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1-Anemias by Minwoldu

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Published on February 27, 2014

Author: minwoldu

Source: authorstream.com

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Anemias: Anemias By Minyahil A Woldu Bpharm ., MSc in Clincal Pharmacy Definition: Definition Anemia is a reduction in red cell mass . It often is described as a decrease in the number of red blood cells (RBC) per cubic millimeter (mm 3 ) or as a decrease in the hemoglobin concentration in blood to a level below the normal physiologic requirement for adequate tissue oxygenation. The term anemia is not a diagnosis , but rather an objective sign of a disease. Definition…: Definition… An exact diagnosis is important to the understanding of the problem and to implement specific therapy to correct the anemia. Diagnostic terminology for anemia requires the inclusion of the pathogenesis (e.g., megaloblastic anemia secondary to folate deficiency, microcytic anemia secondary to iron deficiency). Pathophysiology: Pathophysiology Anemia is a symptom of many pathologic conditions. It is associated with nutritional deficiencies and acute and chronic diseases ; it also can be drug induced . Anemia can be caused by decreased red cell production , increased red cell destruction , or increased red cell loss . If the anemia is caused by decreased red cell production , it may be the result of disturbances in stem cell proliferation or differentiation . Pathophysiology…: Pathophysiology … Anemias caused by increased red cell destruction can be secondary to hemolysis , whereas increased red cell loss may be caused by acute or chronic bleeding . Anemias associated with acute blood loss , those that are iron related , and those caused by chronic disease comprise most of all anemias . Pathophysiology…: Pathophysiology … Normally , RBC mass is maintained by feedback mechanisms that regulate levels of erythropoietin (EPO), a hormone that stimulates proliferation and differentiation of erythroid precursors in the bone marrow. Two types of erythroid precursors reside in the bone marrow: the burst-forming unit, erythroid ( BFUe ) and colony-forming unit, erythroid ( CFUe ). The BFUe is the earliest progenitor, which eventually develops into a CFUe . BFUe is moderately sensitive to EPO and is under the influence of other cytokines (e.g., interleukin [IL]-3, granulocyte-macrophage colony-stimulating factor [GM-CSF] ). Pathophysiology…: Pathophysiology … In contrast, CFUe is highly sensitive to EPO and differentiates into erythroblasts and reticulocytes . Of EPO, 90% is produced in the kidney ; liver synthesis accounts for the remaining 10%. Reduced oxygen-carrying capacity is sensed by renal peritubular cells , and this stimulates release of EPO into the bloodstream. Patients with chronic anemia may have a blunted and inadequate response for the degree of anemia present. Classifications of Anemia: Classifications of Anemia Pathophysiologic ( Classifies Anemias Based on Pathophysiologic Presentation) Blood Loss Acute : trauma, ulcer, hemorrhoids Chronic : ulcer, vaginal bleeding, aspirin ingestion Inadequate Red Blood Cell Production Nutritional deficiency : B 12 , folic acid, iron Erythroblast deficiency : bone marrow failure ( aplastic anemia, irradiation, chemotherapy, folic acid antagonists) or bone marrow infiltration (leukemia, lymphoma, myeloma, metastatic solid tumors, myelofibrosis ) Endocrine deficiency : pituitary, adrenal, thyroid, testicular Chronic disease: renal, liver, infection, granulomatous , collagen vascular Excessive Red Blood Cell Destruction Intrinsic factors : hereditary (G6PD), abnormal hemoglobin synthesis Extrinsic factors : autoimmune reactions, drug reactions, infection ( endotoxin ) Classifications of Anemia…: Classifications of Anemia… Morphologic ( Classifies Anemias by Red Blood Cell Size [ Microcytic , Normocytic , Macrocytic ] and Hemoglobin Content [ Hypochromic , Normochromic , Hyperchromic ]) Macrocytic Defective maturation with decreased production Megaloblastic: pernicious (vitamin B 12 deficiency), folic acid deficiency Normochromic , normocytic Recent blood loss Hemolysis Chronic disease Renal failure Autoimmune Endocrine Microcytic , hyperchromic Iron deficiency Genetic abnormalities: sickle cell, thalassemia G6PD, glucose-6-phosphate dehydrogenase . Detection: Detection Signs and Symptoms Signs and symptoms of anemia vary with the degree of RBC reduction as well as with the time interval over which it develops. Onset of anemia can be acute or can develop slowly, resulting in tissue hypoxia caused by the decreased oxygen-carrying capacity of the reduced red cell mass. As a result, perfusion to nonvital tissues (e.g., skin, mucous membranes, extremities) is decreased to sustain tissue perfusion of vital organs (e.g., brain, heart, kidneys). Slowly developing anemias can be asymptomatic initially or include symptoms such as slight exertional dyspnea , increased angina, fatigue, or malaise. Uncorrected tissue hypoxia can lead to a number of complications in quality of life, cognition, and respiratory and gastrointestinal (GI) systems. Changes in the blood hemoglobin concentration also lead to changes in the kidney tissue oxygen tension . Detection…: Detection… Signs and Symptoms… In severe anemia , a hemoglobin ( Hgb ) <8 mg/ dL , heart rate, and stroke volume often increase in an attempt to improve oxygen delivery to tissues. These changes in heart rate and stroke volume can result in systolic murmurs , angina pectoris , high output congestive heart failure , pulmonary congestion , ascites , and edema . Thus, anemia is generally not well tolerated in patients with cardiac disease . Skin and mucous membrane pallor , jaundice , smooth or beefy tongue , cheilosis , and spoon-shaped nails ( koilonychia ) also may be associated with severe anemia of different causes of anemia. Detection…: Detection… History A thorough history and physical examination are essential because of the complexity of the pathologic conditions associated with anemia. A time line, which begins with the onset of symptoms (and surrounding events) and extends to current status, is important. Because longstanding anemias can indicate hereditary disorders , the family history should be noted. Past Hgb or hematocrit ( Hct ) determinations, transfusion history, as well as occupational , environmental, and social histories may be valuable. Finally, a medication history can help eliminate drug reactions or interactions as the cause of the anemia. Detection…: Detection… Physical Examination On physical examination of a patient with anemia, pallor is most easily observed in the conjunctiva , mucous membranes , nail beds , and palmar creases of the hand . In addition, postural hypotension and tachycardia can be seen when hypovolemia (acute blood loss) is the primary cause of anemia. Patients with B 12 deficiency may exhibit neurologic findings , which include changes in deep tendon reflexes , ataxia , and loss of vibration and position sense ; all are consistent with nerve fiber demyelination . Patients with anemia from hemolysis may be slightly jaundiced from bilirubin release. Manifestations of hemorrhage can include petechiae , ecchymoses , hematomas , epistaxis , bleeding gums , and blood in the urine or the stool . Detection…: Detection… Laboratory Evaluation Although anemia may be suspected from the history and physical examination, a full laboratory evaluation is necessary to confirm the diagnosis , establish its severity , and determine its cause . The cornerstone of this evaluation is the complete blood count ( CBC ). Male patients have higher hematocrit ( Hct ) values than do female patients . The Hct is increased in individuals living at altitudes above 4,000 feet in response to the diminished oxygen content of the atmosphere and blood. Detection…: Detection… Laboratory Evaluation… The morphologic appearance of the RBC provides useful information about the nature of the anemia. Microscopic evaluation of the peripheral blood smear can detect the presence of macrocytic (large) RBC, which usually are present when anemia results from a vitamin B 12 or folic acid deficiency ; microcytic (small) RBC usually are associated with iron deficiency anemia . Acute blood loss generally is associated with normocytic cells. If still not identified after routine evaluation, problems such as autoimmune disease , collagen vascular disease , chronic infection , endocrine disorders , or drug-induced destruction may be causing the anemia. Routine Laboratory Evaluation for Anemia Workup: Routine Laboratory Evaluation for Anemia Workup Complete blood count (CBC): Hgb , Hct , RBC count, red cell indices (MCV, MCH, MCHC), WBC count (and differential) Platelet count Red cell morphology Reticulocyte count Bilirubin and LDH Serum iron, TIBC, serum ferritin, transferrin saturation Peripheral blood smear examination Stool examination for occult blood Bone marrow aspiration and biopsy a a Performed in patients with abnormal peripheral blood smears. Hct , hematocrit ; Hgb , hemoglobin; LDH, lactic dehydrogenase ; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; RBC, red blood cell; TIBC, total iron-binding capacity; WBC, white blood cell. Normal Hematology Values: Normal Hematology Values Laboratory Test Pediatric Adult 1–15 yr Male Female RBC (× 10 6 /mm 3 ) ±4.7–6 5.4–0.7 ±4.8–6 Hgb (g/ dL ) ±13–2 16–2 ±14–2 Hct (%) ±40–5 47–5 ±42–2 MCV (µm 3 ) ±80–5 87–7 ±90–9 MCH (pg/cell) ±33.5–2 29–2 ±34–2 MCHC (g/dL) ±31–36 31–36 ±31–36 Erythropoietin (mU/mL) 4–26 4–26 4–26 Reticulocyte count (%) 0.5–1.5 0.5–1.5 0.5–1.5 TIBC (mg/dL) 250–400 250–400 250–400 Fe (mg/dL) 50–120 50–160 40–150 Folate (ng/mL) 7–25 7–25 7–25 RBC folate (ng/mL) — 140–960 140–960 Fe/TIBC (%) 20–30 20–40 16–38 Vitamin B 12 (pg/mL) >200 >200 >200 Ferritin (ng/mL) 7–140 15–200 12–150 Fe, iron; Hgb , hemoglobin; Hct , hematocrit ; MCH, mean corpuscular hemoglobin; MCV, mean corpuscular volume; RBC, red blood cell; TIBC, total iron-binding capacity. Iron Deficiency Anemia: Iron Deficiency Anemia Iron deficiency is a state of negative iron balance in which the daily iron intake and stores are unable to meet the RBC and other body tissue needs. The body contains approximately 3.5 g of iron, of which 2.5 g are found in Hgb. A significant amount of iron is stored as ferritin or aggregated ferritin ( hemosiderin ) in the reticuloendothelial cells of the liver, spleen, and bone marrow and by hepatocytes . Ferritin circulates at concentrations that reflect total iron body stores. Only a small fraction of iron is found in plasma (100 to 150 mcg/ dL ), and most is bound to transferrin , the transport protein. Iron Deficiency Anemia…: Iron Deficiency Anemia… Despite the continuing turnover of RBC, iron stores are well preserved because the iron is recovered and reutilized in new erythrocytes . Only about 0.5 to 1 mg/day of iron is lost from urine, sweat, and the sloughing of intestinal mucosal cells that contain ferritin in men and in non-menstruating women. Menstruating women lose approximately 0.6 % to 2.5 % more iron per day. Pregnancy and lactation are other common sources of iron loss. Individuals with normal iron stores absorb roughly 10% of ingested dietary iron . The average American diet contains 6 mg of elemental iron/1,000 Kcal . Iron Deficiency Anemia…: Iron Deficiency Anemia… Thus, the average daily intake ranges between 10 and 12 mg, enough to replace the 1 mg lost daily (based on 10% absorption). For menstruating , pregnant , or lactating women, however, the daily iron intake requirement may be as high as 20 mg . Iron, which is absorbed from the duodenum and upper jejunum by an active transport mechanism , is enhanced in the presence of an acidic gastric environment . Dietary iron , which is primarily in the ferric state , is converted to the more readily absorbed ferrous form in the acid environment of the stomach. It is the ferrous form that binds to transferrin for its journey to the bone marrow , where it is incorporated into the Hgb of mature erythrocytes. Iron Deficiency Anemia…: Iron Deficiency Anemia… Gastrointestinal absorption of iron is increased from the usual 10% to as much as three- to fivefold in iron deficiency states or when erythropoiesis occurs at a more rapid rate. Animal sources of iron, heme iron, are better absorbed than plant sources, nonheme iron. A gastrectomy or vagotomy may decrease the conversion of the ferric form of iron to the ferrous state, thereby diminishing iron absorption. In addition, certain foods and drugs can complex with iron , decreasing its absorption. Iron Deficiency Anemia…: Iron Deficiency Anemia… Anemia caused by iron deficiency is the most common nutritional deficiency worldwide . Although iron deficiency anemia has many causes blood loss is considered one of the more common . Each milliliter of whole blood contains 0.5 mg of iron, whereas each milliliter of packed RBC contains 1 mg of iron. Common causes of chronic blood loss include peptic ulcer disease , hemorrhoids , ingestion of GI irritants , menstruation , multiple pregnancies , and multiple blood donations . Iron Deficiency Anemia…: Iron Deficiency Anemia… The increased amounts of iron required by pregnant or lactating women are difficult to obtain through diet alone; thus, oral iron supplementation generally is necessary . Although maternal iron usually provides term infants with sufficient stored iron for the first 6 months, infants 6 months to 3 years of age experience rapid growth and a threefold increase in blood volume, which can increase the risk of iron deficiency . Premature infants have reduced iron stores and thus require replacement therapy . Supplementation of 10 to 15 mg/day of iron may be required for up to the first year of life. Iron Deficiency Anemia…: Iron Deficiency Anemia… Maintenance iron therapy for healthy older infants and children is roughly 1 to 2 mg/kg/day (not to exceed 20 mg/day). If iron deficiency develops in the pediatric patient, 3 to 6 mg/kg/day of elemental iron should be administered in two to three divided doses. Iron Deficiency Anemia Causes: Iron Deficiency Anemia Causes Blood Loss Menstruation, gastrointestinal (e.g., peptic ulcer), trauma Decreased Absorption Medications, gastrectomy , regional enteritis Increased Requirement Infancy, pregnant/lactating women Impaired Utilization Hereditary, Iron use Dietary Reference Intake for Iron: Dietary Reference Intake for Iron   description mg per day Healthy, non-menstruating adults 8 Menstruating women 18 Pregnant women 27 Lactating women 9 Vegetarians 16 Comparisons of Iron Preparations: Comparisons of Iron Preparations Preparation Dose (mg) Fe ++ Content (mg) Fe (%) Ferrous sulfate 325 65 20 Ferrous fumarate 324 106 33 Ferrous gluconate 300 34 11 Feosol tablets 200 65 33 Slow Fe (time released) 160 50 31 Combination Iron Products: Combination Iron Products Drug DOSS (mg) Vitamin C (mg) Fe ++ Content (mg) Ferro-Grad 500 ( Filmtabs ) 0 500 105 Vitron C 0 125 66 Ferro DSS/Ferro-Sequel 100 0 50 DOSS, dioctyl sodium sulfosuccinate ; docusate sodium; Fe, iron. Goals of Therapy: Goals of Therapy The goals of iron therapy are to normalize the Hgb and Hct concentrations and to replete iron stores. Initially, if the doses of iron are adequate , the reticulocyte count will begin to increase by the third to fourth day and peak by the seventh to tenth day of therapy . By the end of the second week of iron therapy, the reticulocyte count will fall back to normal . The Hgb response is a convenient index to monitor in outpatients . Hematologic response is usually seen in 2 to 3 weeks with a 1 g/ dL increase in hemoglobin and a 6% increase in the hematocrit . Goals of Therapy: Goals of Therapy Therapy duration is related to the absorption pattern of iron. During the first month of therapy , as much as 35 mg of elemental iron is absorbed from the daily dose. With time, the percentage of iron absorbed from the dose decreases , and by the third month of therapy, only 5 to 10 mg of elemental iron is absorbed. Patient Information: Patient Information Iron should be dispensed in a childproof container. Accidental ingestion of even small amounts (three to four tablets) of oral iron can cause serious consequences in small children. Gastric side effects, which occur in 5% to 20% of patients, include nausea, epigastric pain, constipation, abdominal cramps, and diarrhea. Constipation does not appear to be dose related, but side effects (e.g., nausea and epigastric pain) occur more frequently as the quantity of soluble elemental iron in contact with the stomach and duodenum increases. To minimize gastric intolerance, oral iron therapy can be initiated with a single tablet of ferrous sulfate 325 mg/day; the dose is increased by increments of one tablet per day every 2 to 3 days until the full therapeutic dose of ferrous sulfate, 325 mg three times daily, can be administered Parenteral Iron Therapy : Parenteral Iron Therapy Indications Several indications exist for parenteral iron administration. Failure to respond to oral iron therapy would prompt a re-evaluation of causes of oral therapy failure can include nonadherence , misdiagnosis (e.g., inflammation), malabsorption (e.g., sprue , radiation enteritis, duodenal or upper small intestine resection), and continuing blood loss equal to or greater than the rate of RBC production. Malabsorption can be evaluated by measuring iron levels every 30 minutes for 2 hours after the administration of 50 mg of ferrous sulfate. If her plasma iron levels increase by >50%, absorption is adequate . Besides failure to respond to oral therapy as one indication for parenteral iron administration, other indications include intolerance to oral therapy , required antacid therapy , or significant blood loss in patients refusing transfusion. All can warrant injectable iron therapy. Preferred Route : Preferred Route Iron can be given parenterally in the form of ferric gluconate ( Ferrlecit ), iron dextran ( INFeD and Dexferrum ), and iron sucrose ( Venofer ). Iron dextran , the oldest of the parenteral iron agents, is U.S. Food and Drug Administration (FDA)-approved for the treatment of iron deficiency when oral supplementation is impossible or ineffective. In this particular formulation, iron is a complex of ferric hydroxide and dextran . Iron dextran can be administered undiluted intramuscularly or by very slow intravenous (IV) injection. Although not included in the labeling approved by the FDA, iron- dextran injection is commonly diluted in 250 to 1,000 mL 0.9% NaCl and administered by IV infusion. Preferred Route…: Preferred Route… IV administration is preferred to intramuscular (IM) administration when muscle mass available for an IM injection is limited ; when absorption from the muscle is impaired (e.g., stasis, edema); when uncontrolled bleeding is a risk (e.g., secondary to hemophilia, thrombocytopenia, anticoagulation therapy); and when large doses are indicated for therapy. Preferred Route…: Preferred Route… In a few instances, IM iron dextran is the preferred treatment e.g., patients with limited IV access. In these cases, undiluted drug should be administered using a Z-track technique to avoid staining the skin. The skin should be pulled laterally before injection; then the drug is injected and the skin is released to avoid leakage of dextran into the subcutaneous tissue. IM iron dextran is absorbed in two phases. In the first 72 hours, 60% of the dose is absorbed, whereas the remaining drug is absorbed over weeks to months. Preferred Route…: Preferred Route… Infusion rates of undiluted IV iron dextran should not exceed 50 mg (i.e., 1 mL ) per minute . The upper limit of each daily dose is based on the patient's weight and should not be >100 mg/day. Although the data are limited, total dose iron- dextran infusion is given in clinical practice and has proved to be effective and convenient. Infusions generally are given over 1 to 6 hours to minimize local pain and phlebitis . The total dose method of administration can be associated with a higher prevalence of fever , malaise , flushing , and myalgias . Preferred Route…: Preferred Route… Ferric gluconate and iron sucrose are parenteral iron formulations, which are FDA approved for the treatment of iron deficiency anemia in patients undergoing chronic hemodialysis and receiving supplemental EPO. Ferric gluconate can be administered undiluted as a slow IV injection (rate not to exceed 12.5 mg/minute ) or as an IV infusion (125 mg ferric gluconate in 100 mL 0.9% NaCl over 1 hour). Likewise, iron sucrose can be administered undiluted as a slow IV injection (rate not to exceed 20 mg/minute ) or as an IV infusion (dilute in a maximum of 100 mL 0.9% NaCl and infuse at a rate of 100 mg over 15 minute). Iron requirements in these patients typically exceed 1 to 2 g and, therefore, multiple doses of ferric gluconate and iron sucrose are needed to achieve the total dose of iron. Side Effects: Side Effects Anaphylactoid reactions can occur in <1% of patients treated with parenteral iron therapy. This reaction is more commonly associated with iron dextran than with ferric gluconate and iron sucrose. As a result, a 25-mg test dose of iron dextran should be given IM or by IV infusion over 5 to 10 minutes . If headache, chest pain, anxiety, or signs of hypotension are not experienced, the remainder of the dose can be administered parenterally . Side Effects…: Side Effects… Nevertheless, delayed reactions (e.g., fever, urticaria , arthralgias , and lymphadenopathy ) can be occurred after 24 to 48 hours of large doses of IV iron dextran and can be lasted 3 to 7 days in 1% to 2% of patients. A test dose is not indicated for ferric gluconate and iron sucrose because of the lower incidence of serious anaphylactoid reactions with these agents. Other side effects seen with parenteral iron agents include hypotension , nausea and vomiting , cramps , and diarrhea . Parenteral iron medications should not be mixed with (or added to) other medications or parenteral nutrition solutions for IV infusion. Megaloblastic Anemias: Megaloblastic Anemias Megaloblastic anemia is a common disorder that can have several causes: (a) anemia associated with vitamin B 12 deficiency ; (b) anemia associated with folic acid deficiency ; or (c) anemia caused by metabolic or inherited defects associated with decreased ability to utilize vitamin B 12 or folic acid. Megaloblastosis results from impaired DNA synthesis in replicating cells , which is signaled by a large immature nucleus. RNA and protein synthesis remain unaffected, and the cytoplasm matures normally. Megaloblastic changes can be observed microscopically in RBC and in proliferating cells (e.g., in the cervix, skin, GI tract). Although the clinical effects of vitamin B 12 and folic acid deficiencies can differ in various organ systems, they are similar in their effects on the hematopoietic system. Megaloblastic Anemias…: Megaloblastic Anemias … Typically, macrocytic anemia develops slowly and can be identified by large, oval, well- hemoglobinized red cells; anisocytosis ; and nuclear remnants. The reticulocyte count is low and the bilirubin level is elevated . Thrombocytopenia is present and the platelets are large. Leukopenia occurs with hypersegmentation of polymorphonuclear leukocyte nuclei. If biopsied , the bone marrow is markedly hypercellular . Nuclear immaturity is present , but the megaloblasts have normal maturation of the cytoplasm. Megaloblastic Anemias…: Megaloblastic Anemias … Iron stores in the marrow are increased as a result of the intramedullary hemolysis . Symptoms include fatigue; exaggeration of pre-existing cardiovascular or pulmonary problems; a sore, pale, smooth tongue; diarrhea or constipation; and anorexia. Edema and urticaria also may be present. Vitamin B12 Deficiency Anemia: Vitamin B 12 Deficiency Anemia Two mechanisms for the development of megaloblastic anemia are Deficiency and poor utilization of vitamin B 12 . Cobalamin (vitamin B 12 ) is naturally synthesized by microorganisms, but because humans are incapable of doing so, vitamin B 12 must be provided nutritionally. Animal protein, and roots and legumes of plants provide dietary sources of vitamin B 12 . Meats richest in vitamin B 12 include oysters, clams, liver, and kidney; moderate amounts of vitamin B 12 are found in muscle meats, milk products, and egg yolks. Vitamin B12 Deficiency Anemia…: Vitamin B 12 Deficiency Anemia… Other causes of vitamin B 12 deficiency include inadequate proteolytic degradation of vitamin B 12 from protein, or congenital intrinsic factor deficiency. In addition, the gastric mucosa may be unable to produce intrinsic factor under conditions such as partial gastrectomy , autoimmune destruction (e.g., addisonian or juvenile pernicious anemia), or destruction of the gastric mucosa from caustic agents . Vitamin B12 Deficiency Anemia…: Vitamin B 12 Deficiency Anemia… Pernicious anemia can result in vitamin B 12 deficiency. It can be caused by chronic atrophic gastritis accompanied by reduced intrinsic factor and hydrochloric acid secretion or acquired as a result of gastrectomy , pancreatic disease, or malnutrition. Pernicious anemia occurs commonly in patients with thyrotoxicosis , Hashimoto's thyroiditis , vitiligo , rheumatoid arthritis, or gastric cancer. Anti-intrinsic factor antibodies have been observed in the serum of some patients with pernicious anemia. Vitamin B12 Deficiency Anemia…: Vitamin B 12 Deficiency Anemia… The neurologic symptoms of vitamin B 12 deficiency are associated with a defect in myelin synthesis and often are described as stocking-glove peripheral neuropathy or nonspecific complaints (e.g., tinnitus, neuritis, vertigo, headaches). Patients with neurologic symptoms have difficulty determining position and vibration sense and have an increase in deep tendon reflexes. These symptoms may progress to spastic ataxia, motor weakness, and paraparesis . Interestingly, no correlation exists between the extent of neurologic manifestations and the severity of anemia . Anorexia, pallor, and dyspnea on exertion are bothersome symptoms that may overshadow the diagnostic triad. Laboratory Evaluation: Laboratory Evaluation In general, the serum vitamin B 12 level reliably reflects vitamin B 12 tissue stores. False low vitamin B 12 concentrations may be observed in patients with folic acid deficiency, transcobalamin I deficiency, multiple myeloma, pregnancy, or in those who take very large doses of vitamin C. Falsely elevated vitamin B 12 concentrations may be observed in patients with myeloproliferative diseases, hepatomas , autoimmune diseases, monoblastic leukemias , and histiocytic lymphomas. Measuring serum methylmalonic acid and homocysteine levels may assist in differentiating between folate and vitamin B 12 deficiency. Once vitamin B 12 therapy has been instituted, serum levels of these chemicals decrease if true vitamin B 12 deficiency is present. Laboratory Evaluation…: Laboratory Evaluation… The cause of vitamin B 12 deficiency may be determined by the use of antibody testing ( antiparietal cells and anti-intrinsic factor antibodies ). Patients with pernicious anemia are not able to absorb vitamin B 12 because intrinsic factor is not available for binding. Some patients produce intrinsic factor but are still unable to absorb dietary vitamin B 12 . Malabsorption can be caused by lack of intestinal bacteria that usurp vitamin B 12 , achlorhydria , pancreatic insufficiency, inadequate disassociation of vitamin B 12 from proteins, or lack of intrinsic factor receptors secondary to ileal loops, bypass, or surgical resection. Pernicious Anemia: Pernicious Anemia Signs, Symptoms, and Laboratory Findings Pertinent findings on physical examination include pallor, red tongue, vibratory sense loss in the lower extremities, disorientation, muscle weakness , and ataxia . Pernicious anemia develops from a lack of gastric intrinsic factor production, which causes vitamin B 12 malabsorption and, ultimately, vitamin B 12 deficiency. The elevated MCV suggests megaloblastic anemia. Folate and iron are two other factors that can affect the MCV and should be evaluated during the workup of a patient for anemia. Significant laboratory findings: Significant laboratory findings Hgb , low (normal, 14 to 18); Hct , low (normal, 42% to 52%); MCV, high (normal, 76 to 100); MCH, high (normal, 27 to 33); MCHC, normal (normal, 33% to 37%); reticulocytes , low (normal, 0.5% to 1.5%); poikilocytosis and anisocytosis on the blood smear; white blood cell (WBC) count, normal (normal, 3,200 to 9,800); platelets, low (normal, 130,000 to 400,000); serum iron, normal (normal, 50 to 160); TIBC, normal (normal, 200 to 1,000); ferritin , normal (normal, 15 to 200); RBC folate , normal (normal, 140 to 460); serum vitamin B 12 , low (normal, 200 to 1,000); and anti-intrinsic factor antibody, positive. Treatment: Treatment Pt should receive parenteral vitamin B 12 in a dose sufficient to provide not only the daily requirement of approximately 2 mcg, but also the amount needed to replenish tissue stores (about 2,000 to 5,000 mcg; average, 4,000 mcg). To replete vitamin B 12 stores, cyanocobalamin can be given IM in accordance with various regimens. Pt may receive 100 mcg of cyanocobalamin daily for 1 week, then 100 mcg every other day for 2 weeks, followed by 100 mcg every 3 to 4 days for 2 to 3 weeks. A monthly maintenance dose of cyanocobalamin (100 mcg) would then be required for the remainder of Pt's life. Folic Acid Deficiency Anemia: Folic Acid Deficiency Anemia Folate is abundant in virtually all food sources, especially fresh green vegetables, fruits, yeast, and animal protein . excessive or prolonged cooking (>15 minutes) in large quantities of water destroys a high percentage of the folate that is contained in food. Human requirements for folate vary with age and depend on the rate of metabolism and cell turnover but are generally 3 mcg/kg/day . The minimal daily adult requirement of folate is 50 mcg , but because absorption from food is incomplete, a daily intake of 200 mcg is recommended. Folate requirements are increased in conditions in which the metabolic rate and rate of cellular division are increased (e.g., pregnancy, infancy, infection, malignancies, hemolytic anemia ). Sickle Cell Anemia: Sickle Cell Anemia

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