Sideroblastic anemia
BASIC INFORMATION
Sideroblastic anemia is a group of disorders characterized by hypochromic anemia associated with tissue iron overload and the presence of ringed sideroblasts in the bone marrow. The disorder can be hereditary or acquired. As a result, iron is deposited in the mitochondria of normoblasts, and characteristic rings surround the nucleus of this cell.
Sideroblastic anemias can be acquired or hereditary; the acquired form, in turn, can be primary or secondary. In many instances, hereditary sideroblastic anemia responds to treatment with pyridoxine (vitamin B6). Correction of the secondary acquired form depends on the causative disorder; the primary acquired (idiopathic) form resists treatment and usually proves fatal within 10 years after onset of complications or a concomitant disease.
SYNONYMS
• Primary hereditary sideroblastic anemia
• Primary acquired refractory anemia with ringed sideroblasts (RARS)
• Secondary toxin associated
CAUSES
Hereditary sideroblastic anemia is most prevalent in young males and appears to be transmitted by X-linked inheritance; females are carriers and usually show no signs of this disorder. The acquired form may be secondary to ingestion of or exposure to toxins, such as alcohol and lead, or to drugs, such as isoniazid and chloramphenicol. It can also occur as a complication of neoplastic and inflammatory diseases, such as lymphoma, rheumatoid arthritis, lupus erythematosus, multiple myeloma, tuberculosis, and severe infections. The primary acquired form, whose cause is unknown, is most common in elderly people but occasionally develops in young people. It's often associated with thrombocytopenia or leukopenia.
• Primary hereditary sideroblastic anemia
• Primary acquired refractory anemia with ringed sideroblasts (RARS)
• Secondary toxin associated
CAUSES
Hereditary sideroblastic anemia is most prevalent in young males and appears to be transmitted by X-linked inheritance; females are carriers and usually show no signs of this disorder. The acquired form may be secondary to ingestion of or exposure to toxins, such as alcohol and lead, or to drugs, such as isoniazid and chloramphenicol. It can also occur as a complication of neoplastic and inflammatory diseases, such as lymphoma, rheumatoid arthritis, lupus erythematosus, multiple myeloma, tuberculosis, and severe infections. The primary acquired form, whose cause is unknown, is most common in elderly people but occasionally develops in young people. It's often associated with thrombocytopenia or leukopenia.
EPIDEMIOLOGY & DEMOGRAPHICS
• Hereditary sideroblastic anemia, being sex-linked, primarily affects males.
• Primary acquired sideroblastic anemia is usually a disease of the elderly.
PHYSICAL FINDINGS & CLINICAL PRESENTATION
The symptoms for sideroblastic anemia are the same for any anemia:
• Symptoms include fatigue, weakness, palpitations, shortness of breath, headaches, irritability, and chest pain.
• Physical findings may include pallor, tachycardia, hepatosplenomegaly, S3 , JVD, and rales.
ASSESSMENT FINDINGS
Sideroblastic anemias usually produce nonspecific clinical effects that can exist for several years before being identified. The patient's history may reveal anorexia, fatigue, weakness, and dizziness. The patient may also have a history of dyspnea. On inspection, you may observe pale skin and oral mucous membranes. You may also note slight jaundice, caused by excessive iron accumulation in the liver, and petechiae or bruises, caused by thrombocytopenia. Palpation may reveal enlarged lymph nodes, If iron accumulates in the liver and the patient has jaundice, palpation also may disclose hepatosplenomegaly. Hereditary sideroblastic anemia is associated with increased GI absorption of iron, causing signs of hemosiderosis (eventually, hepatomegaly, cardiomyopathy and, possibly, endocrine problems). Additional symptoms in secondary sideroblastic anemia depend on the underlying cause.
ETIOLOGY
• Primary hereditary sideroblastic anemia is usually inherited as a sex-linked recessive disease.
• Primary acquired sideroblastic anemia is idiopathic.
• Secondary acquired sideroblastic anemia can be caused by alcohol, isoniazid, pyrazinamide, cycloserine, chloramphenical, and copper deficiency.
• Hereditary sideroblastic anemia, being sex-linked, primarily affects males.
• Primary acquired sideroblastic anemia is usually a disease of the elderly.
PHYSICAL FINDINGS & CLINICAL PRESENTATION
The symptoms for sideroblastic anemia are the same for any anemia:
• Symptoms include fatigue, weakness, palpitations, shortness of breath, headaches, irritability, and chest pain.
• Physical findings may include pallor, tachycardia, hepatosplenomegaly, S3 , JVD, and rales.
ASSESSMENT FINDINGS
Sideroblastic anemias usually produce nonspecific clinical effects that can exist for several years before being identified. The patient's history may reveal anorexia, fatigue, weakness, and dizziness. The patient may also have a history of dyspnea. On inspection, you may observe pale skin and oral mucous membranes. You may also note slight jaundice, caused by excessive iron accumulation in the liver, and petechiae or bruises, caused by thrombocytopenia. Palpation may reveal enlarged lymph nodes, If iron accumulates in the liver and the patient has jaundice, palpation also may disclose hepatosplenomegaly. Hereditary sideroblastic anemia is associated with increased GI absorption of iron, causing signs of hemosiderosis (eventually, hepatomegaly, cardiomyopathy and, possibly, endocrine problems). Additional symptoms in secondary sideroblastic anemia depend on the underlying cause.
ETIOLOGY
• Primary hereditary sideroblastic anemia is usually inherited as a sex-linked recessive disease.
• Primary acquired sideroblastic anemia is idiopathic.
• Secondary acquired sideroblastic anemia can be caused by alcohol, isoniazid, pyrazinamide, cycloserine, chloramphenical, and copper deficiency.
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
• Sideroblastic anemia must be differentiated from other causes of microcytic hypochromic anemia: iron deficiency anemia, thalassemia, anemia of chronic disease, lead poisoning, and blood loss.
• Tissue iron overload from sideroblastic anemia may act similar to hereditary hemochromatosis with liver cirrhosis, diabetes, congestive heart failure, and cardiac arrhythmias.
DIAGNOSTIC TESTS
Ringed sideroblasts on microscopic examination of bone marrow aspirate stained with Prussian blue dye confirm the diagnosis. Microscopic examination of blood shows erythrocytes to be hypochromic or normochromic and slightly macrocytic. Red cell precursors may be megaloblastic, with anisocytosis (abnormal variation in red blood cell [RBC] size) and poikilocytosis (abnormal variation in RBC shape). Vitamin B12 and folic acid levels are normal unless combined anemias are present. The reticulocyte count is low because young cells die in the marrow. Unlike iron deficiency anemia, sideroblastic anemia lowers hemoglobin levels and raises serum iron and transferrin levels. In turn, faulty hemoglobin production raises urobilinogen and bilirubin levels. Platelets and leukocytes remain normal, but occasionally, thrombocytopenia or leukopenia occurs.
WORKUP
The diagnostic workup of suspected sideroblastic anemia includes laboratory evaluation and bone marrow aspiration and biopsy.
LABORATORY TESTS
• CBC(low Hgb, low Hct, low MCV, high RDW)
• Peripheral smear: dimorphic large and small cells revealing “Pappenheimer bodies” or siderocytes when stained for iron.
• Bone marrow shows the classic ringed sideroblasts not seen in normal bone marrow tissue.The ringed sideroblasts represent iron storage in the mitochondria of normoblasts.
TREATMENT
The underlying cause determines the course of treatment. Hereditary sideroblastic anemia usually responds to several weeks of treatment with high doses of pyridoxine. The acquired secondary form subsides after the causative drug or toxin is removed or the underlying condition is adequately treated. Folic acid supplements may be beneficial when concomitant megaloblastic nuclear changes in RBC precursors are present. Deferoxamine may be used to treat chronic iron overload in selected patients. Carefully crossmatched transfusions (providing needed hemoglobin) or high doses of androgens are effective palliative measures for some patients with the primary acquired form of sideroblastic anemia. This form is essentially refractory to treatment and usually leads to death from acute leukemia or from respiratory or cardiac complications. Some patients with sideroblastic anemias may benefit from phlebotomy to prevent hemochromatosis. Phlebotomy increases the rate of erythropoiesis and uses up excess iron stores; thus, it reduces serum and total-body iron levels.
• Avoid alcohol.
• Secondary sideroblastic anemia due to isoniazid, pyrazinamide, and cycloserine can expect a full recovery by withdrawing the medication and by the use of vitamin B6 (50 to 200 mg/day).
ACUTE GENERAL Rx
• Hereditary sideroblastic anemia:
1. Nearly 35% of patients receiving vitamin B6 (50 to 200 mg/day) will improve their red blood cell to near normal values.
2. The remainder of patients will require blood transfusions to treat symptoms of anemia.
• Primary acquired sideroblastic anemia:
1. Most patients do not respond to vitamin B6.
2. Erythropoietin has shown some success in improving the anemia.
3. Blood transfusions are indicated for patients with symptomatic anemia.
CHRONIC Rx
• Hereditary sideroblastic anemia:
1. Organ dysfunction resulting from iron overload will require periodic phlebotomies.
2. In advanced cases, desferoxamine 40 mg/kg/day IV is given.
• Primary acquired sideroblastic anemia:
1. As in the hereditary form, periodic phlebotomies are indicated when serum iron levels increase to >500 mg/L and desferoxamine is used in patients requiring frequent blood transfusions.
DISPOSITION
• Hereditary sideroblastic anemia:
1. With above mentioned treatment, prognosis is good for a normal life expectancy.
• Primary acquired sideroblastic anemia:
1. In patients with anemia alone, life expectancy is normal. In patients dependent on blood transfusions one can expect morbidity from organ dysfunction.
2. Some patients with acquired sideroblastic anemia can go on to develop leukemia.
DIFFERENTIAL DIAGNOSIS
• Sideroblastic anemia must be differentiated from other causes of microcytic hypochromic anemia: iron deficiency anemia, thalassemia, anemia of chronic disease, lead poisoning, and blood loss.
• Tissue iron overload from sideroblastic anemia may act similar to hereditary hemochromatosis with liver cirrhosis, diabetes, congestive heart failure, and cardiac arrhythmias.
DIAGNOSTIC TESTS
Ringed sideroblasts on microscopic examination of bone marrow aspirate stained with Prussian blue dye confirm the diagnosis. Microscopic examination of blood shows erythrocytes to be hypochromic or normochromic and slightly macrocytic. Red cell precursors may be megaloblastic, with anisocytosis (abnormal variation in red blood cell [RBC] size) and poikilocytosis (abnormal variation in RBC shape). Vitamin B12 and folic acid levels are normal unless combined anemias are present. The reticulocyte count is low because young cells die in the marrow. Unlike iron deficiency anemia, sideroblastic anemia lowers hemoglobin levels and raises serum iron and transferrin levels. In turn, faulty hemoglobin production raises urobilinogen and bilirubin levels. Platelets and leukocytes remain normal, but occasionally, thrombocytopenia or leukopenia occurs.
WORKUP
The diagnostic workup of suspected sideroblastic anemia includes laboratory evaluation and bone marrow aspiration and biopsy.
LABORATORY TESTS
• CBC(low Hgb, low Hct, low MCV, high RDW)
• Peripheral smear: dimorphic large and small cells revealing “Pappenheimer bodies” or siderocytes when stained for iron.
• Bone marrow shows the classic ringed sideroblasts not seen in normal bone marrow tissue.The ringed sideroblasts represent iron storage in the mitochondria of normoblasts.
TREATMENT
The underlying cause determines the course of treatment. Hereditary sideroblastic anemia usually responds to several weeks of treatment with high doses of pyridoxine. The acquired secondary form subsides after the causative drug or toxin is removed or the underlying condition is adequately treated. Folic acid supplements may be beneficial when concomitant megaloblastic nuclear changes in RBC precursors are present. Deferoxamine may be used to treat chronic iron overload in selected patients. Carefully crossmatched transfusions (providing needed hemoglobin) or high doses of androgens are effective palliative measures for some patients with the primary acquired form of sideroblastic anemia. This form is essentially refractory to treatment and usually leads to death from acute leukemia or from respiratory or cardiac complications. Some patients with sideroblastic anemias may benefit from phlebotomy to prevent hemochromatosis. Phlebotomy increases the rate of erythropoiesis and uses up excess iron stores; thus, it reduces serum and total-body iron levels.
• Avoid alcohol.
• Secondary sideroblastic anemia due to isoniazid, pyrazinamide, and cycloserine can expect a full recovery by withdrawing the medication and by the use of vitamin B6 (50 to 200 mg/day).
ACUTE GENERAL Rx
• Hereditary sideroblastic anemia:
1. Nearly 35% of patients receiving vitamin B6 (50 to 200 mg/day) will improve their red blood cell to near normal values.
2. The remainder of patients will require blood transfusions to treat symptoms of anemia.
• Primary acquired sideroblastic anemia:
1. Most patients do not respond to vitamin B6.
2. Erythropoietin has shown some success in improving the anemia.
3. Blood transfusions are indicated for patients with symptomatic anemia.
CHRONIC Rx
• Hereditary sideroblastic anemia:
1. Organ dysfunction resulting from iron overload will require periodic phlebotomies.
2. In advanced cases, desferoxamine 40 mg/kg/day IV is given.
• Primary acquired sideroblastic anemia:
1. As in the hereditary form, periodic phlebotomies are indicated when serum iron levels increase to >500 mg/L and desferoxamine is used in patients requiring frequent blood transfusions.
DISPOSITION
• Hereditary sideroblastic anemia:
1. With above mentioned treatment, prognosis is good for a normal life expectancy.
• Primary acquired sideroblastic anemia:
1. In patients with anemia alone, life expectancy is normal. In patients dependent on blood transfusions one can expect morbidity from organ dysfunction.
2. Some patients with acquired sideroblastic anemia can go on to develop leukemia.
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