Vitamin B12 is a water-soluble vitamin that is naturally present in some foods, added to others, and available as a dietary supplement

and a prescription medication. Vitamin B12 exists in several forms and contains the mineral cobalt [1-4], so compounds with vitamin B12 activity are collectively called "cobalamins". Methylcobalamin and 5deoxyadenosylcobalamin are the forms of vitamin B12 that are active in human metabolism [5]. Vitamin B12 is required for proper red blood cell formation, neurological function, and DNA synthesis [1-5]. Vitamin B12 functions as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase. Methionine synthase catalyzes the conversion of homocysteine to methionine [5,6]. Methionine is required for the formation of Sadenosylmethionine, a universal methyl donor for almost 100 different substrates, including DNA, RNA, hormones, proteins, and lipids. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to succinyl-CoA in the degradation of propionate [3,5,6], an essential biochemical reaction in fat and protein metabolism. Succinyl-CoA is also required for hemoglobin synthesis. Vitamin B12, bound to protein in food, is released by the activity of hydrochloric acid and gastric protease in the stomach [5]. When synthetic vitamin B12 is added to fortified foods and dietary supplements, it is already in free form and, thus, does not require this separation step. Free vitamin B12 then combines with intrinsic factor, a glycoprotein secreted by the stomach's parietal cells, and the resulting complex undergoes absorption within the distal ileum by receptor-mediated endocytosis [5,7]. Approximately 56% of a 1 mcg oral dose of vitamin B12 is absorbed, but absorption decreases drastically when the capacity of intrinsic factor is exceeded (at 1-2 mcg of vitamin B12) [8]. Pernicious anemia is an autoimmune disease that affects the gastric mucosa and results in gastric atrophy. This leads to the destruction of parietal cells, achlorhydria, and failure to produce intrinsic factor, resulting in vitamin B12 malabsorption [3,5,9-11]. If pernicious anemia is left untreated, it causes vitamin B12 deficiency, leading to megaloblastic anemia and neurological disorders, even in the presence of adequate dietary intake of vitamin B12. Vitamin B12 status is typically assessed via serum or plasma vitamin B12 levels. Values below approximately 170 250 pg/mL (120180 picomol/L) for adults [5] indicate a vitamin B12 deficiency. However, evidence suggests that serum vitamin B12 concentrations might not accurately reflect intracellular concentrations [6]. An elevated serum homocysteine level (values >13 micromol/L) [12] might also suggest a vitamin B12 deficiency. However, this indicator has poor specificity because it is influenced by other factors, such as low vitamin B6 or folate levels [5]. Elevated methylmalonic acid levels (values >0.4 micromol/L) might be a more reliable indicator of vitamin B12 status because they indicate a metabolic change that is highly specific to vitamin B12 deficiency [5-7,12].

Mechanism of action

Metabolism of folic acid. The role of Vitamin B12 is seen at bottom-left. Vitamin B12 normally plays a significant role in the metabolism of every cell of the body, especially affecting the DNA synthesis and regulation but also fatty acid synthesis and energy production.[40] However, many (though not all) of the effects of functions of B12 can be replaced by sufficient quantities of folic acid (vitamin B9), since B12 is used to regenerate folate in the body. Most vitamin B12 deficiency symptoms are actually folate deficiency symptoms, since they include all the effects of pernicious anemia and megaloblastosis, which are due to poor synthesis of DNA when the body does not have a proper supply of folic acid for the production of thymine.[41] When sufficient folic acid is available, all known B12 related deficiency syndromes normalize, save those narrowly connected with the vitamin B 12dependent enzymes Methylmalonyl Coenzyme A mutase, and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), also known as methionine synthase; and the buildup of their respective substrates (methylmalonic acid, MMA) and homocysteine. Coenzyme B12's reactive C-Co bond participates in three main types of enzyme-catalyzed reactions.[42][43] 1. Isomerases. Rearrangements in which a hydrogen atom is directly transferred between two adjacent atoms with concomitant exchange of the second substituent, X, which may be a carbon atom with substituents, an oxygen atom of an alcohol, or an amine. 2. Methyltransferases. Methyl (-CH3) group transfers between two molecules. 3. Dehalogenases. Reactions in which a halogen atom is removed from an organic molecule. Enzymes in this class have not been identified in humans. In humans, two major coenzyme B12-dependent enzyme families corresponding to the first two reaction types, are known. These are typified by the following two enzymes: 1. MUT is an isomerase which uses the AdoB12 form and reaction type 1 to catalyze a carbon skeleton rearrangement (the X group is -COSCoA). MUT's reaction converts MMl-CoA to Su-CoA, an important step in the extraction of energy from proteins and fats (for more see MUT's reaction mechanism). This functionality is lost in vitamin B12 deficiency, and can be measured clinically as an increased methylmalonic acid (MMA) level. Unfortunately, an elevated MMA, though sensitive to B12 deficiency, is probably overly sensitive, and not all who have it actually have B12 deficiency. For example, MMA is elevated in 9098% of patients with B12 deficiency; however 2025% of patients over the age of 70 have elevated levels of MMA, yet 25 33% of them do not have B12 deficiency. For this reason, assessment of MMA levels is not routinely recommended in the elderly. There is no "gold standard" test for B12 deficiency because as a B12 deficiency occurs, serum values may be maintained while tissue B12 stores become depleted. Therefore, serum B12 values above the cut-off point of deficiency do not necessarily indicate adequate B12 status[14] The MUT function cannot be affected by folate supplementation, which is necessary for myelin synthesis (see mechanism below) and certain other functions of the central nervous system. Other functions of B12 related to DNA synthesis related to MTR dysfunction (see below) can often be corrected with supplementation with the vitamin folic acid, but not the elevated levels of homocysteine, which is normally converted to methionine by MTR. 2. MTR, also known as methionine synthase, is a methyltransferase enzyme, which uses the MeB12 and reaction type 2 to catalyze the conversion of the amino acid homocysteine (Hcy) back into methionine (Met) (for more see MTR's reaction mechanism).[44] This functionality is lost in vitamin B12 deficiency, and can be

measured clinically as an increased homocysteine level in vitro. Increased homocysteine can also be caused by a folic acid deficiency, since B12 helps to regenerate the tetrahydrofolate (THF) active form of folic acid. Without B12, folate is trapped as 5-methyl-folate, from which THF cannot be recovered unless a MTR process reacts the 5-methyl-folate with homocysteine to produce methionine and THF, thus decreasing the need for fresh sources of THF from the diet. THF may be produced in the conversion of homocysteine to methionine, or may be obtained in the diet. It is converted by a non-B12-dependent process to 5,10-methylene-THF, which is involved in the synthesis of thymine. Reduced availability of 5,10-methylene-THF results in problems with DNA synthesis, and ultimately in ineffective production cells with rapid turnover, in particular blood cells, and also intestinal wall cells which are responsible for absorption. The failure of blood cell production results in the once-dreaded and fatal disease, pernicious anemia. All of the DNA synthetic effects, including the megaloblastic anemia of pernicious anemia, resolve if sufficient folate is present (since levels of 5,10methylene-THF still remain adequate with enough dietary folate). Thus the best-known "function" of B12 (that which is involved with DNA synthesis, cell-division, and anemia) is actually a facultative function which is mediated by B12-conservation of an active form of folate which is needed for efficient DNA production.[45] Other cobalamin-requiring methyltransferase enzymes are also known in bacteria, such as Me-H4-MPT, coenzyme M methyl transferase. [edit] Enzyme function If folate is present in quantity, then of the two absolutely vitamin B 12-dependent enzyme-family reactions in humans, the MUT-family reactions show the most direct and characteristic secondary effects, focusing on the nervous system (see below). This is because the MTR (methyltransferase-type) reactions are involved in regenerating folate, and thus are less evident when folate is in good supply. Since the late 1990s, folic acid has begun to be added to fortify flour in many countries, so folate deficiency is now more rare. At the same time, since DNA synthetic-sensitive tests for anemia and erythrocyte size are routinely done in even simple medical test clinics (so that these folate-mediated biochemical effects are more often directly detected), the MTR-dependent effects of B12 deficiency are becoming apparent not as anemia due to DNA-synthetic problems (as they were classically), but now mainly as a simple and less obvious elevation of homocysteine in the blood and urine (homocysteinuria). This condition may result in long term damage to arteries and in clotting (stroke and heart attack), but this effect is difficult to separate from other common processes associated with atherosclerosis and aging. The specific myelin damage resulting from B12 deficiency, even in the presence of adequate folate and methionine, is more specifically and clearly a vitamin deficiency problem. It has been connected to B12 most directly by reactions related to MUT, which is absolutely required to convert methylmalonyl coenzyme A into succinyl coenzyme A. Failure of this second reaction to occur results in elevated levels of MMA, a myelin destabilizer. Excessive MMA will prevent normal fatty acid synthesis, or it will be incorporated into fatty acid itself rather than normal malonic acid. If this abnormal fatty acid subsequently is incorporated into myelin, the resulting myelin will be too fragile, and demyelination will occur. Although the precise mechanism(s) are not known with certainty, the result is subacute combined degeneration of central nervous system and spinal cord.[46] Whatever the cause, it is known that B12 deficiency causes neuropathies, even if folic acid is present in good supply, and therefore anemia is not present. Vitamin B12-dependent MTR reactions may also have neurological effects, through an indirect mechanism. Adequate methionine (which, like folate, must otherwise be obtained in the diet, if it is not regenerated from homocysteine by a B12 dependent reaction) is needed to make S-adenosyl-methionine (SAMe), which is in turn necessary for methylation of myelin sheath phospholipids. Although production of SAMe is not B12 dependent, help in recycling for provision of one adequate substrate for it (the essential amino acid methionine) is assisted by B12. In addition, SAMe is involved in the manufacture of certain neurotransmitters, catecholamines and in brain metabolism. These neurotransmitters are important for maintaining mood, possibly explaining why depression is associated with B12 deficiency. Methylation of the myelin sheath phospholipids may also depend on adequate folate, which in turn is dependent on MTR recycling, unless ingested in relatively high amounts. [edit] Absorption and distribution The human physiology of vitamin B12 is complex, and therefore is prone to mishaps leading to vitamin B12 deficiency. Protein-bound vitamin B12 must be released from the proteins by the action of digestive proteases in both the stomach and small intestine.[47] Gastric acid releases the vitamin from food particles; therefore antacid and acid-blocking

medications (especially proton-pump inhibitors) may inhibit absorption of B12. In addition some elderly people produce less stomach acid as they age thereby increasing their probability of B12 deficiencies.[48] B12 taken in a low-solubility, non-chewable supplement pill form may bypass the mouth and stomach and not mix with gastric acids, but these are not necessary for the absorption of free B12 not bound to protein. R-proteins (such as haptocorrins and cobalaphilin) are B12 binding proteins that are produced in the salivary glands. They must wait until B12 has been freed from proteins in food by pepsin in the stomach. B12 then binds to the RProteins to avoid degradation of it in the acidic environment of the stomach.[49] This pattern of secretion of a binding protein secreted in a previous digestive step, is repeated once more before absorption. The next binding protein is intrinsic factor (IF), a protein synthesized by gastric parietal cells that is secreted in response to histamine, gastrin and pentagastrin, as well as the presence of food. In the duodenum, proteases digest R-proteins and release B12, which then binds to IF, to form a complex (IF/B12). B12 must be attached to IF for it to be absorbed, as receptors on the enterocytes in the terminal ileum of the small bowel only recognize the B12-IF complex; in addition, intrinsic factor protects the vitamin from catabolism by intestinal bacteria. Absorption of food vitamin B12 thus requires an intact and functioning stomach, exocrine pancreas, intrinsic factor, and small bowel. Problems with any one of these organs makes a vitamin B12 deficiency possible. Individuals who lack intrinsic factor have a decreased ability to absorb B12. In pernicious anemia, there is a lack of IF due to autoimmune atrophic gastritis, in which antibodies form against parietal cells. Antibodies may alternately form against and bind to IF, inhibiting it from carrying out its B12 protective function. Due to the complexity of B12 absorption, geriatric patients, many of whom are hypoacidic due to reduced parietal cell function, have an increased risk of B 12 deficiency.[50] This results in 80100% excretion of oral doses in the feces versus 3060% excretion in feces as seen in individuals with adequate IF.[50] Once the IF/B12 complex is recognized by specialized ileal receptors, it is transported into the portal circulation. The vitamin is then transferred to transcobalamin II (TC-II/B12), which serves as the plasma transporter. Hereditary defects in production of the transcobalamins and their receptors may produce functional deficiencies in B 12 and infantile megaloblastic anemia, and abnormal B12 related biochemistry, even in some cases with normal blood B12 levels.[51] For the vitamin to serve inside cells, the TC-II/B12 complex must bind to a cell receptor, and be endocytosed. The transcobalamin-II is degraded within a lysosome, and free B12 is finally released into the cytoplasm, where it may be transformed into the proper coenzyme, by certain cellular enzymes (see above). The total amount of vitamin B12 stored in body is about 25 mg in adults. Around 50% of this is stored in the liver.[14] Approximately 0.1% of this is lost per day by secretions into the gut, as not all these secretions are reabsorbed. Bile is the main form of B12 excretion; however, most of the B12 secreted in the bile is recycled via enterohepatic circulation.[14] Due to the extremely efficient enterohepatic circulation of B12, the liver can store several years worth of vitamin B12; therefore, nutritional deficiency of this vitamin is rare. How fast B12 levels change depends on the balance between how much B12 is obtained from the diet, how much is secreted and how much is absorbed. B12 deficiency may arise in a year if initial stores are low and genetic factors unfavourable, or may not appear for decades. In infants, B12 deficiency can appear much more quickly.[52] [edit] History Table 1: Recommended Dietary Allowances (RDAs) for Vitamin B12 [5] Age Male Female Pregnancy Lactation 0-6 months* 0.4 mcg 0.4 mcg 7-12 months* 0.5 mcg 0.5 mcg 1-3 years 4-8 years 9-13 years 14+ years 0.9 mcg 0.9 mcg 1.2 mcg 1.2 mcg 1.8 mcg 1.8 mcg 2.4 mcg 2.4 mcg 2.6 mcg 2.8 mcg

* Adequate Intake Vitamin B12 Deficiency

Vitamin B12 deficiency is characterized by megaloblastic anemia, fatigue, weakness, constipation, loss of appetite, and weight loss [1,3,27]. Neurological changes, such as numbness and tingling in the hands and feet, can also occur [5,28]. Additional symptoms of vitamin B12 deficiency include difficulty maintaining balance, depression, confusion, dementia, poor memory, and soreness of the mouth or tongue [29]. The neurological symptoms of vitamin B12 deficiency can occur without anemia, so early diagnosis and intervention is important to avoid irreversible damage [6]. During infancy, signs of a vitamin B12 deficiency include failure to thrive, movement disorders, developmental delays, and megaloblastic anemia [30]. Many of these symptoms are general and can result from a variety of medical conditions other than vitamin B12 deficiency. Typically, vitamin B12 deficiency is treated with vitamin B12 injections, since this method bypasses potential barriers to absorption. However, high doses of oral vitamin B12 may also be effective. The authors of a review of randomized controlled trials comparing oral with intramuscular vitamin B12 concluded that 2,000 mcg of oral vitamin B12 daily, followed by a decreased daily dose of 1,000 mcg and then 1,000 mcg weekly and finally, monthly might be as effective as intramuscular administration [24,25]. Overall, an individual patient's ability to absorb vitamin B12 is the most important factor in determining whether vitamin B12 should be administered orally or via injection [8]. In most countries, the practice of using intramuscular vitamin B12 to treat vitamin B12 deficiency has remained unchanged [24]. Folic acid and vitamin B12 Large amounts of folic acid can mask the damaging effects of vitamin B12 deficiency by correcting the megaloblastic anemia caused by vitamin B12 deficiency [3,5] without correcting the neurological damage that also occurs [1,31]. Moreover, preliminary evidence suggests that high serum folate levels might not only mask vitamin B12 deficiency, but could also exacerbate the anemia and worsen the cognitive symptoms associated with vitamin B12 deficiency [6,11]. Permanent nerve damage can occur if vitamin B12 deficiency is not treated. For these reasons, folic acid intake from fortified food and supplements should not exceed 1,000 mcg daily in healthy adults [5].

LDH Medical use Tissue breakdown releases LDH, and therefore LDH can be measured as a surrogate for tissue breakdown, e.g. hemolysis. Other disorders indicated by elevated LDH include cancer, meningitis, encephalitis, acute pancreatitis, and HIV. [edit] Hemolysis In medicine, LDH is often used as a marker of tissue breakdown as LDH is abundant in red blood cells and can function as a marker for hemolysis. A blood sample that has been handled incorrectly can show false-positively high levels of LDH due to erythrocyte damage. It can also be used as a marker of myocardial infarction. Following a myocardial infarction, levels of LDH peak at 34 days and remain elevated for up to 10 days. In this way, elevated levels of LDH (where the level of LDH1 is higher than that of LDH2) can be useful for determining whether a patient has had a myocardial infarction if they come to doctors several days after an episode of chest pain. [edit] Tissue turnover Other uses are assessment of tissue breakdown in general; this is possible when there are no other indicators of hemolysis. It is used to follow-up cancer (especially lymphoma) patients, as cancer cells have a high rate of turnover with destroyed cells leading to an elevated LDH activity

MCV= Ht eri

x 10 (Normal 80-97 fl)

MCH = Hb x 10 (Normal 27-31 pg) eri MCHC= Hb x 100 (Normal 32-36 %) Ht MCV : Mikro/Makro MCH , MCHC : Hipo / Hiper Mean corpuscular volume (MCV) measures the mean or average size of individual red blood cells. To obtain the MCV, the hematocrit is divided by the total RBC count. The MCV is an indicator of the size of red blood cells. If the MCV is low, the cells are microcytic or smaller than normal. Microcytic red blood cells are seen in iron deficiency anemia, lead poisoning and the genetic diseases thalassemia major and thalassemia minor. If the MCV is high, the cells are macrocytic, or larger than normal. Macrocytic red blood cells are associated with pernicious anemia and folic acid deficiencies. If the MCV is within the normal range, the cells are referred to as normocytic. A patient who has anemia from an acute hemorrhage would have a normocytic anemia. Mean corpuscular hemoglobin (MCH) measures the amount, or the mass, of hemoglobin present in one RBC. The weight of hemoglobin in an average cell is obtained by dividing the hemoglobin by the total RBC count. The result is reported by a very small weight called a picogram (pg). Mean corpuscular hemoglobin concentration (MCHC) measures the proportion of each cell taken up by hemoglobin. The results are reported in percentages, reflecting the proportion of hemoglobin in the RBC. The hemoglobin is divided by the hematocrit and multiplied by 100 to obtain the MCHC. The MCH and the MCHC are used to assess whether red blood cells are normochromic, hypochromic, or hyperchromic. An MCHC of less than 32% or an MCH under 27 %. indicates that the red blood cells are deficient in hemoglobin concentration. This situation is most often seen with iron deficiency anemia. Normal values for erythrocyte indices are:

MCV: MCV values are higher in newborns and infants Men: 80-98 fl (femoliters) Women: 96-108 fl MCH - 17-31 pg (picograms) MCHC- 32-36%
o o o

Anemias can be classified using erythrocyte indices in the following way:

MCV, MCH and MCHC normal --- normocytic, normochromic anemia --- most often caused by acute blood loss Decreased MCV, MCH, and MCHC --- microcytic, hypochromic anemia --- most often caused by iron deficiency Increased MCV, variable MCH and MCHC --- macrocytic anemia --- most often caused by Vitamin B12 deficiency (due to pernicious anemia) and folic acid deficiency

Abnormal erthryocyte indices are helpful to classify types of anemia. However, diagnosis must be based on the patient's history, physical examination, and other diagnostic procedures. Measurement of Hematocrit

The hematocrit (Hct, "crit") is the ratio of the volume of red blood cells to the volume of whole blood. In the past, the hematocrit was determined by centrifugation of whole blood in a narrow glass tube (capillary blood tube) sealed at one end ("spun hematocrit"). The spun hematocrit is spuriously elevated if plasma becomes trapped in the red cell layer. This phenomenon occurs in patients with polycythemia, macrocytosis, spherocytosis, hypochromic anemias, and RBC fragment syndromes. Improper mixing of the specimen or the addition of excessive anticoagulant can also lead to false Hct values. Since "crit" tubes are also fragile and dangerous to use, spun hematocrits are rarely used today. The automated hematology analyzer calculates the Hct from the RBC and MCV by the following formula: Hct (L/L, %) = RBC (cells/L) x MCV (L/cell) Since the Hct is a calculated value, it is less accurate than either the RBC or Hb, and is affected by errors in either or both of these measurements. The MCV, mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) are the red blood cell indices. The MCH is the hemoglobin concentration per cell (hemoglobin mass/red blood cell), expressed in picograms per cell (pg, 10-12 g). The MCH is calculated from the hemoglobin and RBC by the following formula:

The MCH is decreased in patients with anemia caused by impaired hemoglobin synthesis. The MCH may be falsely elevated in blood specimens with turbid plasma (usually caused by hyperlipidemia) or severe leukocytosis. The MCHC is the average hemoglobin concentration per total red blood cell volume (ratio of hemoglobin mass to RBC volume), as determined from the following equation:

The MCHC is decreased in microcytic anemias where the decrease in hemoglobin mass exceeds the decrease in the size of the red blood cell. It is increased in hereditary spherocytosis and in patients with hemoglobin variants, such as sickle cell disease and hemoglobin C disease). Measurement of Hemoglobin Nearly all automated hematology analyzers utilize the cyanomethemoglobin method to measure the hemoglobin content of the red blood cell. In this method, hemoglobin is converted to cyanated methemoglobin (cyanmethemoglobin) by the addition of a solution (Drabkin solution) containing potassium ferricyanide and potassium cyanide. Cyanated methemoglobin maximally absorbs light at 540 nm, and the total amount of hemoglobin is determined by spectrophotometry. The hemoglobin concentration is measured in grams per deciliter (g/dL) of whole blood. Hyperlipidemia, fat droplets (from hyperalimentation), hypergammaglobinemia, cryoglobulinemia, and leukocytosis (> 50 x 109/mL) can result in spurious elevations of hemoglobin concentration. Spurious hemoconcentration or hemodilution, occurring with improper specimen collection, may falsely elevate or decrease hemoglobin concentrations. In addition, the age, sex, and race of the patient must also be considered in the interpretation of hemoglobin levels. Hemoglobin levels fall during the first month of life and remain relatively low until after puberty. The mean male hemoglobin level is 1 - 2 g/dL higher than the mean female level. Blacks of both sexes and all ages have hemoglobin levels which are 0.5 - 1.0 g/dL lower than whites of the same age and sex. A peripheral blood smear (peripheral blood film) is a glass microscope slide coated on one side with a thin layer of venous blood. The slide is stained with a dye, usually Wrights stain, and examined under a microscope. Microscopic examination of the peripheral blood is used to supplement the information provided by

automated hematology analyzers ("blood cell counters"). Hematology analyzers provide accurate quantitative information about blood cells and can even identify specimens with abnormal cells. However, the precise classification of abnormal cells requires a trained microscopist, a well-made peripheral blood smear, and a light microscope with good optical characteristics. In practice, hematology analyzers of varying sophistication are used for cell counting in all but the smallest hematology laboratories. In addition to providing cell counts and graphical displays of the information recovered, these instruments also provide a warning ("flag") that atypical cells were found and provide a presumptive identification of the abnormality. The instrument operator reviews the information from each specimen and decides if smear preparation and light microscopy are necessary. If not, the information is released to the clinician.

Spherocytosis, hereditary. Blood film. Many of the cells are small dense cells referred to as spherocytes. The vertical arrows point to several such cells. Some of the spherocytes have a very small circular area of central pallor and are spherostomatocytes (horizontal arrows). At least two large cells with a slightly bluish tint are presumably reticulocytes (asterisks)

target cells or codocytes (black arrows) appear as a target with a bullseye. Dog, blood smear, Wright stain.

Leptocyte Definition: Erythrocyte with excessive central pallor and very thin area of stained cytoplasm. The diameter of this cell is larger than the diameter of normocyte, but the volume is the same. Occurrence in blood: normally not present Comment: The arrow indicates a typical leptocyte, which has a very wide perinuclear halo, and very slim part of cytoplasm. Staining: MGG Magnification: x 1000

Burr cells-1. target-cell 2. elliptocyte 3. Schistocyte

Acanthocytes, or spiked red blood cells, in a peripheral blood smear.

Table 1. Changes in erythrocyte morphology associated with various medical disorders. Common Name Burr cell Scientific Name Morphology Disease or Disorder(s)

Echinocyte

Spiculated erythrocyte with short, equally-spaced projections

Uremia Pyruvate kinase deficiency Liver disease Artifact due to improper drying

Spur cell

Acanthocyte

Blunted spicules of varying length, irregularly distributed over cell surface

Liver disease Lipid disorders Hemangiosarcoma Disseminated intravascular coagulation

Elliptocyte

Ovalocyte, pencil cell, cigar cell

Oval to elongated, ellipsoid erythrocyte with central area of pallor and hemoglobin at both ends of cell

Hereditary elliptocytosis (band 4.1 defect) Normal in Camellidae

Sickle cell

Drepanocyte

Cell contain polymerized hemoglobin, crescent shaped with pointed ends

Hereditary sickle cell disorder Deer erythrocytes

Fragmented cell

Schistocyte

Fragmented erythrocyte, often crescent-shaped with pointed ends; must be smaller than intact erythrocytes

Dissemintaed intravascular coagulation Intravascular hemolysis, Immune-mediated anemia Severe burns Uremia Turbulent blood flow Common in young ruminants

Target cell

Codocyte

Erythrocyte with increased surface area to volume ratio; appear as target with bullseye

Liver disease Iron lack or deficiency Post-splenectomy Decreased lecithin cholesterol acyltransferase activity Thalassemia (hemoglobinopathy)