Macrocytic anemia

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Macrocytic anemia
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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= 10−15 L). In metric terms the size is given in equivalent cubic micrometers (1 μm3 = 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.

Contents

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. Different pathologies result in macrocytic-type anemias. Some of these pathologies 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.

Presentation

Causes

Megaloblastic anemias

Megaloblastic anemias represent a type of macrocytic anemia characterized by certain morphologic abnormalities noted on a peripheral blood smear examination. These abnormalities include the presence of enlarged oval shaped red blood cells (macroovalocytes) and hypersegmented neutrophils (defined as a neutrophil with six or more lobes). [1] Hypersegmented neutrophils may be seen in the absence of macroovalocytes as hypersegmentation of neutrophils is an early sign of megaloblastic anemia and may precede the appearance of macroovalocytes; they may also be seen in other anemias (e.g., iron deficiency anemia) and thus are suggestive of megaloblastic anemia but not specific for it. [1] An increased red cell distribution width (anisocytosis) also suggests megaloblastosis and is commonly seen in Vitamin B12 deficiency and folic acid deficiency. [1] This type of anemia is caused by impaired DNA synthesis and repair, often from deficient thymidine production. [1] Thiamine responsive megaloblastic anemia syndrome also causes megaloblastic anemia. [1]

The red blood cells grow larger because they cannot produce DNA quickly enough to divide at the right time as they grow and thus grow too large before division.[ citation needed ] Additional causes of megaloblastic anemia include medications that interfere with DNA synthesis or with the absorption or metabolism of Vitamin B12 or folate such as methotrexate, sulfasalazine, metformin, anticonvulsant medications (e.g., valproic acid or phenytoin), certain antibiotics (e.g., trimethoprim/sulfamethoxazole), antiretroviral medications, cholestyramine, triamterene, and nitrous oxide. [1]

Non-Megaloblastic anemias

Red cell membrane disorders producing codocytes

Other disorders which cause macrocytosis without DNA replication problems (i.e., non-megaloblastic macrocytic anemias), are disorders associated with increased red cell membrane surface area, such as pathologies of the liver and spleen which produce codocytes or "target cells" which have a central collection of hemoglobin surrounded by a pallor (a thin area) then followed by a thicker collection of hemoglobin at the rim of the cell.[ citation needed ]

Alcohol

Round macrocytes which are not codocytes are produced in chronic alcoholism (which produces a mild macrocytosis even in the absence of vitamin deficiency), apparently as a direct toxic effect of alcohol specifically on the bone marrow. [2] Excessive alcohol consumption is one of the most common causes of macrocytosis and non-megaloblastic macrocytic anemia. [1]

Association with rapid red cell turnover and reticulocytosis

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. The macrocytosis associated with COPD is also attributed to excess cell water secondary to carbon dioxide retention. 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. [2]

Diagnosis

Several tests can help to elucidate the underlying cause of a person's macrocytic anemia. A peripheral blood smear is often recommended as a first step in the evaluation to determine if the macrocytic anemia has megaloblastic features since the causes of megaloblastic and non-megaloblastic macrocytic anemia differ and making this distinction can narrow the list of differential diagnoses. [1]

For non-megaloblastic macrocytic anemias, a reticulocyte count may be helpful. Non-megaloblastic macrocytic anemias with a low reticulocyte count (indicating a poor bone marrow response to the anemia) suggest liver disease (e.g., cirrhosis), hypothyroidism, toxic effects of alcohol on the bone marrow, or myelodysplasia. [1] In contrast, non-megaloblastic macrocytic anemias associated with a high reticulocyte count (reticulocytosis) may be caused by hemolysis or bleeding. [1]

For megaloblastic macrocytic anemias, useful tests may include serum levels of Vitamin B12, methylmalonic acid, and homocysteine. [1] If there is no clear evidence of Vitamin B12 or folic acid deficiency, additional causes of megaloblastic anemia include copper deficiency, medications, and certain inborn errors of metabolism. [1]

Treatment

Epidemiology

Macrocytic anemias have several causes but with the implementation of folic acid fortification in North America, folic acid deficiency has become a rare cause of megaloblastic macrocytic anemia in that part of the world. [1] In this region, Vitamin B12 deficiency is a far more common cause of megaloblastic macrocytic anemia. [1] In countries that have not put such practices into place — including most European nations — folic acid deficiency remains a common cause of macrocytic anemia. [1]

See also

Related Research Articles

<span class="mw-page-title-main">Folate</span> Vitamin B9; nutrient essential for DNA synthesis

Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage. Folate is required for the body to make DNA and RNA and metabolise amino acids necessary for cell division and maturation of blood cells. As the human body cannot make folate, it is required in the diet, making it an essential nutrient. It occurs naturally in many foods. The recommended adult daily intake of folate in the U.S. is 400 micrograms from foods or dietary supplements.

<span class="mw-page-title-main">Anemia</span> Reduced ability of blood to carry oxygen

Anemia or anaemia is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin available for oxygen transport, or abnormalities in hemoglobin that impair its function. The name is derived from Ancient Greek ἀν- (an-) 'not', and αἷμα (haima) 'blood'. When anemia comes on slowly, the symptoms are often vague, such as tiredness, weakness, shortness of breath, headaches, and a reduced ability to exercise. When anemia is acute, symptoms may include confusion, feeling like one is going to pass out, loss of consciousness, and increased thirst. Anemia must be significant before a person becomes noticeably pale. Additional symptoms may occur depending on the underlying cause. Anemia can be temporary or long term and can range from mild to severe.

<span class="mw-page-title-main">Hereditary spherocytosis</span> Medical condition

Hereditary spherocytosis (HS) is a congenital hemolytic disorder wherein a genetic mutation coding for a structural membrane protein phenotype causes the red blood cells to be sphere-shaped (spherocytosis), rather than the normal biconcave disk shape. This abnormal shape interferes with the cells' ability to flex during blood circulation, and also makes them more prone to rupture under osmotic stress, mechanical stress, or both. Cells with the dysfunctional proteins are degraded in the spleen, which leads to a shortage of erythrocytes and results in hemolytic anemia.

<span class="mw-page-title-main">Pernicious anemia</span> Anemia caused by vitamin B12 deficiency

Pernicious anemia is a disease where not enough red blood cells are produced due to a deficiency of vitamin B12. Those affected often have a gradual onset. The most common initial symptoms are feeling tired and weak. Other symptoms may include shortness of breath, feeling faint, a smooth red tongue, pale skin, chest pain, nausea and vomiting, loss of appetite, heartburn, numbness in the hands and feet, difficulty walking, memory loss, muscle weakness, poor reflexes, blurred vision, clumsiness, depression, and confusion. Without treatment, some of these problems may become permanent.

The mean corpuscular volume, or mean cell volume (MCV), is a measure of the average volume of a red blood corpuscle. The measure is obtained by multiplying a volume of blood by the proportion of blood that is cellular, and dividing that product by the number of erythrocytes in that volume. The mean corpuscular volume is a part of a standard complete blood count.

<span class="mw-page-title-main">Red blood cell distribution width</span> Measure of red blood cell volume variation as part of a standard blood test

Red blood cell distribution width (RDW), as well as various types thereof, is a measure of the range of variation of red blood cell (RBC) volume that is reported as part of a standard complete blood count. Red blood cells have an average volume of 80–100 femtoliters, but individual cell volumes vary even in healthy blood. Certain disorders, however, cause a significantly increased variation in cell size. Higher RDW values indicate greater variation in size. Normal reference range of RDW-CV in human red blood cells is 11.5–15.4%. If anemia is observed, RDW test results are often used together with mean corpuscular volume (MCV) results to determine the possible causes of the anemia. It is mainly used to differentiate an anemia of mixed causes from an anemia of a single cause.

<span class="mw-page-title-main">Erythropoiesis</span> Process which produces red blood cells

Erythropoiesis is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.

<span class="mw-page-title-main">Megaloblastic anemia</span> Medical condition

Megaloblastic anemia is a type of macrocytic anemia. An anemia is a red blood cell defect that can lead to an undersupply of oxygen. Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing cell growth without division, which presents as macrocytosis. Megaloblastic anemia has a rather slow onset, especially when compared to that of other anemias. The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically vitamin B12 deficiency or folate deficiency. Loss of micronutrients may also be a cause.

<span class="mw-page-title-main">Microcytic anemia</span> Medical condition

Microcytic anaemia is any of several types of anemia characterized by smaller than normal red blood cells. The normal mean corpuscular volume is approximately 80–100 fL. When the MCV is <80 fL, the red cells are described as microcytic and when >100 fL, macrocytic. The MCV is the average red blood cell size.

<span class="mw-page-title-main">Macrocytosis</span> Medical condition

Macrocytosis is a condition where red blood cells are larger than normal. These enlarged cells, also known as macrocytes, are defined by a mean corpuscular volume (MCV) that exceeds the upper reference range established by the laboratory and hematology analyzer. Upon examination of a peripheral blood smear under microscope, these macrocytes appear larger than standard erythrocytes. It’s noteworthy that macrocytosis is a common morphological feature in neonatal peripheral blood. The presence of macrocytosis can indicate a range of conditions, from benign, treatable illnesses to more serious underlying disorders.

Reticulocytopenia is the medical term for an abnormal decrease in circulating red blood cell precursors (reticulocytes) that can lead to anemia due to resulting low red blood cell (erythrocyte) production. Reticulocytopenia may be an isolated finding or it may not be associated with abnormalities in other hematopoietic cell lineages such as those that produce white blood cells (leukocytes) or platelets (thrombocytes), a decrease in all three of these lineages is referred to as pancytopenia.

<span class="mw-page-title-main">Folate deficiency</span> Abnormally low level of folate (vitamin B9) in the body

Folate deficiency, also known as vitamin B9 deficiency, is a low level of folate and derivatives in the body. This may result in a type of anemia in which red blood cells become abnormally large and is a late finding in folate deficiency and folate deficiency anemia is the term given for this medical condition. Signs of folate deficiency are often subtle. Symptoms may include feeling tired, heart palpitations, shortness of breath, feeling faint, open sores on the tongue, loss of appetite, changes in the color of the skin or hair, irritability, and behavioral changes. Temporary reversible infertility may occur. Folate deficiency anemia during pregnancy may give rise to the birth of low weight birth premature infants and infants with neural tube defects.

<span class="mw-page-title-main">Subacute combined degeneration of spinal cord</span> Medical condition

Subacute combined degeneration of spinal cord, also known as myelosis funiculus, or funicular myelosis, also Lichtheim's disease, and Putnam-Dana syndrome, refers to degeneration of the posterior and lateral columns of the spinal cord as a result of vitamin B12 deficiency (most common). It may also occur similarly as result of vitamin E deficiency, and copper deficiency. It is usually associated with pernicious anemia.

<span class="mw-page-title-main">Orotic aciduria</span> Medical condition

Orotic aciduria is a disease caused by an enzyme deficiency, resulting in a decreased ability to synthesize pyrimidines. It was the first described enzyme deficiency of the de novo pyrimidine synthesis pathway.

<span class="mw-page-title-main">Hypersegmented neutrophil</span>

Neutrophil hypersegmentation can be defined as the presence of neutrophils whose nuclei have six or more lobes or the presence of more than 3% of neutrophils with at least five nuclear lobes. This is a clinical laboratory finding. It is visualized by drawing blood from a patient and viewing the blood smeared on a slide under a microscope. Normal neutrophils are uniform in size, with an apparent diameter of about 13 μm in a film. When stained, neutrophils have a segmented nucleus and pink/orange cytoplasm under light microscope. The majority of neutrophils have three nuclear segments (lobes) connected by tapering chromatin strands. A small percentage have four lobes, and occasionally five lobes may be seen. Up to 8% of circulating neutrophils are unsegmented.

Normocytic anemia is a type of anemia and is a common issue that occurs for men and women typically over 85 years old. Its prevalence increases with age, reaching 44 percent in men older than 85 years. The most common type of normocytic anemia is anemia of chronic disease.

Anemia is a deficiency in the size or number of red blood cells or in the amount of hemoglobin they contain. This deficiency limits the exchange of O2 and CO2 between the blood and the tissue cells. Globally, young children, women, and older adults are at the highest risk of developing anemia. Anemia can be classified based on different parameters, and one classification depends on whether it is related to nutrition or not so there are two types: nutritional anemia and non-nutritional anemia. Nutritional anemia refers to anemia that can be directly attributed to nutritional disorders or deficiencies. Examples include Iron deficiency anemia and pernicious anemia. It is often discussed in a pediatric context.

<span class="mw-page-title-main">Imerslund–Gräsbeck syndrome</span> Medical condition

Imerslund–Gräsbeck syndrome is a rare autosomal recessive, familial form of vitamin B12 deficiency caused by malfunction of the "Cubam" receptor located in the terminal ileum. This receptor is composed of two proteins, amnionless (AMN), and cubilin. A defect in either of these protein components can cause this syndrome. This is a rare disease, with a prevalence about 1 in 200,000, and is usually seen in patients of European ancestry.

<span class="mw-page-title-main">Nucleated red blood cell</span> Red blood cell with a cell nucleus

A nucleated red blood cell (NRBC), also known by several other names, is a red blood cell that contains a cell nucleus. Almost all vertebrate organisms have hemoglobin-containing cells in their blood, and with the exception of mammals, all of these red blood cells are nucleated. In mammals, NRBCs occur in normal development as precursors to mature red blood cells in erythropoiesis, the process by which the body produces red blood cells.

Anemia is a condition in which blood has a lower-than-normal amount of red blood cells or hemoglobin. Anemia in pregnancy is a decrease in the total red blood cells (RBCs) or hemoglobin in the blood during pregnancy. Anemia is an extremely common condition in pregnancy world-wide, conferring a number of health risks to mother and child. While anemia in pregnancy may be pathologic, in normal pregnancies, the increase in RBC mass is smaller than the increase in plasma volume, leading to a mild decrease in hemoglobin concentration referred to as physiologic anemia. Maternal signs and symptoms are usually non-specific, but can include: fatigue, pallor, dyspnea, palpitations, and dizziness. There are numerous well-known maternal consequences of anemia including: maternal cardiovascular strain, reduced physical and mental performance, reduced peripartum blood reserves, increased risk for peripartum blood product transfusion, and increased risk for maternal mortality.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Green, R; Dwyre, DM (October 2015). "Evaluation of Macrocytic Anemias". Seminars in Hematology. 52 (4): 279–86. doi:10.1053/j.seminhematol.2015.06.001. PMID   26404440.
  2. 1 2 Macrocytosis at eMedicine