Iron Deficiency without Anemia: A Common Yet Under-Recognized Diagnosis in Young Women with Heavy Menstrual Bleeding

Background Iron deficiency anemia is a common complication of heavy menstrual bleeding (HMB) in adolescents both with and without underlying bleeding disorders. As such, the Centers for Disease Control recommends screening young women with HMB for iron deficiency anemia annually. However, iron deficiency, even without anemia, is also associated with a variety of physical symptoms, including fatigue and decreased tolerance for exercise, as well as neuropsychological sequelae such as irritability, apathy, depressive symptoms, and decreased cognitive function and quality of life. Screening for iron deficiency is routinely tested in the primary care setting with point of care hemoglobin (Hgb) or complete blood count (CBC). However, these tests are unable to identify iron deficiency without anemia. Objectives Given the commonality of iron deficiency without anemia in adolescent females, the primary objective of this study was to determine the percentage of iron deficiency that would have been missed by screening with 1) Hgb or 2) CBC testing with MCV, as compared to performing screening ferritin levels, in a population of young women with HMB. Additionally, we examined potential risk factors contributing to iron deficiency, including age at diagnosis of HMB, presence of an underlying bleeding disorder, body mass index (BMI), and household income. Methods We retrospectively reviewed data for 114 adolescent females ages 9-19 years referred as new patients to the Young Women’s Hematology Clinic at Nationwide Children’s Hospital, Columbus, Ohio, for evaluation of HMB. Exclusion criteria included patients who did not have a CBC and ferritin drawn on the same day or within the preceding month and those patients with histories of prior transfusions, thrombocytopenia, or hemoglobinopathies. Iron deficiency was defined as ferritin <20 ng/mL, anemia as hemoglobin <12 g/dL, and microcytosis as MCV <80. Results The mean age of patients at evaluation for HMB was 14.3 (SD = 2.0) years of age, and 80 (70.2%) were ultimately diagnosed with an underlying bleeding disorder. Fifty-eight (50.9%) patients had ferritin levels indicating iron deficiency, twenty-nine (25.4%) patients were anemic, and 26 (23.9%) patients had microcytic MCV levels. To compare the sensitivities of a Hb vs. full CBC in detecting iron deficiency, only iron deficient patients with full CBC testing results (including an MCV) were included in the analysis (n=54). Of these 54 patients, Hgb correctly identified 42.6% (n=23) of iron-deficient patients vs. 46.3% (n=25) that were correctly identified with CBC (which could show either low hemoglobin and/or microcytosis). Though the CBC captured an additional 2 patients, this was not a statistically significant difference (p=0.5). Patients had significantly higher odds of having iron deficiency if they were overweight or obese [2.81, 95% CI: (1.25, 6.29)] when compared to patients with normal BMIs. Age at evaluation of HMB, the presence of an underlying bleeding disorder, and median household income were not significantly associated with iron deficiency. Discussion Iron deficiency with and without anemia remains a common yet treatable condition in adolescent females with HMB. Iron deficiency with and without anemia was found commonly in our patient population. Our study shows that screening Hgb or CBC alone may miss over half of patients with iron deficiency. We recommend serum ferritin in addition to Hgb as a screening tool for iron deficiency in adolescent females with HMB. Additionally, a higher index of suspicion for iron deficiency should be noted in adolescent females with an increased BMI. Primary care and specialty physicians caring for young women need to be aware that iron deficiency without anemia can lead to clinical symptoms and that adolescent females with HMB are at high risk for iron deficiency. Improved screening strategies will allow for earlier implementation of iron therapy and improvement of symptoms. Disclosures No relevant conflicts of interest to declare.