Will the White Blood Cell (WBC) count be different in a patient with myeloperoxidase (MPO) deficiency?

WBC Count in Myeloperoxidase (MPO) Deficiency

The total WBC count is typically normal in patients with MPO deficiency, but automated hematology analyzers will frequently report falsely low neutrophil counts (pseudoneutropenia) with falsely elevated monocyte or large unstained cell (LUC) counts due to misclassification of MPO-deficient neutrophils. 1, 2

Understanding the Analyzer Artifact

The key issue is not an actual change in WBC production or count, but rather a technical artifact in how automated analyzers classify white blood cells:

• Automated analyzers like the ADVIA 2120i identify neutrophils based on their myeloperoxidase staining properties and calculate a mean peroxidase index (MPXI). 1

• When MPO deficiency is present, neutrophils lack normal peroxidase activity and are incorrectly counted as monocytes, resulting in pseudoneutropenia with falsely elevated monocyte counts. 1, 2

• In partial MPO deficiency (MPOp), automated counts show monocyte dominance (33.2%±21.3%), while manual differential reveals normal neutrophil predominance (66.63%±12.31%). 2

• In total MPO deficiency (MPOt), automated analyzers report large unstained cells (LUC) as the dominant population (72.6%±8.64%), which are actually normal neutrophils that fail to stain properly. 2

Diagnostic Clues to Recognize MPO Deficiency

The hallmark finding is a markedly low MPXI value below -20 combined with abnormally high automated monocyte or LUC counts. 1

Key diagnostic features include:

• Discrepancy between automated differential (showing high monocytes/LUC with low neutrophils) and manual differential (showing normal neutrophil predominance). 1, 2

• Normal total WBC count with the abnormal differential pattern. 2

• No clinical signs of true severe neutropenia (no recurrent infections in most cases). 1, 3

Clinical Implications and Pitfalls

The critical pitfall is misinterpreting the automated analyzer results as true severe neutropenia, which could lead to unnecessary therapy, invasive workup, or inappropriate treatment delays. 1

Important considerations:

• Always perform a manual differential count when automated results show unexplained neutropenia with elevated monocytes or LUC, especially with low MPXI values. 1, 2

• MPO deficiency can be hereditary (complete deficiency) or acquired (partial deficiency), with acquired forms associated with preleukemia, diabetes mellitus, and thrombotic diseases. 4, 5

• In preleukemia patients, partial MPO deficiency occurs in approximately 48% of cases (11 of 23 patients) and represents a useful diagnostic criterion. 5

• Despite the enzyme deficiency, most MPO-deficient patients do not show increased susceptibility to infection, as the cells retain normal or even enhanced phagocytic function. 3

Functional Consequences

MPO-deficient neutrophils actually demonstrate enhanced phagocytosis (>200% of normal) and prolonged superoxide production compared to normal neutrophils. 3

This compensatory mechanism explains why:

• Most patients with hereditary MPO deficiency remain asymptomatic without increased infection risk. 3, 5

• The absence of MPO removes a negative modulator of phagocytic receptor function, resulting in hyperactive rather than hypoactive neutrophils. 3