#10 – Approach to Anemia in Adults



The textbook definition of anemia is a reduction of the absolute number or mass of circulating red blood cells.  This then causes a global reduction in the oxygen carrying capacity of the patient’s circulatory system.  Clinically, we use hemoglobin and hematocrit as the surrogate markers and define anemia as 2 SD below the mean for gender:

  • Men
    • Hemoglobin < 13.5 g/dL
    • Hematocrit < 41%
  • Women
    • Hemoglobin < 12.0 g/dL
    • Hematocrit < 36%



Patel KV. Haematologica. 2008;93(9):1281-1283.


  • Special Populations
    • Athletes
      • May have a baseline anemia due to:
        • Dilution from increased plasma volume
        • Hemolytic breakdown from exercise
        • Exercise induced cytokines decreases RBC production
      • A normal H/H in a competitive athlete may suggest performance enhancing drugs
    • High altitudes
      • May have elevated hemoglobin concentration as baseline
    • Smokers
      • Baseline higher hemoglobin due to carboxyhemoglobin

General Causes of Anemia

There are two general approaches you can use to help identify the cause of anemia in adults.

  • The Kinetic Approach (the mechanisms responsible for the low hemoglobin)
    • 3 independent mechanisms
      • Decreased RBC production
        • Lack of nutrients
        • Bone marrow failure
        • Decreased erythopoetic stimulation factors
          • Erythropoietin, T3, androgens
        • Inflammation
      • Increased RBC destruction
        • Hemolysis, hypersplenism
      • Blood loss
  • The Morphologic Approach (categories based on RBC size and reticulocyte response)
    • Macrocytic (MCV > 100 fL)
      • Vitamin B12, folate, EtOH, liver disease
      • Any condition causing reticulocytosis
    • Microcytic (MCV < 80 fL)
      • 3 most common in clinical practice
        • Iron deficiency
          • ↓ serum iron, ↓ serum ferritin, ↑ TIBC
        • Alpha or beta thalassemia minor
          • Normal iron studies
        • Anemia of chronic disease
          • ↓ serum iron, normal serum ferritin, ↓ TIBC

History Questions

  • Is the patient symptomatic?
    • Fatigue, dyspnea, bleeding, bruising, dizziness, syncope
  • Any history of weight loss, night sweats, fever, anorexia?
    • Infection or malignancy
  • Past medical history for chronic illness
    • PUD, renal disease, autoimmune conditions, liver disease, past malignancies
  • Family history for hemoglobinopathies
  • Social history for alcohol use
  • Occupational exposures

Physical Exam Findings

  • Pallor
    • Palms, nail beds, face, conjunctiva
  • Jaundice
  • Hepatosplenomegaly
  • Lymphadenopathy
  • Petechiae, purpura, bruising
  • Bone tenderness

Laboratory Testing

Anemia is usually first diagnosed by CBC.  Once you have a documented low H/H, then you need order follow-up studies to help differentiate the cause of the anemia.  These include:

  • RBC indices
  • Reticulocyte count and index
  • Peripheral smear
    • Helmet cells or schistocytes à microangiopathic hemolysis
    • Microspherocytes à autoimmune hemolysis
    • Tear drop RBC à myelofibrosis
    • Bite cells à oxidative hemolysis
    • Parasites à malaria, babeosis
    • Hypersegmented neutrophils à Vitamin B12 or folate deficiency
    • Nucleated RBC
    • Siderocytes
    • Target cells à thalassemias
  • WBC and platelet count from CBC
  • If hemolysis is suspected:
    • ↑ Serum LDH, ↓ serum haptoglobin, and ↑ serum indirect bilirubin
    • Direct Coombs test (antibodies against RBC)
  • Bone marrow evaluation

Schrier SL, et al. Approach to adults with anemia. In: Up To Date. Waltham, MA (Accessed 03/23/2016)

The Cottage Physician Management

Something new I thought I would bring to the PAINE Podcast.  As you all know, I am quite a fan of medicine and antiquity.  Shortly after I married my wife, her grandfather past away from a progressive esophageal cancer.  One of the things I was able to keep when helping clean out his house, was a copy of The Cottage Physician printed in 1893.  It was basically a handbook on how to treat common ailments of the time. I will try to add excerpts from this book when appropriate so you can have a sense of how medicine was practiced in the late 19th century.

Cottage Physician - Anemia

The Cottage Physician. 1863


  1. Patel KV. Variability and heritability of hemoglobin concentration: An opportunity to improve understanding of anemia in older adults.  Haematologica.  2008;93(9):1281-1283.
  2. Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration?. Blood. 2006;107(5):1747-50.
  3. Shaskey DJ, Green GA. Sports haematology. Sports Med. 2000;29(1):27-38.
  4. Ruíz-argüelles GJ. Altitude above sea level as a variable for definition of anemia. Blood. 2006;108(6):2131.
  5. Nordenberg D, Yip R, Binkin NJ. The effect of cigarette smoking on hemoglobin levels and anemia screening. JAMA. 1990;264(12):1556-9.
  6. Hillman RS, Ault KA, Leporrier M, Rinder HM. Clinical Approach to Anemia.  In: Hematology in Clinical Practice.  5th McGraw-Hill. New York. 2010.
  7. Tefferi A. Anemia in adults: a contemporary approach to diagnosis. Mayo Clin Proc. 2003;78(10):1274-80.
  8. Nardone DA, Roth KM, Mazur DJ, Mcafee JH. Usefulness of physical examination in detecting the presence or absence of anemia. Arch Intern Med. 1990;150(1):201-4.
  9. Hung OL, Kwon NS, Cole AE, et al. Evaluation of the physician’s ability to recognize the presence or absence of anemia, fever, and jaundice. Acad Emerg Med. 2000;7(2):146-56.

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