Abstract
Introduction
Hypoglycemia is a potentially life-threatening condition. However, a low laboratory glucose value does not always represent true systemic hypoglycemia. Artifactual hypoglycemia is a preanalytical phenomenon caused by ongoing in vitro glucose consumption by metabolically active blood cells before sample processing. It is particularly likely with marked leukocytosis and delayed separation of serum or plasma from cellular components.
Case Info
A 54-year-old man with a history of HIV and rectal adenocarcinoma on chemotherapy presented to our outpatient clinic for routine follow-up. He had seen his HIV Nurse Practitioner the day before and had routine lab monitoring ordered to include a CBC and BMP. Laboratory evaluation from the previous day revealed an elevated WBC of 653000/µL, increased from a baseline of ~4,000/µL (normal range of 4000 to 11000 /uL) with predominant neutrophilia. A basic metabolic panel showed low serum glucose of 32 mg/dL (normal range 70-99 mg/dL), raising concern for level 2 hypoglycemia.
Discussion with his oncologist revealed that the patient had received prophylactic Filgrastim (G-CSF) to support his Bone marrow a few days earlier. He was asymptomatic with normal vital signs and denied diaphoresis, palpitations, weakness, confusion, or altered sensorium.
Repeat point-of-care fingerstick capillary glucose measured immediately was normal at 97 mg/dL. The patient was diagnosed with artifactual hypoglycemia related to marked leukocytosis due to G-CSF. No intervention was required, and glucose values remained normal on subsequent testing.
Disc Clinical
Hypoglycemia is an important clinical condition that can lead to autonomic and neuroglycopenic symptoms, which can be life-threatening. Hypoglycemia can be categorized as Level 1 hypoglycemia (Blood sugar 70 mg/dL but ≥54 mg/dL), Level 2 hypoglycemia (Blood sugar 54 mg/dL), or Level 3 hypoglycemia (requiring assistance).
Artifactual hypoglycemia is a false low blood glucose reading that can occur due to improper blood sample collection or consumption of glucose from an abundance of cells in the blood, such as leukocytes or erythrocytes. Risk factors for artifactual hypoglycemia include delayed sample processing and extreme leukocytosis. Our patient, unfortunately, did not have his CMP tube processed for about 8 hours, compounding the risk of artifactual hypoglycemia due to his leukocytosis.
G-CSF can induce marked neutrophilic leukocytosis. When leukocyte counts rise to 50,000–100,000/µL, rapid glycolysis by metabolically active leukocytes, as in our patient, can artifactually lower measured serum glucose, especially if blood samples are not processed promptly. This artifactual hypoglycemia is well described in leukemic blasts but can also occur with reactive neutrophilia.
Bedside fingerstick capillary glucose, which was normal in our patient, or immediate plasma fluoride-oxalate tube processing helps confirm the diagnosis. Capillary glucose fingerstick circumvents delayed processing and glucose consumption by Leukocytes, whereas Fluoride acts as a preservative and can inhibit glycolysis in leukocytes.
Conclusion
Artifactual hypoglycemia from leukocytosis is solely an in vitro phenomenon. It should be recognized promptly to avoid unnecessary dextrose administration, endocrine evaluation, and Emergency Department visits and hospitalizations, which can be costly.