Challenging Cases: Diagnosis and Treatment of Anemia or Iron Overload
Key Points
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In pregnant patients with iron-deficiency anemia, intravenous (IV) iron is appropriate after 14 weeks of gestation; however, oral iron may be an alternative option.
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When differentially diagnosing anemia, bone marrow biopsy can identify underlying bone marrow failure syndromes and inform relevant treatments.
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In patients with iron overload, phlebotomy should be considered only when there is clear evidence of significant iron deposition or high symptom burden.
Causes of Anemia or Iron Overload
Marina Beltrami-Moreira, MD, of The Ohio State University, discussed differential diagnoses and some potential treatments for three challenging cases of anemia or iron overload with the Oncology Brothers podcast cohosts, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center.
Managing Iron-Deficiency Anemia During Pregnancy
The first case described a 34-year-old woman entering her second trimester of pregnancy with ongoing concerns of fatigue and shortness of breath upon exertion. Her workup showed ferritin of 4 ng/mL, transferrin saturation of 5%, total iron-binding capacity (TIBC) of 452, serum iron of 45 mcg/dL, hemoglobin of 9.5 g/dL, and mean corpuscular volume (MCV) of 75.
For this patient, Dr. Beltrami-Moreira recommended IV iron as she is past 14 weeks of gestation and showing significant anemia. IV iron would increase hemoglobin and quickly improve symptoms such as fatigue, concentration, or memory problems. The IV iron options with the most robust data in pregnant patients are Venofer and Feraheme. In her practice, Dr. Beltrami-Moreira prefers Feraheme. However, if it’s not available, she uses Venofer and doesn’t exceed 200 mg in a single infusion to avoid infusion-related reactions.
Oral iron could be an alternative option, although there are some additional considerations for pregnant patients. “I tend to get creative using alternative formulations of oral iron that have lower concentrations that are gentler on the stomach, anything between 18 mg of iron to 65 mg of ferrous sulfate,” said Dr. Beltrami-Moreira.
Differential Diagnosis of Anemia
Next, the doctors discussed a 78-year-old man with a history of hypertension, prostate cancer (controlled with leuprolide acetate), diabetes mellitus type 2, and chronic kidney disease (CKD) who presented with ongoing fatigue and chronic diffuse joint pain. Iron and blood workups returned a ferritin of 450 ng/mL, transferrin saturation of 15%, TIBC of 200, serum iron of 30 mcg/dL, hemoglobin of 9.2 g/dL, MCV of 89, and lactate dehydrogenase (LDH) of 270 IU/L.
In cases with a mixed picture like this, there is often more than one factor contributing to the anemia, said Dr. Beltrami-Moreira. While this patient has high ferritin levels, low ferritin plus low transferrin saturation could indicate unrecognized iron-deficiency anemia driven by chronic anticoagulation or a history of gastrointestinal bleeding. Based on the patient’s age and potential therapy exposures for prostate cancer, primary bone marrow disorders or secondary malignancies like myelodysplastic syndrome (MDS) could be part of the differential diagnosis.
Considering all the possible drivers and the severity of the anemia in this case, Dr. Beltrami-Moreira said she would discuss performing a bone marrow biopsy to investigate bone marrow disorders. For patients reluctant to undergo a bone marrow biopsy, molecular studies of peripheral blood could help clarify the risk of abnormal bone marrow function. However, they would not provide a definitive diagnosis.
With either, if findings are suggestive of low-risk MDS, options such as luspatercept or epoetin alfa can treat anemia and alleviate symptoms. Evidence of higher-risk MDS or acute leukemias would also inform prognosis and help determine treatment opportunities. Confirming an underlying bone marrow abnormality would also justify using erythropoietin-stimulating agents, which are associated with a higher risk of thrombosis in patients with CKD not on dialysis.
Diagnosis and Treatment of Iron Overload
The final case depicted a 47-year-old woman who was overweight with a history of hypercholesterolemia, diabetes, and obstructive sleep apnea. Routine labs identified persistently elevated hemoglobin, prompting further iron studies. Studies returned a ferritin of 500 ng/mL, transferring saturation of 47%, TIBC of 200, serum iron of 160 mcg/dL, hemoglobin of 19 g/DL, hematocrit level of 57%, MCV of 89, and LDH of 300 IU/L. Genetic testing ruled out common homozygous mutations for hemochromatosis.
The elevated ferritin could be a response to the patient’s chronic inflammation, but a transferrin saturation of 47% is higher than expected with anemia of chronic disease. In addition, the risk for chronic iron overload in patients without homozygous mutations is typically low.
“In this patient, I might actually reach out for a liver MRI to help us estimate the actual iron deposition and clarify how much is reaction and how much is true iron overload… and might even consider an extended hemachromatosis genetic panel testing to see if there is anything else that we might be missing here,” said Dr. Beltrami-Moreira.
For this patient, Dr. Beltrami-Moreira would consider phlebotomy only if there were tissue evidence of heart or significant liver iron overload, or if there was a diagnosis of polycythemia vera or highly-symptomatic secondary erythrocytosis. When assessing treatment response, she saidd that she might focus on how hemoglobin levelsrespondg, as ferritin levels might notreflectf her true iron storesdue tof chronic inflammation.