Anemia × Paraphyllitidis
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Anemia (also spelt anaemia in
British English British English is the set of Variety (linguistics), varieties of the English language native to the United Kingdom, especially Great Britain. More narrowly, it can refer specifically to the English language in England, or, more broadly, to ...
) is a
blood disorder Hematologic diseases are disorders which primarily affect the blood and blood-forming organs. Hematologic diseases include rare genetic disorders, anemia, HIV, sickle cell disease and complications from chemotherapy or transfusions. Myeloid * ...
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 is com ...
has a reduced ability to carry
oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...
. This can be due to a lower than normal number of
red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...
s, a reduction in the amount of
hemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. Hemoglobin ...
available for oxygen transport, or abnormalities in hemoglobin that impair its function. The name is derived . When anemia comes on slowly, the symptoms are often vague, such as
tiredness Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated with medical conditions ...
,
weakness Weakness is a symptom of many different medical 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, ...
,
shortness of breath Shortness of breath (SOB), 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 discomfort that con ...
,
headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...
s, and a reduced ability to exercise. When anemia is acute, symptoms may include
confusion In psychology, confusion is the quality or emotional state of being bewildered or unclear. The term "acute mental confusion"
, feeling like one is going to pass out,
loss of consciousness Unconsciousness is a state in which a living individual exhibits a complete, or near-complete, inability to maintain an awareness of self and environment or to respond to any human or environmental stimulus. Unconsciousness may occur as the re ...
, and increased thirst. Anemia must be significant before a person becomes noticeably
pale Pale may refer to: Jurisdictions * Medieval areas of English conquest: ** Pale of Calais, in France (1360–1558) ** The Pale, or the English Pale, in Ireland *Pale of Settlement, area of permitted Jewish settlement, western Russian Empire (179 ...
. Additional symptoms may occur depending on the underlying cause. 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 blood loss include bleeding due to inflammation of the stomach or intestines, bleeding from
surgery Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...
, serious
injury Injury is physiological damage to the living tissue of any organism, whether in humans, in other animals, or in plants. Injuries can be caused in many ways, including mechanically with penetration by sharp objects such as teeth or with ...
, or
blood donation A 'blood donation'' occurs when a person voluntarily has blood drawn and used for transfusions and/or made into biopharmaceutical medications by a process called fractionation (separation of whole blood components). A donation may be of wh ...
. 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 ...
,
folate deficiency Folate deficiency, also known as vitamin B9 deficiency, is a low level of folate and derivatives in the body. This may result in megaloblastic anemia in which red blood cells become abnormally large, and folate deficiency anemia is the term given ...
,
vitamin B12 deficiency Vitamins are organic molecules (or a set of closely related molecules called vitamers) that are essential to an organism in small quantities for proper metabolic function. Essential nutrients cannot be synthesized in the organism in suff ...
,
thalassemia Thalassemias are a group of Genetic disorder, inherited blood disorders that manifest as the production of reduced hemoglobin. Symptoms depend on the type of thalassemia and can vary from none to severe, including death. Often there is mild to ...
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 chromosome abnormality. Although polygenic disorders ...
s such as
sickle cell anemia Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the oxygen-carrying ...
, infections such as
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
, and certain
autoimmune disease An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated tha ...
s like
autoimmune hemolytic anemia Autoimmune hemolytic anemia (AIHA) occurs when a person's immune system produces antibodies directed against their own red blood cells (RBCs). These antibodies attach to red cells, causing them to break down ( lyse), and reducing the number of ox ...
. 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; if they are large, it is called
macrocytic anemia Macrocytic anemia is a condition and blood disorder characterized by the presence of predominantly larger-than-normal erythrocytes (red blood cells, or ''RBCs'') accompanied by low numbers of RBC, which often carry an insufficient amount of hemogl ...
; 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 people 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 anemia o ...
. 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. Treatment depends on the specific cause. Certain groups of individuals, such as pregnant women, can benefit from the use of iron pills for prevention.
Dietary supplement A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients eithe ...
ation, 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 Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used ...
s is typically based on a person's signs and symptoms. 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 t ...
s are only recommended in those with severe anemia. Anemia is the most common blood disorder, affecting about a fifth to a third of the global population.
Iron-deficiency anemia Iron-deficiency anemia is anemia caused by a iron deficiency, 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 Fatigue ( ...
is the most common cause of anemia worldwide, and affects nearly one 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). Anemia is one of the six
WHO The World Health Organization (WHO) is a specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Geneva, Switzerland, and has 6 regional offices and 15 ...
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 World Health Organization#Membership, member states. It is the world's highest health policy setting body and is composed of h ...
in 2012 and 2013. Efforts to reach global targets contribute to reaching
Sustainable Development Goals The ''2030 Agenda for Sustainable Development'', adopted by all United Nations (UN) members in 2015, created 17 world Sustainable Development Goals (SDGs). The aim of these global goals is "peace and prosperity for people and the planet" – wh ...
(SDGs), with anemia as one of the targets in SDG 2 for achieving zero world hunger.


Signs and symptoms

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), 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 discomfort that con ...
on
exertion Exertion is the Action (physics), 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 ''e ...
. These symptoms are unspecific and none of the symptoms alone or in combination show a good predictive value for the presence of anemia in non-clinical patients. 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 Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...
, headaches, intolerance to physical exertion, shortness of breath, difficulty concentrating, irregular or
rapid Rapid(s) or RAPID may refer to: Hydrological features * Rapids, sections of a river with turbulent water flow * Rapid Creek (Iowa River tributary), Iowa, United States * Rapid Creek (South Dakota), United States, namesake of Rapid City Sport ...
heartbeat, cold hands and feet,
cold intolerance Cold sensitivity or cold intolerance is unusual discomfort felt by some people when in a cool environment. Cold sensitivity may be a symptom of hypothyroidism, anemia, low body weight, iron deficiency, vitamin B12 deficiency, fevers, fibromyalgia ...
,
pale Pale may refer to: Jurisdictions * Medieval areas of English conquest: ** Pale of Calais, in France (1360–1558) ** The Pale, or the English Pale, in Ireland *Pale of Settlement, area of permitted Jewish settlement, western Russian Empire (179 ...
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 t ...
skin, poor appetite, easy bruising and bleeding, and
muscle weakness Muscle weakness is a lack of muscle strength. Its causes are many and can be divided into conditions that have either true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, includ ...
. Anemia that develops quickly, often, has more severe symptoms, including, feeling faint,
chest pain Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with n ...
, 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 In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: tha ...
. The person may have symptoms related to this, such as
palpitations Palpitations occur when a person becomes aware of their heartbeat. The heartbeat may feel hard, fast, or uneven in their chest. Symptoms include a very fast or irregular heartbeat. Palpitations are a sensory symptom. They are often described as ...
,
angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of parti ...
(if pre-existing
heart disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina pectoris, angina, myocardial infarction, heart attack), heart failure, ...
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 ...
of the legs, and symptoms of
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...
. On examination, the signs exhibited may include
pallor Pallor is a pale color of the skin that can be caused by illness, emotional shock or stress, stimulant use, or anemia, and is the result of a reduced amount of oxyhaemoglobin and may also be visible as pallor of the conjunctivae of the eye ...
(pale skin,
mucosa A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It ...
,
conjunctiva In the anatomy of the eye, the conjunctiva (: conjunctivae) 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 gobl ...
and
nail beds A nail is a protective plate characteristically found at the tip of the digits (fingers and toes) of all primates, corresponding to the claws in other tetrapod animals. Fingernails and toenails are made of a tough rigid protein called alpha-k ...
), but this is not a reliable sign. Iron-deficiency anemia may give symptoms that can include spoon-shaped nails, restless legs syndrome, and pica (the medical condition indicates the desire for things that are not food, such as ice, dirt, etc.). A blue coloration of the
sclera The sclera, also known as the white of the eye or, in older literature, as the tunica albuginea oculi, is the opaque, fibrous, protective outer layer of the eye containing mainly collagen and some crucial elastic fiber. In the development of t ...
may be noticed in some cases of iron-deficiency anemia. Vitamin B12 deficiency anemia may result in decreased ability to think, memory loss, confusion, personality or mood changes, depression, difficulty walking, blurred vision, and irreversible nerve damage. Other specific causes of anemia may have signs and/or complications such as,
jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
with the rapid break down of
red blood cells Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...
as with
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 commonl ...
, bone abnormalities with thalassemia major, or leg
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 ...
as seen in
sickle cell disease Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited Hemoglobinopathy, haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the ...
. 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, presentin ...
:
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, flow murmurs, and
cardiac The heart is a muscular organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrients to the tissu ...
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 vent ...
(enlargement). There may be signs of
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...
. 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, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. Hemoglobin ...
. 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 a neurological disorder, usually chronic, that causes an overwhelming urge to move one's legs. There is often an unpleasant feeling in the legs that improves temporaril ...
is more common in people with
iron-deficiency anemia Iron-deficiency anemia is anemia caused by a iron deficiency, 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 Fatigue ( ...
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 mult ...
Table 12-1 in: **
Aplastic anemia Aplastic anemia (AA) is a severe hematologic condition in which the body fails to make blood cells in sufficient numbers. Normally, blood cells are produced in the bone marrow by stem cells that reside there, but patients with 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 anemia (FA) is a rare, autosomal recessive genetic disease characterized by aplastic anemia, congenital defects, endocrinological abnormalities, and an increased incidence of developing cancer. The study of Fanconi anemia has improve ...
is a hereditary disorder or defect featuring aplastic anemia and various other abnormalities. ** Anemia of
kidney failure Kidney failure, also known as renal failure or end-stage renal disease (ESRD), 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 fa ...
due to insufficient production of the
hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
erythropoietin 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 th ...
** 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: # Endocri ...
* Disturbance of proliferation and maturation of
erythroblast A nucleated red blood cell (NRBC), also known by #Nomenclature, 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 mamm ...
s **
Pernicious anemia Pernicious anemia is a disease where not enough red blood cells are produced due to a deficiency of Vitamin B12, vitamin B12. Those affected often have a gradual onset. The most common initial symptoms are Fatigue, feeling tired and weak. Other ...
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 replication, DNA synthesis during red blood cell production. ...
due to
vitamin B12 deficiency Vitamins are organic molecules (or a set of closely related molecules called vitamers) that are essential to an organism in small quantities for proper metabolic function. Essential nutrients cannot be synthesized in the organism in suff ...
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. This may result in megaloblastic anemia in which red blood cells become abnormally large, and folate deficiency anemia is the term given ...
, 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 replication, DNA synthesis during red blood cell production. ...
**
Anemia of prematurity Anemia of prematurity (AOP) refers to a form of anemia affecting preterm infants with decreased hematocrit. AOP is a normochromic, normocytic hypoproliferative anemia. The primary mechanism of AOP is a decrease in erythropoietin (EPO), a red blood ...
, 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 nor ...
levels, combined with blood loss from laboratory testing, generally occurs in premature infants at two to six weeks of age. ** Iron-deficiency anemia, resulting in deficient heme synthesis **
Thalassemia Thalassemias are a group of Genetic disorder, inherited blood disorders that manifest as the production of reduced hemoglobin. Symptoms depend on the type of thalassemia and can vary from none to severe, including death. Often there is mild to ...
s, causing deficient globin synthesis **
Congenital dyserythropoietic anemia Congenital dyserythropoietic anemia (CDA) is a rare blood disorder, similar to the thalassemias. CDA is one of many types of anemia, characterized by ineffective erythropoiesis, and resulting from a decrease in the number of red blood cells (RBCs) ...
s, causing ineffective erythropoiesis ** Anemia of kidney failure (also causing stem cell dysfunction) * Other mechanisms of impaired RBC production ** Myelophthisic anemia or
myelophthisis Myelophthisic anemia (or myelophthisis) is a severe type of anemia found in some people with diseases that affect the bone marrow. Myelophthisis refers to the displacement of hemopoietic bone-marrow tissue by fibrosis, tumors, or granulomas. The w ...
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 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 includ ...
** anemia of
chronic inflammation Chronic systemic inflammation 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 such ...
** Leukoerythroblastic anemia is caused by space-occupying lesions in the
bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, 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 i ...
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 commonl ...
s. These types generally feature
jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
, 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 pyruvic acid, pyruvate to lactic acid, lactate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that t ...
. * 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 ...
, 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 chromosome abnormality. Although polygenic disorders ...
s. **
Hereditary spherocytosis Hereditary spherocytosis (HS) is a congenital hemolytic disorder wherein a genetic genetic mutation, mutation coding for a structural membrane protein phenotype causes the red blood cells to be sphere-shaped (spherocytosis), rather than the norma ...
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 (, from Ancient Greek '' σπλήν'', splḗn) is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The spleen plays important roles in reg ...
. **
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 distinctiv ...
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 characterized by abnormal absorption of fat and ...
, 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. Pyruv ...
and
hexokinase A hexokinase is an enzyme that irreversibly 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 p ...
deficiencies, causing defect
glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvic acid, pyruvate and, in most organisms, occurs in the liquid part of cells (the cytosol). The Thermodynamic free energy, free energy released in this process is used to form ...
***
Glucose-6-phosphate dehydrogenase deficiency Glucose-6-phosphate dehydrogenase deficiency (G6PDD), also known as favism, is the most common enzyme deficiency anemia worldwide. It is an inborn error of metabolism that predisposes to red blood cell breakdown. Most of the time, those who ar ...
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), also simply called sickle cell, is a group of inherited haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the oxygen-carrying ...
*** 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 ...
* Extrinsic (extracorpuscular) abnormalities **
Antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
-mediated ***
Warm autoimmune hemolytic anemia Warm antibody autoimmune hemolytic anemia (WAIHA) is the most common form of autoimmune haemolytic anemia. About half of the cases are of unknown cause, with the other half attributable to a predisposing condition or medications being taken. Contr ...
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 ...
diseases. It can be
idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin. For some medical conditions, one or more causes are somewhat understood, but in a certain percentage of people with the condition, the cause ...
, that is, without any known cause, drug-associated or secondary to another disease such as
systemic lupus erythematosus Lupus, formally called systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common ...
, 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, one of the causes of hemolytic disease of the newborn *** Transfusion reaction to
blood transfusion Blood transfusion is the process of transferring blood products into a person's Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used ...
s ** Mechanical trauma to red blood cells *** Microangiopathic hemolytic anemias, including thrombotic thrombocytopenic purpura and disseminated intravascular coagulation *** Infections, including
malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...
*** Heart surgery *** Haemodialysis ** Parasitic *** ''Trypanosoma congolense'' alters the surfaces of RBCs of its host and this may explain ''T. c.'' induced anemia


Blood loss

*
Anemia of prematurity Anemia of prematurity (AOP) refers to a form of anemia affecting preterm infants with decreased hematocrit. AOP is a normochromic, normocytic hypoproliferative anemia. The primary mechanism of AOP is a decrease in erythropoietin (EPO), a red blood ...
, from frequent blood sampling for laboratory testing, combined with insufficient RBC production * Physical trauma, Trauma or
surgery Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...
, causing acute blood loss * Gastrointestinal tract lesions, causing either acute bleeds (e.g. variceal lesions, peptic ulcers, Hemorrhoid, hemorrhoids) 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 fibroma, fibroids * Many type of cancers, including colorectal cancer and cancer of the urinary bladder, may cause acute or chronic blood loss, especially at advanced stages * Infection by intestinal nematodes feeding on blood, such as hookworms and the whipworm ''Trichuris trichiura'' * Iatrogenic anemia, 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 Systemic effect, 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) 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 sixth 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 that leads to decreased access of iron to the circulation. * ''Helicobacter pylori'' infection. * Gluten-related disorders: untreated celiac disease and non-celiac gluten sensitivity. 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; review article, reviews 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 a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...
. An operational definition is a decrease in whole-blood
hemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. Hemoglobin ...
concentration of more than 2 standard deviations below the mean of an age- and sex-matched Reference ranges for blood tests#Hematology, reference range. 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 nor ...
(amount of RBCs) or the hemoglobin (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 is com ...
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. Apart from reporting the number of
red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...
s and the hemoglobin level, the Automated analyser, 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 using a microscope 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 also include Ferritin, serum ferritin, Serum iron, iron studies, Serum vitamin B12, vitamin B12, genetic testing, and a Bone marrow examination, bone marrow sample, if needed. 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 count is a quantitative measure of the
bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, 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 i ...
's production of new red blood cells. The reticulocyte production index 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 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: erythrocyte sedimentation rate, ESR, serum iron, transferrin, folate, RBC folate level, hemoglobin electrophoresis, renal function tests (e.g. serum creatinine) although the tests will depend on the clinical hypothesis that is being investigated. When the diagnosis remains difficult, a bone marrow examination 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 femtolitre, fl), the anemia is said to be microcytic anemia, 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 anemia, 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 (medicine), iron deficiency. 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 (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 (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 with signs of hemolysis; elevated Lactate dehydrogenase, 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 Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, 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 i ...
.


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 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 Menorrhagia, 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. In India it is even more than 50%. Studies have linked iron deficiency without anemia to 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, Fecal occult blood testing, esophagogastroduodenoscopy, upper endoscopy and colonoscopy, 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 Polyp (medicine), colon polyps or colorectal cancer. * Worldwide, the most common cause of iron-deficiency anemia is parasitic infestation (hookworms, amebiasis, schistosomiasis and Trichuris trichiura, whipworms). The Mentzer index (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, the most common cause of macrocytic anemia, is due to a deficiency of either vitamin B12, vitamin B12, folic acid, or both. Deficiency in folate or vitamin B12 can be due either to inadequate intake or malabsorption, insufficient absorption. Folate deficiency normally does not produce neurological symptoms, while B12 deficiency does. **
Pernicious anemia Pernicious anemia is a disease where not enough red blood cells are produced due to a deficiency of Vitamin B12, vitamin B12. Those affected often have a gradual onset. The most common initial symptoms are Fatigue, feeling tired and weak. Other ...
is caused by a lack of intrinsic factor, which is required to absorb vitamin B12 from food. A lack of intrinsic factor may arise from an autoimmune 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, 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 nor ...
is below 10%.


Refractory anemia

Refractory anemia, an anemia which does not respond to treatment, is often seen secondary to myelodysplastic syndromes. Iron-deficiency anemia 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

The global market for anemia treatments is estimated at more than USD 23 billion per year and is fast growing because of the rising prevalence and awareness of anemia. The types of anemia treated with drugs are iron-deficiency anemia,
thalassemia Thalassemias are a group of Genetic disorder, inherited blood disorders that manifest as the production of reduced hemoglobin. Symptoms depend on the type of thalassemia and can vary from none to severe, including death. Often there is mild to ...
, aplastic anemia,
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 commonl ...
, sickle cell disease, sickle cell anemia, and pernicious anemia, the most important of them being deficiency and sickle cell anemia with together 60% of market share because of highest prevalence as well as higher treatment costs compared with other types. Treatment for anemia depends on cause and severity. Vitamin supplements given orally (folic acid or vitamin B12) or intramuscularly (Cyanocobalamin, vitamin B12) will replace specific deficiencies. Apart from that, iron supplements, antibiotics, immunosuppressant, bone marrow stimulants, corticosteroids, gene therapy and iron chelating agents are forms of anemia treatment drugs, with immunosuppressants and corticosteroids accounting for 58% of the market share. A paradigm shift towards gene therapy and monoclonal antibody therapies is observed.


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 with one-third of them having an 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 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 th ...
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 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 th ...
to ensure sufficient iron for increased rates of erythropoiesis.


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 caused by loss of intrinsic factor 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 (EPO) 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-operative hemoglobin 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 a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...
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 Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used ...
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.


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 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. Globally, the prevalence of anaemia in women aged 15 to 49 years increased from 28.5% in 2012 to 29.9% in 2019 and is projected to reach 32.3% by 2030, missing the Sustainable Development Goals, Sustainable Development Goal target of a 50 percent reduction by 2030.


History

Signs of severe anemia in human bones from 4000 years ago have been uncovered in Thailand.


Sources


References


External links


WHO fact sheet on anaemia


{{Authority control Anemias Hematopathology Wikipedia medicine articles ready to translate Wikipedia emergency medicine articles ready to translate Transfusion medicine