Anemia

Anemia (/nimi/; also spelled anaemia and anmia); is a decrease in number of red blood cells (RBCs) or less than the normal quantity of hemoglobin in the blood.[1][2] Anemia may also be diagnosed where there is decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin deficiency. The name is derived from Ancient Greek: anaimia, meaning lack of blood, from - an-, "not" + haima, "blood". Because hemoglobin (found inside RBCs) normally carries oxygen from the lungs to the capillaries, anemia leads to hypoxia (lack of oxygen) in organs. Since all human cells depend on oxygen for survival, varying degrees of anemia can have a wide range of clinical consequences. Anemia is the most common disorder of the blood. The several kinds of anemia are produced by a variety of underlying causes. It can be classified in a variety of ways, based on the morphology of RBCs, underlying etiologic mechanisms, and discernible clinical spectra, to mention a few. The three main classes include excessive blood loss (acutely such as a hemorrhage or chronically through low-volume loss), excessive blood cell destruction (hemolysis) or deficient red blood cell production (ineffective hematopoiesis). Of the two major approaches to diagnosis, the "kinetic" approach involves evaluating production, destruction and loss,[3] and the "morphologic" approach groups anemia by red blood cell size. The morphologic approach uses a quickly available and low-cost lab test as its starting point (the MCV), although this test can lack sensitivity and specificity in many diseases.[4] On the other hand, focusing early on the question of production may allow the clinician to expose cases more rapidly where multiple causes of anemia coexist.

Signs and symptoms

Main symptoms that may appear in anemia[5] Anemia goes undetected in many people, and symptoms can be minor or vague. The signs and symptoms can be related to the underlying cause or the anemia itself. Most commonly, people with anemia report feelings of weakness, or fatigue, general malaise, and sometimes poor concentration. They may also report dyspnea (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, mucosal linings, 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 scholastic performance in children of school age. Restless legs syndrome is more common in those with iron-deficiency anemia.

Causes
Broadly, causes of anemia may be classified as impaired red blood cell (RBC) production, increased RBC destruction (hemolytic anemias), blood loss and fluid overload (hypervolemia). Several of these may interplay to cause anemia eventually. Indeed, 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.[6] (See Iron deficiency anemia)

Impaired production

Disturbance of proliferation and differentiation of stem cells [7] o Pure red cell aplasia [7] o Aplastic anemia affects all kinds of blood cells. Fanconi anemia is a hereditary disorder or defect featuring aplastic anemia and various other abnormalities. [7] o Anemia of renal failure by insufficient erythropoietin production o Anemia of endocrine disorders Disturbance of proliferation and maturation of erythroblasts [7] o Pernicious anemia is a form of megaloblastic anemia due to vitamin B12 deficiency dependent on impaired absorption of vitamin B12. Lack of dietary B12 causes non-pernicious megaloblastic anemia [7] o Anemia of folic acid deficiency, as with vitamin B12, causes megaloblastic anemia o Anemia of prematurity, by diminished erythropoietin response to declining hematocrit levels, combined with blood loss from laboratory testing, generally occurs in premature infants at two to six weeks of age. [7] o Iron deficiency anemia, resulting in deficient heme synthesis [7] o thalassemias, causing deficient globin synthesis o Congenital dyserythropoietic anemias, causing ineffective erythropoiesis [7] o Anemia of renal failure (also causing stem cell dysfunction)

Other mechanisms of impaired RBC production [7] o Myelophthisic anemia or myelophthisis is a severe type of anemia resulting from the replacement of bone marrow by other materials, such as malignant tumors or granulomas. [7] o Myelodysplastic syndrome [7] o anemia of chronic inflammation

Increased destruction
Further information: Hemolytic anemia Anemias of increased red blood cell destruction are generally classified as hemolytic anemias. These are generally featuring jaundice and elevated lactate dehydrogenase levels.

Intrinsic (intracorpuscular) abnormalities[7] cause premature destruction. All of these, except paroxysmal nocturnal hemoglobinuria, are hereditary genetic disorders.[8] [7] o Hereditary spherocytosis is a hereditary defect that results in defects in the RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by the spleen. [7] o Hereditary elliptocytosis is another defect in membrane skeleton proteins. [7] o Abetalipoproteinemia, causing defects in membrane lipids o Enzyme deficiencies [7] Pyruvate kinase and hexokinase deficiencies, causing defect glycolysis Glucose-6-phosphate dehydrogenase deficiency and glutathione synthetase deficiency,[7] causing increased oxidative stress o Hemoglobinopathies [7] Sickle cell anemia [7] Hemoglobinopathies causing unstable hemoglobins [7] o Paroxysmal nocturnal hemoglobinuria Extrinsic (extracorpuscular) abnormalities o Antibody-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 hemolytic diseases.[9] It can be idiopathic, 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.[10][10] Cold agglutinin hemolytic anemia is primarily mediated by IgM. It can be idiopathic[11] or result from an underlying condition. [7] Rh disease, one of the causes of hemolytic disease of the newborn [7] Transfusion reaction to blood transfusions o Mechanical trauma to red cells Microangiopathic hemolytic anemias, including thrombotic thrombocytopenic purpura and disseminated intravascular coagulation[7] [7] Infections, including malaria

Heart surgery Haemodialysis

Blood loss

Anemia of prematurity from frequent blood sampling for laboratory testing, combined with insufficient RBC production Trauma[7] or surgery, causing acute blood loss Gastrointestinal tract lesions,[7] causing either acute bleeds (e.g. variceal lesions, peptic ulcers or chronic blood loss (e.g. angiodysplasia) Gynecologic disturbances,[7] also generally causing chronic blood loss From menstruation, mostly among young women or older women who have fibroids

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.[12] Anemia of pregnancy is induced by blood volume expansion experienced in pregnancy.

Diagnosis
Peripheral blood smear microscopy of a patient with iron-deficiency anemia Anemia is typically diagnosed on a complete blood count. Apart from reporting the number of red blood cells and the hemoglobin 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 using a microscope can also be helpful, and it is sometimes a necessity in regions of the world where automated analysis is less accessible. In modern counters, four parameters (RBC count, hemoglobin concentration, MCV and RDW) are measured, allowing others (hematocrit, MCH and MCHC) to be calculated, and compared to values adjusted for age and sex. Some counters estimate hematocrit from direct measurements