Hematology Study Guide

Based on Harrison's Principles of Internal Medicine

Diagnostic Approaches in Hematology

Diagnosing hematologic disorders requires a systematic approach. This section outlines the key diagnostic tools and methods used to identify blood disorders, from initial evaluation to specialized testing.

Diagnostic Approach to Hematologic Disorders

Flowchart showing the systematic approach to diagnosing hematologic disorders

Initial Evaluation

History and Physical Examination

The diagnostic process begins with a thorough history and physical examination:

  • Medical History: Previous illnesses, medications, family history of blood disorders
  • Symptoms: Fatigue, weakness, bleeding, bruising, infections, bone pain
  • Physical Findings: Pallor, jaundice, petechiae (small red spots), purpura (larger bruises), lymphadenopathy (enlarged lymph nodes), hepatosplenomegaly (enlarged liver and spleen)

Complete Blood Count (CBC)

The CBC is the most important initial laboratory test for evaluating blood disorders. It includes:

  • Red Blood Cell (RBC) Count: Number of red blood cells per volume of blood
  • Hemoglobin (Hb): Amount of oxygen-carrying protein in the blood
  • Hematocrit (Hct): Percentage of blood volume occupied by red blood cells
  • White Blood Cell (WBC) Count: Total number of white blood cells
  • WBC Differential: Percentages of different types of white blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils)
  • Platelet Count: Number of platelets per volume of blood
  • Red Cell Indices: Measurements that help characterize red blood cells
    • Mean Corpuscular Volume (MCV): Average size of red blood cells
    • Mean Corpuscular Hemoglobin (MCH): Average amount of hemoglobin per red blood cell
    • Mean Corpuscular Hemoglobin Concentration (MCHC): Average concentration of hemoglobin in red blood cells
    • Red Cell Distribution Width (RDW): Measure of variation in red blood cell size

Peripheral Blood Smear

Examination of a stained blood smear under a microscope provides valuable information about blood cell morphology:

  • Red Blood Cell Morphology: Size, shape, color, and inclusions
  • White Blood Cell Morphology: Maturity, abnormal forms, inclusions
  • Platelet Morphology: Size, number, and appearance

Abnormal findings may include:

  • Microcytic (small) or macrocytic (large) red blood cells
  • Hypochromic (pale) red blood cells
  • Poikilocytosis (abnormally shaped red blood cells)
  • Immature white blood cells or blasts
  • Abnormal lymphocytes
  • Giant or clumped platelets

Specialized Blood Tests

Tests for Anemia

  • Iron Studies: Serum iron, total iron-binding capacity (TIBC), transferrin saturation, ferritin
  • Vitamin B12 and Folate Levels
  • Reticulocyte Count: Measures bone marrow response to anemia
  • Hemolysis Evaluation: Haptoglobin, lactate dehydrogenase (LDH), bilirubin
  • Hemoglobin Electrophoresis: Identifies abnormal hemoglobin types
  • Direct Antiglobulin Test (DAT/Coombs Test): Detects antibodies attached to red blood cells

Tests for White Blood Cell Disorders

  • Flow Cytometry: Identifies cell surface markers to determine cell lineage and maturity
  • Cytochemical Stains: Help classify leukemias
  • Molecular Testing: Detects genetic abnormalities associated with leukemias and lymphomas

Tests for Bleeding and Clotting Disorders

  • Prothrombin Time (PT)/International Normalized Ratio (INR): Evaluates the extrinsic and common pathways of coagulation
  • Activated Partial Thromboplastin Time (aPTT): Evaluates the intrinsic and common pathways of coagulation
  • Fibrinogen: Measures the level of this important clotting protein
  • D-dimer: Indicates active clot formation and breakdown
  • Specific Clotting Factor Assays: Measure levels of individual clotting factors
  • von Willebrand Factor Tests: Evaluate quantity and function of von Willebrand factor
  • Platelet Function Tests: Assess platelet aggregation and function

Bone Marrow Examination

Bone marrow examination is crucial for diagnosing many hematologic disorders. It involves two procedures:

  1. Bone Marrow Aspiration: Removal of liquid bone marrow for examination
  2. Bone Marrow Biopsy: Removal of a small core of bone with marrow for examination

Bone marrow examination provides information about:

  • Cellularity: Whether the marrow is hypocellular, normocellular, or hypercellular
  • Maturation: Whether cells are developing normally
  • Morphology: Appearance of cells
  • Presence of Abnormal Cells: Blasts, dysplastic cells, or malignant cells
  • Iron Stores: Amount of stored iron in the marrow

Additional studies on bone marrow samples may include:

  • Flow Cytometry: Identifies cell surface markers
  • Cytogenetics: Examines chromosomal abnormalities
  • Fluorescence In Situ Hybridization (FISH): Detects specific genetic abnormalities
  • Molecular Testing: Identifies gene mutations

Imaging Studies

Imaging studies may be used to evaluate the extent of disease or complications:

  • Ultrasound: Evaluates liver and spleen size, lymph nodes
  • Computed Tomography (CT): Assesses lymphadenopathy, organomegaly, and masses
  • Magnetic Resonance Imaging (MRI): Evaluates bone marrow and soft tissues
  • Positron Emission Tomography (PET): Identifies metabolically active disease sites

Diagnostic Approach by Disorder Category

Approach to Anemia

  1. Classify based on MCV: microcytic, normocytic, or macrocytic
  2. Evaluate reticulocyte count to determine if bone marrow response is appropriate
  3. Perform specific tests based on classification:
    • Microcytic: Iron studies, hemoglobin electrophoresis
    • Normocytic: Hemolysis evaluation, renal function tests
    • Macrocytic: Vitamin B12 and folate levels, liver function tests
  4. Consider bone marrow examination if diagnosis remains unclear

Approach to Leukocytosis/Leukopenia

  1. Examine peripheral blood smear to identify abnormal cells
  2. Consider reactive causes (infection, inflammation, stress)
  3. If persistent or severe, perform flow cytometry
  4. Perform bone marrow examination if malignancy is suspected
  5. Conduct cytogenetic and molecular testing for classification and prognosis

Approach to Thrombocytopenia/Thrombocytosis

  1. Rule out pseudothrombocytopenia (laboratory artifact)
  2. Examine peripheral blood smear to assess platelet morphology
  3. Evaluate for increased destruction (immune thrombocytopenia, DIC) vs. decreased production
  4. Consider bone marrow examination if decreased production is suspected
  5. For thrombocytosis, distinguish between reactive and clonal causes

Approach to Bleeding Disorders

  1. Determine if bleeding is due to platelet dysfunction, coagulation factor deficiency, or vascular abnormality
  2. Perform screening tests: platelet count, PT/INR, aPTT
  3. Conduct specific factor assays based on abnormal screening tests
  4. Evaluate for von Willebrand disease if mucocutaneous bleeding is prominent
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