A data-driven framework for predicting PEG-defined MacroB12 in hypercobalaminemia.

Area of Science:

• Clinical Chemistry
• Diagnostic Immunology
• Hematology

Background:

• MacroB12 interference poses a diagnostic challenge for Vitamin B12 status.
• Accurate diagnosis is crucial, especially in hypercobalaminemia cases.

Purpose of the Study:

• To identify predictors of MacroB12.
• To quantify the diagnostic utility of pre-polyethene glycol (PEG) B12 levels.
• To establish a clinical and laboratory phenotype for suspected MacroB12.

Main Methods:

• Retrospective analysis of 875 individuals with hypercobalaminemia.
• Multivariable regression modeling and Receiver Operating Characteristic (ROC) analysis.
• Used multiple imputation for missing data and Abbott Alinity i platform.

Main Results:

• PEG-defined MacroB12 positivity associated with older age and autoimmune diagnosis.
• Higher hemoglobin and Mean Corpuscular Volume predicted MacroB12.
• Pre-PEG B12 had moderate discriminatory power (AUC=0.744); combined model improved prediction (AUC=0.802).

Conclusions:

• A clinical and laboratory phenotype for MacroB12 was defined.
• An optimal pre-PEG B12 threshold (1584.0 pg/mL) aids suspicion stratification but doesn't replace confirmatory testing.
• Confirmatory PEG precipitation is essential for accurate MacroB12 diagnosis, particularly in older patients and those with autoimmune disease.