We recently received a venous blood sample for blood gas analysis from the operation room. We analyzed the specimen according to manufacturer’s instructions on the ABL800 FLEX blood gas instrument (Radiometer, Copenhagen, Denmark). Multiple error codes were present for the results of ctHb, sO2, FO2Hb, FCOHb, FHHb, and FMetHb. Text messages accompanying the report read, “Detection of SHb” and “OXI spectrum mismatch.” The sample was re-tested on the ABL800 but the same error codes were flagged.
A closer look at the patient’s chart revealed that patient is heterozygous for hemoglobin M-Saskatoon variant, which causes the replacement of histidine by tyrosine in position 63 on the beta chain of hemoglobin (beta codon 63, CAT>TAT/His63Tyr). This renders the NADH methemoglobin reductase system incapable of reducing oxidized iron. A group of mutations in the globin chain gene can result in such dysfunction of ferric iron reduction and are referred to as methemoglobin forming hemoglobin variants (Hgb M).
HbM variants usually have a different absorbance spectrum from the physiologic methemoglobin. Modern day CO-oximeters use more than 100 wavelengths and can detect most unknown substances. We speculated that Hgb M in the patient is the reason the ABL800 reported error codes. The clinical team collected another venous blood sample and it was tested on the GEM5000 blood gas instrument (Instrumentation Laboratory, Bedford, MA, USA). This specimen also reported with error codes.
Non-invasive pulse-oximetry devices use two wavelengths (660 nm and 940 nm) to calculate hemoglobin oxygen saturation based on oxyhemoglobin and deoxygenated hemoglobin, and thus are unable to report interferences from dyshemoglobins. In a nut shell, Hgb M variants can possibly interfere with CO-oximetry measurements. Caution is needed to interpret the results. Pulse oximetry usage should be avoided for these patients.
- Schiemsky T, Penders J, Kieffer D. Failing blood gas measurement due to methemoglobin forming hemoglobin variants: acase report and review of the literature. Acta Clin Belg. 2016 Jun;71(3):167-70.
- Stucke AG, Riess ML, Connolly LA. Hemoglobin M (Milwaukee) Affects Arterial Oxygen Saturation and Makes Pulse Oximetry Unreliable. Anesthesiology 4 2006, Vol.104, 887-888.
-Jayson Pagaduan, PhD, is a senior year clinical chemistry fellow Texas Children’s Hospital in Houston, TX.
-Jing Cao, PhD, DABCC, FACB, is a board-certified clinical chemist, serving as the Associate director of Clinical Chemistry at Texas Children’s Hospital in Houston, TX and an Assistant Professor of Pathology and Immunology at Baylor College of Medicine.