Recreational use of nitrous oxide resulting in severe B12 deficiency, pancytopenia and hemolytic anemia Free

Introduction: B12 deficiency is often seen in pernicious anemia, gastric surgeries, and strict vegetarian/vegan, but there are an increasing number of young, healthy patients presenting with severe pancytopenia secondary to vitamin B12 deficiency from excessive recreational nitrous oxide use. Approximately 6% of people aged less than 60 and 20% of adults older than 60 are vitamin B12 deficient in the U.S. and UK1, compared to 42.2% of recreational nitrous oxide users, who have a circulating concentration of total vitamin B12 lower than the reference interval2. The psychophysiology of vitamin B12 deficiency from excessive nitrous oxide is due to oxidation of cobalt in vitamin B12 (cobalamin), which irreversibly inactivates the cobalamin; hence, it is unable to function as a coenzyme.

Case description We present a case of a 24-year-old female with a past medical history of iron deficiency anemia, substance-use disorder including fentaNYL abuse and recreational nitrous oxide presented to the emergency department with shortness of breath, weakness, fatigue, and recurrent fevers, chills, myalgia, and lightheadedness. Vitals: BP 107/56 HR 56 RR 18 T 98.4 F 100 % on room air. Exam with a pale, ill-appearing female and no focal neurological deficit. Labs with WBC 3.2 (ANC 0.6, slight left shift), hemoglobin 3.5 on arrival (MCV 94) with prior baseline of 12.4 in 2021, platelet 15. Reticulocyte absolute 0.02. D-dimer 7.32, INR 1.4, PTT 26, fibrinogen 196. AST 56, ALT 20, total bilirubin 1.4, direct bilirubin 0.6, indirect 0.8, ALP 35. Cr 0.79.

Patient tested negative for Treponema pallidum, strep pneumoniae, Legionella, mycoplasma, influenza, HIV, RSV. Antibody screen negative on blood bank testing. CT head was unremarkable. CT chest abdomen pelvis showed minimal early/developing infectious changes in the left upper lobe of the lung, mild periportal edema in the liver, and small amount of pelvic ascites. Patient started on vancomycin and cefepime for septic shock.

Patient was admitted to the ICU and received 2U PRBC and 1 unit platelets. Hemoglobin improved to 7.7. Peripheral blood smear revealed severe normocytic anemia with circulating nuclear cells and rare schistocytes, marked absolute neutropenia with left-shifted neutrophils show toxic changes and marked absolute monocytopenia, eosinophilia, and basophilia, severe thrombocytopenia. Hemolysis labs with haptoglobin < 10 (30-200) and LDH 1800 (135-214). Inappropriately low reticulocyte count 2.3. B12 level is undetectably low. A bone marrow biopsy was performed which showed pancytopenia. Severe vitamin B12 deficiency is likely related to persistent Whippet use, which ultimately led to pancytopenia and hemolytic anemia. Patient was treated with a vitamin B12 supplement, and discharged on hospital day 5.

Follow-up with PCP in a week showed improvement of all cell counts with complete blood count showed hemoglobin 11.5, WBC 5.6 and platelets of 155

Discussion

Patients with excessive recreational nitrous oxide use are at greater risk of developing severe vitamin B12 deficiency and can present with pancytopenia, hemolytic anemia, and exonal neuropathy. For many patients, stopping recreational nitrous oxide and supplementing vitamin B12 is sufficient to improve pancytopenia, but prolonged deficiency of vitamin B12 can lead to permanent axonal damage. This case highlights the importance of recognizing vitamin B12 deficiency in recreational nitrous oxide users, and preventing hematological and long-term neurological complications.