Neutropenia

Aka: Neutropenia, Granulocytopenia, Agranulocytosis, Schultz's Disease, Pseudoneutropenia

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II. Epidemiology

  1. Prevalence: 1.24% (U.S.)

III. Precautions

  1. See Neutropenic Fever
  2. Avoid Rectal Exam in Neutropenia (theoretic risk of bacteremia)

IV. Causes

  1. See Neutropenia Causes

V. Differential Diagnosis: Pseudoneutropenia (automated)

  1. Blood examined after long delay after Phlebotomy
  2. Margination (see Neutropenia Causes)
  3. Neutrophil clumping
    1. Paraproteinemia
    2. Anticoagulant use

VI. History

  1. B-Symptoms
    1. Fever
    2. Night Sweats
    3. Weight loss
  2. Other focus areas
    1. Recurrent Fevers or infections
    2. Family History of hematologic disorders including Neutropenia
    3. Rheumatologic history
    4. Nutritional deficiency or risks

VII. Exam: Neutropenia

  1. Fever (>=100.4 F, >=38 C)
    1. See Neutropenic Fever
  2. Head and Neck
    1. Lymphadenopathy
    2. Oral Lesions
      1. Aphthous Ulcers
      2. Gingivitis
      3. Periodontal Disease
  3. Cardiopulmonary findings
    1. Hypotension
    2. Tachycardia
    3. Respiratory Distress
  4. Gastrointestinal
    1. Hepatomegaly
    2. Splenomegaly
  5. Skin
    1. Atopic Dermatitis
    2. Cutaneous Vasculitis findings

VIII. Signs: Recurrent Infection

  1. General
    1. Typical inflammation signs less commonly seen
    2. Swelling and heat less often seen with Neutropenia
  2. Organisms
    1. Staphylococcus Aureus (skin)
    2. Gram Negative (Gastrointestinal, Genitourinary)
  3. Early severe Neutropenia
    1. Oropharyngeal infections
    2. Skin Infections or delayed Wound Healing
  4. Persistent severe Neutropenia
    1. Pulmonary infection
    2. Gastrointestinal infection
    3. Sepsis

IX. Labs: General

  1. Complete Blood Count with Differential and Platelet Count
    1. Differential including Absolute Neutrophil Count (ANC)
  2. Other testing to consider (see evaluation protocol below)
    1. Peripheral Blood Smear
    2. Bone Marrow Biopsy (see indications below)
    3. Genetic Testing (see indications below)

X. Labs: Bone Marrow Biopsy

  1. Indications
    1. Indicated in most Neutropenia cases
    2. Not required in mild Drug-Induced Neutropenia
  2. Increased Granulocytes in Bone Marrow
    1. Suggests increased destruction (e.g. immune)
  3. Decreased Granulocytes in Bone Marrow
    1. Increased cells seen in marrow
      1. Suggests marrow infiltration (e.g. Leukemia)
    2. Decreased cells seen in marrow
      1. Suggests marrow injury (e.g. medications)

XI. Labs: Genetic Testing Indications

  1. Family History or Past Medical History Indications
    1. Congenital Neutropenia
    2. Autoimmune Neutropenia
    3. Myelodysplastic Syndrome
    4. Acute Myelogenous Leukemia
  2. Past Medical History Indications
    1. Recurrent serious infections of the skin or mucous membranes since childhood
  3. Exam Indications
    1. Dysmorphic facial features
    2. Growth Delay
    3. Inflammatory Bowel Disease
    4. Hepatomegaly
    5. Splenomegaly
    6. Persistent or severe Neutropenia without identified cause
    7. Skeletal abnormalities
    8. Cardiovascular abnormalities
    9. Urogenital abnormalities
    10. Skin findings (e.g. Atopic Dermatitis, abnormal pigmentation)

XII. Diagnosis: Adults and Children >1 year old

  1. Neutropenia
    1. Adults and children >1 year: ANC < 1500/mm3
    2. Infants <1 year old: ANC < 1000/mm3
  2. Agranulocytosis (severe Neutropenia)
    1. Complete absence of Neutrophils
  3. Absolute Neutrophil Count (ANC) based grading
    1. Mild Neutropenia: ANC 1000 to 1500 Neutrophils/mm3
    2. Moderate Neutropenia: ANC 500 to 1000 Neutrophils/mm3
    3. Severe Neutropenia: ANC <500 Neutrophils/mm3

XIII. Evaluation: Approach

  1. See Neutropenia Causes
  2. Step 1: Diagnose Neutropenia (ANC <1500/uL, <1000/uL in age <1 year)
    1. See above
  3. Step 2: Admit or transfer patient for emergent findings
    1. Severe Neutropenia with ANC <500/uL
    2. Ill appearance
    3. Febrile Neutropenia
  4. Step 3: Identify Chronic Neutropenia Syndromes (history of Neutropenia on prior CBC)
    1. Episodic Neutropenia (cyclical Neutropenia)
      1. Obtain CBC with differential twice weekly for >=6 weeks
      2. Identify 2 ANC nadirs followed by return to normal ANC
    2. Ethnic Neutropenia
      1. Mild Neutropenia in patients from Africa, Caribbean, Middle East or West Indies
    3. Chronic persistent Neutropenia in age <5 years
      1. Primary Autoimmune Neutropenia
        1. Consider antineutrophil antibodies
      2. Congenital syndrome (genetic disorders)
        1. See Genetic Testing indications above
  5. Step 4: Consider Drug-Induced Neutropenia
    1. Chemotherapy-Induced Neutropenia
      1. Consult with patient's oncologist
      2. Consider Granulocyte Colony Stimulating Factors (G-CSF)
    2. Drug-Induced Neutropenia
      1. Stop causative agent
      2. Monitor serial Complete Blood Counts for Neutrophil recovery
      3. Hospitalize patients with severe Neutropenia (ANC <500/uL)
        1. Initiate urgent evaluation and management
        2. Initiate broad spectrum Antibiotics
  6. Step 5: Obtain Testing for other Neutropenia Causes
    1. See Neutropenia Causes
    2. Viral or Bacterial Infection in last 6 weeks
      1. See Infectious Causes of Neutropenia
      2. Mononucleosis (EBV, CMV)
      3. HIV Test
      4. Hepatitis B Serology
      5. Hepatitis C Serology
      6. Influenza Test
    3. Nutritional Deficiency (e.g. Bariatric Surgery, Eating Disorder, malabsorption, Alcoholism)
      1. Vitamin B12 Level
      2. Folic Acid Level
      3. Copper level
    4. Autoimmune disorder cause suspected (Autoimmune Neutropenia)
      1. Rheumatoid Arthritis
        1. C-RP
        2. Rheumatoid Factor
        3. Anticyclic Citrullinated Peptide Antibody
      2. Sjogren Syndrome
        1. Antinuclear Antibody (ANA)
        2. Anti-SS-A Antibody (Ro)
        3. Anti-SS-B Antibody (La)
        4. Rheumatoid Factor
      3. Systemic Lupus Erythematosus
        1. Antinuclear Antibody (ANA)
        2. Anti-dsDNA Antibody
        3. Anti-Smith Antibody
        4. Anti-Cardiolipin Antibody
  7. Step 6: Hematology Consultation
    1. Peripheral Blood Smear
    2. Consider Bone Marrow Biopsy (see above)
    3. Consider Genetic Testing (see above)

XIV. Management

  1. Specific cause evaluation and management
  2. Consult hematology as needed
  3. Management when specifically indicated
    1. G-CSF
    2. Antibiotic prophylaxis
  4. Hospitalization when indicated
    1. Moderate to severe Neutropenic Fever
    2. Agranulocytosis (ANC <100/uL)

XV. Complications

  1. Severe Neutropenia predisposes to serious infection
  2. Neutropenic Fever

XVI. Resources

  1. Rout (2025) Neutropenia, Stat Pearls
    1. https://www.ncbi.nlm.nih.gov/books/NBK507702/

XVII. References

  1. Katsaras (2024) Hematol Rep 16(2):375-89 +PMID: 38921186 [PubMed]
  2. Kim (2025) Am Fam Physician 112(6): 618-28 [PubMed]
  3. Min (2025) Blood Res 60(1):30 +PMID: 40418265 [PubMed]

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