Unexpectedly low pulse oximetry measurements associated with variant hemoglobins: A systematic review
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Pulse oximetry estimates arterial blood oxygen saturation based on light absorbance of oxy- and deoxy-hemoglobin at 660 and 940 nm wavelengths. Patients with unexpectedly low SpO₂ often undergo cardio-pulmonary testing to ascertain the cause of their hypoxemia. However, in a subset of patients, a variant hemoglobin is responsible for low SpO₂ measurements. The extent of this problem is unclear. We performed a systematic literature review for reports of low SpO₂ associated with variant hemoglobins. We also reviewed unpublished cases from an academic hemoglobin diagnostic reference laboratory. Twenty-five publications and four unpublished cases were identified, representing 45 patients with low SpO₂ and confirmed variant hemoglobin. Fifty-seven family members of patients had confirmed or suspected variant hemoglobin. Three low oxygen affinity variant hemoglobins had concordantly low SpO₂ and SaO₂. Eleven variant hemoglobins were associated with unexpectedly low SpO₂ measurements but normal SaO₂. Hemoglobin light absorbance testing was reported in three cases, all of which showed abnormal absorption spectra between 600 and 900 nm. Seven other variant hemoglobins had decreased SpO₂, with unreported or uncertain SaO₂. Twenty-one variant hemoglobins were found to be associated with low SpO₂. Most variant hemoglobins were associated with spuriously low SpO₂. Abnormal absorption spectra explain the discrepancy between SpO₂ and SaO(2) for some variants. The differential diagnosis of possible variant hemoglobin ought to be considered in asymptomatic patients found to have unexpectedly low SpO₂. The correct diagnosis will help to spare patients from unnecessary investigations and anxiety.
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