Hydroxocobalamin mimicking intravascular hemolysis in therapeutic plasma exchange

Abstract

A 58-year-old man developed cardiogenic shock 12 months after undergoing orthotopic heart transplant. On hospital day 0, a heart biopsy was performed and mixed antibody-and cellular-mediated rejection was diagnosed. Underdosing of his immunosuppressive medication was suspected, as the patient reported compliance with his medication regimen and had no other recent illnesses. After failing to improve with methylprednisolone, intravenous immunoglobulin, thymoglobulin, and mycophenolate mofetil, therapeutic plasma exchange (TPE) was requested as part of management of the antibody-mediated rejection. A series of five TPE was planned, exchanging one plasma volume using plasma as the replacement fluid (Spectra Optia Apheresis System, Terumo BCT, Lakewood, Colorado). 1 Donor plasma was chosen as the replacement fluid due to extracorporeal membrane oxygenation requirement and the possible need for emergent surgical intervention. Within minutes of initiating the first TPE, the patient's waste plasma was noted to have a reddish-brown discoloration, as typically seen in patients with intravascular hemolysis (Figure 1). A review of the patient's medical record revealed that hydroxocobalamin 5000 mg had been administered intravenously approximately 24 hours previously to treat vasoplegic syndrome (VS). VS is defined as "hypotension with evidence of endorgan hypoperfusion in the presence of normal or elevated cardiac output" and is typically treated with vasopressors. 2 Hydroxocobalamin, also known as vitamin B12, is a nitric oxide scavenger that has an emerging role as an adjunct therapy for VS not responsive to vasopressors. Hydroxocobalamin is known to cause red or purple discoloration of plasma and urine, which may result in interference with clinical laboratory assays that rely on colorimetric methodologies. 3-5 Intravascular hemolysis was excluded by a stable hemoglobin (9.0 g/ dL pre-TPE, 8.9 g/dL post-TPE). Although post-TPE total bilirubin was mildly elevated at 1.3 mg/dL (reference range: 0.1-0.9 mg/dL), indirect bilirubin was 0.5 mg/dL (reference range 0.1-0.6 mg/dL), and lactate dehydrogenase was mildly elevated but stable at 388 IU/L compared to 376 IU/L pre-TPE (reference range: 125-240 IU/L). Haptoglobin was not measured. Apheresis providers should be aware that hydroxocobalamin may cause discoloration of waste plasma that mimics intravascular hemolysis.