What is pancytopenia?

Definition of Pancytopenia

Pancytopenia is defined as the simultaneous reduction of all three major blood cell lines: red blood cells, white blood cells, and platelets below normal reference ranges. 1

Diagnostic Criteria

Pancytopenia is characterized by:

• Decreased red blood cells (anemia)
• Decreased white blood cells (leukopenia)
• Decreased platelets (thrombocytopenia)

The specific threshold values may vary slightly between laboratories, but generally include:

• Hemoglobin < 10 g/dL or hematocrit < 30%
• White blood cell count < 4,000 cells/μL
• Platelet count < 150,000/μL

Pathophysiological Mechanisms

Pancytopenia results from one of three basic mechanisms:

1. Decreased production of blood cells in bone marrow:

   • Aplastic anemia
   • Myelodysplastic syndromes
   • Leukemia
   • Megaloblastic anemia (B12 or folate deficiency)
   • Bone marrow infiltration

2. Increased destruction or consumption of blood cells:

   • Hypersplenism
   • Autoimmune disorders
   • Disseminated intravascular coagulation

3. Ineffective hematopoiesis:

   • Myelodysplastic syndromes
   • Megaloblastic anemia

Common Etiologies

The most common causes of pancytopenia worldwide include:

• Vitamin B12 deficiency and hypersplenism (20.5% of cases in some studies) 2
• Hematological malignancies (16% of cases) including:
  • Acute leukemia
  • Lymphoma
  • Multiple myeloma 2
• Myelodysplastic syndromes (10.7% of cases) 2
• Infections (10.7% of cases) 2
• Drug-induced pancytopenia (5.4% of cases) 2
• Autoimmune disorders like systemic lupus erythematosus (4.5% of cases) 2
• Aplastic anemia (1.8% of cases) 2

Clinical Manifestations

The clinical presentation of pancytopenia reflects the deficiency of each cell line:

• Anemia: Fatigue, weakness, pallor, dyspnea on exertion
• Leukopenia: Increased susceptibility to infections, fever
• Thrombocytopenia: Bleeding manifestations (petechiae, purpura, mucosal bleeding)

In severe cases, particularly with radiation exposure, patients may progress through distinct phases:

• Prodromal phase (first 48 hours)
• Latent phase (transient improvement)
• Manifest illness phase (severe immunosuppression)
• Recovery phase 1

Classification in Myelodysplastic Syndromes

In the context of myelodysplastic syndromes (MDS), pancytopenia is specifically addressed in the WHO classification:

• Cases with pancytopenia and unilineage dysplasia are classified as MDS-unclassified (MDS-U) 1
• This distinguishes them from cases with bicytopenia, which may be classified under refractory cytopenia with unilineage dysplasia (RCUD) 1

Diagnostic Approach

The diagnosis of pancytopenia requires:

1. Complete blood count showing reduction in all three cell lines
2. Peripheral blood smear examination
3. Bone marrow aspiration and biopsy in most cases

Bone marrow findings vary based on etiology:

• Hypercellular marrow: Megaloblastic anemia, myelodysplastic syndrome
• Hypocellular marrow: Aplastic anemia
• Infiltrated marrow: Leukemia, lymphoma, metastatic cancer

Prognostic Implications

The prognosis of pancytopenia depends entirely on the underlying cause:

• Nutritional deficiencies (B12, folate): Excellent prognosis with replacement therapy
• Drug-induced: Good prognosis with drug withdrawal
• Aplastic anemia: Poor prognosis without treatment, improved with bone marrow transplantation
• Hematological malignancies: Variable, depending on type and stage

Pancytopenia represents a serious hematological finding that requires prompt evaluation to identify the underlying cause and initiate appropriate treatment to prevent potentially life-threatening complications.