The Diagnosis of Sulfated Hemoglobin (SulfHb) Secondary to Sulfur Dioxide Poisoning Using Matrix-Assisted Laser Desorption Time-of-Flight Mass Spectrometry (MALDI-ToF MS)—A Novel Approach to an Unusual Clinical Problem

Abstract

Sulfhemoglobinemia is a rare entity caused by irreversible sulfation of the heme moiety in haemoglobin to form sulfated haemoglobin (SulfHb) and has been caused by H2S arising from certain metabolites of drugs and bacterial infection. Clinical presentation is similar to that of methemoglobin (MetHb). Furthermore, it is often difficult to distinguish between the diagnosis of SulfHb from MetHb in arterial blood gas analysers due to the broad overlap in the optical density (OD) absorption spectra—that of SulfHb swamping the more distinct OD absorption shift seen with MetHb. The presence of SulfHb was suspected in a 73-year-old lady with low oxygen saturation (SaO2 ~75%), central cyanosis, and normal arterial oxygen partial pressure (pO2 ~12 kPa). Repeated arterial blood gas analysis on different systems returned error messages for MetHb quantification. There was an improvement in oxygen saturation and cyanosis after an exchange transfusion. A full OD spectrophotometry (500−700 nm) of the patient’s whole blood was suggestive of the presence of SulfHb, with a minor peak absorption at 620 nm. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF MS) was undertaken on whole blood samples from the patient pre- and post-transfusion, alongside normal controls. These demonstrated the presence of SulfHb in the patient’s blood, identifying sulfur, sulfur monoxide, and sulfur dioxide bound to the heme moiety. This gave vital identification as to the cause of Hb sulfation, which was distinct from that previously reported. Levels fell after the exchange transfusion and were completely eradicated after the correct source, an Epsom Salts constipation tonic, was identified. MALDI-ToF mass spectrometry is a new, rapid, specific, and sensitive diagnostic test for rare hematological syndromes such as SulfHb. In addition, it can identify the specific compounds bound to heme. Here, we provide useful diagnostic evidence as to the source of SulfHb, which was via SO2 rather than the previously described H2S.

Keywords

• sulfated haemoglobin
• methb sulfhb diagnosis
• mass spectrometry
• maldi-tof ms
• oxygen saturation
• arterial blood gas analysers