What is the typical blood picture in a patient with agranulocytosis?

Agranulocytosis Blood Picture

Defining Laboratory Features

Agranulocytosis is characterized by a peripheral absolute neutrophil count (ANC) below 0.5 × 10⁹/L (500 cells/μL), often accompanied by severe leukopenia with white blood cell (WBC) counts frequently dropping to 0.5-2.0 × 10³ cells/μL. 1, 2

Complete Blood Count Findings

White Blood Cell Parameters

• Severe leukopenia: WBC count typically ranges from 0.5-2.0 × 10³ cells/μL, though can be as low as 0.6 × 10³ cells/μL 3
• Profound neutropenia: ANC <0.5 × 10⁹/L by definition, with severe cases showing ANC of 0.0-0.1 × 10⁹/L 4, 5, 3
• Relative lymphocytosis: Lymphocytes may appear proportionally increased on differential count, though absolute lymphocyte count may be normal or decreased 6

Other Cell Lines

• Thrombocytopenia: May be present but is not a defining feature; when present, platelet counts typically range from 50,000-140,000/μL, occasionally dropping below 20,000/μL 6
• Anemia: Generally develops later in the clinical course if present, occurring in approximately 50% of cases 6
• Monocytopenia: Often accompanies the neutropenia 6

Peripheral Blood Smear Characteristics

Granulocyte Findings

• Marked reduction or complete absence of neutrophils on manual differential count 1, 2
• Absence of immature granulocytic forms (no left shift, no bands, no metamyelocytes) distinguishes this from other causes of neutropenia 6
• No toxic granulation or Döhle bodies unless concurrent infection is present 6

Morphologic Features

• Normal red blood cell morphology in most cases, unless concurrent nutritional deficiency or other pathology exists 6
• Normal platelet morphology when platelets are present 6
• Absence of blasts on peripheral smear (presence of blasts would suggest acute leukemia rather than agranulocytosis) 6

Bone Marrow Findings

Cellular Composition

• Normocellular or hypercellular marrow is typical, distinguishing drug-induced agranulocytosis from aplastic anemia 6, 3
• Marked reduction or absence of mature granulocytes with preservation of early myeloid precursors in some cases 6
• Maturation arrest at the promyelocyte or myelocyte stage may be observed 2
• Normal erythroid and megakaryocytic lineages unless concurrent pathology exists 6

Key Distinguishing Features

• No evidence of malignancy (no increased blasts, no dysplasia) 3
• No fibrosis (unlike myelofibrotic disorders) 6
• No hypocellularity (unlike aplastic anemia, which shows hypocellular marrow <25% cellularity) 6

Associated Laboratory Abnormalities

Biochemical Markers

• Elevated hepatic transaminases (ALT, AST) may be present, particularly with certain causative drugs 6, 4
• Elevated lactate dehydrogenase (LDH) may occur with cell turnover 6
• Normal or elevated serum ferritin (not decreased, as iron stores are typically adequate) 6

Inflammatory Markers

• Elevated C-reactive protein (CRP) if concurrent infection is present 7
• Positive blood cultures in 20-30% of febrile cases with agranulocytosis 1, 7

Critical Diagnostic Thresholds

Severity Classification

• Mild neutropenia: ANC 1,000-1,500/μL (not agranulocytosis) 4
• Moderate neutropenia: ANC 500-1,000/μL (not agranulocytosis) 4
• Agranulocytosis: ANC <500/μL by definition 1, 2
• Severe agranulocytosis: ANC <100/μL, associated with highest infection risk and mortality 1, 7

Common Pitfalls in Interpretation

Avoiding Misdiagnosis

• Do not confuse with aplastic anemia: Agranulocytosis shows normocellular/hypercellular marrow with isolated granulocyte depletion, while aplastic anemia shows pancytopenia with hypocellular marrow (<25% cellularity) 6
• Do not confuse with acute leukemia: Agranulocytosis lacks blasts on peripheral smear and bone marrow, whereas acute leukemia shows ≥20% blasts 6
• Do not confuse with myelodysplastic syndrome: MDS shows dysplastic changes in multiple cell lines and may have cytogenetic abnormalities, which are absent in drug-induced agranulocytosis 6

Timing Considerations

• Peak incidence occurs within first 3 months of drug exposure for most causative agents 5, 1
• Recovery typically begins 5-10 days after discontinuation of the offending drug, with complete recovery by 2-3 weeks in most cases 3, 1
• Monitoring must continue for 4 weeks after drug discontinuation, as agranulocytosis can persist 4, 8