What is Pancytopenia?
Pancytopenia is a hematological condition defined by the simultaneous reduction of all three major blood cell lineages: red blood cells (causing anemia), white blood cells (causing leukopenia), and platelets (causing thrombocytopenia). 1, 2, 3
Definition and Clinical Significance
Pancytopenia represents a laboratory finding rather than a specific disease entity, serving as a common manifestation of numerous underlying pathological processes ranging from reversible nutritional deficiencies to life-threatening malignancies. 2, 4 The condition reflects either:
- Decreased production of blood cells in the bone marrow (most common mechanism) 1
- Increased peripheral destruction or sequestration of blood cells 1, 3
Common Etiological Categories
The causes of pancytopenia can be systematically organized:
Bone Marrow Disorders (Most Common)
- Megaloblastic anemia (particularly Vitamin B12 deficiency) represents one of the most frequent reversible causes, accounting for up to 74% of cases in some populations 4, 5
- Aplastic anemia causes bone marrow failure with hypocellular marrow 1, 4
- Myelodysplastic syndromes characterized by ineffective hematopoiesis and dysplastic changes, affecting approximately 10.7% of cases 6, 1, 3
- Hematological malignancies including acute leukemia, lymphoma, and multiple myeloma account for approximately 16% of cases 3
Peripheral Destruction/Sequestration
- Hypersplenism causes sequestration and is a leading cause alongside Vitamin B12 deficiency (20.5% of cases) 3
- Hemophagocytic syndrome presents with pancytopenia and requires prompt immunosuppressive treatment 1
- Autoimmune disorders such as systemic lupus erythematosus (4.5% of cases) 3
Infectious Causes
- Infections represent a significant etiology in certain populations, including brucellosis (which commonly presents with mild transaminitis and pancytopenia), tickborne rickettsial diseases like ehrlichiosis, miliary tuberculosis, and parvovirus B19 1, 7, 8
- HIV and HCV can cause pancytopenia through multiple mechanisms 1
Drug-Induced and Toxic Causes
- Chemotherapy agents cause direct bone marrow suppression 1
- Methotrexate can rarely cause pancytopenia even with low-dose weekly therapy, particularly in patients with impaired renal function or concomitant sulfonamide-based medications, typically occurring 4-6 weeks after dose increases 1
- Immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-L1 agents) cause immune-related hematological toxicity in less than 5% of patients but carry significant mortality risk 1
- Radiation exposure can cause acute radiation syndrome with hematopoietic failure at doses exceeding 1 Gy 1, 7
Clinical Presentation
Patients typically present with symptoms reflecting the deficiency of multiple cell lines:
- Generalized weakness and easy fatigability (from anemia) 4, 5
- Fever and recurrent infections (from leukopenia/neutropenia) 4, 8
- Bleeding manifestations (from thrombocytopenia) 8
- Physical findings commonly include pallor (most frequent), followed by splenomegaly and hepatomegaly 4
- Additional symptoms may include arthralgias, weight loss, and failure to thrive in pediatric cases 8
Critical Diagnostic Pitfall
A common pitfall is assuming pancytopenia always indicates bone marrow failure or malignancy. In reality, reversible causes like Vitamin B12 deficiency and hypersplenism are among the most common etiologies and should be prioritized in the initial diagnostic workup. 3, 5 Vitamin B12 deficiency can present with vague clinical manifestations and sometimes mimic serious hematologic conditions, making prompt recognition essential to avoid unnecessary invasive procedures. 5
The WHO classification specifically notes that patients with pancytopenia and unilineage morphologic dysplasia are classified as having MDS-unclassifiable due to uncertain clinical significance, highlighting the complexity of diagnosis in certain presentations. 6