These cases remind us that IgM monoclonal proteins (M-proteins) have earned a reputation as saboteurs of many laboratory assays owing to their self-aggregation, aggregation of latex particles, binding to analytes and reagents, and cryoprecipitation. One additional point is that some IgM M-proteins also play havoc with their own detection and measurement by electrophoretic techniques.
Student Discussion Document (pdf)
Stacey A. Simons, Alejandro R. Molinelli, Kimia Sobhani, Petrie M. Rainey, and Andrew N. Hoofnagle*
Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA
*Address correspondence to this author at: University of Washington Medical Center Department of Laboratory Medicine, 1959 NE Pacific Street, Box 357110, Seattle, WA 98195. Fax (206)598-6189; e-mail email@example.com.
Patient A was a 68-year-old woman with a history of lymphoplasmacytic lymphoma who presented after several weeks of mucosal bleeding. On admission, her cancer involved 95% of bone marrow cells. She was pancytopenic and febrile (38.3 °C). Leukocyte count was 0.39 × 103/μL (neutrophils, 0.03 × 103/μL), hematocrit 25%, platelet count 21 × 103/μL, relative serum viscosity 2.3 (reference interval, 1.4–1.8), blood urea nitrogen 6.4 mmol/L (18 mg/dL), creatinine 62 μmol/L (0.7 mg/dL), and estimated glomerular filtration rate >60 mL/min/1.73 m2. She had an IgMκ monoclonal component of 42.8 g/L. This patient was started on vancomycin 1 g intravenously (IV) every 12 h, ceftazidime 2 g IV every 8 h, and a course of chemotherapy. On day 3 after the beginning of antibiotic treatment, a trough specimen was collected for measurement of vancomycin. The concentration, measured with a Beckman Coulter Synchron competitive turbidimetric immunoassay, was <0.1 mg/L. The result, which was incompatible with ongoing vancomycin therapy, signaled a problem to the technologist. No analytical issues were evident upon review of calibration, controls, and results for other chemistry tests performed on the same specimen. In an attempt to resolve an apparent falsely low result, a 1:1 mix of the specimen was made with the Beckman liquid comprehensive control serum (level 3, 30.4 mg/L) and demonstrated near complete recovery (result of mix after adjusting for dilution, 28.6 mg/L). However, a 1:1 mix with pooled patient serum containing vancomycin (11 mg/L) led to only 15% recovery (result of mix after adjustment for dilution, 1.7 mg/L). The specimen was subsequently sent to another laboratory, where a vancomycin concentration of 9.8 mg/L was measured by use of a competitive enzyme-linked immunoassay (Emit, Olympus).
Patient B was a 64 year-old woman with a history of non-Hodgkin lymphoma admitted for stem cell transplantation. Her hospital course included acute renal failure, mental status changes, and disseminated intravascular coagulation. Leukocyte count was 2.18 × 103/μL (neutrophils 1.79 × 103/μL), hematocrit 28%, platelet count 7 × 103/μL, blood urea nitrogen 23 mmol/L (64 mg/dL), creatinine 160 mmol/L (1.8 mg/dL), and estimated glomerular filtration rate of 22 mL/min/1.73 m2. She had an IgMλ monoclonal component of 10.0 g/L, with decreased normal gammaglobulins. This patient was started on vancomycin 750 mg IV every 24 h and imipenim-cilastatin 250 mg IV every 8 h for fever of unknown origin (38.2 °C). On day 2, a vancomycin trough specimen was collected just before administration of the second dose. The result was suppressed by the analyzer, which reported “reaction rate high,” i.e., faster than would be seen even in the absence of vancomycin. Calibration, controls, and the day’s vancomycin test results were reviewed and showed no problems. The inappropriate reaction rate repeated with dilution, and also occurred with analysis of 2 other specimens from patient B. The specimen was subsequently sent to another laboratory, where a vancomycin concentration of 6.9 mg/L was measured with a competitive enzyme-linked immunoassay (Emit, Ortho-Clinical).
Questions to Consider
- What might have caused the problems in measuring vancomycin observed in these two patients?
- What other laboratory tests might demonstrate interferences for these patients?
- What are the recommendations for monitoring vancomycin?
Final Publication and Comments
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