title: Unexpectedly low pulse oximetry measurements associated with variant hemoglobins: a systematic review.
abstract: 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 We also reviewed unpublished cases from an academic hemoglobin diagnostic reference laboratory. Twenty-five publications and four unpublished cases were identified, representing 45 patients with low SpO₂ and confirmed variant hemoglobin.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.
authors.affiliation: Section of Hematology and Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. verhovm@mcmaster.ca
authors.forename: Madeleine
authors.initials: M
authors.lastname: Verhovsek
authors.forename: Matthew P A
authors.initials: MP
authors.lastname: Henderson
authors.forename: Gerard
authors.initials: G
authors.lastname: Cox
authors.forename: Hong-yuan
authors.initials: HY
authors.lastname: Luo
authors.forename: Martin H
authors.initials: MH
authors.lastname: Steinberg
authors.forename: David H K
authors.initials: DH
authors.lastname: Chui
mesh_terms: D003937:Diagnosis, Differential; D014644:Genetic Variation; D006453:Hemoglobinopathies / Q000175:diagnosis; D006454:Hemoglobins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D010092:Oximetry / Q000706:statistics & numerical data*
chemical_list: D006454:Hemoglobins