Anemia Evaluation in Adults

Anemia is a reduction in the proportion of red blood cells. It's diagnosed when hemoglobin levels are below 13.5 g/dL in men and 12.0 g/dL in women.

Objectives

Review the different blood cell lineages and their functions.
Understand the metabolic and physiological responses to anemia in patients.
Examine microcytic, normocytic, and macrocytic anemia, their characteristics, causes, diagnoses, and treatments.
Review guidelines for hematology referrals.

Anemia as a Primary Diagnosis

Anemias account for 2.8 billion office visits, 778,000 emergency department visits, and 5,380 deaths annually. (CDC, 2015)

Red Blood Cell (RBC) Function

RBCs transport oxygen from the lungs to tissues.
RBCs transport carbon dioxide (CO2) from tissues to the lungs.
RBCs carry other substances like electrolytes, hormones, vitamins, antibodies, heat, and immune cells. (Kuhn et al., 2017)

Normal Hematologic Parameters in Adults

Hemoglobin (Men: 13.6-16.9 g/dL; Women: 11.9-14.8 g/dL)
Hematocrit (Men: 40-50%; Women: 35-43%)
RBC count (Men: 4.2-5.7 x 10^6/µL; Women: 3.8-5.0 x 10^6/µL)
MCV (80-100 fL)
MCHC (33-37 g/dL)
RDW (11.5-14%)
Reticulocyte count (16-130 x 10^3/µL or 16-98 x 10^9/L)
Platelet count (152-324 x 10^3/µL or 153-361 x 10^9/L)
WBC count (3.8-10.4 x 10^3/µL)

Anemia by Morphology

Microcytic anemia: Circulating red blood cells (RBCs) are smaller than normal, often paler (hypochromic) in color. MCV < 80 fL and MCHC < 33 g/dL.
- Causes of microcytic anemia: iron deficiency anemia, thalassemia, lead poisoning, sideroblastic anemia, copper deficiency, inflammation, and anemia of chronic disease.
Normocytic anemia: RBCs are normal size, and normal color. Normocytic: MCV 81-99 fL and Normochromic: MCHC 33-37 g/dL.
- Causes: acute anemia, anemia of chronic disease/inflammation, chronic renal insufficiency, bone marrow suppression, and excess alcohol use.
Macrocytic anemia: RBCs are larger than normal. Macrocytic: MCV > 100 fL, Hyperchromic; MCHC < 37 g/dL.
- Causes of macrocytic anemia: B12/folate deficiency, liver disease, medications, and myelodysplastic syndrome (MDS).

Iron Deficiency Anemia (IDA)

Iron is essential for blood production, and the body recycles and conserves it.
Iron levels vary throughout the day.
Ferritin is the iron storage protein.
Normal iron levels range from 50-150 mcg/dL. TIBC ranges from 250-450 mcg/dL; % saturation of transferrin is 20%–50%. Ferritin levels are 13.0-150.0 ng/mL.
Causes of IDA: blood loss(GI ulcerations, lesions, malignancy, menorrhagia, milk-anemia (infants), and malabsorption (gastric resection, celiac disease, and inflammatory disorders).
Common symptoms: Fatigue, exercise intolerance, shortness of breath (SOB), headache, concentration difficulty, and pallor.
Rare symptoms: Pica, glossitis, cheilosis, koilonychia, and dysphagia.

IDA Diagnosis

CBC abnormalities: low hemoglobin and hematocrit (Hgb/Hct). RDW is increased (greater than 15). MCV, MCH, and MCHC are decreased.
Iron studies: decreased serum iron, increased TIBC, and decreased % saturation. Decreased ferritin.

IDA Treatment

Ferrous sulfate (PO)
IV iron
Investigating the cause of iron loss.

Thalassemia

Disruption in the normal alpha/beta globin production ratio. Caused by a variant in one or more globin genes.
Alpha Thalassemia: A defect in the alpha globin chain gene. Major- results in severe or fatal condition due to lack of Hgb A or F. Minor- mild anemia.
Beta Thalassemia: A defect in the beta globin chain gene. Major- requires frequent transfusion. Intermedia/Minor - tends to have mild anemia. -Diagnosis and Treatment: Specific lab tests and management vary by type and severity and may include PRBC transfusions, iron chelation therapy, folic acid supplementation, splenectomy, and stem cell transplantation.

Lead Poisoning

Lead is a naturally occurring metal that binds to proteins and changes their function, acting as a competitive inhibitor of calcium binding sites
Symptoms depend on blood lead levels (BLL).
Lead exposure sources: workplace exposure, paint, gasoline, bullets, drinking water, cosmetics/personal care products, herbal supplements.
Effects: impaired heme synthesis and increased red blood cell destruction.
Common symptoms: abdominal pain, constipation, anorexia, joint pain, muscle aches, fatigue, sleep disturbance, increased risk of CNS effects

Sideroblastic Anemia

Group of disorders, congenital or acquired, characterized by a defect in erythroid maturation. This issue results in the body's inability to utilize iron to produce hemoglobin. Iron accumulates within mitochondria within RBC precursors. Cells appear "ringed" underneath the microscope.
- Congenital and acquired forms. The classification of causes include genetic issues, infections/other conditions or due to exposure to chemicals or drugs.

Normocytic Anemia

RBCs are normal size and color.
Causes: acute anemia, chronic disease/inflammation, chronic renal disease, bone marrow suppression, and excessive alcohol consumption.

Anemia of Chronic Disease (ACD)

Immune-mediated dysregulation of iron homeostasis.
Hepcidin is produced by the liver and is the major iron regulator. Cytokines induce hepcidin production, increasing macrophage iron uptake and retention, reducing erythropoietin, decreasing RBC production and decreasing RBC survival.
Causes: Inflammatory disorders, malignancy, and infections (COPD, CHF).
Diagnosis: CBC, retic count, peripheral smear, iron studies (ferritin increased, serum iron decreased, TIBV decreased), and inflammatory markers (ESR, CRP).
Treatment: Treat the underlying disorder.

Anemia in Chronic Renal Insufficiency (CRI)

Decreased production of RBCs due to insufficient erythropoietin (EPO) production. (EPO levels diminish as kidney function deteriorates) RBCs become coated with waste products that cannot be excreted by a compromised kidney functioning.
Common symptoms: Fatigue, weakness, shortness of breath (SOB), pallor, headaches, concentration difficulties, orthostatic symptoms, palpitations, ascites, loss of appetite, headaches, generalized body aches, myalgias, and cold intolerance.
Treatment: EPO stimulation, likely with the need for PRBC transfusions.

Aplastic Anemia

Regulates blood cell production depends on presence of an adequate number of functional multipotent hematopoietic stem cells.
Causes: viruses, radiation, chemotherapy, exposure to toxic chemicals, medications, autoimmune disorders, idiopathic.
Symptoms: fatigue, exercise intolerance, shortness of breath (SOB), tachycardia, pallor, frequent infections, unexplained or easy bruising, nosebleeds and bleeding gums, prolonged bleeding from cuts, skin rash, dizziness, and headache.
Diagnosis: Blood cell counts may indicate pancytopenia, bone marrow biopsy often required; RBCs may appear normal.
Treatment: Identification of the cause and prompt treatment needing bone marrow recovery.

Anemia and Hypothyroidism

Bone marrow depression and a decrease in erythropoietin production are possible results of comorbid diseases.
Concomitant iron, vitamin B12, or folate deficiencies can contribute to this condition.
Symptoms: Weight gain, unexplained easy bruising, sensitivity to cold, constipation, edema, thinning hair, concentration difficulties, fatigue, exercise intolerance, and pallor.
Diagnosis: CBC, thyroid studies, rule out concomitant iron, vitamin B12, and folate deficiencies.
Treatment: Treatment of the underlying condition is required.

Macrocytic Anemia Causes

B12/folate deficiency
Excess alcohol use
Liver disease
Medications
MDS

Macrocytic Anemia Diagnoses

Hallmark: Oval macrocytes
CBC abnormalities: Low Hb/Hct, increased MCV and MCH/MCHC, and Increased RDW
History and PE
Rule out concomitant iron, B12, folate deficiencies

Macrocytic Anemia Treatment

B12 supplementation
Folic acid (1 mg PO daily)

Summary of Anemia Approach

A "shotgun" approach involves performing an initial comprehensive laboratory evaluation for a new onset of anemia.
Results are used to further discriminate between the different types of anemia (microcytic, normocytic, macrocytic), possible causative mechanisms, and specific treatment directions.