Red cell indices in adolescents with iron deficiency and heavy menstrual bleeding

Abstract Background: Iron deficiency (ID) and iron deficiency anemia (IDA) are common in adolescents with heavy menstrual bleeding (HMB), yet IDA is classically characterized as a microcytic anemia—a feature that often appears late in the disease course. In the combined hematology-gynecology clinic at OHSU (Spots, Dots, & Clots Clinic), clinicians have observed that many adolescents with significant ID or IDA present without microcytosis on complete blood count (CBC), raising concern for underrecognition of ID when relying solely on red cell indices. Aims: This study aims to characterize red cell indices and ferritin levels in adolescents with HMB, determine the prevalence of normocytosis versus microcytosis in the context of ID and IDA, and inform future clinical evaluation strategies, particularly the utility of concurrent iron studies with CBCs in this population. Methods: This retrospective chart review includes patients aged 14–21 who presented for initial evaluation of HMB to the Spots, Dots, & Clots Clinic at OHSU between January 1, 2015, and January 1, 2023. Inclusion criteria required a CBC and ferritin value obtained within 3 months of the index visit. Patients who received a blood transfusion within 3 months of testing were excluded. Data collected included demographic information, presence of bleeding disorder or comorbidities, and laboratory parameters (CBC, ferritin, iron studies). Data abstraction was performed using EPIC and stored securely in a REDCap database. Descriptive statistics were used to analyze red cell indices, ferritin levels, and patterns of iron status. Pearson correlation was calculated to evaluate the relationship between MCV and ferritin levels. Results: Of the 182 patients evaluated, 105 met inclusion criteria. The median age was 15.0 years (range: 10.0 - 21.0). The median hemoglobin was 12.5 g/dL (range: 6.8–15.7), median mean corpuscular volume (MCV) was 86.5 fL (range: 60.4–98.2), and median ferritin was 12.4 ng/mL (range: 2.0–154.0). The proportion of patients who had anemia (Hgb <12) was 36.6%. Within this cohort, 52.5% had ferritin <15, 71.3% had ferritin <25, and 89.1% had ferritin <50. Most patients presented with normocytosis (defined as MCV between 78 and 100 fL) (77.2%) rather than microcytosis (defined as MCV <78 fL) (22.8%). Among the normocytic group, 44.9% had ferritin <15 ng/mL, compared to 78.3% in the microcytic group. Overall, a majority (89.1%) of patients had low ferritin, yet only 5.0% had an MCV <70 fL. A modest positive correlation was found between MCV and ferritin (r = 0.288), indicating that while lower MCV tends to be associated with lower ferritin, the relationship is weak. These findings suggest that MCV alone is an unreliable marker for iron deficiency, as a substantial proportion of patients with normal MCV values still had severely depleted iron stores. Conclusions: This study addresses an important diagnostic gap in evaluating adolescents with HMB. The findings suggest that normocytic indices are common among iron-deficient patients and support broader implementation of iron studies, regardless of CBC morphology. These results may inform clinical practice guidelines and help optimize early identification and treatment of ID and IDA, ultimately improving quality of life and reducing symptom burden in this vulnerable population.