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Anemia may lead to malaise, pallor and associated symptoms such as palpitations.
Low platelet counts (thrombocytopenia) if present is associated with an increased risk of hemorrhage, bruising and petechiae. Low white blood cell counts (leukocytopenia) if present leads to an increased risk of infections which can be severe.
In general, signs of anemia (pallor, fatigue, shortness of breath, and potential for heart failure) are present. In small children, failure to thrive may occur in any form of anemia. Certain aspects of the medical history can suggest a cause for hemolysis, such as drugs, consumption of fava beans due to Favism, the presence of prosthetic heart valve, or other medical illness.
Chronic hemolysis leads to an increased excretion of bilirubin into the biliary tract, which in turn may lead to gallstones. The continuous release of free hemoglobin has been linked with the development of pulmonary hypertension (increased pressure over the pulmonary artery); this, in turn, leads to episodes of syncope (fainting), chest pain, and progressive breathlessness. Pulmonary hypertension eventually causes right ventricular heart failure, the symptoms of which are peripheral edema (fluid accumulation in the skin of the legs) and ascites (fluid accumulation in the abdominal cavity).
Anemia goes undetected in many people and symptoms can be minor. The symptoms can be related to an underlying cause or the anemia itself.
Most commonly, people with anemia report feelings of weakness or tired, and sometimes poor concentration. They may also report shortness of breath on exertion. In very severe anemia, the body may compensate for the lack of oxygen-carrying capability of the blood by increasing cardiac output. The patient may have symptoms related to this, such as palpitations, angina (if pre-existing heart disease is present), intermittent claudication of the legs, and symptoms of heart failure.
On examination, the signs exhibited may include pallor (pale skin, lining mucosa, conjunctiva and nail beds), but this is not a reliable sign. There may be signs of specific causes of anemia, e.g., koilonychia (in iron deficiency), jaundice (when anemia results from abnormal break down of red blood cells — in hemolytic anemia), bone deformities (found in thalassemia major) or leg ulcers (seen in sickle-cell disease).
In severe anemia, there may be signs of a hyperdynamic circulation: tachycardia (a fast heart rate), bounding pulse, flow murmurs, and cardiac ventricular hypertrophy (enlargement). There may be signs of heart failure.
Pica, the consumption of non-food items such as ice, but also paper, wax, or grass, and even hair or dirt, may be a symptom of iron deficiency, although it occurs often in those who have normal levels of 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 is more common in those with iron-deficiency 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, but usually in the spleen). It has numerous possible consequences, ranging from relatively harmless to life-threatening. The general classification of hemolytic anemia is either inherited or acquired. Treatment depends on the cause and nature of the breakdown.
Symptoms of hemolytic anemia are similar to other forms of anemia (fatigue and shortness of breath), but in addition, the breakdown of red cells leads to jaundice and increases the risk of particular long-term complications, such as gallstones and pulmonary hypertension.
AIHA is classified as either warm autoimmune hemolytic anemia or cold autoimmune hemolytic anemia, which includes cold agglutinin disease and paroxysmal cold hemoglobinuria. These classifications are based on the characteristics of the autoantibodies involved in the pathogenesis of the disease. Each has a different underlying cause, management, and prognosis, making classification important when treating a patient with AIHA.
Symptoms of sideroblastic anemia include skin paleness, fatigue, dizziness, and enlarged spleen and liver. Heart disease, liver damage, and kidney failure can result from iron buildup in these organs.
Reticulocytopenia, also known as an "aplastic crisis" or "marrow failure", is the medical term for an abnormal decrease of reticulocytes in the body. Reticulocytes are immature red blood cells. Reticulocytopenia may be a result of viral parvovirus B19 infection, which invades and destroys red blood cell precursors and halts the red cell production. If infection occurs in individuals with sickle cell anemia, spherocytosis, or Beta thalassemia that will lead to incorporation of two anemia-induced mechanisms: decreased red cell production and hemolysis. The result is a rapid and severe anemia (aplastic crisis) which may require blood transfusion.
Microcytic anaemia is any of several types of anaemia characterized by small red blood cells (called microcytes). The normal mean corpuscular volume (abbreviated to MCV on full blood count results) is 80-100 fL, with smaller cells (100 fL) as macrocytic (the latter occur in macrocytic anemia).The MCV is the average red blood cell size.
In microcytic anaemia, the red blood cells (erythrocytes) are usually also hypochromic, meaning that the red blood cells appear paler than usual. This is reflected by a lower-than-normal mean corpuscular hemoglobin concentration (MCHC), a measure representing the amount of hemoglobin per unit volume of fluid inside the cell; normally about 320-360 g/L or 32-36 g/dL. Typically, therefore, anemia of this category is described as "microcytic, hypochromic anaemia".
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.
Autoimmune hemolytic anemia (or autoimmune haemolytic anaemia; AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases. The intracellular components of the RBCs are released into the circulating blood and into tissues, leading to some of the characteristic symptoms of this condition. The antibodies are usually directed against high-incidence antigens, therefore they also commonly act on allogenic RBCs (RBCs originating from outside the person themselves, e.g. in the case of a blood transfusion). AIHA is a relatively rare condition, affecting one to three people per 100,000 per year.
The terminology used in this disease is somewhat ambiguous. Although MeSH uses the term "autoimmune hemolytic anemia", some sources prefer the term "immunohemolytic anemia" so drug reactions can be included in this category. The National Cancer Institute considers "immunohemolytic anemia", "autoimmune hemolytic anemia", and "immune complex hemolytic anemia" to all be synonyms.
Sideroblastic anemia is typically divided into subtypes based on its cause.
- Hereditary or congenital sideroblastic anemia may be X-linked or autosomal.
GLRX5 has also been implicated.
- Acquired, or secondary, sideroblastic anemia develops after birth and is divided according to its cause.
The condition needs to be differentiated from pure red cell aplasia. In aplastic anemia, the patient has pancytopenia (i.e., leukopenia and thrombocytopenia) resulting in decrease of all formed elements. In contrast, pure red cell aplasia is characterized by reduction in red cells only. The diagnosis can only be confirmed on bone marrow examination. Before this procedure is undertaken, a patient will generally have had other blood tests to find diagnostic clues, including a complete blood count, renal function and electrolytes, liver enzymes, thyroid function tests, vitamin B and folic acid levels.
The following tests aid in determining differential diagnosis for aplastic anemia:
1. Bone marrow aspirate and biospy: to rule out other causes of pancytopenia (i.e. neoplastic infiltration or significant myelofibrosis).
2. History of iatrogenic exposure to cytotoxic chemotherapy: can cause transient bone marrow suppression
3. X-rays, computed tomography (CT) scans, or ultrasound imaging tests: enlarged lymph nodes (sign of lymphoma), kidneys and bones in arms and hands (abnormal in Fanconi anemia)
4. Chest X-ray: infections
5. Liver tests: liver diseases
6. Viral studies: viral infections
7. Vitamin B and folate levels: vitamin deficiency
8. Blood tests for paroxysmal nocturnal hemoglobinuria
9. Test for antibodies: immune competency
Typical causes of microcytic anemia include:
- Childhood
- Iron deficiency anemia, by far the most common cause of anemia in general and of microcytic anemia in particular
- Thalassemia
- Adulthood
- Iron deficiency anemia
- Sideroblastic anemia, In congenital sideroblastic anemia the MCV (mean corpuscular volume) is either low or normal. In contrast, the MCV is usually high in the much more common acquired sideroblastic anemia.
- Anemia of chronic disease, although this more typically causes normochromic, normocytic anemia. Microcytic anemia has been discussed by Weng et al.
- Lead poisoning
- Vitamin B (pyridoxine) deficiency
Other causes that are typically thought of as causing normocytic anemia or macrocytic anemia must also be considered, and the presence of two or more causes of anemia can distort the typical picture.
There are five main causes of microcytic anemia forming the acronym TAILS. Thalassemia, Anemia of chronic disease, Iron deficiency, Lead poisoning and Congenital sideroblastic anemia. Only the first three are common in most parts of the world. In theory, these three can be differentiated by their red blood cell (RBC) morphologies. Anemia of chronic disease shows unremarkable RBCs, iron deficiency shows anisocytosis, anisochromia and elliptocytosis, and thalessemias demonstrate target cells and coarse basophilic stippling. In practice though elliptocytes and anisocytosis are often seen in thalessemia and target cells occasionally in iron deficiency. All three may show unremarkable RBC morphology. Coarse basophlic stippling is one reliable morphologic finding of thalessemia which does not appear in iron deficiency or anemia of chronic disease. The patient should be in an ethnically at risk group and the diagnosis is not confirmed without a confirmatory method such as hemoglobin HPLC, H body staining, molecular testing or another reliable method. Course basophlic stippling occurs in other cases as seen in Table 1
The two most common signs and symptoms of bone marrow failure are bleeding and bruising. Blood may be seen throughout the gums, nose or the skin, and tend to last longer than normal. Children have a bigger chance of seeing blood in their urine or stools, which results in digestive problems with an unpleasant scent. Individuals with this condition may also encounter tooth loss or tooth decay. Chronic fatigue, shortness of breath, and recurrent colds can also be symptoms of bone marrow failure.
Mechanical hemolytic anemia is a form of hemolytic anemia due to mechanically induced damage to red blood cells. Red blood cells, while flexible, may in some circumstances succumb to physical shear and compression. This may result in hemoglobinuria. The damage is induced through repetitive mechanical motions such as prolonged marching ("march hemoglobinuria") and marathon running. Mechanical damage can also be induced through the chronic condition microangiopathic hemolytic anemia or due to prosthetic heart valves.
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.
Anisocytosis is a medical term meaning that a patient's red blood cells are of unequal size. This is commonly found in anemia and other blood conditions. False diagnostic flagging may be triggered by an elevated WBC count, agglutinated RBCs, RBC fragments, giant platelets or platelet clumps. In addition, it is a characteristic feature of bovine blood.
The red cell distribution width (RDW) is a measurement of anisocytosis and is calculated as a coefficient of variation of the distribution of RBC volumes divided by the mean corpuscular volume (MCV)
Mild macrocytosis is a common finding associated with rapid blood restoration or production, since in general, "fresh" or newly produced red cells (reticulocytes) are larger than the mean (average) size, due to slow shrinkage of normal cells over a normal red cell circulating lifetime. Thus, chronic obstructive pulmonary disease (COPD), in which red cells are rapidly produced in response to low oxygen levels in the blood, often produces mild macrocytosis. Also, rapid blood replacement from the marrow after a traumatic blood loss, or rapid red blood cell turnover from rapid hemolysis (G6PD deficiency), also often produces mild macrocytosis in the associated anemia.
A normocytic anemia is defined as an anemia with a mean corpuscular volume (MCV) of 80–100 which is the normal range. However, the hematocrit and hemoglobin is decreased.
Normochromic is a form of anemia in which the concentration of hemoglobin in the red blood cells is within the standard range. However, there are insufficient numbers of red blood cells. This includes: aplastic, posthemorrhagic, and hemolytic anemias and anemia of chronic disease.
MCH or MCHC in these cells are normal.
Anisocytosis is identified by RDW and is classified according to the size of RBC measured by MCV. According to this, it can be divided into
- Anisocytosis with microcytosis – Iron deficiency, sickle cell anemia
- Anisocytosis with macrocytosis – Folate or vitamin B deficiency, autoimmune hemolytic anemia, cytotoxic chemotherapy, chronic liver disease, myelodysplastic syndrome
Increased RDW is seen in iron deficiency anemia and decreased or normal in thalassemia major (Cooley's anemia), thalassemia intermedia
- Anisocytosis with normal RBC size – Early iron, vit B12 or folate deficiency, dimorphic anemia, Sickle cell disease, chronic liver disease, Myelodysplastic syndrome
Congenital hypoplastic anemia (or constitutional aplastic anemia) is a type of aplastic anemia which is primarily due to a congenital disorder.
Associated genes include "TERC", "TERT", "IFNG", "NBS1", "PRF1", and "SBDS".
Examples include:
- Fanconi anemia
- Diamond-Blackfan anemia
Runner’s macrocytosis is a phenomenon of increased red blood cell size as a compensatory mechanism for increased red blood cell turnover. The impact forces from running can lead to red blood cell hemolysis and accelerate red blood cell production. This can shift the ratio of red blood cells towards younger, larger cells. This shift may be reflected in higher than normal mean corpuscular volume (MCV) values, an indicator of red blood cell size.
This is not a pathological condition but may indicate a propensity toward iron deficiency anemia due to high red blood cell turnover.
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 normal volume. The normal erythrocyte volume in humans is about 80 to 100 femtoliters (fL= 10 L). In metric terms the size is given in equivalent cubic micrometers (1 μm = 1 fL). The condition of having erythrocytes which (on average) are too large, is called macrocytosis. In contrast, in microcytic anemia, the erythrocytes are smaller than normal.
In a macrocytic anemia, the larger red cells are always associated with insufficient "numbers" of cells and often also insufficient hemoglobin content per cell. Both of these factors work to the opposite effect of larger cell size, to finally result in a "total blood hemoglobin concentration" that is less than normal (i.e., anemia).
Macrocytic anemia is not a disease in the sense of having a single pathology but, rather, is a condition. As such, it is the class name for a set of pathologies that all produce somewhat the same red blood cell abnormality. Many specific pathologies are known which result in macrocytic-type anemias. Some of these produce slightly different sets of appearances in blood cells that are detectable from red and white cell morphology, and others are only detectable with chemical testing.
Pancytopenia is a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets.
If only two parameters from the full blood count are low, the term bicytopenia can be used. The diagnostic approach is the same as for pancytopenia.