Tomas Ganz, MD, PhD
Distinguished Professor of Medicine and Pathology
David Geffen School of Medicine
University of California, Los Angeles
CLINICAL DILEMMA
A 60-year-old male patient presented with beta thalassemia minor and a hemoglobin level of 12.5 g/dL. He was noted to have persistently elevated serum ferritin levels by his primary care physician with the most recent being 999 mcg/L. The liver iron concentration (LIC) by MRI was 3.9 mg Fe/g dry weight, consistent with mild iron overload. Would you consider oral iron chelation in this patient?
EXPERT OPINION
The patient has mild iron overload by liver MRI and high ferritin levels. Although iron overload is a life-threatening complication of more severe forms of thalassemia, in thalassemia minor (also called thalassemia trait), clinically significant iron overload is very rare1 and has been reported to require other contributing causes (e.g., hemochromatosis-related mutations in the HFE gene or very rarely other hemochromatosis-linked genes). Among other potential contributing factors, alcohol consumption should be assessed because it increases iron overload in other settings. Any iron supplements, which are inappropriately prescribed for some thalassemia minor patients, should be stopped.
Assessment of potential end-organ damage from iron overload should include measurements of serum liver enzymes and symptom review targeted at cardiovascular and endocrine systems. To establish that ferritin is a true measure of iron loading, it is important to check if the patient has systemic inflammation (as assessed by serum C-reactive protein), which may raise ferritin independently of iron. In the absence of systemic inflammation, serum ferritin is reflective of the patient’s iron load and could be followed to assess his treatment response. Measurements of transferrin saturation can also be used to document response to therapy, but may remain elevated in some patients with iron overload despite effective iron depletion.
The patient has systemic iron overload that may worsen and puts him at future risk for complications, including chronic liver disease, cardiomyopathy, diabetes, and testosterone deficiency. Treatment is indicated. Because the patient has only very mild anemia, the initial approach should be phlebotomy rather than chelation, which is more burdensome and has more side effects. If the patient tolerates it, phlebotomy should aim for the removal of one unit every two weeks until ferritin is below 100 mcg/L. At that point, maintenance phlebotomy every two to six months should be sufficient to maintain serum ferritin below 100 mcg/L.
Reference
- Piperno A, Mariani R, Arosio C, et al. Haemochromatosis in patients with beta-thalassaemia trait. Br J Haematol. 2000;111(3):908-914.
NEXT MONTH'S CLINICAL DILEMMA
A 58-year-old female presented with headaches. An MRI of the brain revealed cystic enhancing brain masses with marked swelling and mid-line shift. Extensive pulmonary, mediastinal, hilar, left axillary, inguinal, and left pelvic adenopathy was also seen on a CT scan. A left axillary lymph node biopsy, endobronchial ultrasound with biopsy, and brain biopsy were ordered, all of which were non-diagnostic. A wedge resection conducted in the following weeks was consistent with grade 3 lymphomatoid granulomatosis. The patient was then treated with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and six cycles of high-dose methotrexate, leading to a complete remission.
A follow-up brain MRI confirmed central nervous system (CNS) remission, but recurrent pulmonary lesions were identified on CT scan. I have ordered a biopsy to confirm disease recurrence. If there is recurrence, how should I approach treatment? The patient is currently asymptomatic, but due to recurrent strokes and recent varicella zoster virus CNS vasculitis, her functional status is an Eastern Cooperative Oncology Group performance status of 2-3. The tentative plan is observation, but at some point, a treatment will need to be initiated.
How would you respond? Email us at [email protected].
Disclaimer: ASH does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this article is solely at your own risk.