Anemia

Is it anemia? NOTE: All ranges are given as average normals for adults.

• Presentation is variable, but usually includes fatigue, cold intolerance, pallor, tachycardia, tachypnea, dyspnea on exertion, headache, fever.
• Remember that in anemia, as in any physiologic deficit, can only really have three causes - decreased production, increased destruction, or increased loss. All of the disorders covered here fit into one of those three categories.
• Hemoglobin (Hgb) is the most accurate indicator. Normal ranges are: =14-17 =12-15. If your patient has values below normal, he/she has an anemia. Hgb measures the concentration of hemoglobin released from a known volume of whole blood.
• Hematrocrit (HCT, "crit") is also a sensitive marker. Normal ranges are: =39-49% =33-43%. Values lower than these in your patient can confirm an anemia. HCT measures the percentage of a volume of whole blood taken up by red cells.
• Red Blood Cells (RBC) is an often ignored lab value. Normal ranges are: =4.36-5.78 =3.86-5.04.
Another useful way to confirm an anemia. RBC measures how many millions of cells are in a known volume (mm³) of blood.
• A Reticulocyte Count should always be part of an anemia workup. Remember that reticulocytes are immature RBCs released into the blood. They are elevated when RBCs are being destroyed peripherally, but NOT when there is a hypoproductive disease - this distinction is important to make.
• Your next step, once you've determined an anemia is present, is to determine the size of the average red cell. Look at the MCV (Mean Corpuscular Volume). The normal range is 81-98.
• If your MCV is less than 81, you've got a microcytic anemia. The most common causes are Fe deficiency, lead poisoning, and thalassemias.
• If your MCV is in the normal range, you've got a normocytic anemia The most common causes are chronic disease, acute blood loss, or spherocytosis.
• If your MCV is greater than 98, you've got a macrocytic anemia. The most common causes are folate or B₁₂ deficiencies, liver disease, or aplastic anemia.
• Once you've determined with which class of anemia you're dealing, look under that heading for your next step (you'll always start with an RDW).

Microcytic Anemias Check the RDW (Red Cell Distribution Width). This measures the amount of variability in the sizes of red cells in the sample. The normal range is from 11.5-14.5%. A Normal RDW microcytic anemia is associated primarily with two conditions: Anemia of Chronic Disease: A chronic production problem. Seen in a variety of conditions: Chronic infections - TB xray, PPD, osteomyelitis xray, abscess, endocarditis ekg, ultrasound Autoimmune disorders - SLE ANA, rheumatoid arthritis rheumatoid levels Malignancy Diagnosis: Serum iron studies show iron, ferritin, and TIBC. Marrow shows hypoplasia. Heterozygous Thalassemia: Two major subtypes: Beta Thalassemia Minor Two genes involved in beta hemoglobin - 1 is affected in minor. Target cells are often seen on smears. Patients are generally asymptomatic. Can be diagnosed by family history or quantitative Hgb A2. Alpha Thalassemias - severity depends on number of deletions. 4 genes involved in alpha hemoglobin. One or two deletions generally asymptomatic. Three deletions (Hemoglobin H Disease) gives severe anemia, circulating Hg H diagnosable by special stain. Four deletions (Hydrops Fetalis) = stillborn. Hemoglobin E Disease: NOT AN ANEMIA, but often mistaken for a thalassemia on smear. Common in Southeast Asia, asymptomatic. Target cells on smear. Dx by hemoglobin electropheresis An Elevated RDW microcytic anemia is associated primarily with two conditions: Iron Deficiency: CAUSES: Nutritional: infancy, mentsruation, pregnancy, vegetarian diet. Malabsorption: sprue, gastrectomy. Bleeding: GI, uterine, traumatic, retroperitoneal ultrasound, CT PNH: "Paroxysmal Nocturnal Hematuria." Stem cell mutation. Only microcytic if iron loss (common). Low reticulocytes, neutropenia, thrombocytopenia. Erythroid hyperplasia in marrow. Screen with sugar-water test, dx with flow cytometry. Mean survival 10 years. Diagnosis by iron studies: LOW SERUM IRON - it is iron deficiency, after all. LOW FERRITIN - the storage form of iron - with low iron, nothing to store. HIGH TRANSFERRIN - the molecule that transports iron from the gut to the blood. When the blood sees low iron, it sends more messengers to absorb more - that's transferrin. Homozygous Beta Thalassemia ("Thalassemia Major"): There are only two beta thalassemia genes - when both are defective, a devastating illness requiring transfusions throughout life results - iron induced cardiomyopathy results from transfusions. History of very sick child with horrible anemia = thal major until proven otherwise. Smear shows target cells, hypochromic cells, and circulating nucleated red cell precursors Marrow shows erythroid hyperplasia

Normocytic Anemias Check the RDW (Red Cell Distribution Width). This measures the amount of variability in the sizes of red cells in the sample. The normal range is from 11.5-14.5%. A Normal RDW normocytic anemia is associated primarily with seven conditions: Acute Blood Loss: From trauma, GI, uterine or retroperitoneal bleed ultrasound, CT Hemolysis: haptoglobin From external causes: Microangiopathic Hemolysis: intravascular lesions lead to trauma and hemolysis. DIC: (Disseminated Intravascular Coagulation) microthrombi. SLE: Arteritis Malignant Hypertension: Narrowed arterioles Prosthetic Heart Valves: Shearing forces, microtrauma Bugs: Malaria, Babesiosis, Clostridium Heat: From other causes: Transfusion Reaction: Host cells attack and cause lysis of transfused cells. Automimmune Hemolytic Anemias: Warm and Cold AIHA covered elsewhere - see normocytic anemia with normal and elevated RDW. Spherocytosis: Covered elsewhere - see normocytic anemia with elevated RDW. PNH: Covered elsewhere - see normocytic anemia with elevated RDW. G6PD Deficiency: Covered elsewhere - see normocytic anemia with elevated RDW. Smear reveals schistocytes, Burr cells, helmet cells. Also, Dx underlying cause. Anemia of Chronic Disease: See microcytic anemia with normal RDW for details. Anemia of Chronic Renal Failure: Erythropoeitin production drops, and GI bleeding occurs from platelet malfunction. Red cell life span is decreased significantly from normal of 120 days. Smear reveals low retic count and burr cells Serum iron studies show iron, ferritin, and TIBC. Renal function tests (BUN, Creat) Marrow reveals erythroid hypoplasia with no sideroblasts (similar to Anemia of Chronic Disease) Cold Agglutinin: IgM attacks blood cells in cold, extremities affected in winter. Seen with Raynaud's, splenomegaly. Often 2o recent acute illness. Acute form is self-limiting. Positive Coombs test Smear reveals red cell agglutination Bone marrow mild erythroid hyperplasia Endocrine disorders: Typically with low retic count. Usually diagnosed by Sx from endocrine disorder rather than by hemagram. Hypothyroid: Anemia results from O2 demand. Can be macrocytic. Pituitary Dysfunction: hypopituitarism from TSH, and growth hormone also contributes. Gonadal Dysfunction: Androgens stimulate erythropoietin - no androgens (prepubertal, elderly, castrated) Hgb & HCT by ~2%. PNH: See microcytic anemia with elevated RDW for details. An Elevated RDW normocytic anemia is associated primarily with seven conditions: Early Iron, Folate, or B12 Deficiency: Advanced iron deficiency becomes microcytic, advanced B12 or folate deficiencies become macrocytic, but both are normocytic in the early stages. Hereditary Spherocytosis: Mutation in RBC membrane, RBC's destroyed in spleen splenomegaly. Pt's display pigment gallstones. Can experience hemolytic crises or aplastic crises 2o infection. Osmotic fragility test Smear reveals spherocytes, reticulocytosis, so retic count. Sickle Cell Anemia: Disease only with homozygotes (heterozygotes only symptomatic under extreme hypoxia or acidosis). Mutation of Hgb A chain. Splenomegaly splenic autoinfarct (suspceptible to encapsulated organisms). X-ray changes in bone. Episodic painful vasocclusive crises, sequestration crises, and aplastic crises. Excellent article discovered by Chris Pineda-Massari at the Emory site. Sickling test with metabulsulfite Hemoglobin electropheresis done with both homozygotes and heterozygotes Smear reveals sickle cells, reticulocytosis, bone marrow reveals erythroid hyperplasia Hyperbilirubinemic G6PD Deficiency: Hemolysis after oxidant stress due to lack of enzyme, particularly in older cells. Predominantly in males, particularly in African, Mediterranean, and Middle Eastern populations. Episodes triggered by primaquine, nitrofurantoin, mothballs. Heinz body prep Quantitative G6PD assay may be falsely normal during crisis - reticulocytes have more enzyme. Smear reveals "bite cells" and spherocytes. Bite cells are RBC's that have had Heinz bodies removed by spleen. Warm AIHA: Extravascular (splenic) hemolysis from autoantibody. Present with jaundice and splenomegaly, often 2o lymphoproliferative disease, other automimmune diease, drugs. Remissions and relapses. CAN be macrocytic 2o brisk reticulocyte response (reticulocytes are large). Coombs test positive (detects antibodies on RBC's). Usually IgG antibodies. Smear reveals schistocytes, spherocytes, reticulocytosis. Bone marrow shows erythroid hyperplasia. Hyperbilirubinemia Cold Agglutinin: Covered in normocytic anemia with normal RDW section, also possible with elevated RDW. Hemolysis: Covered in normocytic anemia with normal RDW section, also possible with elevated RDW.

Macrocytic Anemias Check the RDW (Red Cell Distribution Width). This measures the amount of variability in the sizes of red cells in the sample. The normal range is from 11.5-14.5%. A Normal RDW macrocytic anemia is associated primarily with three conditions: Aplastic Anemia: Often causes pancytopenia. Can be 2o drugs, but often idiopathic. Bone marrow fails. Presents as fatigue, bleeding, infection, pallor. Requires transfusions, often marrow transplant. Marrow with complete aplasia, no hematopoetic cells, abundant fat. Thrombocytopenic and leukopenic on blood count, low retic count. Liver Disease: A multifactorial response to liver disease. Hypercholesterolemia excess lipid excess membrane. Also, alcohol marrow dysplasia macrocytosis (see myelodysplasia, below) Myelodysplasia: The nucleus grows slowly in this condition, but the cytoplasm doesn't. The cell isn't released until the nucleus is normal sized, and by then the cell is quite large. An Elevated RDW macrocytic anemia is associated primarily with three conditions: B12 Deficiency: B12 level Many causes: Pernicious Anemia: No intrinsic factor, so no absorption (antobodies to parietal cells). Schilling test and B12 level. S/P Gastrectomy: Often 5-6 years after surgery. Reduced stomach = reduced absorption. Intestinal Disorders: Include ileal resection or ileitis, malabsorption, blind loop syndrome, tape worm. Dietary Deficiency: Possible in vegans. Folate Deficiency: Check folate level. Folate needed for essential biochemical processes involving one-carbon transfers (like DNA synthesis). Many causes: Dietary Deficiency: Folate destroyed with prolonged cooking. Folate stored in body for 4 months. Impaired Absoprtion: Sprue (Dx by history, dietary change, intestinal biopsy, diffuse intestinal disease. Increased Folate Requirements in pregnancy, infancy,hemolytic anemia, malignancy. Immune Hemolytic: See Warm AIHA & Cold Agglutinin Disease in normocytic anemia with normal RDW. Special thanks to Dr. John Lunde for his invaluable help with this page. It's basically a reorganization/regurgitation of his class notes from Path 302...




Quick and Dirty Drill-Down



Find anemia with hemagram. If WBC and platelets normal: Check corrected retic count If , likely 2o acute blood loss, hemolysis Coombs, diet. If retic count normal, see chart above. Sorry... If abnormal WBC or platelets: If WBC or immature WBCs, think chronic leukemias. If WBC or platelets, consider acute leukemias (usually neutropenic and thrombocytopenic), aplastic anemia, hypersplenism, B12/folate deficiencies, PNH, myeloma, myelofibrosis, metastatic CA, lymphoma, myelodysplasia.