What is the diagnosis for a patient with leukopenia (White Blood Cell count of 4.5), macrocytosis (Mean Corpuscular Volume of 101.2), and thrombocytopenia (Platelet count of 128)?

Diagnostic Evaluation: Pancytopenia with Macrocytosis

This patient presents with pancytopenia (mild leukopenia, thrombocytopenia) and macrocytosis (MCV 101.2), which most likely represents megaloblastic anemia due to vitamin B12 or folate deficiency, though other causes including myelodysplastic syndrome, alcohol use, liver disease, and medication effects must be excluded. 1, 2, 3

Immediate Diagnostic Steps

Confirm True Cytopenias

• Examine peripheral blood smear immediately to rule out pseudothrombocytopenia from platelet clumping in EDTA (occurs in 0.1% of adults) and to assess for oval macrocytes, hypersegmented neutrophils, and platelet clumps 4, 1, 5
• Look specifically for oval macrocytes and hypersegmented neutrophils (>5 lobes), which strongly suggest megaloblastic anemia 2, 3

Essential Laboratory Testing

• Vitamin B12 and folate levels are the most reliable criteria for diagnosing megaloblastic anemia and should be obtained before initiating therapy 2, 3
• Reticulocyte count to assess bone marrow response (typically low in megaloblastic anemia) 2, 3
• Comprehensive metabolic panel including liver function tests 3
• Thyroid-stimulating hormone (TSH), as hypothyroidism causes macrocytosis 3
• HIV testing, as HIV infection is commonly associated with thrombocytopenia and cytopenias 4, 1

Clinical History Priorities

Medication Review

• Screen for drugs causing thrombocytopenia: heparin, quinidine, sulfonamides, aspirin, alcohol 4, 1
• Assess for chemotherapy exposure, immunosuppressants (azathioprine causes macrocytosis and leukopenia), or other myelosuppressive agents 4, 3

Targeted History Elements

• Alcohol consumption (most common cause of macrocytic anemia in adults) 3
• Dietary intake of folate-rich foods and B12 sources 2, 3
• Bleeding symptoms: type, severity, duration (petechiae, mucosal bleeding, menorrhagia) 4
• HIV risk factors 4, 1
• Symptoms of autoimmune disease (arthralgias, rash, alopecia) 4
• Neurologic symptoms (paresthesias, ataxia suggesting B12 deficiency) 2
• Weight loss, fever, night sweats (suggesting malignancy) 4

Physical Examination Focus

• Absence of splenomegaly (present in <3% of ITP cases; if present, suggests alternative diagnosis like lymphoproliferative disorder or liver disease) 4
• Signs of liver disease or lymphadenopathy 4, 1
• Neurologic examination for posterior column deficits (B12 deficiency) 4
• Bleeding manifestations: petechiae, purpura, mucosal bleeding 4

Differential Diagnosis Algorithm

Most Likely: Megaloblastic Anemia

The combination of macrocytosis (MCV 101.2), mild leukopenia, and thrombocytopenia is classic for megaloblastic anemia 2, 3

• If B12 or folate levels are low: Proceed with Schilling test (for B12), gastric analysis, or small bowel imaging to identify malabsorption 2
• If serum levels unavailable: Initial treatment should include both vitamins, especially if anemia is severe 2

Alternative Diagnoses to Exclude

Myelodysplastic Syndrome (MDS)

• Consider if patient is older, has refractory cytopenias, or atypical features 3
• Bone marrow aspirate and biopsy with cytogenetics required for diagnosis 4, 1, 3
• Particularly suspect in adolescents/young adults with monosomy 7 or trisomy 8 (may indicate germline GATA2 mutation) 4

Alcohol-Related

• Most common cause of macrocytic anemia in adults 3
• Associated with liver disease and direct bone marrow suppression 4

Medication-Induced

• Azathioprine causes macrocytosis and can cause pancytopenia 4
• Review all medications for myelosuppressive effects 1, 3

Hereditary Thrombocytopenia Syndromes

• ETV6 mutations (THC5): thrombocytopenia, macrocytosis, leukemia predisposition 4
• RUNX1 mutations (FPD/AML): thrombocytopenia with leukemia risk 4
• GATA2 deficiency: cytopenias, infections, MDS/AML risk 4

Management Based on Severity

Platelet Count 128 × 10⁹/L (Mild Thrombocytopenia)

• Outpatient management appropriate with no prophylactic platelet transfusion needed 4, 1
• Spontaneous serious bleeding is rare (<5%) with platelets >100 × 10⁹/L 4
• Safe for most procedures: central line placement requires >20 × 10⁹/L, lumbar puncture requires >50 × 10⁹/L 4, 1

WBC 4.5 × 10⁹/L (Borderline Low-Normal)

• Not severely leukopenic, but monitor for infection risk 6
• If neutrophil count <1.0 × 10⁹/L, infection risk increases significantly 4

Critical Pitfalls to Avoid

• Failing to examine peripheral blood smear before pursuing extensive workup 1, 5
• Missing medication-induced causes, especially heparin and common antibiotics 4, 1
• Overlooking alcohol use as the most common cause of macrocytic anemia 3
• Initiating therapy before obtaining B12/folate levels, which makes retrospective diagnosis difficult 2
• Assuming ITP without excluding other causes, particularly when macrocytosis is present 4, 1