Leukopenia

Low white blood cell count associated with increased risk of infection

Leukopenia
Synonyms	Leucopenia, leukocytopenia, low white blood cell count
Pronounce	N/A
Specialty	N/A
Symptoms	Often none; may include fever, recurrent infections, fatigue, weight loss, mouth ulcers, or skin infections
Complications	Infection, opportunistic infection, febrile neutropenia, sepsis
Onset	Sudden or gradual
Duration	Temporary, recurrent, or chronic depending on cause
Types	N/A
Causes	Bone marrow suppression, chemotherapy, radiation therapy, autoimmune disease, viral infection, aplastic anemia, leukemia, myelodysplastic syndrome, HIV/AIDS, lupus, medications, malnutrition
Risks	Chemotherapy, radiation therapy, immunosuppression, autoimmune disease, bone marrow disorder, HIV infection, certain medications
Diagnosis	Complete blood count with differential, absolute neutrophil count, peripheral blood smear, evaluation for underlying cause
Differential diagnosis	Neutropenia, lymphocytopenia, pancytopenia, anemia, thrombocytopenia, bone marrow failure
Prevention	Avoiding reversible causes, medication monitoring, infection prevention, vaccination when appropriate, prophylactic antimicrobials in selected high-risk patients
Treatment	Depends on cause; may include stopping causative medications, treating infections, growth factors, antibiotics, antivirals, antifungal drugs, immunosuppressants, or treatment of marrow disease
Medication	N/A
Prognosis	Varies by cause, severity, duration, and response to treatment
Frequency	Common in patients receiving chemotherapy, radiation therapy, immunosuppressive therapy, or those with certain marrow, autoimmune, or infectious diseases
Deaths	N/A

Educational infographic showing leukopenia, common causes, symptoms, diagnosis, treatment, and related conditions.

Leukopenia is a decrease in the number of circulating white blood cells or leukocytes in the blood. Because white blood cells are essential parts of the immune system, leukopenia can increase susceptibility to infection, especially when the decrease involves neutrophils, the white blood cells most important for early defense against many bacterial and fungal infections.Definition of leukopenia(link). National Cancer Institute.Overview of Leukopenias(link). MSD Manual Professional Edition.

In many clinical settings, leukopenia is discovered incidentally on a complete blood count (CBC). Some people have no symptoms, while others develop recurrent infections, fever, mouth ulcers, skin infections, or signs of serious systemic infection. Leukopenia is not a single disease by itself; it is a laboratory finding or clinical sign that requires evaluation for an underlying cause.

Overview

White blood cells are produced mainly in the bone marrow and circulate in the blood and lymphatic tissues. They help the body fight pathogens, remove damaged tissue, coordinate inflammation, and support immune memory. A low white blood cell count may occur because of decreased production in the bone marrow, increased destruction or use of white cells, abnormal distribution of cells, or a combination of these mechanisms.

The major white blood cell types include:

• Neutrophils - Important for fighting bacterial and fungal infections.
• Lymphocytes - Include T cells, B cells, and natural killer cells; important for viral defense and adaptive immunity.
• Monocytes - Become macrophages and help with phagocytosis and immune regulation.
• Eosinophils - Involved in allergic disease and defense against some parasites.
• Basophils - Involved in allergic and inflammatory responses.

Leukopenia may involve one type of white blood cell or several types at once. When all major blood cell lines are reduced, the condition is called pancytopenia.

Definition

Leukopenia generally refers to a total white blood cell count below the reference range for the laboratory performing the test. Many adult laboratories define leukopenia as a WBC count below about 4,000 cells per microliter, or less than 4.0 × 10⁹/L, although exact ranges vary by laboratory, age, sex, pregnancy status, ethnicity, and clinical context.Overview of Leukopenias(link). MSD Manual Professional Edition.

A white blood count is part of a complete blood count and measures the number of white blood cells in the blood. White blood cells, also called leukocytes, are immune cells made in the bone marrow and found in blood and lymph tissue.White Blood Count (WBC)(link). MedlinePlus.

Types of leukopenia

Leukopenia can be classified according to which white blood cell type is reduced.

Neutropenia

Neutropenia is a low neutrophil count. It is the most clinically important and common form of leukopenia. Neutrophils are the first-line white blood cells against many bacterial and fungal infections. Severe neutropenia markedly increases the risk of serious infection, and fever in a severely neutropenic patient is considered a medical emergency.Neutropenia(link). MSD Manual Professional Edition.Definition of neutropenia(link). National Cancer Institute.

Common severity categories for neutropenia are:

Category	Absolute neutrophil count	Clinical significance
Mild neutropenia	1,000 to 1,500/µL	Often low risk if otherwise healthy
Moderate neutropenia	500 to 1,000/µL	Increased infection risk
Severe neutropenia	Less than 500/µL	High risk of serious bacterial and fungal infection
Profound neutropenia	Less than 100/µL	Very high infection risk, especially if prolonged

Lymphocytopenia

Lymphocytopenia, also called lymphopenia or lymphocytic leukopenia, is a low lymphocyte count. It can occur with HIV infection, severe systemic illness, corticosteroid use, autoimmune disease, congenital immune disorders, certain cancer therapies, and malnutrition.Definition of lymphocytic leukopenia(link). National Cancer Institute.

Monocytopenia

Monocytopenia is a low monocyte count. It may occur with some bone marrow disorders, certain infections, immunosuppressive therapies, or rare inherited syndromes.

Eosinopenia and basopenia

Low eosinophil or basophil counts are less commonly emphasized clinically because these cells are normally present in smaller numbers. Eosinopenia may occur with acute stress, corticosteroid exposure, or severe infection.

Pancytopenia

Pancytopenia is a reduction in all three major blood cell lines: red blood cells, white blood cells, and platelets. It suggests a broader marrow, immune, nutritional, infectious, or malignant process and requires prompt evaluation.

Causes

Leukopenia has a broad differential diagnosis. Major causes include decreased bone marrow production, increased destruction of white blood cells, sequestration, medication effects, infection, autoimmune disease, and nutritional deficiency.

Cancer treatment

Chemotherapy and radiation therapy are common causes of leukopenia. These treatments may suppress rapidly dividing cells in the bone marrow, reducing production of neutrophils and other blood cells. Leukopenia from chemotherapy is often temporary but may be severe, especially after intensive regimens or in people with underlying marrow disease.

Bone marrow disorders

Bone marrow disorders can reduce white blood cell production.

• Aplastic anemia
• Myelodysplastic syndrome
• Leukemia
• Lymphoma involving bone marrow
• Multiple myeloma
• Myelofibrosis
• Bone marrow failure
• Metastatic cancer involving bone marrow
• Congenital marrow failure syndromes

Autoimmune disease

Autoimmune disease can cause leukopenia by immune-mediated destruction of white blood cells or by marrow suppression related to inflammation or therapy.

Examples include:

• Systemic lupus erythematosus
• Rheumatoid arthritis
• Felty syndrome
• Sjögren syndrome
• Autoimmune neutropenia
• Autoimmune lymphoproliferative syndrome

Infections

Many infections can cause temporary or persistent leukopenia. Viral infections are particularly common causes.

• HIV/AIDS
• Hepatitis
• Influenza
• COVID-19
• Epstein-Barr virus infection
• Cytomegalovirus infection
• Parvovirus B19 infection
• Measles
• Dengue fever
• Tuberculosis
• Sepsis
• Typhoid fever
• Malaria

Medications

Medication-induced leukopenia can result from marrow suppression, immune-mediated destruction, or direct drug toxicity. Some cases are mild and reversible; others can progress to severe neutropenia or agranulocytosis.

Examples include:

• Chemotherapy drugs
• Clozapine
• Antithyroid drugs such as methimazole and propylthiouracil
• Some antibiotics
• Some anticonvulsants
• Some antipsychotics
• Some antidepressants
• Immunosuppressants
• Methotrexate
• Azathioprine
• Mycophenolate mofetil
• Rituximab
• Sulfasalazine
• Interferon
• Antiretroviral drugs in selected cases

Nutritional deficiencies

Malnutrition and specific nutrient deficiencies can contribute to leukopenia, especially when they impair bone marrow function.

Important deficiencies include:

• Vitamin B12 deficiency
• Folate deficiency
• Copper deficiency
• Severe protein-energy malnutrition
• Anorexia nervosa
• Malabsorption syndromes

Hypersplenism

Hypersplenism occurs when an enlarged spleen sequesters or destroys blood cells. It can contribute to leukopenia, thrombocytopenia, and anemia.

Causes may include:

• Cirrhosis
• Portal hypertension
• Lymphoma
• Leukemia
• Chronic infection
• Autoimmune disease
• Storage diseases

Inherited and constitutional conditions

Some people have chronically low white blood cell or neutrophil counts without frequent infections. Benign ethnic neutropenia, more accurately related to Duffy-null associated neutrophil count in many individuals of African, Middle Eastern, or certain other ancestries, may show low neutrophil counts without increased infection risk in otherwise healthy people.Overview of Leukopenias(link). Merck Manual Professional Edition.

Other inherited causes include:

• Severe congenital neutropenia
• Cyclic neutropenia
• Shwachman-Diamond syndrome
• Glycogen storage disease type Ib
• WHIM syndrome
• GATA2 deficiency
• Congenital immunodeficiency syndromes

Risk factors

Risk factors for leukopenia include:

• Current or recent chemotherapy
• Radiation therapy
• Bone marrow transplant
• Stem cell transplant
• Cancer
• Leukemia
• Lymphoma
• Autoimmune disease
• HIV infection
• Chronic viral infection
• Immunosuppressive therapy
• Certain psychiatric medications such as clozapine
• Antithyroid drug therapy
• Severe malnutrition
• Vitamin B12 deficiency
• Folate deficiency
• Copper deficiency
• Enlarged spleen
• Recurrent infections
• Family history of congenital neutropenia

Pathophysiology

Leukopenia develops through one or more mechanisms:

• Reduced white blood cell production in the bone marrow
• Direct marrow injury from chemotherapy, radiation, toxins, or infection
• Marrow replacement by cancer or fibrosis
• Immune destruction of leukocytes
• Increased use of white blood cells during severe infection or inflammation
• Sequestration in an enlarged spleen
• Nutritional deficiency affecting marrow cell division
• Genetic abnormalities affecting leukocyte development

The clinical impact depends heavily on which white blood cell type is reduced. Low neutrophils increase risk of bacterial and fungal infection, while low lymphocytes may increase vulnerability to viral and opportunistic infections.

Signs and symptoms

Leukopenia itself often causes no symptoms. Symptoms usually occur because of an underlying disorder or because the immune system cannot respond adequately to infection.

Possible symptoms include:

• Recurrent infections
• Fever
• Chills
• Fatigue
• Weakness
• Sore throat
• Mouth ulcers
• Gum infections
• Sinusitis
• Pneumonia
• Skin infections
• Slow wound healing
• Weight loss
• Night sweats
• Enlarged lymph nodes
• Skin rash
• Painful urination
• Diarrhea

Warning signs

Urgent medical evaluation is needed when leukopenia is associated with signs of infection or systemic illness.

Seek urgent care for:

• Fever of 100.4°F or 38°C or higher, especially in a person receiving chemotherapy
• Shaking chills
• Shortness of breath
• Chest pain
• Confusion
• Severe weakness
• New rash with fever
• Painful mouth sores with fever
• Persistent vomiting or diarrhea
• Signs of sepsis
• Low blood pressure
• Rapid heart rate
• Severe abdominal pain
• Burning urination with fever
• Red, swollen, painful skin lesion

Fever with severe neutropenia is known as febrile neutropenia and requires prompt medical evaluation and often empiric broad-spectrum antibiotics.Definition of febrile neutropenia(link). National Cancer Institute.Neutropenia(link). MSD Manual Professional Edition.

Diagnosis

Leukopenia is diagnosed by a complete blood count (CBC), usually with a white blood cell differential. The differential identifies which white blood cell type is decreased.

Initial evaluation

Important first tests may include:

• Complete blood count
• White blood cell differential
• Absolute neutrophil count
• Absolute lymphocyte count
• Hemoglobin
• Platelet count
• Peripheral blood smear
• Reticulocyte count if anemia is present
• Review of previous CBC results
• Medication review
• Infection history
• Autoimmune history
• Cancer treatment history

Additional testing

Further evaluation depends on severity, duration, symptoms, and suspected cause.

• Vitamin B12 level
• Folate level
• Copper level
• Liver function tests
• Kidney function tests
• HIV test
• Hepatitis testing
• Viral serology or PCR when indicated
• Autoimmune antibody testing
• Antinuclear antibody
• Inflammatory markers
• Blood cultures if fever is present
• Urine culture
• Chest imaging if respiratory symptoms are present
• Bone marrow biopsy
• Flow cytometry
• Cytogenetic testing
• Molecular testing for marrow disorders

Bone marrow biopsy

A bone marrow biopsy may be considered when leukopenia is severe, persistent, unexplained, associated with anemia or thrombocytopenia, or suspicious for marrow failure, leukemia, lymphoma, myelodysplastic syndrome, aplastic anemia, or metastatic cancer.

Differential diagnosis

Conditions that may be confused with or associated with leukopenia include:

• Neutropenia
• Lymphocytopenia
• Pancytopenia
• Anemia
• Thrombocytopenia
• Leukemia
• Aplastic anemia
• Myelodysplastic syndrome
• Bone marrow failure
• Sepsis
• Hypersplenism
• Autoimmune neutropenia
• Medication-induced neutropenia
• Benign ethnic neutropenia
• Primary immunodeficiency

Treatment

Treatment depends on the cause, white blood cell type affected, severity, duration, symptoms, and infection risk. Mild, asymptomatic leukopenia may require monitoring only, while severe neutropenia with fever requires urgent treatment.

General principles

• Identify and treat the underlying cause.
• Stop or replace causative medications when possible.
• Treat bacterial, viral, fungal, or parasitic infections.
• Monitor CBC and differential over time.
• Assess infection risk based on absolute neutrophil count.
• Use infection prevention measures.
• Consider specialist referral for severe, persistent, or unexplained cases.

Medication adjustment

If a medication is suspected, the clinician may stop, reduce, or replace it. This should generally be done under medical supervision, especially for psychiatric medications, antithyroid drugs, chemotherapy, immunosuppressants, and antiseizure drugs.

Treatment of infection

Infections should be treated promptly. In severe neutropenia, fever may be the only sign of serious infection. Empiric broad-spectrum antibiotics are often needed while cultures and diagnostic testing are pending.

Treatment may include:

• Antibiotics
• Antiviral drugs
• Antifungal drugs
• Antiparasitic drugs when indicated
• Source control such as drainage of abscess
• Hospitalization for severe infection
• Intravenous fluids
• Oxygen therapy
• Sepsis management

Growth factors

Granulocyte colony-stimulating factor (G-CSF) and related growth factors may be used in selected patients to stimulate neutrophil production, especially in chemotherapy-induced neutropenia, severe chronic neutropenia, or high-risk settings.

Examples include:

• Filgrastim
• Pegfilgrastim
• Sargramostim

Nutritional treatment

When leukopenia is related to nutritional deficiency, treatment may include:

• Vitamin B12 replacement
• Folate replacement
• Copper replacement
• Protein-calorie nutrition support
• Evaluation for malabsorption
• Treatment of eating disorders
• Dietitian referral

Autoimmune leukopenia

Autoimmune leukopenia may be treated by managing the underlying autoimmune disease. Depending on severity, treatment may include corticosteroids, immunosuppressants, biologic therapies, or observation.

Cancer-related leukopenia

Cancer-related leukopenia may be caused by the cancer itself or by therapy. Management may include treatment delay, dose adjustment, growth factors, antimicrobial prophylaxis, transfusion support for other cytopenias, or evaluation for marrow involvement.

Prevention

Not all leukopenia can be prevented, but risk can sometimes be reduced.

• Monitor CBC during chemotherapy or high-risk medications.
• Use growth factors when clinically indicated.
• Avoid unnecessary immunosuppressive drugs.
• Treat vitamin and mineral deficiencies.
• Manage autoimmune disease.
• Screen for infections when appropriate.
• Follow infection-prevention precautions during neutropenia.
• Stay current with recommended vaccines when appropriate.
• Avoid live vaccines in certain immunocompromised patients unless approved by a clinician.
• Use prophylactic antimicrobials only when medically indicated.

Infection prevention for patients

People with clinically significant leukopenia or neutropenia may be advised to take infection-prevention steps.

• Wash hands frequently.
• Avoid close contact with sick people.
• Seek prompt care for fever.
• Avoid raw or undercooked meat, seafood, and eggs if severely immunocompromised.
• Wash fruits and vegetables carefully.
• Maintain good oral hygiene.
• Avoid gardening or soil exposure during severe neutropenia unless protected.
• Avoid cleaning litter boxes or bird cages if immunocompromised.
• Keep wounds clean and covered.
• Avoid crowded indoor spaces during high-risk periods when advised.
• Stay up to date on vaccines recommended by a clinician.

Leukopenia in special populations

Chemotherapy patients

Leukopenia is common after chemotherapy because many chemotherapy drugs suppress bone marrow. The timing of the lowest blood count, called the nadir, varies by regimen. Fever during chemotherapy-related neutropenia requires urgent evaluation.

People with HIV

HIV can cause leukopenia through direct immune effects, opportunistic infections, marrow involvement, medications, or advanced disease. Antiretroviral therapy and treatment of coinfections may improve counts in some patients.

Autoimmune disease patients

Patients with lupus, rheumatoid arthritis, or other autoimmune diseases may develop leukopenia from the disease itself or from medications used for treatment.

Children

Children may develop leukopenia after viral infections, medication exposure, congenital neutropenia, marrow disorders, or immune disorders. Persistent or severe leukopenia in children requires pediatric evaluation.

Older adults

In older adults, leukopenia may be related to medications, nutritional deficiency, marrow disorders, malignancy, chronic infection, or autoimmune disease. Persistent unexplained leukopenia should not be dismissed as normal aging.

Prognosis

The prognosis of leukopenia depends on the cause and severity. Temporary leukopenia after a viral infection may resolve without specific treatment. Medication-induced leukopenia may improve after the causative drug is stopped. Severe or persistent leukopenia from bone marrow failure, leukemia, myelodysplastic syndrome, advanced HIV, or intensive chemotherapy may require specialized treatment and close monitoring.

Key prognostic factors include:

• Absolute neutrophil count
• Duration of leukopenia
• Presence or absence of fever
• Underlying cause
• Bone marrow function
• Other blood count abnormalities
• Age and comorbidities
• Immune status
• Response to treatment

Patient education

Leukopenia should be understood as a warning sign rather than a diagnosis by itself. Patients should ask their healthcare provider which type of white blood cell is low, how severe the decrease is, whether the condition is temporary or chronic, and what symptoms should trigger urgent care.

Questions to ask include:

• What is my total white blood cell count?
• What is my absolute neutrophil count?
• Is this mild, moderate, or severe?
• Could a medication be causing it?
• Do I need additional tests?
• Do I need to avoid crowds or sick contacts?
• When should I go to the emergency room?
• Do I need antibiotics, antivirals, or growth factors?
• How often should my CBC be repeated?
• Should I see a hematologist?

When to call a doctor

Call a healthcare provider promptly for:

• Fever
• Chills
• Sore throat
• Mouth sores
• New cough
• Shortness of breath
• Burning urination
• Persistent diarrhea
• Skin redness, swelling, or pus
• Unusual fatigue
• Unexplained weight loss
• Night sweats
• New rash
• Exposure to contagious illness

Seek emergency care for fever with severe neutropenia, confusion, low blood pressure, chest pain, severe shortness of breath, or signs of sepsis.

See also

• White blood cell
• Leukocyte
• Complete blood count
• White blood cell differential
• Neutropenia
• Febrile neutropenia
• Lymphocytopenia
• Pancytopenia
• Anemia
• Thrombocytopenia
• Aplastic anemia
• Myelodysplastic syndrome
• Leukemia
• Bone marrow
• Bone marrow biopsy
• Chemotherapy
• Radiation therapy
• Immunosuppression
• Autoimmune disease
• HIV/AIDS
• Lupus
• Sepsis
• Infection
• Hematology
• Granulocyte colony-stimulating factor

Further reading

• Definition of leukopenia(link). National Cancer Institute.
• Overview of Leukopenias(link). MSD Manual Professional Edition.
• Neutropenia(link). MSD Manual Professional Edition.
• White Blood Count (WBC)(link). MedlinePlus.
• Definition of neutropenia(link). National Cancer Institute.
• Definition of febrile neutropenia(link). National Cancer Institute.
• Definition of lymphocytic leukopenia(link). National Cancer Institute.
• "How to Interpret and Pursue an Abnormal Complete Blood Cell Count in Adults".Mayo Clinic Proceedings.2005;80(7)

923-936.PMID:16007898.

External links

• National Cancer Institute - Leukopenia definition
• MedlinePlus - White Blood Count
• MSD Manual - Overview of Leukopenias
• MSD Manual - Neutropenia