Vitamin B6 deficiency: A cause of unexplained anemia in hospitalized patients in a tertiary care center Free

Introduction: Anemia is a frequent clinical problem in hospitalized patients. While iron, vitamin B12, and folate deficiencies are routinely investigated, vitamin B6 deficiency remains an under-recognized etiology. Pyridoxine deficiency can impair heme synthesis and lead to sideroblastic anemia. This study aims to evaluate the incidence of vitamin B6 deficiency among hospitalized patients with anemia in the absence of other known causes of anemia.

Methods: A retrospective study was conducted using the University of Florida's Integrated Data Repository (IDR) to identify adult inpatients (≥18 years) at UF Health Jacksonville (Downtown campus) from January 2020 to December 2023 who had serum vitamin B6 levels measured during their hospital admission. Data collected included demographics (age, sex), laboratory values (hemoglobin, MCV, ferritin, vitamin B12, folate, haptoglobin), and discharge diagnoses coded using ICD-10. Vitamin B6 deficiency was defined as a serum level <7.4 µg/L. Exclusion criteria included patients with ICD-10 codes for other known causes of anemia to reduce confounding: nutritional anemias (D53, E53.1, E53), iron deficiency anemia (D50), vitamin B12 or folate deficiency anemia (D51, D52), anemia of chronic disease or chronic kidney disease (D63.0, D63.1, D63.8, N18.9), hemolytic anemia (D59), aplastic and red cell aplasia (D60, D61), anemia unspecified (D64.9), and GI hemorrhage (K92.2). Data were stored securely and analyzed using Microsoft Excel.

Results: A total of 696 hospitalized patients met the inclusion criteria. Of these, 461 patients (66%) were vitamin B6 deficient by the defined cutoff. The mean age of the B6-deficient cohort was 49.8 years; 57% were male and 43% female. The lowest recorded hemoglobin in this cohort was 3.9 g/dL. Most B6-deficient patients had normocytic anemia; 73 patients (16%) had microcytosis and 37 (8%) were macrocytic. To account for confounding causes of anemia, we identified 68 patients with ferritin <30 ng/mL (suggestive of iron deficiency), 77 patients with vitamin B12 <300 pg/mL, three patients with folate <3 ng/mL, and three patients with haptoglobin <25 mg/dL (suggestive of hemolysis). These findings excluded a total of 91 patients who had a potential alternative cause of anemia. After accounting for these confounders, 370 (53%) patients remained with both vitamin B6 deficiency and unexplained anemia. Notably, most of these patients exhibited normocytic indices, contrary to the classically described microcytic sideroblastic pattern. Vitamin B6 replacement was not consistently prescribed in this cohort.

Conclusions: Vitamin B6 deficiency was common among hospitalized patients who had levels tested, with over half of patients showing concurrent anemia not attributable to other common causes. Most of these patients had normocytic anemia, which suggests that vitamin B6 deficiency may present atypically and may be under-recognized in clinical practice. These findings support the inclusion of vitamin B6 measurement in the diagnostic evaluation of unexplained anemia in the inpatient setting. Early identification and treatment of vitamin B6 deficiency, especially given its ease and safety of administration, may help avoid unnecessary workup or transfusion and improve patient outcomes.