What are the causes and treatment options for pancytopenia?

Causes of Pancytopenia

The most common causes of pancytopenia include bone marrow disorders (megaloblastic anemia, aplastic anemia, myelodysplastic syndromes, and hematological malignancies), followed by peripheral destruction or sequestration mechanisms, and infections. 1

Major Etiological Categories

Bone Marrow Failure/Production Defects

• Megaloblastic anemia - Most common cause in many populations (74% in some studies), primarily due to vitamin B12 deficiency 2, 3
• Aplastic anemia - Second most common cause in some populations (18.26%), characterized by hypocellular bone marrow 2
• Myelodysplastic syndromes (MDS) - Characterized by ineffective hematopoiesis and dysplastic changes, affecting approximately 10.7% of pancytopenia cases 1, 4
• Hematological malignancies - Including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), lymphoma, and multiple myeloma 5
• Bone marrow infiltration - From metastatic solid tumors or granulomatous diseases 3

Peripheral Destruction or Sequestration

• Hypersplenism - Major cause (20.5% in some studies) due to splenic sequestration of blood cells 3
• Autoimmune disorders - Including systemic lupus erythematosus (SLE) and hemophagocytic syndrome 1, 3
• Disseminated intravascular coagulation (DIC) - Associated with sepsis and other critical illnesses 1

Infectious Causes

• Viral infections - Including HIV, HCV, parvovirus B19, and EBV 4, 1
• Bacterial infections - Particularly enteric fever (typhoid), tuberculosis, and brucellosis 6
• Parasitic infections - Including malaria, leishmaniasis, and kala-azar 1

Other Causes

• Drug-induced - Chemotherapeutic agents, antibiotics, anticonvulsants, and immunosuppressants 3
• Radiation exposure - Causing acute radiation syndrome with hematopoietic failure 1
• Nutritional deficiencies - Besides B12, also folate deficiency 1, 7
• Paroxysmal nocturnal hemoglobinuria (PNH) - An acquired clonal stem cell disorder 4

Age-Specific Considerations

• Pediatric population - More commonly due to aplastic anemia (41.43%), infections, and nutritional causes 7
• Young adults (11-30 years) - Infections are the leading cause (17.9%), followed by megaloblastic anemia (17%) 6
• Adults (>45 years) - AML accounts for the majority of cases (53.5%) 5
• Elderly (70-79 years) - Most commonly affected age group in some studies 3

Diagnostic Approach

1. Initial evaluation:

   • Complete blood count with differential to confirm pancytopenia 1
   • Peripheral blood smear examination to identify morphological abnormalities 4, 1
   • Reticulocyte count to differentiate between production defects and peripheral destruction 1

2. Secondary investigations:

   • Bone marrow examination (aspiration and biopsy) is indicated in most cases of pancytopenia, especially in:
     • Patients over 60 years of age
     • Those with systemic symptoms or abnormal physical findings
     • Cases where diagnosis remains unclear after initial testing 1
   • Vitamin B12 and folate levels 3
   • HIV and HCV testing in all adult patients 1
   • Autoimmune workup if systemic symptoms suggest autoimmune disease 1

Treatment Considerations

• Primary approach: Treat the underlying cause with supportive care, including transfusions for symptomatic anemia or severe thrombocytopenia 1
• Specific treatments:
  • Vitamin B12 or folate supplementation for megaloblastic anemia 3
  • Immunosuppressive therapy for non-severe aplastic anemia 1
  • Hematopoietic stem cell transplantation for severe aplastic anemia in appropriate candidates 1
  • Hypomethylating agents for higher-risk MDS patients not eligible for stem cell transplantation 1
  • Antimicrobial therapy directed at specific pathogens in infection-related pancytopenia 1

Clinical Pitfalls and Caveats

• Pancytopenia may be the presenting feature of a reversible condition, so early diagnosis and treatment can prevent over-investigation 6
• Dimorphic anemia is a predominant blood picture in pancytopenia, which should prompt evaluation for megaloblastic anemia 2
• In developing countries, infections are a major cause of pancytopenia and should be thoroughly investigated 6
• Regional variations exist in the etiology of pancytopenia, necessitating consideration of local epidemiological patterns 3, 5
• Drug history is crucial as medication-induced pancytopenia accounts for 5.4% of cases in some studies 3