is initially mild, and then the symptoms become worse as the anemia worsens. A patient with anemia may report feeling tired, weak, decreased ability to concentrate, and sometimes shortness of breath
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...
on exertion
Exertion is the physical or perceived use of energy.Newton's Third Law, Elert, Glenn. “Forces.” ''Viscosity – The Physics Hypertextbook'', physics.info/newton-first/. Exertion traditionally connotes a strenuous or costly ''effort'', resulting ...
.
Symptoms of anemia can come on quickly or slowly. Early on there may be few or no symptoms. If the anemia continues slowly (chronic), the body may adapt and compensate for this change. In this case, no symptoms may appear until the anemia becomes more severe. Symptoms can include feeling tired, weak, dizziness
Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness.
Dizziness is a common medical c ...
, headaches, lack of physical exertion, shortness of breath, difficulty concentrating, irregular or rapid heartbeat, cold hands and feet, cold intolerance
Cold sensitivity or cold intolerance is unusual discomfort felt by some people when in a cool environment.
There is much variation in the sensitivity to cold experienced by different people, with some putting on many layers of clothing while other ...
, pale or yellow
Yellow is the color between green and orange on the spectrum of light. It is evoked by light with a dominant wavelength of roughly 575585 nm. It is a primary color in subtractive color systems, used in painting or color printing. In the ...
skin, poor appetite, easy bruising and bleeding, and muscle weakness. Anemia that develops quickly, often, has more severe symptoms, including, feeling faint, chest pain, sweating, increased thirst, and confusion. There may be also additional symptoms depending on the underlying cause.
In more severe anemia, the body may compensate for the lack of oxygen-carrying capability of the blood by increasing cardiac output. The person may have symptoms related to this, such as palpitations, angina (if pre-existing heart disease is present), intermittent claudication
Claudication is a medical term usually referring to impairment in walking, or pain, discomfort, numbness, or tiredness in the legs that occurs during walking or standing and is relieved by rest. The perceived level of pain from claudication can be ...
of the legs, and symptoms of heart failure.
On examination, the signs exhibited may include pallor ( pale skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other animal coverings, such as the arthropod exoskeleton, have different de ...
, mucosa, conjunctiva
The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epithelium ...
and nail beds), but this is not a reliable sign. A blue coloration of the sclera may be noticed in some cases of iron-deficiency anemia. There may be signs of specific causes of anemia, e.g. koilonychia
Koilonychia, also known as spoon nails,James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . is a nail disease that can be a sign of hypochromic anemia, especially ...
(in iron deficiency), jaundice (when anemia results from abnormal break down of red blood cells – in hemolytic anemia
Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...
), nerve cell damage (vitamin B12 deficiency), bone deformities (found in thalassemia major) or leg
A leg is a weight-bearing and locomotive anatomical structure, usually having a columnar shape. During locomotion, legs function as "extensible struts". The combination of movements at all joints can be modeled as a single, linear element ca ...
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 ...
(seen in sickle-cell disease
Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blo ...
). In severe anemia, there may be signs of a hyperdynamic circulation Hyperdynamic circulation is abnormally increased circulatory volume. Systemic vasodilation and the associated decrease in peripheral vascular resistance results in decreased pulmonary capillary wedge pressure and decreased blood pressure, presen ...
: tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
(a fast heart rate), bounding pulse
Bounding may refer to:
* Establishing limits on the behavior of a process or device, see Listing and approval use and compliance
* Bounding overwatch, a variety of military maneuver
* A cyclical type of jumping
Jumping or leaping is a for ...
, flow murmurs, and cardiac
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...
ventricular hypertrophy
Ventricular hypertrophy (VH) is thickening of the walls of a ventricle (lower chamber) of the heart. Although left ventricular hypertrophy (LVH) is more common, right ventricular hypertrophy (RVH), as well as concurrent hypertrophy of both ventr ...
(enlargement). There may be signs of heart failure.
Pica, the consumption of non-food items such as ice, paper, wax, grass, hair or dirt, may be a symptom of iron deficiency; although it occurs often in those who have normal levels of 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 ...
.
Chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants, and reduced academic performance in children of school age. Restless legs syndrome
Restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), is generally a long-term disorder that causes a strong urge to move one's legs. There is often an unpleasant feeling in the legs that improves somewhat by moving them. This ...
is more common in people with 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 ...
than in the general population.
Causes
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
Hypervolemia, also known as fluid overload, is the medical condition where there is too much fluid in the blood. The opposite condition is hypovolemia, which is too little fluid volume in the blood. Fluid volume excess in the intravascular compa ...
). Several of these may interplay to cause anemia. The most common cause of anemia is blood loss, but this usually does not cause any lasting symptoms unless a relatively impaired RBC production develops, in turn, most commonly by 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 ...
.[
]
Impaired production
* Disturbance of proliferation and differentiation of stem cells
** Pure red cell aplasia
Pure red cell aplasia (PRCA) or erythroblastopenia refers to a type of aplastic anemia affecting the precursors to red blood cells but usually not to white blood cells. In PRCA, the bone marrow ceases to produce red blood cells. There are multiple ...
[Table 12-1 in: ]
** Aplastic anemia[ affects all kinds of ]blood cell
A blood cell, also called a hematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes) ...
s. Fanconi anemia
Fanconi anaemia (FA) is a rare genetic disease resulting in impaired response to DNA damage. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of no ...
is a hereditary disorder or defect featuring aplastic anemia and various other abnormalities.
** Anemia of kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
[ due to insufficient production of the ]hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...
erythropoietin
** Anemia of endocrine disease
Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology.
Types of disease
Broadly speaking, endocrine disorders may be subdivided into three groups:
# Endocrin ...
* Disturbance of proliferation and maturation of erythroblast
A nucleated red blood cell (NRBC), also known by several other names, is a red blood cell that contains a cell nucleus. Almost all vertebrate organisms have hemoglobin-containing cells in their blood, and with the exception of mammals, all of t ...
s
** Pernicious anemia
Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic fa ...
[ is a form of ]megaloblastic anemia
Megaloblastic anemia is a type of macrocytic anemia. An anemia is a red blood cell defect that can lead to an undersupply of oxygen. Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell production. When DNA synth ...
due to vitamin B12 deficiency dependent on impaired absorption of vitamin B12. Lack of dietary B12 causes non-pernicious megaloblastic anemia.
** Anemia of folate deficiency
Folate deficiency, also known as vitamin B9 deficiency, is a low level of folate and derivatives in the body. Signs of folate deficiency are often subtle. A low number of red blood cells (anemia) is a late finding in folate deficiency and folate ...
,[ as with vitamin B12, causes ]megaloblastic anemia
Megaloblastic anemia is a type of macrocytic anemia. An anemia is a red blood cell defect that can lead to an undersupply of oxygen. Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell production. When DNA synth ...
** Anemia of prematurity, by diminished erythropoietin response to declining 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 ...
levels, combined with blood loss from laboratory testing, generally occurs in premature infants at two to six weeks of age.
** 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 ...
, resulting in deficient heme synthesis[
** Thalassemias, causing deficient globin synthesis][
** Congenital dyserythropoietic anemias, causing ineffective erythropoiesis
** Anemia of kidney failure][ (also causing stem cell dysfunction)
* 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.
** ]Myelodysplastic syndrome
A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may ...
[
** anemia of ]chronic inflammation
Chronic systemic inflammation (SI) is the result of release of pro-inflammatory cytokines from immune-related cells and the chronic activation of the innate immune system. It can contribute to the development or progression of certain conditions ...
[
** Leukoerythroblastic anemia is caused by space-occupying lesions in the bone marrow that prevent normal production of blood cells.
]
Increased destruction
Anemias of increased red blood cell destruction are generally classified as hemolytic anemia
Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly ...
s. These types generally feature jaundice, and elevated levels of lactate dehydrogenase
Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of lactate to pyruvate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that transfers a hydride from one ...
.
* Intrinsic (intracorpuscular) abnormalities[ cause premature destruction. All of these, except ]paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occu ...
, are hereditary genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
s.
** Hereditary spherocytosis
Hereditary spherocytosis (HS) is a congenital hemolytic disorder, wherein a genetic mutation coding for a structural membrane protein phenotype leads to a spherical shaping of erythrocytic cellular morphology. As erythrocytes are sphere-shaped (s ...
[ is a hereditary defect that results in defects in the RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by the ]spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes . .
** Hereditary elliptocytosis
Hereditary elliptocytosis, also known as ovalocytosis, is an inherited blood disorder in which an abnormally large number of the person's red blood cells are elliptical rather than the typical biconcave disc shape. Such morphologically distinctive ...
[ is another defect in membrane skeleton proteins.
** ]Abetalipoproteinemia
Abetalipoproteinemia (also known as: Bassen-Kornzweig syndrome, microsomal triglyceride transfer protein deficiency disease, MTP deficiency, and betalipoprotein deficiency syndrome) is a disorder that interferes with the normal absorption of fat ...
,[ causing defects in membrane lipids
** Enzyme deficiencies
*** ]Pyruvate kinase
Pyruvate kinase is the enzyme involved in the last step of glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), yielding one molecule of pyruvate and one molecule of ATP. P ...
and hexokinase
A hexokinase is an enzyme that phosphorylates hexoses (six-carbon sugars), forming hexose phosphate. In most organisms, glucose is the most important substrate for hexokinases, and glucose-6-phosphate is the most important product. Hexok ...
deficiencies,[ causing defect glycolysis
*** ]Glucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency (G6PDD), which is the most common enzyme deficiency worldwide, is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who are affected have no symptoms. ...
and glutathione synthetase
Glutathione synthetase (GSS) () is the second enzyme in the glutathione (GSH) biosynthesis pathway. It catalyses the condensation of gamma-glutamylcysteine and glycine, to form glutathione. Glutathione synthetase is also a potent antioxidan ...
deficiency,[ causing increased ]oxidative stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...
** Hemoglobinopathies
*** Sickle cell anemia
Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red bl ...
[
*** Hemoglobinopathies causing unstable hemoglobins][
** ]Paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occu ...
[
* Extrinsic (extracorpuscular) abnormalities
** ]Antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
-mediated
*** Warm autoimmune hemolytic anemia is caused by autoimmune attack against red blood cells, primarily by IgG. It is the most common of the autoimmune
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...
hemolytic
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 ...
diseases. It can be idiopathic
An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin. From Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approximately "a disease of its own kin ...
, 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.["Autoimmune Hemolytic Anemia (AIHA)"]
By J.L. Jenkins. The Regional Cancer Center. 2001
*** Cold agglutinin hemolytic anemia is primarily mediated by IgM. It can be idiopathic or result from an underlying condition.
*** Rh disease
Rh disease (also known as rhesus isoimmunization, Rh (D) disease, and blue baby disease) is a type of hemolytic disease of the fetus and newborn (HDFN). HDFN due to anti-D antibodies is the proper and currently used name for this disease as the ...
,[ one of the causes of ]hemolytic disease of the newborn
Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis foetalis, is an alloimmune condition that develops in a fetus at or around birth, when the IgG molecules (one of the five ...
*** Transfusion reaction
Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mod ...
to blood transfusion
Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
s[
** Mechanical trauma to red blood cells
*** ]Microangiopathic hemolytic anemia
Microangiopathic hemolytic anemia (MAHA) is a microangiopathic subgroup of hemolytic anemia (loss of red blood cells through destruction) caused by factors in the small blood vessels. It is identified by the finding of anemia and schistocytes ...
s, including thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that results in blood clots forming in small blood vessels throughout the body. This results in a low platelet count, low red blood cells due to their breakdown, and often kidney, h ...
and disseminated intravascular coagulation[
*** Infections, including ]malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
[
*** ]Heart surgery
Cardiac surgery, or cardiovascular surgery, is surgery on the heart or great vessels performed by cardiac surgeons. It is often used to treat complications of ischemic heart disease (for example, with coronary artery bypass grafting); to corr ...
*** Haemodialysis
Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatini ...
** Parasitic
*** ''Trypanosoma congolense
''Trypanosoma congolense'' is a species of trypanosomes and is the major pathogen responsible for the disease nagana in cattle and other animals including sheep, pigs, goats, horses and camels, dogs, as well as laboratory mice. It is the mo ...
'' alters the surfaces of RBCs of its host and this may explain ''T. c.'' induced anemia
Blood loss
* Anemia of prematurity, from frequent blood sampling for laboratory testing, combined with insufficient RBC production
* Trauma
Trauma most often refers to:
* Major trauma, in physical medicine, severe physical injury caused by an external source
* Psychological trauma, a type of damage to the psyche that occurs as a result of a severely distressing event
*Traumatic i ...
[ or surgery, causing acute blood loss
* Gastrointestinal tract lesions,][ causing either acute bleeds (e.g. variceal lesions, ]peptic ulcers
Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines i ...
) or chronic blood loss (e.g. angiodysplasia)
* Gynecologic disturbances,[ also generally causing chronic blood loss
* From menstruation, mostly among young women or older women who have fibroids
* Many type of cancers, including colorectal ]cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
and cancer of the urinary bladder
The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine ente ...
, may cause acute or chronic blood loss, especially at advanced stages
* Infection by intestinal nematodes
The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a broa ...
feeding on blood, such as hookworms and the whipworm ''Trichuris trichiura
''Trichuris trichiura, Trichocephalus trichiuris'' or whipworm, is a parasitic roundworm (a type of helminth) that causes trichuriasis (a type of helminthiasis which is one of the neglected tropical diseases) when it infects a human large intes ...
''
* Iatrogenic anemia
Iatrogenic anemia, also known as nosocomial anemia or hospital-acquired anemia, is a condition in which a person develops anemia due to medical interventions, most frequently repeated blood draws. Other factors that contribute to iatrogenic anemi ...
, blood loss from repeated blood draws and medical procedures.
The roots of the words ''anemia'' and ''ischemia'' both refer to the basic idea of "lack of blood", but anemia and ischemia are not the same thing in modern medical terminology. The word ''anemia'' used alone 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). In contrast, the word ''ischemia'' refers solely to the lack of blood (poor perfusion). Thus ischemia in a body part can cause localized anemic effects within those tissues.
Fluid overload
Fluid overload (hypervolemia
Hypervolemia, also known as fluid overload, is the medical condition where there is too much fluid in the blood. The opposite condition is hypovolemia, which is too little fluid volume in the blood. Fluid volume excess in the intravascular compa ...
) causes decreased hemoglobin concentration and apparent anemia:
* General causes of hypervolemia include excessive sodium or fluid intake, sodium or water retention and fluid shift into the intravascular space.
* From the 6th week of pregnancy, hormonal changes cause an increase in the mother's blood volume due to an increase in plasma.
Intestinal inflammation
Certain gastrointestinal disorders can cause anemia. The mechanisms involved are multifactorial and not limited to malabsorption but mainly related to chronic intestinal inflammation, which causes dysregulation of hepcidin
Hepcidin is a protein that in humans is encoded by the ''HAMP'' gene. Hepcidin is a key regulator of the entry of iron into the circulation in mammals.
During conditions in which the hepcidin level is abnormally high, such as inflammation, se ...
that leads to decreased access of iron to the circulation.
* ''Helicobacter pylori
''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is thoug ...
'' infection.
* Gluten-related disorders: untreated celiac disease
Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...
and non-celiac gluten sensitivity
Non-celiac gluten sensitivity (NCGS) or gluten sensitivity is "a clinical entity induced by the ingestion of gluten leading to intestinal and/or extraintestinal symptoms that improve once the gluten-containing foodstuff is removed from the diet, a ...
. Anemia can be the only manifestation of celiac disease, in absence of gastrointestinal or any other symptoms.
* Inflammatory bowel disease.
Diagnosis
Definitions
There are a number of definitions of anemia; reviews
A review is an evaluation of a publication, product, service, or company or a critical take on current affairs in literature, politics or culture. In addition to a critical evaluation, the review's author may assign the work a rating to indic ...
provide comparison and contrast of them. 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
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...
. An operational definition
An operational definition specifies concrete, replicable procedures designed to represent a construct. In the words of American psychologist S.S. Stevens (1935), "An operation is the performance which we execute in order to make known a concept." F ...
is a decrease in whole-blood 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 ...
concentration of more than 2 standard deviations below the mean
There are several kinds of mean in mathematics, especially in statistics. Each mean serves to summarize a given group of data, often to better understand the overall value (magnitude and sign) of a given data set.
For a data set, the '' ari ...
of an age- and sex-matched reference range
In medicine and health-related fields, a reference range or reference interval is the range or the interval of values that is deemed normal for a physiological measurement in healthy persons (for example, the amount of creatinine in the blood, o ...
.
It is difficult to directly measure RBC mass, so the 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 ...
(amount of RBCs) or the 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 ...
(Hb) in the blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
are often used instead to indirectly estimate the value. Hematocrit; however, is concentration dependent and is therefore not completely accurate. For example, during pregnancy a woman's RBC mass is normal but because of an increase in blood volume the hemoglobin and hematocrit are diluted and thus decreased. Another example would be bleeding where the RBC mass would decrease but the concentrations of hemoglobin and hematocrit initially remains normal until fluids shift from other areas of the body to the intravascular space.
The anemia is also classified by severity into mild (110 g/L to normal), moderate (80 g/L to 110 g/L), and severe anemia (less than 80 g/L) in adults. Different values are used in pregnancy and children.[
]
Testing
Anemia is typically diagnosed on a complete blood count
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and pl ...
. Apart from reporting the number of red blood cell
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 ''erythros'' for "red" and ''kytos'' for "holl ...
s and the 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 ...
level, the automatic counters also measure the size of the red blood cells by flow cytometry, which is an important tool in distinguishing between the causes of anemia. Examination of a stained blood smear
A blood smear, peripheral blood smear or blood film is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically. Blood smears are examined in the ...
using a microscope
A microscope () is a laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic means being invisi ...
can also be helpful, and it is sometimes a necessity in regions of the world where automated analysis is less accessible.
A blood test will provide counts of white blood cells, red blood cells and platelets. If anemia appears, further tests may determine what type it is, and whether it has a serious cause. although of that, it is possible to refer to the genetic history and physical diagnosis. These tests may include:
* complete blood count
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and pl ...
(CBC); a CBC is used to count the number of blood cells in a sample of the blood. For anemia, it will likely to be interested in the levels of the red blood cells contained in blood (hematocrit), hemoglobin, mean corpuscular volume.
* determine the size and shape of red blood cells; some of red blood cells might also be examined for unusual size, shape and color.
* serum ferritin; This protein helps store iron in the body, a low levels of ferritin usually indicates a low levels of stored iron.
* serum vitamin B12; low levels usually develop an anemia, vitamin B12 is needed to make red blood cells, which carry oxygen to all parts of human body.
* blood tests to detect rare causes; such as an immune attack on red blood cells, red blood cell fragility, and defects of enzymes, hemoglobin, and clotting.
* a bone marrow sample; when the cause is unclear, a bone marrow test is performed, most often, when some blood cell defect is suspected.
Reticulocyte counts, and the "kinetic" approach to anemia, have become more common than in the past in the large medical centers of the United States and some other wealthy nations, in part because some automatic counters now have the capacity to include reticulocyte counts. A reticulocyte
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 ma ...
count is a quantitative measure of the bone marrow's production of new red blood cells. The reticulocyte production 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. ...
is a calculation of the ratio between the level of anemia and the extent to which the reticulocyte count has risen in response. If the degree of anemia is significant, even a "normal" reticulocyte count actually may reflect an inadequate response.
If an automated count is not available, a reticulocyte count can be done manually following special staining of the blood film. In manual examination, activity of the bone marrow can also be gauged qualitatively by subtle changes in the numbers and the morphology of young RBCs by examination under a microscope. Newly formed RBCs are usually slightly larger than older RBCs and show polychromasia. Even where the source of blood loss is obvious, evaluation of erythropoiesis
Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' "to make") is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
It is stimulated by decrea ...
can help assess whether the bone marrow will be able to compensate for the loss and at what rate.
When the cause is not obvious, clinicians use other tests, such as: ESR, serum iron
Serum iron is a medical laboratory test that measures the amount of circulating iron that is bound to transferrin (90%) and serum ferritin (10%). Clinicians order this laboratory test when they are concerned about iron deficiency, which can cause ...
, transferrin
Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encode ...
, RBC folate level, hemoglobin electrophoresis
Hemoglobin electrophoresis is a blood test that can detect different types of hemoglobin. The test can detect hemoglobin S, the form associated with sickle cell disease, as well as other abnormal types of hemoglobin, such as hemoglobin C. It can a ...
, renal function tests (e.g. serum creatinine
Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass).
Biological relevance
Serum creatinine (a blood measurement) is an importa ...
) although the tests will depend on the clinical hypothesis that is being investigated.
When the diagnosis remains difficult, a bone marrow examination
Bone marrow examination refers to the pathologic analysis of samples of bone marrow obtained by bone marrow biopsy (often called trephine biopsy) and bone marrow aspiration. Bone marrow examination is used in the diagnosis of a number of conditi ...
allows direct examination of the precursors to red cells, although is rarely used as is painful, invasive and is hence reserved for cases where severe pathology needs to be determined or excluded.
Red blood cell size
In the morphological approach, anemia is classified by the size of red blood cells; this is either done automatically or on microscopic examination of a peripheral blood smear. The size is reflected in the mean corpuscular volume (MCV). If the cells are smaller than normal (under 80 fl), the anemia is said to be microcytic; if they are normal size (80–100 fl), normocytic; and if they are larger than normal (over 100 fl), the anemia is classified as macrocytic. This scheme quickly exposes some of the most common causes of anemia; for instance, a microcytic anemia is often the result of 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 ...
. In clinical workup, the MCV will be one of the first pieces of information available, so even among clinicians who consider the "kinetic" approach more useful philosophically, morphology will remain an important element of classification and diagnosis.
Limitations of MCV include cases where the underlying cause is due to a combination of factors – such as iron deficiency (a cause of microcytosis) and vitamin B12 deficiency
Vitamin B12 deficiency, also known as cobalamin deficiency, is the medical condition in which the blood and tissue have a lower than normal level of vitamin B12. Symptoms can vary from none to severe. Mild deficiency may have few or absent symp ...
(a cause of macrocytosis) where the net result can be normocytic cells.
Production vs. destruction or loss
The "kinetic" approach to anemia yields arguably the most clinically relevant classification of anemia. This classification depends on evaluation of several hematological parameters, particularly the blood reticulocyte
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 ma ...
(precursor of mature RBCs) count. This then yields the classification of defects by decreased RBC production versus increased RBC destruction or loss. Clinical signs of loss or destruction include abnormal peripheral blood smear
A blood smear, peripheral blood smear or blood film is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically. Blood smears are examined in the ...
with signs of hemolysis; elevated LDH suggesting cell destruction; or clinical signs of bleeding, such as guaiac-positive stool, radiographic findings, or frank bleeding.
The following is a simplified schematic of this approach:
''*'' ''For instance, sickle cell anemia with superimposed iron deficiency; chronic gastric bleeding with B12 and folate deficiency; and other instances of anemia with more than one cause.''
''**'' ''Confirm by repeating reticulocyte count: ongoing combination of low reticulocyte production index, normal MCV and hemolysis or loss may be seen in bone marrow failure or anemia of chronic disease, with superimposed or related hemolysis or blood loss.''
Here is a schematic representation of how to consider anemia with MCV as the starting point:
Other characteristics visible on the peripheral smear may provide valuable clues about a more specific diagnosis; for example, abnormal white blood cells may point to a cause in the bone marrow.
Microcytic
Microcytic anemia is primarily a result of hemoglobin synthesis failure/insufficiency, which could be caused by several etiologies:
Iron deficiency anemia is the most common type of anemia overall and it has many causes. RBCs often appear hypochromic (paler than usual) and microcytic (smaller than usual) when viewed with a microscope.
* Iron deficiency anemia is due to insufficient dietary intake or absorption of 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 ...
to meet the body's needs. Infants, toddlers, and pregnant women have higher than average needs. Increased iron intake is also needed to offset blood losses due to digestive tract issues, frequent blood donations, or heavy menstrual periods.[Recommendations to Prevent and Control Iron Deficiency in the United States]
MMWR 1998;47 (No. RR-3) p. 5 Iron is an essential part of hemoglobin, and low iron levels result in decreased incorporation of hemoglobin into red blood cells. In the United States, 12% of all women of childbearing age have iron deficiency, compared with only 2% of adult men. The incidence is as high as 20% among African American and Mexican American women. Studies have shown iron deficiency without anemia causes poor school performance and lower IQ in teenage girls, although this may be due to socioeconomic factors. Iron deficiency is the most prevalent deficiency state on a worldwide basis. It is sometimes the cause of abnormal fissuring of the angular (corner) sections of the lips ( angular stomatitis).
* In the United States, the most common cause of iron deficiency is bleeding or blood loss, usually from the gastrointestinal tract. Fecal occult blood testing, upper endoscopy
Esophagogastroduodenoscopy (EGD) or oesophagogastroduodenoscopy (OGD), also called by various other names, is a diagnostic endoscopic procedure that visualizes the upper part of the gastrointestinal tract down to the duodenum. It is considered ...
and lower endoscopy should be performed to identify bleeding lesions. In older men and women, the chances are higher that bleeding from the gastrointestinal tract could be due to colon polyp
A colorectal polyp is a polyp (fleshy growth) occurring on the lining of the colon or rectum. Untreated colorectal polyps can develop into colorectal cancer.
Colorectal polyps are often classified by their behaviour (i.e. benign vs. malignant) o ...
s or colorectal cancer.
* Worldwide, the most common cause of iron deficiency anemia is parasitic infestation ( hookworms, amebiasis
Amoebiasis, or amoebic dysentery, is an infection of the intestines caused by a parasitic amoeba ''Entamoeba histolytica''. Amoebiasis can be present with no, mild, or severe symptoms. Symptoms may include lethargy, loss of weight, colonic ulc ...
, schistosomiasis and whipworm
''Trichuris trichiura, Trichocephalus trichiuris'' or whipworm, is a parasitic roundworm (a type of helminth) that causes trichuriasis (a type of helminthiasis which is one of the neglected tropical diseases) when it infects a human large intes ...
s).
The Mentzer index
The Mentzer index, described in 1973 by William C. Mentzer, is the MCV divided by the RBC count. It is said to be helpful in differentiating iron deficiency anemia from beta thalassemia.
The index is calculated from the results of a complete bloo ...
(mean cell volume divided by the RBC count) predicts whether microcytic anemia may be due to iron deficiency or thalassemia, although it requires confirmation.
Macrocytic
* Megaloblastic anemia
Megaloblastic anemia is a type of macrocytic anemia. An anemia is a red blood cell defect that can lead to an undersupply of oxygen. Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell production. When DNA synth ...
, the most common cause of macrocytic anemia, is due to a deficiency of either vitamin B12, folic acid
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
, or both. Deficiency in folate or vitamin B12 can be due either to inadequate intake or insufficient absorption. Folate deficiency normally does not produce neurological symptoms, while B12 deficiency does.
** Pernicious anemia
Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic fa ...
is caused by a lack of intrinsic factor
Intrinsic factor (IF), cobalamin binding intrinsic factor, also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the parietal cells (in humans) or chief cells (in rodents) of the stomach. It is necessary for the absorption ...
, which is required to absorb vitamin B12 from food. A lack of intrinsic factor may arise from an autoimmune
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". ...
condition targeting the parietal cells (atrophic gastritis) that produce intrinsic factor or against intrinsic factor itself. These lead to poor absorption of vitamin B12.
** Macrocytic anemia can also be caused by the removal of the functional portion of the stomach, such as during gastric bypass surgery, leading to reduced vitamin B12/folate absorption. Therefore, one must always be aware of anemia following this procedure.
* Hypothyroidism
* Alcoholism commonly causes a macrocytosis, although not specifically anemia. Other types of liver disease can also cause macrocytosis.
* Drugs such as methotrexate, zidovudine, and other substances may inhibit DNA replication such as heavy metals
Macrocytic anemia can be further divided into "megaloblastic anemia" or "nonmegaloblastic macrocytic anemia". The cause of megaloblastic anemia is primarily a failure of DNA synthesis with preserved RNA synthesis, which results in restricted cell division of the progenitor cells. The megaloblastic anemias often present with neutrophil hypersegmentation (six to 10 lobes). The nonmegaloblastic macrocytic anemias have different etiologies (i.e. unimpaired DNA globin synthesis,) which occur, for example, in alcoholism.
In addition to the nonspecific symptoms of anemia, specific features of vitamin B12 deficiency include peripheral neuropathy and subacute combined degeneration of the cord with resulting balance difficulties from posterior column spinal cord pathology. Other features may include a smooth, red tongue and glossitis.
The treatment for vitamin B12-deficient anemia was first devised by William Murphy (scientist), William Murphy, who bled dogs to make them anemic, and then fed them various substances to see what (if anything) would make them healthy again. He discovered that ingesting large amounts of liver seemed to cure the disease. George Richards Minot, George Minot and George Whipple then set about to isolate the curative substance chemically and ultimately were able to isolate the vitamin B12 from the liver. All three shared the 1934 Nobel Prize in Physiology or Medicine, Nobel Prize in Medicine.
Normocytic
Normocytic anemia occurs when the overall hemoglobin levels are decreased, but the red blood cell size ( mean corpuscular volume) remains normal. Causes include:
Dimorphic
A dimorphic appearance on a peripheral blood smear occurs when there are two simultaneous populations of red blood cells, typically of different size and hemoglobin content (this last feature affecting the color of the red blood cell on a stained peripheral blood smear). For example, a person recently transfused for iron deficiency would have small, pale, iron deficient red blood cells (RBCs) and the donor RBCs of normal size and color. Similarly, a person transfused for severe folate or vitamin B12 deficiency would have two cell populations, but, in this case, the patient's RBCs would be larger and paler than the donor's RBCs. A person with sideroblastic anemia (a defect in heme synthesis, commonly caused by alcoholism, but also drugs/toxins, nutritional deficiencies, a few acquired and rare congenital diseases) can have a dimorphic smear from the sideroblastic anemia alone. Evidence for multiple causes appears with an elevated RBC distribution width (RDW), indicating a wider-than-normal range of red cell sizes, also seen in common nutritional anemia.
Heinz body anemia
Heinz body, Heinz bodies form in the cytoplasm of RBCs and appear as small dark dots under the microscope. In animals, Heinz body anemia has many causes. It may be drug-induced, for example in cats and dogs by acetaminophen (paracetamol), or may be caused by eating various plants or other substances:
* In cats and dogs after eating either raw or cooked plants from the genus ''Allium'', for example, onions or garlic.
* In dogs after ingestion of zinc, for example, after eating Penny (United States coin), U.S. pennies minted after 1982.
* In horses which eat dry or wilted Acer rubrum, red maple leaves.
Hyperanemia
Hyperanemia is a severe form of anemia, in which the 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 ...
is below 10%.
Refractory anemia
Refractory anemia, an anemia which does not respond to Therapy, treatment, is often seen secondary to myelodysplastic syndromes. 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 ...
may also be refractory as a manifestation of gastrointestinal problems which disrupt Human iron metabolism, iron absorption or cause occult bleeding.
Transfusion dependent
Transfusion dependent anemia is a form of anemia where ongoing blood transfusion are required. Most people with myelodysplastic syndrome develop this state at some point in time.[ Beta thalassemia may also result in transfusion dependence. Concerns from repeated blood transfusions include iron overload.] This iron overload may require chelation therapy.
Treatment
Treatment for anemia depends on cause and severity. Vitamin supplements given orally (folic acid
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
or vitamin B12) or intramuscularly (Cyanocobalamin, vitamin B12) will replace specific deficiencies.
Oral iron
Nutritional iron deficiency is common in developing nations. An estimated two-thirds of children and of women of childbearing age in most developing nations are estimated to have iron deficiency without anemia; one-third of them have iron deficiency with anemia. Iron deficiency due to inadequate dietary iron intake is rare in men and postmenopausal women. The diagnosis of iron deficiency mandates a search for potential sources of blood loss, such as gastrointestinal bleeding from ulcers or colon cancer.
Mild to moderate iron-deficiency anemia is treated by oral iron supplementation with Iron(II) sulfate, ferrous sulfate, ferrous fumarate, or ferrous gluconate. Daily iron supplements have been shown to be effective in reducing anemia in women of childbearing age. When taking iron supplements, stomach upset or darkening of the feces are commonly experienced. The stomach upset can be alleviated by taking the iron with food; however, this decreases the amount of iron absorbed. Vitamin C aids in the body's ability to absorb iron, so taking oral iron supplements with orange juice is of benefit.
In the anemia of chronic kidney disease, recombinant protein, recombinant erythropoietin or epoetin alfa is recommended to stimulate RBC production, and if iron deficiency and inflammation are also present, concurrent parenteral iron is also recommended.
Injectable iron
In cases where oral iron has either proven ineffective, would be too slow (for example, pre-operatively), or where absorption is impeded (for example in cases of inflammation), parenteral iron preparations can be used. Parenteral iron can improve iron stores rapidly and is also effective for treating people with postpartum haemorrhage, inflammatory bowel disease, and chronic heart failure. The body can absorb up to 6 mg iron daily from the gastrointestinal tract. In many cases, the patient has a deficit of over 1,000 mg of iron which would require several months to replace. This can be given concurrently with erythropoietin to ensure sufficient iron for increased rates of erythropoiesis
Erythropoiesis (from Greek 'erythro' meaning "red" and 'poiesis' "to make") is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
It is stimulated by decrea ...
.
Blood transfusions
Blood transfusions in those without symptoms is not recommended until the hemoglobin is below 60 to 80 g/L (6 to 8 g/dL).[ In those with coronary artery disease who are not actively bleeding transfusions are only recommended when the hemoglobin is below 70 to 80g/L (7 to 8 g/dL).][ Transfusing earlier does not improve survival.] Transfusions otherwise should only be undertaken in cases of cardiovascular instability.
A 2012 review concluded that when considering blood transfusions for anaemia in people with advanced cancer who have fatigue and breathlessness (not related to cancer treatment or haemorrhage), consideration should be given to whether there are alternative strategies can be tried before a blood transfusion.
Vitamin B12 intramuscular injections
In many cases, vitamin B12 is used by intramuscular injection in severe cases or cases of malabsorption of dietary-B12. Pernicious anemia
Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic fa ...
caused by loss of intrinsic factor
Intrinsic factor (IF), cobalamin binding intrinsic factor, also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the parietal cells (in humans) or chief cells (in rodents) of the stomach. It is necessary for the absorption ...
cannot be prevented. If there are other, reversible causes of low vitamin B12 levels, the cause must be treated.
Vitamin B12 deficiency anemia is usually easily treated by providing the necessary level of vitamin B12 supplementation. The injections are quick-acting, and symptoms usually go away within one to two weeks. As the condition improves, doses are reduced to weeks and then can be given monthly. Intramuscular therapy leads to more rapid improvement and should be considered in patients with severe deficiency or severe Neurological disorder, neurologic symptoms. Treatment should begin rapidly for severe neurological symptoms, as some changes can become permanent. In some individuals lifelong treatment may be needed.
Erythropoiesis-stimulating agents
The objective for the administration of an erythropoiesis-stimulating agent (ESA) is to maintain hemoglobin at the lowest level that both minimizes transfusions and meets the individual person's needs. They should not be used for mild or moderate anemia.[ They are not recommended in people with chronic kidney disease unless hemoglobin levels are less than 10 g/dL or they have symptoms of anemia. Their use should be along with parenteral iron.] The 2020 Cochrane Anaesthesia Review Group review of Erythropoietin plus iron versus control treatment including placebo or iron for preoperative anaemic adults undergoing non‐cardiac surgery demonstrated that patients were much less likely to require red cell transfusion and in those transfused, the volumes were unchanged (mean difference -0.09, 95% CI -0.23 to 0.05). Pre-op Hb concentration was increased in those receiving 'high dose' EPO, but not 'low dose'.
Hyperbaric oxygen
Treatment of exceptional blood loss (anemia) is recognized as an indication for hyperbaric oxygen (HBO) by the Undersea and Hyperbaric Medical Society. The use of HBO is indicated when oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...
delivery to tissue is not sufficient in patients who cannot be given blood transfusion
Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
s for medical or religious reasons. HBO may be used for medical reasons when threat of blood product incompatibility or concern for Transmission (medicine), transmissible disease are factors.[ The beliefs of some religions (ex: Jehovah's Witnesses and blood transfusions, Jehovah's Witnesses) may require they use the HBO method.][ A 2005 review of the use of HBO in severe anemia found all publications reported positive results.
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Preoperative anemia
An estimated 30% of adults who require non-cardiac surgery have anemia. In order to determine an appropriate preoperative treatment, it is suggested that the cause of anemia be first determined. There is moderate level medical evidence that supports a combination of iron supplementation and erythropoietin treatment to help reduce the requirement for red blood cell transfusions after surgery in those who have preoperative anemia.
Epidemiology
Anemia affects 27% of the world's population with iron-deficiency anemia accounting for more than 60% of it. A moderate degree of 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 ...
affected approximately 610 million people worldwide or 8.8% of the population.[ It is somewhat more common in females (9.9%) than males (7.8%).][ Mild iron deficiency anemia affects another 375 million.][ Severe anaemia is prevalent globally, and especially in sub-Saharan Africa where it is associated with infections including malaria and invasive bacterial infections.
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History
Signs of severe anemia in human bones from 4000 years ago have been uncovered in Thailand.
References
External links
Anemia, U.S. National Library of Medicine
{{Authority control
[About Anemia]
Anemias
Hematopathology
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Transfusion medicine