Hematology case Nursing 870

Case An 18 –year- old female presents to the NP for consultation. She complained of generalized weakness, lethargy and inability to perform her usual activities; with progression over the past few months.

What HPI Questions are Important to Ask?

HPI General: No fever or weight loss, decreased appetite; desire to eat ice HEENT: negative Resp: Reported breathlessness with climbing stairs CV: Reported palpitations with climbing stairs GI: No abdominal pain, n,v or diarrhea GU: Excessive menstrual bleeding x 6 months MS: Reports leg cramping Neuro: Periods of feeling lightheaded, no syncope

What PE is needed?

PE General: 98.2-110-18 108/62 Wt. 118, No change Skin: Pale skin HEENT: pale gums, tongue was swollen, No enlarge nodes Resp: Clear CV/PV: Tachycardia, no murmurs, S3 or S4; pale nail beds Abdomen: Normal Neuro: Normal

Diagnostics What labs are needed?

Diagnostics Red Blood Cell Count -3.5 million/mm3 Hemoglobin (Hb) -7 g/dl Hematocrit (Hct)- 30% Serum Iron – low Mean Corpuscular Volume (MCV) – low Mean Corpuscular Hemoglobin (MCH)-low Mean Corpuscular Hb Concentration (MCHC)- low Total Iron Binding Capacity in the Blood (TIBC)- high

What do the labs tell you?

Labs: CBC RBC: 3.5 million/mm3 Hb: 7 g/dl Hct: 30 % Number of erythrocytes (RBC) in 1 cubic mm of blood, thin cell membrane so gases pass easily Nrl: Male: 4.5-5.9 x 106/ul, Female: 4.5-5.1 x 106/ul Made of Hgb, life span of 120 days Production: erythropoesis Need: Fe, B12, folic acid, B6 (pyridoxine) RBC: transport O2 Waste product is bilirubin Hb: 7 g/dl Hgb, the oxygen carrying compound carried on each RBC Nrl: Male: 14-18g/dl, Female: 12-16g/dl Hct: 30 % Hct: The percentage of blood that is the RBC Nrl: Male: 41.5% - 50.4%, Female: 35.9%-44.6% CBC: Normals vary by age, gender, and race. African Americans: lower Hg, WBC, neutrophil and platelets

Labs: CBC Mean Corpuscular Volume (MCV) – low Average size of cell (Small: microcytic; Large: macrocytic) Nrl: 80-100 Mean Corpuscular Hemoglobin (MCH)-low Average weight of Hg in RBC (Low: hypochromic; High Nrl: 27-311 Mean Corpuscular Hb Concentration (MCHC)- low Avg concentration of Hb per RBC Nrl: 32-36%

Labs Total Iron Binding Capacity (TIBC)- high (262-474g/dL) Available binding sites Serum Iron – low (Male: 76-198 g/dL, Female 26- 170 g/dL) Measures Fe in the blood Serum ferratin - low (Male: 12-300mcg/L; Female 12-150 mcg/L) Reflects Fe storage in the body Drops before serum Fe Ferratin: Low ferratin diagnostic for IDA with microcytosis; Be aware false normal related to inflammation, hepatocellular damage and cancer NRL ferratin with microcytosis: consider thallasemia; consider performing electrophoresis

What’s the most likely diagnosis? What History, PE findings and labs support the diagnosis?

What’s the Treatment?

labs CBC This documents the severity of the anemia. In chronic iron deficiency anemia, the cellular indices show a microcytic and hypochromic erythropoiesis MCV and MCHC=)have values below the normal range Often, the platelet count is elevated (>450,000/µL) WBCs usually within reference ranges (4500- 11,000/µL).

labs MCV remains normal in the early stages, then falls and the blood smear shows hypochromic microcytic cells With further progression, anisocytosis (variations in red blood cell size) and poikilocytosis (variation in shape of red cells) develop Severe Fe deficiency will produce a bizarre peripheral blood smear, with severely hypochromic cells, target cells, hypochromic pencil-shaped cells, and occasionally small numbers of nucleated red blood cells, with an increased platelet count

labs Iron deficiency develops in stages. The first is depletion of iron stores. At this point, there is anemia and no change in red blood cell size. Serum Fe Decreases Total iron-binding capacity (TIBC) TIBC rises. Ferritin Will become abnormally low A ferritin value less than 25 mcg/L is a highly reliable indicator of iron deficiency. After iron stores have been depleted, red blood cell formation will continue with deficient supplies of iron. Serum iron values decline to less than 30 mcg/dL and transferrin saturation to less than 15%. A low serum iron and ferritin with an elevated TIBC are diagnostic of iron deficiency. While a low serum ferritin is virtually diagnostic of iron deficiency, a normal serum ferritin can be seen in patients who are deficient in iron and have coexistent diseases (hepatitis, anemia of chronic disorders). These test findings are useful in distinguishing iron deficiency anemia from other microcytic anemias

Function of Iron Essential for multiple metabolic processes Oxygen transport DNA synthesis Electron transport The major role of iron is to carry O2 as part of hemoglobin O2 is also bound by myoglobin in muscle Iron is a critical element in iron-containing enzymes, including the cytochrome system in mitochondria Without iron, cells lose their capacity for electron transport and energy metabolism. In erythroid cells, hemoglobin synthesis is impaired, resulting in anemia and reduced O2 delivery to tissue.

Iron Deficiency Anemia Generalized weakness, exercise intolerance, dyspnea, palpitations, history of blood loss during menstruation, tachycardia and low Hgb, all are suggestive of iron deficiency anemia Iron deficiency is the most prevalent anemia in the world Iron deficiency, is related in part, to abnormal iron metabolism

Iron Deficiency Anemia Overview of iron metabolism Balance of iron is controlled and designed to conserve iron for reutilization There is no regulated excretory pathway for iron Iron is only lost from the body with blood loss (via gastrointestinal bleeding, menses, or other forms of bleeding) and the loss of epithelial cells from the skin, gut, and genitourinary tract Iron comes into the body by absorption from food or from medications and transfusions The margin between the amount of iron available for absorption and the requirement for iron in growing infants and the adult female is narrow; this accounts for the great prevalence of iron deficiency worldwide— currently estimated at one-half billion people.

Fe deficiency Anemia causes Increased demand for iron and/or hematopoiesis Rapid growth (adolescence and infants) Pregnancy Erythropoietin therapy

Fe deficiency Anemia causes Increased Fe loss Chronic blood loss Menses Acute blood loss Blood donation Phlebotomy as treatment for polycythemia vera Decreased iron intake or absorption inadequate diet   malabsorption from disease (Celiac, Crohn’s disease) Malabsorption from surgery (post-gastrectomy)   Acute or chronic inflammation

Diagnostics CBC Ferratin Fe IBC Bone Marrow aspirate Stool for occult blood: useful to establish GI bleed Others Hemoglobinuria and hemosiderinuria Hemoglobin electrophoresis Transferrin receptor protein A bone marrow aspirate can be diagnostic of iron deficiency. Bone marrow biopsy for evaluation of iron stores is now rarely performed because of variation in its interpretation. Hemoglobinuria and hemosiderinuria can be detected by laboratory testing . This documents iron deficiency to be due to renal loss of iron and incriminates intravascular hemolysis as the etiology. Hemoglobin electrophoresis and measurement of hemoglobin A2 and fetal hemoglobin are useful in establishing either beta-thalassemia or hemoglobin C or D as the etiology of the microcytic anemia.  Serum Levels of Transferrin Receptor Protein-Because erythroid cells have the highest numbers of transferrin receptors on their surface of any cell in the body, and because transferrin receptor protein (TRP) is released by cells into the circulation, serum levels of TRP reflect the total erythroid marrow mass. Another condition in which TRP levels are elevated is absolute iron deficiency. Normal values are 4–9 μg/L determined by immunoassay. This laboratory test is becoming increasingly available and, along with the serum ferritin, has been proposed to distinguish between iron deficiency and the anemia of chronic inflammation

Differential Other causes of microcytic anemia Anemia of chronic disease Thalassemia, Sideroblastic anemia Lead poisoning Anemia of chronic disease is characterized by normal or increased iron stores in the bone marrow and a normal or elevated ferritin level; the serum iron is low, often drastically so, and the TIBC is either normal or low. Thalassemia produces a greater degree of microcytosis for any given level of anemia than does iron deficiency. Red blood cell morphology on the peripheral smear is abnormal earlier in the course of thalassemia.

Treatment Most important to establish the cause of the anemia Ferrous sulfate, 325 mg three times daily, which provides 180 mg of iron daily of which up to 10 mg is absorbed (though absorption may exceed this amount in cases of severe deficiency), is the preferred therapy Parenteral Fe RBC transfusion Oral Fe First line treatment. An increase in the hemoglobin level of 1 g per dL (10 g per L) should occur every two to three weeks on iron therapy; however, it may take up to four months for the iron stores to return to normal after the hemoglobin has corrected. Ferrous sulfate in a dose of 325 mg provides 65 mg of elemental iron, whereas 325 mg of ferrous gluconate provides 38 mg of elemental iron. Sustained-release formulations of iron are not recommended as initial therapy because they reduce the amount of iron that is presented for absorption to the duodenal villi. Parenteral Iron The indications are intolerance to oral iron, refractoriness to oral iron, gastrointestinal disease (usually inflammatory bowel disease) precluding the use of oral iron, and continued blood loss that cannot be corrected. Because of the possibility of anaphylactic reactions, parenteral iron therapy should be used only in cases of persistent anemia after a reasonable course of oral therapy.  Red Cell Transfusion It should be considered for asymptomatic cardiac patients with hemoglobin less than 10 g per dL (100 g per L). Transfusion therapy is reserved for individuals who have symptoms of anemia, cardiovascular instability, continued and excessive blood loss from whatever source, and require immediate intervention. The management of these patients is less related to the iron deficiency than it is to the consequences of the severe anemia. Not only do transfusions correct the anemia acutely, but the transfused red cells provide a source of iron for reutilization, assuming they are not lost through continued bleeding. Transfusion therapy will stabilize the patient while other options are reviewed.

Other Considerations Diet Other Foods high in Fe include red meats, egg yolks, dark green leafy veges, dried fruit (prunes, raisins, turkey, beans, liver, others) Interfering substances include phytic acid in cereals, oxacylic acid in some leafy vegetables, tannates (tea) Other GI absorption of Fe enhanced by gastric acidic envt (Vit C) Calcium, copper, zinc, lead and phosphate inhibit absorption

Other Considerations Medications that raise the gastric pH (e.g., antacids, proton pump inhibitors, histamine H2 blockers) reduce absorption and should be avoided if possible

Prognosis Fe deficiency anemia is an easily treated disorder with an excellent outcome It may be caused by an underlying condition with a poor prognosis, such as neoplasia Up to 10% of individuals >65 have GI cancer when evaluated for Fe deficiency anemia The prognosis may be altered by a comorbid condition such as coronary artery disease.