ANEMIA NOTES General Anemia Men: Hematocrit Less than 40%, Hemoglobin less than 13.5 g/dL in Women: Less than 37% hematocrit, Hemoglobin less than 12 g/DL Defining Anemia RBC Indices (Includes): MCV, MCH, MCHC, RDW RDW = a numerical index of distribution or red blood cell volumes…This quantifies the degree of variation in RBC Size Anisocytosis = abnormal sized RBC’s in circulation Sign of Illness, Not Disease Anemia is a sign of illness and not a diagnosis by itself. Anemia indicates either: 1). Decrease in Circulation red cell mass 2). Hemodilution of normal red cell mass by expanded plasma volume (as in pregnancy) Causes of Anemia 1. Defect in Marrow Production 2. Defect in Erythroid Precursor Maturation 3. Diminishment in adult RBC survival Demised production of RBC’s or accelerated destruction Process of Determining the Type of Anemia 1. Reticulocyte Index 2. Red Cell Size (MCV) 3. History, Testing, Hematologic Records – Acquired vs. Inherited Reticulocyte Index 1. Lesion within marrow = hyporegenerative 2. Lesion out of the marrow = hyperregenerative Microcytic, Macrocytic, Normocytic Microcytic = Iron deficiency, thalasemmia, sideroblastic anemia, chronic disease….MCV Less than 70 caused by iron deficiency or thalassemia Macrocytic = Megaloblastic anemia (lack of folate or B12). Folate is decreased due to decreased intake or poor absorption. MCV greater than 125 indicates megaloblastic (a form of macrocytic). Other causes are myelodysplastic syndromes or chemotherapy. Normocytic = Aplastic anemia, bone marrow replacement, red cell aplasia, anemia of chronic disease, hemolytic anemia, recent blood loss Drugs Drugs can cause anemia. They can damage stem cells in the marrow, GI bleeding, iron deficiency or hemolysis by antigenantibodies. African Americans Prone to G6P dehydrogenase deficiencies which causes oxidation of hemoglobin and RBC’s leading to anemia (hemolytic), especially when paired with chemotherapeutic agents (AIDS and cancer drugs) Iron Deficiency Most frequent cause of asymptomatic anemia. Common to women of child bearing age and menstruating women (less than 12 grams/100mL) as well as pregnant women (less than 11 grams per 100 mL). Over the course of the pregnancy, women acquire anemia due to dilution of the blood (lowered hematocrit due to hydremia and increased plasma volume). The case can present with low MCV, low RBC, and high RDW. Serum ferritin less than 15 mcg/L (possibly even 20) indicates likely iron deficiency. Microcytic anemia and serum ferritim below 15 (possibly 20) think iron deficiency anemia. This condition is liked to glossitis of the tongue and with telangiectassia (mouth, lips, palms, soles), angular stomatitis, spooning of the nails-koilonychia (long standing iron deficiency) Complications Men and postmenopausal Women = require .5-1.0 mg of iron daily Menstruating Women and Pregnant Women = require 2-2.5 mg daily We do not absorb all of the iron we take from food or supplements (usually 5-10%). Symptoms Sore mouth, difficulty swallowing, craving ice Progression Iron deficiency progresses in stages. 1. At the time of the first symptoms, iron stores are already depleted. At this point, depletion of the stores is a good indicator of deficiency. Also at this point, RBC size will be normal. Other changes at this point are low serum ferritin (less than 15 micrograms/L) and increased TIBC. 2. Following this stage – RBC formation continues but lacks iron, so serum iron values drop below 30 mcg/dL and trasnferrin saturation drops below 15%. Unexplained Loss of Iron Could indicate chronic occult blood loss from GI tract. May require an endoscpic evaluation in men and post-menopausal women. Best Test for Iron Deficiency Anemia Serum ferritin is the most dependable, practical test for iron deficiency. This test is the best because it develops low levels (less than 15) earlier than drops in hemoglobin, hematocrit, erythrocyte, and MCR. The test also shows a result before RDW increases and free erythrocyte protoporhpyrin increases. Why Other Iron Tests are Not as Good 1. Serum ferritin concentration = Does not reflect stores in people with chronic conditions like RA, infections, liver disease, or cancer. Elevated serum ferritin concentration can be due to disease and can mask iron deficiencies. 2. Serum Iron Assay and TIBC = too insensitive and too nonspecific 3. RDW = Does not increase in chronic diseases Hypochromic Anemia Associated with severe iron deficiency Pernicious Anemia Pernicious anemia is megaloblastic (MCV greater than 115) with lower serum B12 levels. Decreased folate is present during pregnancy, alcoholic liver disease, poor nutrition, anticonvulsant medications (impairs absorption). Lack of B12 can cause neurological problems: Change in mental status, dementia, numbness of feet and hands Another related symptom is mucosal atrophy of the tongue (glossitis). Also, can be related to megaloblastic anemia. Schilling Test This test is used to determine the reason and location for B12 deficiency Other Types (General Info) Thalasemia = Mild anemia in Mediterranean people and Far Eastern People…Normal to increased RBC count, microcytic levels, normal RDW Autoimmune Hemolytic Anemia = Common among women under 50. Sickle Cell = Most common hemoglobinopathy found often in African Americans…Sickle cell is often associated with severe bone pain. Also ask about gallstones, splenomegaly. Hemolytic Anemia Check for history of jaundice, darkened urine, and dark stools. Also ask about drugs taken. Drugs can suppress bone marrow, cause GI bleeding, and hemolysis due to oxidation. Splenomegaly can result with chronic hemolytic disease. Associated Conditions with Anemia Chronic infections, RA, Connective Tissue Disorders People with anemia are also prone to hypovolemic shock. This can be a big concern with acutely developing anemias. Gradual onset anemias usually are not as likely to lead to hypovolemic shock. General Signs Upon Physical Diagnosis Pallor of Skin and Mucous Membranes (occurs with multiple types of anemia and linked with less than 8 g/dL of Hemoglobin) Light Palmar Creases (linked with multiple types and occurs with less than 8 g/dL) Atrophy of Tongue (B12 or Iron Deficiency) Other areas of exam are the spleen, abdomen, rectum Testing For Anemia Significant anemia should immediately be evaluated! Obtain: 1. CBC 2.REticulocyte Count 3. Iron Supply (Serum Irion, TIBC, Serum Ferritin) Later Testing may include bone marrow aspirate assay and Biopsy Most anemias are due to a lack of production from the marrow (hypoproliferative). – Further assess this condition with iron supply tests and bone marrow exam. Decreased RBC, Decreased WBC, Decreased Platelet counts with Reticuloctopenia = Stem Cell Abnormality, Aplastic Anemia, myelodypslasia, Megaoloblastosis Megaloblastic Anemia (MCV is greater than 115) = Test RBC, Serum Folate, Serum Vitamin B12, Thyroid function and bone marrow…An elevated MCV without elevation in the hemoglobin or hematocrit indicates alcoholism (alcohol does not elevated the hyper segmentation of polymorphonucelar cells). Radiologic Testing A chest X-ray can help to screen/monitor for lymphoma or carcinoma. Cancer is associated with aplastic anemia, hemolytic anemia or anemia of chronic disease. Abdominal ultrasound or CT can help determine splenomegaly or lymphoma and associated aplastic or hemolytic anemia. Endoscopy Can be used with occult blood loss associated with iron deficiency anemia or pernicious anemia. Process of Diagnosis/Differential Diagnosis 1. Reticulocyte Count = Differentiates between hypo (marrow) and hyperregenerative (non marrow) anemias A. A hyporegenerative condition can be caused by either lack or erythropoietin or lack of a building block (B12, iron, folate, etc.)…Most anemias are hyporegenerative. B. Most hyperregenerative anemias are due to blood loss and accelerated RBD destruction. 2. MCV Values = Helps categorize the above conditions into Microcytic, Normocytic, Macrocytic A. MCV lower than 80 = microcytic. Low MCV suggests: iron deficiency (primarily iron deficiency), sideroblastic anemia (alcoholics), anemia from chronic disease (hospitalized patients) B. Normal MCV (80-95) = anemia of chronic disease, Marrow Aplasia, Marrow infiltration, Lymph or Myloproliferative disorders, malnutrition, metabolic disorders, low erythropoietin C. Macrocytic Anemia (Greater than 95) = B12 deficiency, folate deficiency (primarily lack of B12 and folate are the causes), myelodisplasia, liver diseases, hypothyroidism A hallmark of hyporegenerative anemias is the lack of an appropriate reticulocyte response. Some Scenarios and Possible Differentials 1. Alcoholism = An elevated MCV without elevation in the hemoglobin or hematocrit 2. Drugs, Cancer, Myelodysplasia = B12 and folate levels are normal but the person still has macrocytic anemia 3. Normocytic anemia = Causes are: Chronic illness, early iron deficiency, hemolytic disorders, primary or secondary bone marrow disorders 4. Aplastic Anemia, Bone Marrow Replacement, Leukemia, Lymphoma, Myeloma = Low Reticulocyte count, Low platelet count, Increased WBC 5. RBC aplasia = Low Reticulocyte Count, Normal WBC, and normal platelet count = 6. Anemia of chronic disease, renal failure, iron deficiency = Low Reticulocye Count, Normal-Increased WBC, NormalIncreased Platelet count 7. Hemolytic Anemia, or blood loss = Elevated Reticulocyte count, Normal-Increased WBC, Normal-Increased Platelet Count 8. Hemolytic Anemia, Blood Loss, Hypersplenism = Normocytic Anemia with High reticulocyte Count 9. Hemolytic anemia = Increased RBC destruction linked with increased unconjugated bilirubin and increased LDH.