Anemia Anemia has been defined as a clinical condition associated with either a decrease in the number of total red

blood cell or a decrease in the concentration of haemoglobin, or a decrease in the hematocrit, as a compared with a normal person. Signs and symptoms of anemia are classified to three groups first, are those due to decrease in oxygen transport (fatigue, syncope, dyspnea, angina pectoris, widespread impairment of organ function in GI and other body system) second, are due to decrease in blood volume (pallor, postural hypotension) and third, are due to increase in cardiac output (palpitation, with pulse pressure, hemic heart murmur, onset of congestive heart failure). Anemia is functionally defined as an insufficient RBC mass to adequately deliver oxygen to peripheral tissues.

Microcytic- hypochromic Anemia Microcytic- hypochromic Anemia exhibit an Mean Corpuscular Volume (MCV)of less than 85fl and an Mean Corpuscular Hemoglobin Concentration (MCHC) of less than 30g/dl. This means that both cell size and haemoglobin content are below normal. This category also includes several different types of anemia, such as Iron Deficiency Anemia(IDA), which is the most common anemia, Sideroblastic Anemias, Thalassemia, and Lead Toxicity Chronic Inflammation

Iron Deficiency Anemia Iron Deficiency is one of the most prevalent forms of malnutrition. It is a condition in which there is anemia in clear evidence of iron lack. Globally, 50% of anemia is attributable to iron deficiency and accounts for ~841,000 deaths annually worldwide. Africa and parts of Asia bear 71% of the global mortality burden; North America represents only 1.4% of the total morbidity and mortality associated with iron deficiency. As in the case of many anemias, the causes of IDA, are many and varied. However they may be grouped into four major categories. First in the Blood Loss, it is the most common cause of IDA. In adult men and in postmenopausal women, bleeding is mainly from the gastrointestinal tract. Blood loss is usually in the form of a chronic hemorrhage caused by gastric or duodenal ulcers, excessive aspirin ingestion, hiatus hernia, carcinoma of stomach or intestines, colitis, diverticulitis, or haemorrhoids. In women of childbearing age, IDA is mostly due to blood loss caused by menstruation, pregnancy and childbirth. In very rare instances, bleeding maybe from the kidneys and bladder, resulting in hematuria and hemoglobinuria.

Second is the Increased Demand . Three groups of people need increase amount of iron. First, pregnant women need more iron, since there body iron is preferentially taken by the developing fetus at the expense of the mother. Further, during pregnancy the blood volume of the mother increases by two-thirds. Second, infants and young children need extra iron, especially those that are almost exclusively breast- or bottle-fed over a long period of time. Milk does not contain iron and iron deficiency may develop unless supplemental iron is given. Third, elder children and adolescent need extra iron since they are experiencing rapid growth. In addition, many children lack a well- balanced diet that provides them with sufficient ferrous iron and heme. Third,is the Malabsortion. Celiac disease, partial or total gastrectomy, atrophic gastritis all may result in achlorhydria and thus predispose the person to iron deficiency. Intestinal parasites, such as hookworms, may take up dietary iron at the expense of the infested person and thus may contribute to IDA. Also tropical sprue will result inability to absorb iron. Sprue is a chronic celiac disease associated with malabsorption of food elements such as fat, xylose, and vitamin B12 from the small intestine. Lastly is Poor Diet. It is rarely the sole cause by iron deficiency, it is an important contributing factor for persons living in many underdeveloped countries. Their poor-quality, largely vegetable diet may produce a backgraound of latent iron deficiency, especially when combined with repeated pregnancies, prolonged lactation, or parasitic infection.

Clinical Features of Iron Deficiency Anemia The first symptoms of IDA are usually those associated with general anemia such as weakness, fatigue, inability to concentrate, headaches, and dizziness. No other overt signs are present at the early stages of IDA. Later phases however, show a number of highly specific signs that may indicate the presence of this type of anemia. This symptoms are mainly epithelial changes caused by a deficiency of intracellular iron containing enzymes. They include angular stomatitis (sores at the corners of the mouth), glossitis (inflammation of the tongue, often associated with open sores), koilonychias (flat or spoon shaped nails), esophageal webbing (lesions of the esophagus), dysphagia (not eating, perhaps due to pain in the esophagus), and pica (craving for unusual foods). Laboratory Findings of Iron Deficiency Anemia The laboratory findings associated with IDA show a low MCV and low MCHC. A blood smear will confirm microcytosis and hypochromia. In severe cases of IDA, poikilocytosis may be observed. If iron deficiency is associated with lack of folate or vit.B12, anisocytosis may be noted, with both microcytic and macrocytic cell present in the blood film. In the latter case the MCV and MCHC may be fairly normal.

The reticulocyte count is always low in IDA, whereas the platelet count is often moderately increased, especially when low level chronic bleeding is present. The bone marrow may show erythroid hyperplasia, but the developing red blood cells will be hypochromic. Staining of the bone marrow smear with Prussian blue will show a complete absence of hemosiderin granules, thus indicating the absence of any iron stores in this erythrocytes precursor cells.

Thalassemia The thalassemia syndromes are inherited disorders of - or - globin biosynthesis. The reduced supply of globin diminishes production of haemoglobin tetramers, causing hypochromia and microcytosis. Unbalanced accumulation of and subunits occurs because the synthesis of the unaffected globins proceeds at a normal rate. Unbalanced chain accumulation dominates the clinical phenotype. Clinical severity varies widely, depending on the degree to which the synthesis of the affected globin is impaired, altered synthesis of other globin chains, and coinheritance of other abnormal globin alleles. Blood pictures show microcytic hypochromic cells with a predominance of target cells. Target cells are red cells with central and peripheral condensation of haemoglobin with the clear zone in between. Blood picture further shows the following: Anisocytosis and increased reticulocyte count (5-15%). Increase nucleated red cells is a characteristic finding. There is also decreased osmotic fragility of red cells. Leukocytosis (10-25 X /L) may be present. Other signs of active red cell regeneration such as polychromatophilic cells, stippled RBC, and Howell- jolly bodies may be seen. Patient also shows splenomegaly, hepatomegaly and jaundice. Striking changes also occur in the skeletal system.

Anemia of Lead Poisoning Lead poisoning has occurred from a wide array of sources that includes lodged bullets, inhaled fumes in various industries or from lead particles in a firing range, ingested contaminated herbs and food supplements, and beverages containing lead solubilized from glazed of utensils and lining of stills. Sideroblastic Anemia The sideroblastic anemias are a heterogeneous group of disorders characterized by amorphous iron deposits in erythroblast mitochondria that are housed within a distinct, mitochondrial ferritin. The iron-glutted mitochondria account for the so called ring sideroblast, an erythroblast

in which numerous Prussian blue-positive granules often appear in a perinuclear distribution, particularly in the later stage of its maturation. Sideroblastic anemias are a singularly instructive set of disorders with respect to physiology and pathophysiology of erythropoiesis. Some sideroblastic anemias fall under the rubric of myelodysplasia while others do not. The presence of ringed sideroblast (abnormal erythroblasts with excessive mitochondrial iron deposition) in the bone marrow is the phenotypic of a heterogeneous group of disorders whose unifying features is deranged heme biosynthesis. Unraveling of the biochemistry and genetics of sideroblastic anemia provides unique insight into heme and iron metabolism along with an expanded understanding of erythropoiesis. Center stage in this drama features the heme molecule. Diagnosis Ferritin

< 20 is diagnostic of iron deficiency. 20-30 is indicative of borderline iron stores May be elevated in chronic inflammatory states/liver disease

Iron saturation (Helpful but not absolute):

Affected by oral iron intake: patients should not take MVI with iron or iron tablets within 24 hours of test for reliable results. < 5% generally diagnostic of iron deficiency 5-10% probable iron deficiency >15% More likely anemia of chronic disease

Indices: MCV usually reduced in proportion to the hemoglobin. Exceptions:

chronic blood loss accompanied by enough iron ingestion to keep red cells normal sized but not to replete iron stores or keep hemoglobin normal Multifactorial (e.g., o combined B12/Fe deficiency, hypothyroidism (MCV higher than expected) o hemoglobinopathies (MCV much lower than expected for anemia)

Treatment and Prevention 1. for uncomplicated iron deficiency anemia (menstruating female; patients with clear source of iron deficiency anemia): Iron sulfate (ferrous sulfate) 325 mg three times a day: best tolerated with food. Work up to full dose over a week. Patients should be advised to use stool softener at first sign of constipation.

Twice a day is often sufficient, but it may take longer to correct the anemia. Expect 6-8 weeks to normalize hemoglobin. To replace iron stores, continue iron at once daily dose for 6 months after correction of anemia. Do not expect ferritin levels to normalize until then (ferritin reflects iron stores; we don't store iron until we replete our red blood cells). Menstruating women with recurrent or severe iron deficiency should take continued iron supplementation until menopausal (with intermittent evaluation of CBC/ferritin to ensure compliance/maintenance of normal hemoglobin). Some women will do well long term with a multivitamin/iron supplement, but must make sure that above initial treatment is completed. 2. For iron deficiency anemia of unknown cause, same treatment applies, but patients should be evaluated for source of bleeding: GI workup mandatory for anyone over 50, consider for those over 40 without a good explanation for iron deficiency; most males at any age should be evaluated for GI blood loss; INCLUDES STOOL FOR OB.

colonoscopy preferred over sigmoidoscopy, because right sided lesions may be more likely to be associated with bleeding). EGD Consider UGI/SBFT xray to rule out small bowel lesions if colonoscopy/EGD noninformative. Should be considered more strongly for patients with recurrent unexplained iron deficiency after adequate primary therapy and for all patients with occult blood positive stools with negative EGD/colon GU workup: urinalysis may reveal hematuria due to GU tract tumors.

3. Iron intolerance: Most patients will be able to tolerate oral iron if they work up to a full dose over several days, take it with food and are prepared to deal with constipation. If a patient does not tolerate ferrous sulfate, a trial of ferrous gluconate should be given (same dosing). It contains less iron (30 mg), so may take a little longer to work. Niferex tablets (nonformulary, prescription required) contain 50 mg elemental iron and may be tried when ferrous sulfate or gluconate are not tolerated. 4. Intravenous iron should be reserved for patients who really do not tolerate oral iron after a reasonable trial period (working up to full dose, trying different preparations, as above) or for patients with excessive iron losses due to untreatable causes (huge hiatal hernias, etc.), very severe iron deficiency intolerant to oral iron, but IV iron does not work any faster than oral iron. It has to be broken down to a usable form of iron within the bone marrow and does not begin to work for about 2 weeks. Expect 6-8 weeks to normalize the hemoglobin. Ferritin levels may abruptly rise and are not helpful in the short run. PDR has a table which gives the total dose of imferon to use based on hemoglobin and weight of patient.

Erythrocyte Count Hematocrit The hematocrit (Ht or HCT) or packed cell volume (PCV) or erythrocyte volume fraction(EVF) is the percentage (%) of the concentration of red blood cells in blood. It is normally about 45% for men and 40% for women.[1] It is considered an integral part of a person's complete blood count results, along with hemoglobin concentration, white blood cell count, and plateletcount.

Haemoglobin This test is used to evaluate:

anemia, polycythemia, response to treatment of anemia or polycythemias, dehydration, blood transfusion decisions for severe symptomatic anemias, and the effectiveness of those transfusions.

The hematocrit is normally ordered as a part of the complete blood count (CBC). It is also repeated at regular intervals for many conditions, including: the diagnosis of anemia and polycythemia, the monitoring of treatment for anemia,

recovery from dehydration, and monitoring of ongoing bleeding to check its severity.

Decreased hematocrit indicates anemia, such as that caused by iron deficiency or other deficiencies. Further testing may be necessary to determine the exact cause of the anemia. Other conditions that can result in a low hematocrit include vitamin or mineral deficiencies, recent bleeding, cirrhosis of the liver, and malignancies. The most common cause of increased hematocrit is dehydration, and with adequate fluid intake, the hematocrit returns to normal. However, it may reflect a condition called polycythemia verathat is, when a person has more than the normal number of red blood cells. This can be due to a problem with the bone marrow or, more commonly, as compensation for inadequate lung function (the bone marrow manufactures more red blood cells in order to carry enough oxygen

throughout your body). Anytime a hematocrit is persistently high, the cause should be determined in consultation with a doctor. With regard to transfusions, this is normally not considered for otherwise healthy persons as long as the hemoglobin level is above 8 grams per deciliter or the hematocrit is above 24%.

Pregnancy usually causes slightly decreased hematocrit values due to extra fluid in the blood. Living at high altitudes causes increased hematocrit valuesthis is your bodys response to the decreased oxygen available at these heights.

Red cell distribution width The red blood cell distribution width (RDW or RCDW) is a measure of the variation of red blood cell (RBC) width that is reported as part of a standard complete blood count. Usually red blood cells are a standard size of about 68 m. Certain disorders, however, cause a significant variation in cell size. Higher RDW values indicate greater variation in size. Normal reference range in human red blood cells is 1115%. 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. Vitamin B12 deficiency produces a macrocytic anemia (large cell anemia) with a normal RDW. However, iron deficiency anemia initially presents with a varied size distribution of red blood cells, and as such shows an increased RDW. In the case of a mixed iron and B12 deficiency, there will normally be a mix of both large cells and small cells, causing the RDW to be elevated. An elevated RDW (red blood cells of unequal sizes) is known as anisocytosis.[1] Calculation The "width" in RDW is sometimes thought of as "misleading," since it in fact is a measure of deviation of the volume of RBCs, and not directly the diameter. However, "width" refers to the width of the volume curve (distribution width), not the width of the cells. Thus, it is a reasonably accurate term.

Mathematically the RDW is calculated with the following formula:

RDW = (Standard deviation of MCV mean MCV) 100.

Peripheral blood smear examination Examination of a blood smear is an integral part of a hemogram. Blood smear analysis allows quantitation of the different types of leukocytes (called the differential count), estimation of the platelet count, and detection of morphologic abnormalities that may be indicators of pathophysiologic processes. In some instances, a diagnosis may be evident. Deriving full value from blood smear examination requires a well-prepared, well-stained blood smear and some basic skills in the methods of assessment. This short movie clip demonstrates the proper technique for making a good quality blood smear. Though some automated hematology analyzers provide a differential count as part of their ouput, this does not fully take the place of a microscopic exam by an experienced observer. A peripheral blood smear is often used as a follow-up test to abnormal results on a complete blood count (CBC). It may be used to help diagnose and/or monitor numerous conditions that affect blood cell populations. At one time, a blood smear was prepared on nearly everyone who had a CBC. With the development of more sophisticated, automated blood cell counting instruments, an automated differential is routinely provided. However, if the results from an automated cell count and/or differential indicates the presence of abnormal white blood cells (WBCs), red blood cells (RBCs), and/or platelets or if there is reason to suspect that abnormal cells are present, then a blood smear will be performed. A blood smear examined by a trained eye is still the best method for definitively evaluating and identifying immature and abnormal cells. A blood smear is often used to categorize and/or identify conditions that affect one or more types of blood cells and to monitor those undergoing treatment for these conditions. There are many diseases, disorders, and deficiencies that can affect the number and type of blood cells produced, their function, and their lifespan. Usually, only normal mature cells are released into the bloodstream, but certain circumstances can induce the bone marrow to release immature and/or abnormal cells into the circulation. When a significant number or type of abnormal cells are present, they can suggest an underlying condition and prompt the doctor to do further testing. The blood smear is primarily ordered to evaluate blood cell populations when a CBC with differential, performed with an automated blood cell counter, indicates the presence of abnormal or immature cells. It may also be performed when a doctor suspects a deficiency, disease, or disorder that is affecting blood cell production or increased cell destruction, such as an anemia, myeloproliferative disorders, bone marrow disorders, or leukemia. Some signs and symptoms that may indicate one of these blood disorders include:

Weakness, fatigue Pale complexion Unexplained jaundice Bleeding episodes

Enlargement of the spleen Bone pain

A blood smear may also be ordered on a regular basis when a person is being treated or monitored for a blood cell-related disease. Findings from the blood smear evaluation are not always diagnostic in themselves and more often indicate the presence of an underlying condition, its severity, and the need for further diagnostic testing. The results are taken into consideration with results of the CBC and other laboratory tests as well as the tested person's clinical signs and symptoms. The results of a blood smear typically include a description of the appearance of the RBCs, WBCs, and platelets as well as any abnormalities that may be seen on the slide.

Anisocytosis Anisocytosis is a medical term meaning that a patient's red blood cells are of unequal size. This is 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. 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) Increased RDW is seen in iron deficiency anemia, Thalassemia Major (Cooley's anemia), Thalassemia Intermedia and myelodysplastic syndromes