Interpreting sulfhemoglobin and methemoglobin in patients with cyanosis: An overview of patients with M‐hemoglobin variants

Abstract

Introduction Methemoglobin (MetHb) and sulfhemoglobin (SHb) measurements are useful in the evaluation of cyanosis. When one or both values are elevated, additional analysis is important to establish the etiology of the disorder. Methemoglobinemia occurs from acquired or hereditary causes with diverse treatment considerations, while true sulfhemoglobinemia is only acquired and treatment is restricted to toxin removal. Some toxic exposures can result in a dual increase in MetHb and SHb. Hereditary conditions, such as M‐Hemoglobin variants (M‐Hbs), can result in increased MetHb and/or SHb values but are clinically compensated and do not require treatment if they are cyanotic but otherwise clinically well. Methods Herein, we report 53 hemoglobin variant cases that have associated MetHb and SHb levels measured by an adapted Evelyn‐Malloy laboratory assay method. Results Our data indicate M‐Hbs cause variable patterns of MetHb and SHb elevation in a fairly reproducible pattern for the particular variant. In particular, α globin chain M‐Hbs can mimic acquired sulfhemoglobinemia due to an isolated increased SHb value. Conclusion If the patient appears clinically well other than cyanosis, M‐Hbs should be considered early in the evaluation process to differentiate from acquired conditions to avoid unnecessary testing and treatment regimens and prompt genetic counseling.

Recommendations for diagnosis and treatment of methemoglobinemia

“…In methemoglobinemia associated with hemoglobin disorders, both HbM and unstable Hb, MB and ascorbic acid treatment are ineffective and should be avoided 25,71 . The reducing ability of erythrocytes is normal and iron oxidation is stabilized by globin chains.…”

“…Some unstable Hbs, such Hb Cheverly, Hb Evans, may allow water to enter the homophobic heme pocket during stressor events, thus methemoglobinemia is only intermittent. If significantly elevated, these subgroup of unstable Hbs could respond to MB 25 Ascorbic Acid …”

“…In methemoglobinemia associated with hemoglobin disorders, both HbM and unstable Hb, MB and ascorbic acid treatment are ineffective and should be avoided. 25 , 71 The reducing ability of erythrocytes is normal and iron oxidation is stabilized by globin chains. In patients who have developed polycythemia, phlebotomy is not recommended as higher erythrocyte mass allows provision of normal tissue oxygenation.…”

Understanding pulse oximetry in hematology patients: Hemoglobinopathies, racial differences, and beyond

“…More than 1000 hemoglobinopathies have been identified, though the majority of hemoglobinopathies do not affect oxygenation 24 . Hemoglobin variants resulting in reduced oxygenation (SpO 2 and/or SaO 2 ) through low oxygen affinity, unstable hemoglobins or methemoglobin are rare and often only published in case reports or small case series 25,26 . Although rare, unexpectedly abnormal SpO2 in these patients can lead to confusion and unnecessary series of cardiorespiratory investigations 24,27 …”

Neonatal cyanosis with Hb St Mandé, a low O2 affinity hemoglobin variant affecting β‐globin

“…To our knowledge, we provided here for the first time, an exhaustive description of a neonatal isolated cyanosis due to Hb St Mandé and more generally to a β variant, while some cases have been published within mutation of γ-globin 5 or α-globin, 6 and two infants with β variants were only mentioned in a recent publication. 7 When patients are unexpectedly found to have low SpO 2 with no sign of respiratory or cardiac failure, such condition should be suspected in order to avoid unnecessary investigations. Pulse oximetry is a simple, noninvasive tool used to estimate a patient's arterial blood oxygen saturation.…”