What is the most likely diagnosis for a patient with fatigue, pallor, sore throat, and petechiae, presenting with thrombocytopenia (low platelet count), and leukopenia (low White Blood Cell (WBC) count)?

Most Likely Diagnosis: Aplastic Anemia

The most likely diagnosis is aplastic anemia (option c), given the combination of pancytopenia (thrombocytopenia and leukopenia), constitutional symptoms (fatigue, pallor), and bleeding manifestations (petechiae, sore throat) in the absence of features suggesting primary hematologic malignancy. 1, 2

Diagnostic Reasoning

Why Aplastic Anemia is Most Likely

• Pancytopenia pattern: The presence of both severe thrombocytopenia (15,000/μL) and leukopenia (3,800/μL) indicates bone marrow failure affecting multiple cell lines, which is the hallmark of aplastic anemia 3, 4

• Clinical presentation: Fatigue and pallor suggest anemia (the third cytopenia likely present), while petechiae reflect severe thrombocytopenia and sore throat may indicate neutropenia with increased infection susceptibility 1, 2

• Bone marrow failure encompasses aplastic anemia: While "bone marrow failure" (option d) is technically correct as an umbrella term, aplastic anemia is the specific acquired bone marrow failure syndrome most commonly presenting with this clinical picture 3, 4

Why Other Options Are Less Likely

ITP (option a) is unlikely because:

• ITP presents with isolated thrombocytopenia, not pancytopenia 5, 1
• The American Society of Hematology guidelines emphasize that ITP diagnosis requires normal hemoglobin and WBC count 5
• The presence of leukopenia (WBC 3,800) excludes isolated ITP 5, 1

Leukemia (option b) is less likely because:

• Leukemia typically presents with elevated WBC counts (often >100 × 10⁹/L in CML chronic phase), not leukopenia 5
• The clinical presentation lacks features suggesting leukemia such as hepatosplenomegaly, lymphadenopathy, or bone pain 5
• While acute leukemia can present with pancytopenia, the absence of these additional features makes it less probable 5

Essential Next Steps

Immediate Laboratory Evaluation Required

• Peripheral blood smear examination to confirm true cytopenias, assess for abnormal cells, and evaluate red cell morphology 1, 2

• Complete blood count with differential to document the degree of anemia (the third expected cytopenia) and assess absolute neutrophil count 1, 2

• Reticulocyte count to distinguish between decreased production (expected in aplastic anemia, typically 0.1-2%) versus increased destruction 3

Definitive Diagnostic Test

• Bone marrow aspiration and biopsy is mandatory for diagnosis 2, 3, 4
  • Aplastic anemia shows hypocellular marrow (typically <25% cellularity) with fatty replacement 3, 4
  • This distinguishes aplastic anemia from other causes of pancytopenia like megaloblastic anemia (hypercellular marrow) or leukemia (abnormal cells) 3

Additional Testing to Consider

• Liver and renal function tests to exclude secondary causes of pancytopenia 2

• HIV testing if risk factors present, as HIV can cause pancytopenia 1, 2

• Vitamin B12 and folate levels to exclude megaloblastic anemia, which was the most common cause of pancytopenia (33%) in one large series 3

Critical Pitfalls to Avoid

• Do not assume isolated ITP when other cytopenias are present; this delays diagnosis of potentially life-threatening conditions like aplastic anemia 1, 4

• Do not delay bone marrow examination when unexplained pancytopenia is present, especially with clinical suspicion for bone marrow failure or malignancy 2, 4

• Do not overlook drug-induced causes: Obtain detailed medication history including recent exposures to chemotherapy, antibiotics, or other marrow-suppressive agents 1, 2

• Consider Evans syndrome (autoimmune hemolytic anemia plus immune thrombocytopenia) if direct Coombs test is positive, though leukopenia would be atypical 6, 7