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First, some terminology and then we’ll dive into each of these conditions separately below:

TABLE 7.1Terminology for Abnormal Cell Counts


  • Definition: Low WBC (<4K/μl). If absolute neutrophil count (ANC) <1000/μl, that is called neutropenia and carries an increased risk of infection. Severe neutropenia is when the ANC <500/μl.

  • Differential diagnosis:

    • - Infection: Often causes leukocytosis, but can cause leukopenia

    • - Malignancy: Bone marrow infiltration

    • - Inflammatory/autoimmune conditions: SLE, others

    • - Medications: Chemotherapy, antibiotics, anti-epileptics, and substances (e.g., alcohol) can all be myelosuppressive

  • Treatment: Treat underlying condition. Patients with ANC <500/μl typically require urgent workup even if asymptomatic.


  • Definition: High WBC (>10K/μl)

  • Differential diagnosis:

    • - Infection

    • - Malignancy: If very high WBC, consider acute leukemia

    • - Inflammatory/autoimmune conditions

    • - De-margination: Stress response, steroids

  • Treatment: Treat underlying condition. Leukocytosis itself does not require treatment except in hyperleukocytosis related to leukemia, for which hydroxyurea and leukapheresis may be indicated.


  • Definition: Low hemoglobin (Hg <13 g/dL in men, Hg <12 g/dL in women)

  • Symptoms: Fatigue, shortness of breath, dizziness, bleeding, pallor

  • Work-up:

    • - Check reticulocyte count

      • Low retic count (reticulocyte index <2%) → Decreased RBC production

      • Normal/high retic count (reticulocyte index >2%) → RBC loss or increased RBC destruction

    • - If underproduction, check MCV and help refine differential diagnosis. Review differential diagnosis for each category below and ask the patient relevant questions.

    • - Check peripheral blood smear, which can also help inform the differential diagnosis:

      • RBC morphologies:

        • - Spherocytes = autoimmune hemolytic anemia (AIHA), splenomegaly, post-splenectomy, hereditary spherocytosis, hemoglobin C, hemoglobinopathies

        • - Schistocytes = disseminated intravascular coagulation (DIC), hemolytic uremic syndrome (HUS), thrombocytopenic purpura (TTP), scleroderma renal crisis, vasculopathies, valvular heart disease, obstetric or hypertensive emergencies

        • - Burr cells (echinocytes) = renal disease, artifact

        • - Spur cells (acanthocytes) = liver disease

      • Pancytopenia +/– blasts = aplastic anemia, myelodysplastic syndrome (MDS), leukemia

    • - Check additional studies based on differential diagnosis (e.g., macrocytic anemia – check folate, B12, TSH, ask about alcohol use, review the patient’s medication list, etc.)

Anemia due to decreased RBC production

Normal reticulocyte index (<2%). Think of three buckets: Microcytic, normocytic, macrocytic

  1. Microcytic (MCV <80 fL)

    • Iron deficiency anemia:

      • - Etiologies: Blood loss (e.g., menorrhagia, GI bleed), malabsorption

      • - Diagnosis: ↓Fe, ↓Ferritin,↑TIBC. Smear with hypochromia, anisocytosis (varied size), poikilocytosis (varied shaped)

      • - Treatment: PO or IV iron. Every other day PO iron dosing is preferred, take on an empty stomach

    • Sideroblastic anemia:

      • - Etiologies: Hereditary (X-linked) or acquired (e.g., lead, alcohol use, vitamin B6 deficiency, isoniazid, chloramphenicol, INH, myelodysplastic syndromes)

      • - Diagnosis: ↑Fe, ↓TIBC. Ringed sideroblasts in marrow. ...

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