Iron-Deficiency Anemia from Menorrhagia with Reactive Thrombocytosis
This patient has iron-deficiency anemia secondary to heavy menstrual bleeding, and the leukopenia is likely spurious or reactive rather than a primary hematologic disorder. The combination of menorrhagia, fatigue, headaches, brain fog, low MCHC, and leukopenia points to severe iron deficiency as the unifying diagnosis, with the leukopenia representing either a laboratory artifact from severe microcytosis or a transient reactive phenomenon that will resolve with iron repletion. 1, 2
Diagnostic Confirmation
Order serum ferritin and transferrin saturation immediately to confirm iron deficiency. A ferritin < 30 µg/L confirms depleted iron stores, while a ferritin < 15 µg/L provides 99% specificity for absolute iron deficiency. 3, 1, 2 Transferrin saturation < 20% is the decisive confirmatory marker, especially if ferritin falls in the 30–100 µg/L range where inflammation might falsely elevate it. 1, 2
Obtain a complete blood count with red-cell indices (MCV, MCH, MCHC, RDW) and an absolute reticulocyte count. Low MCHC together with low MCH indicates hypochromic anemia characteristic of iron deficiency. 1, 2 An elevated RDW > 14% combined with microcytosis strongly favors iron deficiency over thalassemia trait, which typically shows RDW ≤ 14%. 1, 2 The reticulocyte count will be low or inappropriately normal, reflecting inadequate bone marrow response to the anemia. 1
Check a peripheral blood smear to evaluate the reported leukopenia and assess red-cell morphology. Severe microcytosis can cause automated cell counters to misclassify small red cells as platelets or white cells, producing spurious leukopenia. 4 The smear will also confirm hypochromic, microcytic red cells and may reveal reactive thrombocytosis—a common finding in severe iron deficiency that peaks in the third week and can reach platelet counts > 1,000/µL. 5, 6
Key Laboratory Thresholds
- Ferritin < 30 µg/L = iron deficiency confirmed 3, 1, 2
- Transferrin saturation < 20% = iron-deficient erythropoiesis 1, 2
- RDW > 14% + low MCV = iron deficiency (not thalassemia) 1, 2
- Reticulocyte count low/normal = inadequate marrow response 1
Investigation of Menorrhagia
Quantify menstrual blood loss using a pictorial blood loss assessment chart, which has 80% sensitivity and specificity for detecting menorrhagia. 3 Women with menorrhagia lose an average of 5–6 mg of iron per cycle compared to 1 mg in women with normal menses, and iron losses strongly correlate with menstrual fluid volume. 7
Perform pelvic ultrasound to identify structural causes of heavy bleeding. Leiomyomas account for 47.9% of cases presenting with severe anemia from menorrhagia, and endometrial or cervical malignancy is detected in 4.8%. 6 Even though this patient is young, structural evaluation is mandatory because chronic excessive bleeding can mask serious pathology. 6
Do not assume menorrhagia fully explains the anemia without also investigating for gastrointestinal blood loss. All adult women with confirmed iron-deficiency anemia require upper endoscopy with duodenal biopsies and colonoscopy unless menstrual loss completely accounts for the severity and chronicity of anemia. 3, 2 Upper endoscopy excludes celiac disease (present in 2–3% of iron-deficiency anemia cases), gastric malignancy, and NSAID gastropathy. 3, 2 Colonoscopy rules out colonic carcinoma, polyps, and angiodysplasia. 3, 2
When to Pursue GI Evaluation
- All women with hemoglobin < 10 g/dL from iron deficiency warrant bidirectional endoscopy 3, 2
- Women > 45 years should receive full GI investigation regardless of menstrual history 3
- Women < 45 years with upper GI symptoms require upper endoscopy and small bowel biopsy 3
- Colonic investigation in women < 45 years only if specific indications exist 3
Immediate Treatment
Start oral iron supplementation immediately—ferrous sulfate 200 mg three times daily—while diagnostic workup proceeds. 3, 2 Alternative formulations include ferrous gluconate or ferrous fumarate if ferrous sulfate is not tolerated. 3, 2 Adding ascorbic acid enhances iron absorption and should be considered when response is poor. 3, 2
Expect hemoglobin to rise by ≥ 2 g/dL within 3–4 weeks; a rise of ≥ 10 g/L within 2 weeks confirms iron deficiency even when iron studies were equivocal. 3, 2 Failure to respond indicates poor compliance, continued blood loss, malabsorption, or misdiagnosis. 3, 2
Continue iron supplementation for 3–6 months after hemoglobin normalizes to replenish iron stores, targeting ferritin > 50 µg/L. 3, 2 Monitor hemoglobin and red-cell indices at three-monthly intervals for one year, then after a further year. 3, 2
Consider intravenous iron if oral iron is poorly tolerated, malabsorption is documented, or rapid repletion is required to prevent physiological decompensation. 2, 8 Parenteral iron is also indicated when ongoing iron losses exceed absorptive capacity or when the patient requires preoperative optimization for non-deferrable surgery. 8
Management of Menorrhagia
Initiate hormonal therapy to reduce menstrual blood loss while iron repletion proceeds. Combined oral contraceptives (ethinyl estradiol plus norethindrone) effectively reduce menstrual flow and were used successfully in a similar case of severe iron-deficiency anemia with reactive thrombocytosis. 5 Alternatively, levonorgestrel intrauterine system, tranexamic acid, or NSAIDs can reduce menstrual blood loss. 8
Refer to gynecology for definitive management of the underlying cause. If leiomyomas are identified, options include myomectomy, uterine artery embolization, or hysterectomy depending on the patient's age, fertility desires, and symptom severity. 6 Endometrial ablation may be appropriate for women who have completed childbearing. 8
Dual Management Approach
Treat both the iron deficiency and the heavy menstrual bleeding simultaneously. Gynecologists must take the lead in diagnosing, managing, and initiating treatment for iron-deficiency anemia rather than assuming primary care will address it, because dual management significantly improves quality of life. 8
Addressing the Leukopenia
Repeat the complete blood count with manual differential after 2–4 weeks of iron therapy to determine whether leukopenia persists. If the leukopenia was spurious due to severe microcytosis interfering with automated cell counting, it will resolve as red-cell indices normalize. 4 If true leukopenia is confirmed, check for bi- or pancytopenia, which would suggest bone marrow insufficiency and warrant hematology referral. 4
Do not pursue extensive leukopenia workup unless the white blood cell count remains low after iron repletion or the patient develops fever, infection, or other cytopenias. Isolated mild leukopenia in the setting of severe iron deficiency is often reactive and self-limited. 4
Critical Pitfalls to Avoid
Do not attribute severe iron-deficiency anemia in reproductive-age women solely to menstrual blood loss without investigating for gastrointestinal pathology. Even when heavy menstrual bleeding appears explanatory, occult GI bleeding—especially from malignancy—must be excluded. 3, 2
Do not discontinue iron supplementation once hemoglobin normalizes; iron stores must be restored to prevent rapid recurrence. Two-thirds of women with severe anemia from menorrhagia recognize heavy bleeding persisting for more than 6 months without seeking help, and 40.5% have received at least one previous transfusion, indicating a pattern of recurrent severe anemia. 6
Do not delay gastrointestinal investigation while awaiting response to iron therapy; malignancy workup should proceed in parallel. Investigation is indicated at any anemia severity when iron deficiency is present, because mild anemia is not less indicative of serious underlying disease. 3, 2
Do not overlook combined deficiencies. Iron deficiency can coexist with vitamin B12 or folate deficiency, recognizable by an elevated RDW despite normal MCV. 3, 1 Measure vitamin B12 and folate levels if macrocytosis develops or if anemia fails to respond to iron therapy. 1
Do not assume all microcytic anemia is iron deficiency. If iron studies are normal or borderline, order hemoglobin electrophoresis to exclude β-thalassemia trait, particularly in patients of African, Mediterranean, or Southeast Asian ancestry. 1, 2 Thalassemia trait typically shows RDW ≤ 14%, normal iron studies, and MCV disproportionately low relative to the degree of anemia. 1, 2