Definition

Simultaneous leukopenia, nonregenerative anemia, and thrombocytopenia; not a disease itself-rather, a group of laboratory findings that can result from multiple causes.

Pathophysiology

• Mechanisms may include decreased production of cells in the bone marrow or increased peripheral use, destruction, or sequestration; one or more of these mechanisms may occur together.
• Decreased production occurs when pluripotent, multipotent, or committed stem cells are destroyed, their proliferation or differentiation is suppressed, or the maturation of differentiated cells is delayed or arrested.
• If pluripotent stem cells are affected, pancytopenia develops; if committed stem cells are involved, cytopenia of the specific cell type develops.
• Increased use and destruction of cells typically results in increased production in the bone marrow. At least 2–3 days are required before increased production begins to have an effect on peripheral blood cell counts, and peak output usually takes about a week; thus, the rate of use or destruction necessary to cause cytopenia is not as great during the first few days of disease as it is later.
• Sequestration of cells in the microcirculation, especially that of the spleen, intestine, and lungs, can cause cytopenia of the cell type involved.

Systems Affected

Hemic/Lymphatic/Immune-bone marrow, spleen, lymph nodes, and other lymphocytic tissues; depending on the cause, these organs can be affected by cellular depletion, degeneration, necrosis, hyperplasia, dysplasia, or dyscrasia; changes may occur alone or in combination.

Incidence/Prevalence

Pancytopenia is an uncommon occurrence and does not always occur with the causes listed below. One study (Weiss et al. 1999) determined an incidence of 2.4% in dogs.

Geographic Distribution

Unless the cause of pancytopenia is due to an infectious agent that is localized to a certain region (e.g., leishmaniasis, histoplasmosis), no specific geographic distribution exists.

Signalment

• Dogs and cats
• No age, sex, or breed predilection

Signs

Causes

Risk Factors

Vary with individual cause

Differential Diagnosis

• Acute onset with severe clinical signs-more consistent with conditions that cause necrosis, destruction, or sequestration of cells.
• Slow, insidious onset-more consistent with conditions that cause bone marrow suppression.

Laboratory Findings

CBC/Biochemistry/Urinalysis

• Leukopenia-characterized by neutropenia with or without lymphopenia.
• Nonregenerative anemia-severity depends on duration and underlying cause.
• Thrombocytopenia.
• Blood smear evaluation-may reveal infectious agents (e.g., Ehrlichia spp. Histoplasma capsulatum); may reveal abnormal cells of any lineage, suggesting myeloproliferative or lymphoproliferative diseases.
• Toxic changes in leukocytes-may suggest bone marrow injury (e.g., from parvovirus or chemical agent), septicemia, or endotoxemia.
• Biochemical alterations-depends on organ and degree of involvement (e.g., increased liver enzymes may be seen with certain infectious diseases, toxins, and infiltrative diseases).

Other Laboratory Tests

• Reticulocyte count-a regenerative response to anemia suggests destruction, use, or sequestration of RBCs; a nonregenerative response suggests bone marrow suppression and merits bone marrow examination.
• Immunologic tests for infectious diseases (e.g., FeLV, FIV, Ehrlichia spp.).
• PCR for infectious agents.

Diagnostic Procedures

• Bone marrow examination-indicated when cause of pancytopenia cannot be determined with other tests.
• Hypercellular bone marrow associated with myelodysplasia, neoplasia, myelophthisis, or recovery from parvovirus.
• Hypocellular bone marrow associated with necrosis, myelofibrosis, and suppression (e.g., drugs, estrogen, aplastic anemia).
• If a bone marrow aspirate cannot be obtained, myelofibrosis, necrosis, or marked hypocellularity should be suspected and a core biopsy should be evaluated.

Pathologic Findings

Bone marrow core biopsy-may see replacement of normal hematopoietic tissue with necrotic, neoplastic, fibrous, or adipose tissue, depending on the underlying cause.

Drug(s) Of Choice

Treatment should be appropriate for the clinical situation (i.e., the degree to which each cell population is decreased, presence of fever or infection, and established or suspected specific diagnoses); see specific causes.

Contraindications

• Drugs that may suppress hematopoiesis further (see “Causes”).
• NSAIDs, clopidogrel, or other drugs that may interfere with platelet function.

Precautions

Because of the patient's compromised immune status, glucocorticoids and other immunosuppressive drugs should be used only when absolutely necessary and with extreme care and frequent monitoring.

Alternative Drug(s)

Patient Monitoring

• Daily physical examination, including frequent monitoring of body temperature.
• Periodic CBC-frequency depends on severity of cytopenia, age, general physical condition of the patient, and underlying cause.

Prevention/Avoidance

• Castration of cryptorchid males.
• Vaccination for infectious diseases.
• Frequent monitoring of CBC in cancer patients receiving chemotherapy or radiation.

Possible Complications

• Hemorrhage
• Sepsis

Expected Course and Prognosis

• Depends on the underlying cause
• Often a guarded prognosis is warranted

Associated Conditions

Secondary infections-in patients with neutropenia.

Zoonotic Potential

• Tularemia.
• An owner can contract histoplasmosis from the same source as the patient.

Pregnancy/Fertility/Breeding

Stress of underlying disease may cause abortion; see respective topics for the effects of different causes on pregnancy.

See Also

• Anemia, Aplastic
• Anemia, Nonregenerative
• Anemia, Regenerative
• Neutropenia
• Specific causes of pancytopenia
• Thrombocytopenia

Abbreviations

• ACE = angiotensin-converting enzyme
• FeLV = feline leukemia virus
• FIP = feline infectious peritonitis
• FIV = feline immunodeficiency virus
• ICH – infectious canine hepatitis
• PCR = polymerase chain reaction
• PCV = packed cell volume
• RBC = red blood cell
• rhEPO = recombinant human erythropoietin
• rhG-CSF = recombinant human granulocyte colony-stimulating factor

Author R. Darren Wood

Consulting Editor Alan H. Rebar

Client Education Handout Available Online