Postgraduate Medicine
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Sideroblastic anemia Scott Tenner MD, MPH, Carlos Rollhauser MD, Fidelia Butt MD & Pablo Gonzalez MD To cite this article: Scott Tenner MD, MPH, Carlos Rollhauser MD, Fidelia Butt MD & Pablo Gonzalez MD (1992) Sideroblastic anemia, Postgraduate Medicine, 92:7, 147-150, DOI: 10.1080/00325481.1992.11701538 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701538
Published online: 17 May 2016.
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Date: 19 June 2016, At: 05:57
Sideroblastic anemia A diagnosis to consider in alcoholic patients
Scott Tenner, MD, MPH Carlos Rollhauser, MD Fidelia Butt, MD Pablo Gonzalez, MD
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Preview Signs and symptoms of anemia in an alcoholic patient just may be the result of alcohol consumption. One group of disorders known as sideroblastic anemia can be caused by exposure to various drugs and toxins. In this case report, the authors describe a patient in whom hematologic evaluation was highly suggestive of alcohol-induced sideroblastic anemia.
A 58-year-old man who had a history of alcohol abuse presented at the hospital with complaints of fatigue, dizziness, and decreased mentation. The patient stated that he had drunk as much as a pint of alcohol a day for the previous 7 years and that he did not use other drugs. He denied having recent fever, chills, nausea, emesis, melena, hematochezia, or hemoptysis. Past medical history included hypertension and osteoarthritis. He denied having ulcer disease, bleeding disorders, or hemorrhoids. His cunent medications were naproxen, ranitidine, furosemide, potaSSium, glyburide, and a multivitamin that included folate and cyanocobalamin. He had no known allergies to medications. On admission, the patient's blood pressure was 158/90 mm Hg, pulse rate 100 beats per minute, temperature 36.9°C (98.5°F), and respirations 15/min. He was well nourished and obviously intoxicated. Head and neck examination revealed pale sclerae. A grade 2/6 sys-
to lie murmur was audible on heart examination. The lungs were dear to auscultation. The abdomen was sofi: and nontender, and no masses were palpable. Liver span was 10 em in the right rniddavicular line. The spleen was not palpable. There was no edema or
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cyanosis of the extremities. Results of stool guaiac testing were negative. A chest radiograph and an electrocardiogram were unremarkable. Laboratory studies revealed the following values: hematocrit 29% (normal, 38% to 48%), mean corpuscular volume 90 J.Lm' (normal, 78 to 90 J.Lm1), and red blood cell
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distribution width 16% (normal, 11 o/o to 14o/o). Peripheral smear showed numerous macrocytes and microcytes, which were hypochromic and interspersed with normocytic normochromic red blood cells. White blood cell count and differential were within normal ranges for our laboratory. Platelet count was 48,000/mm1 (normal, 150,000 to 300,000/mm'). Total iron-binding capacity was 257 J,Lg/dL (normal, 229 to 365 J,Lg/dL), and serum iron level was 206 J,Lg/dL (normal, 45 to 136 J,LgldL). Serum ferritin level was 278 nglmL (normal, 30 to 284 nglmL). Reticulocyte count was 0.8%. Serum levels of electrolytes, urea nitrogen, creatinine, and lactate dehydrogenase were within normal limits. Total bilirubin level was 3.7 mgldL (normal, 0.2 to 2.0 mgldL) and direct bilirubin level1.7 mgldL (normal, 0 to 0.2 mgldL). Blood alcohol level was 140 mgldL (>80 mgldL is considered legal intoxication). The decision was made to delay further hematologic workup until the patient was alcohol-free and on a normal diet for a week. He remained hospitalized for psychiatric evaluation for alcoholic rehabilitation. Treatment with all of his usual medications except the multivitamin was continued, and he was not allowed to consume alcohol. Five days afi:er admission, hematocontinued
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Figure 1. Hematoxylin-eosin staining of bone marrow aspirate showing sideroblasts. Prussian blue stain enhances iron deposition in red blood cell precursors.
crit rose to 36% and platelet count to 130,000/mml. Discussion
The term "sideroblastic anemia'' refers to a group of disorders of diverse cause that are related to the production of abnormal normablasts (ie, red blood cell precursors) called sideroblasts. Sideroblasts (ringed blasts) derive their name from cytosolic rings that are formed by the precipitation of iron due to an inability to successfully form hemoglobin. The iron-laden mitoScott Tenner, MD, MPH Carlos Rollhauser, MD Fidelia Butt, MD Pablo Gonzalez, MD Dr Tenner is a second-year resident and Dr Rollhauser is a third-year resident, division of internal medicine, George Washington University Medical Center, Washington, DC. Dr Butt is a first-year resident in general surgery, University of Chicago Pritzker School of Medicine. Dr Gonzalez is a fellow in hematology/oncology, University of North Carolina at Chapel Hill School of Medicine.
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chondria of sideroblasts give the appearance of"rings." 1 Sideroblasts are the pathognomonic finding of the disorder and are readily identified by examination of bone marrow aspirate stained with Prussian blue (figure 1). Sideroblastic anemia may result from any number of congenital or acquired causes, including underlying malignancies (table 1). However, alcohol is the most frequently associated toxin, and its abuse is a common cause of anemia in patients seen by primary care physicians.2 An alcoholic patient who presents with anemia can pose a diagnostic challenge. Although the disease often results from a deficiency of iron, vitamin B12 , or folate, marrow suppression of red blood cell production related to the direct toxic effects of alcohol is also a common cause. Alcohol affects hemoglobin synthesis by exerting a toxic effect on delta-arninolevulinic
acid (delta-ALA) synthetase, the initial and rate-limiting step of heme synthesis. Inhibition of this enzyme results in the formation of sideroblasts in bone marrow. Alcoholic patients with sideroblastic anemia usually present with acute alcohol intoxication and anemia characterized by elevated serum iron levels, increased saturation (>60%) of total iron-binding capacity, and reticulocytopenia (table 2). In addition, laboratory evaluation usually reveals evidence of ineffective erythropoiesis, such as elevated lactate dehydrogenase and/or bilirubin levels. A peripheral smear shows a variety of cells, including macrocytes, normocytes, and microcytes. Some investigatorsl have described the smear as dimorphic, referring to the presence of both macrocytes and microcytes. This phenomenon typically is noted on laboratory reports as an elevated red blood cell distribution width. OfTen the peripheral smear appears bizarre and hypochromic with basophilic stippling. 3 The patient in the case described here had a dimorphic anemia, despite supplementation with folate and cyanocobalamin. He also had a high serum iron level and increased saturation of total iron-binding capacity, a hematologic picture that is highly suggestive of sideroblastic anemia. As many as 30% of patients hospital-
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ized for alcoholism have sideroblasts in bone marrow. 2 Associated thrombocytopenia is also common in alcoholics. Long-term, excessive use of alcohol results in decreases in both survival and synthesis of thrombocytes. 4 Sideroblastic anemia can be acquired through exposure to various toxins other than alcohol, especially those that inhibit pyridoxine metabolism. For example, use of isoniazid (Nydrazid) to treat tuberculosis often causes anemia. Delta-ALA synthetase is dependent on the availability of pyridoxine. Sideroblastic anemia has also been associated with use ofbusulfan (Myleran), penicillamine (Cuprimine, Depen), and zinc. 5-8 Hereditary sideroblastic anemia occurs most commonly as an X-linked disorder associated with defective delta-ALA synthetase.9 This condition often responds to administration of pyridoxine hydrochloride. However, lethal syndromes, including X-linked disorders, do exist and are commonly found in males. Although bone marrow aspiration is the diagnostic "gold standard" for sideroblastic anemia, other laboratory findings may also suggest the diagnosis. In alcoholic patients presenting with anemia who have the characteristics described in table 2, the therapeutic goal is abstinence from ethanol.
Table 1. Types and causes of sideroblastic anemia Acquired Certain drugs and toxins Alcohol Busulfan (Myleran) Chloramphenicol (Chloromycetin) Copper deficiency Isoniazid (Nydrazid) Lead Penicillamine (Cuprimine, De pen) Zinc overingestion Neoplastic or inflammatory disease Leukemia Lymphoma Myeloid metaplasia Rheumatoid arthritis Primary sideroblastic anemia (in myelodysplastic syndromes)
Table 2. Characteristic laboratory findings in patients with sideroblastic anemia
Basophilic stippling Dimorphic peripheral smear Elevated bilirubin level Elevated lactate dehydrogenase level Elevated serum iron level and increased saturation of total iron-binding capacity Increased red blood cell distribution width Reticulocytopenia
Hereditary or congenital
Bone marrow aspiration should be reserved for patients whose anemia fails to resolve when the offending agent is removed. Lack of improvement should suggest other diagnoses, such as hemochromatosis, which may present a similar clinical picture during its initial phase.
Summary Alcoholic patients who present with anemia can pose a diagnos-
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tic challenge. Although deficiencies of iron, vitamin Bw and folate commonly result in anemia, bone marrow suppression of red blood cell production related to the direct toxic effects of alcohol can cause a funn called sideroblastic anemia. This case report describes a patient presenting with acute alcohol intoxication and anemia in whom extensive evaluation revealed a hematologic picture compatible with acquired sideroblastic anemia. RN continued
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Address for correspondence: Carlos Rollhauser, MD, Division oflntemal Medicine, Deparrment of Medicine, George Washington University Medical Center, 2150 Pennsylvania Ave NW; Washington, DC 20037.
References I. Bottomley SS, Muller-Fherbard U. Pathophysiology of heme synthesis. Semin Hematol 1988;25(4):282-302 2. Pierce HI, M£uffin RG, Hillman RS. Clinical studies in alcoholic sideroblastosis. Arch Intern Med 1976;136(3):283-9 3. Liu PI, Lim JY. Sideroblastic anemia. JAMA 1987;257(20):2814 4. Gewirtz AM, Hoflinan R. Transitory hypomegakaryocytic thrombocytopenia: aetiological association with ethanol abuse and implications regarding regulation of human megakaryocytopoiesis. Br JHaematol1986;62(2):333-44 5. Fernandez LA, Zay00 E. Busulfan-induced sideroblastic anemia. Am J Hematol 1988;28(3): 199-200 6. Simon SR, Branda RF, Tmdle BF, et al. Copper deficiency and sideroblastic anemia associated with zinc ingestion. Am J Hematol 1988; 28(3):181-3 7. Rarnselaar AC, Dekker AW, HuberBruning 0, et al. Acquired sideroblastic anaemia afi:er aplastic anaemia caused by D-penicillamine therapy for rheumatoid arthritis. Ann Rheum Dis 1987;46(2):156-8 8. Broun ER, Greist A, Tricot G, et al. Excessive zinc ingestion: a reversible cause of sideroblastic anemia and bone marrow depression. JAMA 1990;264(11):1441-3 9. Nusbaum NJ. Concise review: genetic bases for sideroblastic anemia. Am J Hematol 1991; 37(1):41-4
Readers are invited to submit brief reports of perplexing cases related to primary medical care. Address submissions to: Manuscript Administrator, POSTGRADUATE MEDICINE, 4530 W 77th St, Minneapolis, MN 55435.
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