Sideroblastic Anemias 

Updated: Sep 10, 2019
Author: Muhammad A Mir, MD, FACP; Chief Editor: Emmanuel C Besa, MD 


Practice Essentials

[1] The sideroblastic anemias (SAs) are a group of inherited and acquired bone marrow disorders characterized by pathological iron accumulation in the mitochondria of erythroid precursors. Abnormal, iron-laden mitochondria appear to encircle erythroblast nuclei, giving rise to the defining morphological feature of the ring sideroblast (RS).[2] The detection of bone marrow ring sideroblasts can be seen in a variety of clonal hematological and non-clonal disorders. Clonal conditions associated with RS include myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and MDS/MPN overlap syndromes.[3]  Non-clonal conditions include alcoholism, lead poisoning, zinc overdose, copper or pyridoxine deficiency, and congenital sideroblastic anemias (CSA).

Congenital sideroblastic anemias (CSAs) can be attributed to mutations in 1 of 3 mitochondrial pathways: heme synthesis, iron-sulfur cluster biogenesis and protein synthesis.

Sideroblastic anemia is primarily a laboratory diagnosis, made on the basis of bone-marrow examination with Prussian blue stain. The history and physical examination can provide certain clues, but they usually do not pin down the exact diagnosis. Workup may include a complete blood count (CBC), peripheral smear, iron studies (eg, ferritin and total iron-binding capacity [TIBC]), bone marrow aspiration and biopsy, and other studies as appropriate.

Treatment of sideroblastic anemia may include removal of toxic agents; administration of pyridoxine, thiamine, or folic acid; transfusion (along with antidotes if iron overload develops from transfusion); other medical measures; or bone marrow or liver transplantation.


Adult human bone marrow synthesizes 4 × 1014 molecules of hemoglobin every second.[4]  Heme and globin chains (alpha and beta) in adults are manufactured in separate cell compartments—mitochondria and cytoplasm, respectively—and then combined in cytoplasm in an amazingly accurate manner. Four major problems can manifest during this delicate process:

  • Qualitative defects of globin chain synthesis result in hemoglobinopathies such as  sickle cell disease.
  • Quantitative defects of globin chain synthesis result in hemoglobinopathies such as thalassemia.
  • Defects in synthesis of the heme portion result in  porphyrias.
  • Defects involving incorporation of iron into the heme molecule result in sideroblastic anemia.

In some instances, both the synthesis of heme and the incorporation of iron can be altered, and the result is a porphyria with sideroblasts (eg, erythropoietic protoporphyria).[5, 6]


Sideroblasts are not pathognomonic of any one disease but rather are a bone marrow manifestation of several diverse disorders. On a marrow stained with Prussian blue, a sideroblast is an erythroblast that has stainable deposits of iron in the cytoplasm. When abundant, these deposits form a ring around the nucleus, and the cells become ring sideroblasts (see the image below).

Ring sideroblast. Ring sideroblast.

Under normal circumstances, this iron would have been used to make heme. The process only occurs in the bone marrow, because mature erythrocytes lack mitochondria, the nexus of heme synthesis (see the image below).

Heme synthesis. Heme synthesis.

Congenital sideroblastic anemias

Congenital sideroblastic anemias generally present with lower hemoglobin and more microcytosis than myelodysplastic syndrome and are usually associated with higher serum iron levels than myelodysplastic syndrome.[7]

Of the congenital sideroblastic anemias, X-linked sideroblastic anemias are further divided into pyridoxine-responsive (> 50%) and pyridoxine-resistant subtypes.

In the pyridoxine-responsive subtype, point mutations on the X chromosome have been identified that result in a δ-amino levulinic acid synthase (ALAS-2) with very low enzymatic activity.[8] This development impairs the first crucial step in the heme synthesis pathway, the formation of δ-amino levulinic acid, resulting in anemia despite intact iron delivery to the mitochondrion and with a lack of heme in which iron is to be incorporated in the final step of this pathway. This is the most common of the hereditary sideroblastic anemias, followed by mitochondrial transporter defects such as SLC25A38 gene mutation discussed below.[9]

A prototype of pyridoxine-resistant X-linked sideroblastic anemia is the ABC7 gene mutation.[10, 11] ABC-7 is an adenosine triphosphate (ATP)-dependent transporter protein involved in the cytosolic transfer of iron-sulfur complexes. In contrast to pyridoxine-responsive sideroblastic anemia, the ABC7 defect has a nonprogressive cerebellar ataxia component with diminished deep-tendon reflexes, incoordination, and elevated free erythrocyte protoporphyrin.[12]

Autosomal recessive sideroblastic anemia has been described in conjunction with mitochondrial myopathy and lactic acidosis in Jews of Persian descent, resulting from pseudouridine synthase-1 (PUS-1) mutations.[13] Pseudouridine is a nucleoside isomer of uridine that is used as a building block in mitochondrial RNA. The defect results in impaired oxidative phosphorylation, which explains the muscle and nerve manifestations, and sideroblastic anemia due to dysfunctional mitochondria, the center of heme synthesis.

An autosomal dominantly inherited form also exists but is extremely rare.[14]

Pearson (marrow-pancreas) syndrome, described in 1979,[15] is a juvenile multisystem disorder caused by deletions in mitochondrial DNA (mtDNA) and manifested as severe, refractory sideroblastic anemia, neutropenia, vacuolated cells in bone-marrow precursors, exocrine pancreas insufficiency, malabsorption, and growth failure.[16]

Nonclonal acquired sideroblastic anemias

Copper deficiency, which can occur as a part of malabsorption,[17]  nephrotic syndrome (loss of ceruloplasmin),[18]  gastric surgery,[19]  or as a consequence of excessive zinc intake (supplements),[20]  can masquerade as myelodysplastic syndrome with sideroblastic anemia and leukopenia.[21] . Low serum copper and ceruloplasmin are typical. Copper replacement reverses the hematologic abnormalities.[22]

Vitamin B-6 (pyridoxine) forms pyridoxal phosphate, which acts as a coenzyme in the first, rate-limiting step in heme formation catalyzed by δ-ALAS.[23]  Deficiency of vitamin B-6 causes sideroblastic anemia.

Lead poisoning has been known to cause sideroblastic anemia by inhibiting several enzymes involved in heme synthesis, including δ-aminolevulinate dehydratase, coproporphyrin oxidase, and ferrochelatase.[24]

Excessive alcohol consumption can cause several forms of anemia through nutritional deficiencies (eg, of iron or folate), hemolysis, splenic sequestration due to liver cirrhosis, direct bone marrow toxicity to erythroid precursors,[25]  inhibition of pyridoxine,[26]  lead contamination of wine,[27]  and inhibition of ferrochelatase enzyme during heme formation.[28]

Drugs reported to cause sideroblastic anemia include diverse classes, such as the following:

  • Antibiotics (eg, chloramphenicol, [29]  fusidic acid, [30]  linezolid, [31]  tetracycline, [32]  isoniazid [33] )
  • Hormones (eg, progesterone [34] )
  • Pain medicines (eg, phenacetin [35] )
  • Copper chelating agents (eg, penicillamine [36]  and trientine [37] )
  • Chemotherapy agents (eg, busulfan, melphalan) [38]  

In most cases of drug-induced sideroblastic anemia, stopping the drug reverses the sideroblastic changes.

Hypothermia has been reported to cause sideroblastic anemia with a marked reduction in normoblastic erythropoiesis and thrombocytopenia with normal megakaryocytes. The changes reverse in most cases with the normalization of temperature.[39]

Clonal acquired sideroblastic anemias

In the 2016 revised World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia, two myeloid neoplasms synonymous with the presence of bone marrow RS were reclassified.  Refractory anemia with ring sideroblasts (RARS) is now classified under myelodysplastic syndrome with ring sideroblasts (MDS-RS) and RARS with thrombocytosis (RARS-T) is now called MDS/MPN with RS and thrombocytosis (MDS/MPN-RS-T).[40]

The change in the classification of MDS to include MDS-RS is based largely on the link between ring sideroblasts and an SF3B1 mutation, which appears to be an early event in MDS pathogenesis, manifests a distinct gene expression profile, and correlates with a favorable prognosis. Contrary to its poor prognostic significance in chronic lymphocytic leukemia, in MDS this mutation appears to lower transformation into acute leukemia.[41] This mutation is not found in congenital sideroblastic anemias.[7]  Recent studies have shown that in cases of MDS with any ring sideroblasts, the actual percentage of ring sideroblasts is not prognostically relevant.[42]

MDS-RS cases will be subdivided into cases with single lineage dysplasia (MDS-RS SLD) which was previously classified as refractory anemia with ring sideroblasts; and cases with multilineage dysplasia (MDS-RS MLD) which were previously classified as refractory cytopenia with multilineage dysplasia.[3]

MDS/MPN-RS-T is also frequently associated with mutations in the spliceosome gene SF3B1 and is often comutated with JAK2 V617F or less frequently (< 10%) with CALR, or MPL genes.[43]  


Nonclonal sideroblastic anemia

The most common form of congential sideroblastic anemia (CSA) is caused by mutation of erythroid-specific 5-aminolevulinate synthase (ALAS2), the first enzyme of heme synthesis in erythroid cells.[7]  Other CSAs include SLC25A38 related sideroblastic anemia [44] , glutaredoxin 5 (GLRX5) related sideroblastic anemia[45] , and X-linked sideroblastic anemia with ataxia-ABCB7 mutations.

The syndromic CSA phenotypes include:

  • Mitochondrial myopathy with lactic acidosis and sideroblastic anemia (MLASA) caused by PUS1 mutation  [46]
  • Sideroblastic anemia, B cell immunodeficiency, periodic fevers, and developmental delay (SIFD) caused by TRNT1 mutation
  • Pearson marrow-pancreas syndrome (PMPS)  [16]
  • Thiamine-responsive megaloblastic anemia syndrome (TRMA) caused by SLC19A2 mutation [44, 47]

Congenital sideroblastic anemia caused by respiratory insufficiency and loss of complex I stability and activity in patient-derived fibroblasts due to NDUFB11 mutations has been reported.[2]

Causes of nonclonal acquired sideroblastic anemia include the following:

  • Nutritional deficiencies (copper, vitamin B-6)
  • Lead poisoning 
  • Zinc overdose
  • Alcohol
  • Drugs (eg, antituberculous agents, antibiotics, progesterone, chelators, phenacetin, busulfan)
  • Idiopathic

Clonal sideroblastic anemia

Clonal conditions associated with ring sideroblasts (RS) include myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and MDS/MPN overlap syndromes. The WHO classification of these conditions are as follows[40, 3] :

Clonal RS myelodysplastic syndromes (MDSs) 

  • MDS with ring sideroblasts and single lineage dysplasia (MDS-RS SLD)
  • MDS with ring sideroblasts and multilineage dysplasia (MDS-RS-MLD)
  • MDS with excess blasts and ring sideroblasts
  • MDS-U with ring sideroblasts

Clonal RS​ myeloproliferative neoplasms (MPNs) 

  • Essential thrombocythemia with ring sideroblasts
  • Primary myelofibrosis with ring sideroblasts

Clonal RS MDS/MPN overlap syndromes 

  • MDS/MPN with ringed sideroblasts and thrombocytosis (MDS/MPN-RS-T)
  • Chronic myelomonocytic anemia with ring sideroblasts
  • Unclassified MDS/MPN with ring sideroblasts


In 25 bone marrow biopsies of children younger than 13 years from Atlanta, Georgia (United States), with anemia, the prevalence of ringed sideroblasts was 8%.[48]

In France, the prevalence of ringed sideroblasts was 57% in patients with primary MDS.[49] In the United Kingdom, among healthy volunteers undergoing bone marrow biopsy, siderotic granules (not ring sideroblasts) were present in 29% of men and 19% of women.[50]

Although usually manifesting in childhood, congenital X-linked sideroblastic anemia due to ALAS mutation can remain undiagnosed and then present late in the fourth to eighth decades of life.[51, 52] The median age of occurrence of primary acquired sideroblastic anemia is 74 years.[53]

X-linked recessive types of sideroblastic anemia occur more commonly in males. A female would have to inherit 1 abnormal chromosome from each parent to acquire the disease. Progesterone and pregnancy have been reported to induce relapse of sideroblastic anemia.[54]

No racial predominance is reported in sideroblastic anemia.



The prognosis of patients with sideroblastic anemia is highly variable. Cases with reversible causes such as alcohol and drugs do not appear to carry long-term sequelae. On the other hand, patients with transfusion dependence, those with conditions unresponsive to pyridoxine and other therapies, and those with MDS that develops into acute leukemia have a less bright prognosis.

In congenital sideroblastic anemias, mitochondrial abnormalities may produce neuromuscular dysfunction. In acquired sideroblastic anemias, mortality and morbidity is obviously variable as some of the causes are reversible. The anemia itself is usually moderate, with hematocrit in the 20-30% range.[55] In idiopathic sideroblastic anemia with MDS, median survival is 38 months, as compared with 60 months in pure sideroblastic anemia (with dyserythropoiesis only, without abnormal megakaryocytic and granulocytic precursors).[56]

Major causes of death in cases of sideroblastic anemia are secondary hemochromatosis from transfusions and leukemia. The patients who die of acute leukemia tend to have a more severe anemia, a lower reticulocyte count, an increased transfusion requirement, and thrombocytopenia.

Thrombocytosis appears to be a relatively good prognostic sign.[57] Patients with no need for blood transfusions are very likely to be long-term survivors, whereas those who become transfusion dependent are at risk of death from the complications of secondary hemochromatosis.[58]

Patient Education

Genetic counseling and an antenatal diagnosis of sideroblastic anemia have in recent years become of practical relevance to families with known cases of congenital sideroblastic anemia. Careful documentation of the clinical outcome of these cases and of other family members is invaluable.[59]

For patient education resources, see Anemia.




The following clinical history features are suggestive of sideroblastic anemia:

  • Incoordination (cerebellar symptoms)
  • Failure of growth
  • Diarrhea (malabsorption)
  • History of exposure to cold for prolonged periods
  • Family history of mitochondrial disease and anemia
  • Medication history of antibiotics, antituberculous agents, chelators, or chemotherapy
  • Ingestion of supplements, especially zinc
  • Prolonged dependence on parenteral nutrition, with insufficient replacement of copper
  • Chronic dialysis with higher than normal zinc levels in dialysis fluid
  • Psychiatric disease with possible coin ingestion [60]
  • Alcoholism
  • Exposure to lead, such as via pipes in older houses
  • History of myelodysplastic syndrome
  • General symptoms of anemia, including malaise, fatigue, and dyspnea on exertion

Complications of sideroblastic anemia include acute leukemia and secondary hemochromatosis with transfusion therapy.

Physical Examination

The following physical examination features are suggestive of sideroblastic anemia:

  • General - Growth retardation in children
  • Vital signs - Hypothermia
  • Oral - Lead line on teeth margins
  • Skin - Photosensitivity (porphyria), petechiae (myelodysplastic syndrome)
  • Neurologic - Ataxia, diminished deep-tendon reflexes, incoordination
  • Cardiovascular - Fatigue
  • Respiratory - Dyspnea
  • Abdominal - Splenomegaly
  • Musculoskeletal - Muscular weakness
  • Genitourinary - Pink staining of diapers from porphyrins in urine


Diagnostic Considerations

Sideroblastic anemia is primarily a laboratory diagnosis, made on the basis of bone-marrow examination with Prussian blue stain. The history and physical examination can provide certain clues, but they usually do not pin down the exact diagnosis.

Over diagnosis of sideroblastic anemia may occur because of the variable definition of sideroblastosis.

Go to Anemia, Iron Deficiency Anemia, and Chronic Anemia for complete information on these topics.

Other conditions to be considered include the following:

  • Multivitamin deficiencies and malnutrition
  • Drug toxicity

Differential Diagnoses



Approach Considerations

The workup for sideroblastic anemia may include the following:

  • Complete blood count (CBC)
  • Peripheral smear,
  • Iron studies (eg, ferritin and total iron-binding capacity [TIBC])
  • Bone marrow aspiration and biopsy
  • Other studies as appropriate

Complete Blood Cell Count and Peripheral Smear

In patients with sideroblastic anemia, the CBC usually reveals anemia, mostly moderate, although severe anemia has been reported.[61] The mean corpuscular volume (MCV) is usually low, with a microcytic picture; however, normocytic, macrocytic,[62] and classic dimorphic (normocytic + microcytic)[63] smears are not uncommon.

Siderocytes with Pappenheimer bodies (hypochromic erythrocytes with basophilic iron deposits) are sideroblasts that have matured enough to make it to peripheral blood.

Dimorphic anemia is not specific for sideroblastic anemia and is also seen in combined vitamin B-12 deficiency with iron deficiency and after blood transfusions.[64] Other cell lines may be undisturbed in pure sideroblastic anemia, but in sideroblastic anemia that is associated with myelodysplastic syndrome (MDS), leukopenia, thrombocytopenia, or even thrombocytosis may be observed.

The peripheral smear may exhibit basophilic stippling in cases of lead poisoning.[65]

Iron and Other Laboratory Studies

Iron studies may show increased an iron level with decreased TIBC (see the image below) . A very low ferritin level strongly favors iron deficiency as the primary cause of anemia. In fact, iron deficiency may mask underlying sideroblastic anemia as hypochromic anemia, with the appearance of sideroblasts in bone marrow once the iron stores are replenished.[66] Periodic iron studies are essential even for those who are not transfusion dependent.

Iron and total iron-binding capacity in physiology Iron and total iron-binding capacity in physiology and pathology.

Serum lead, alcohol, γ-glutamyltransferase (GGT), copper, and zinc levels can be measured. Surrogates for vitamin B-6 that can be measured in plasma include pyridoxal 5′ phosphate (PLP) and 4-pyridoxic acid (4-PA).[67] 4-PA can also be measured in urine.

Additional Tests

Magnetic resonance imaging (MRI) of the posterior cranial fossa is indicated in anemia-ataxia syndromes to rule out primary cerebellar pathology such as space-occupying lesions.

In congenital or suspected congenital anemias, determination of the exact mutation type (eg, ABC7) may provide useful information for the physician and the family members of affected patients, even if it may not affect immediate patient management. This can be accomplished by means of polymerase chain reaction (PCR) evaluation.

A urine porphyrin profile may reveal erythropoietic porphyria.

Bone Marrow Aspiration and Biopsy

Usually, when a physician is faced with the diagnosis of sideroblastic anemia, bone marrow aspiration and biopsy has already been done. Attention should be paid to other cell lines (ie, megakaryocytes, myelocytes) because MDS is a part of the differential diagnosis (see Differentials). If iron deficiency anemia is of unclear etiology and fails to respond to iron replacement during the workup, bone marrow aspiration and biopsy should be included in the workup.

Patients initially presenting with hypochromic anemia may end up receiving iron supplements if a bone-marrow biopsy is not performed and thus develop iron overload.

It is important to obtain cytogenetic studies on the bone marrow aspirate samples, as quite often this may be the only way confirm a myelodysplastic syndrome.

Histologic Findings

In the revised WHO classification, if an SF3B1 mutation is identified, a diagnosis of MDS-RS may be made if ring sideroblasts comprise as few as 5% of nucleated erythroid cells, whereas at least 15% ring sideroblasts are required in cases lacking a demonstrable SF3B1 mutation.[3]  

The WHO criteria for MDS/MPN-RS-T include thrombocytosis (≥450 × 109/L) associated with refractory anemia, dyserythropoiesis in the bone marrow with ring sideroblasts accounting for 15% or more of erythroid precursors, and megakaryocytes with features resembling those in primary myelofibrosis (PMF) or essential thrombocythemia (ET).Unlike MDS-RS the number of ring sideroblasts required for a diagnosis of MDS/MPN-RS-T is not altered by the presence or absence of a mutation in SF3B1.[3]  



Approach Considerations

Treatment of sideroblastic anemia may include the following:

  • Removal of toxic agents
  • Administration of pyridoxine, thiamine, or folic acid
  • Transfusion (along with antidotes if iron overload develops from transfusion)
  • Other medical measures
  • Bone marrow or liver transplantation

Admission and inpatient care may be needed for patients with sideroblastic anemia and cirrhosis, as well as those who have need of repeated blood transfusions. Regular follow-up is essential, even for patients with sideroblastic anemia whose condition responds to therapy.

Acute idiopathic sideroblastic anemia, refractory anemia with ring sideroblasts (RARS) or MDS must be monitored for potential transformation into acute leukemias.

Go to Anemia, Iron Deficiency Anemia, and Chronic Anemia for complete information on these topics.

Removal of Toxic Agents

Toxic agents such as zinc, lead, and drugs such as penicillamine should be removed whenever possible; however, this may not always be easy. For example, isoniazid is the mainstay of treatment of active tuberculosis, and a risk-benefit analysis of treatment discontinuation is essential for each patient.

Vitamin B Therapy


Pyridoxine (vitamin B-6) deserves a trial in all cases of sideroblastic anemia as many acquired and certain congenital forms of sideroblastic anemia respond to this relatively safe drug. The response will be evident in a few weeks with reticulocytosis and improving hemoglobin levels.

The dose should be tailored to the patient’s tolerance. Dosages up to 1 g/day have been used, but the goal is to find a dosage of pyridoxine (usually 50-200 mg/d) that will maintain the hemoglobin level and yet prevent toxicity (peripheral neuropathy). For those whose condition responds, treatment is life long.

Pyridoxal 5′ phosphate (PLP) is an active form of pyridoxine that has been successfully used in the treatment of sideroblastic anemias in some patients who do not respond to pyridoxine.[68]

Folic acid

Folic acid has been reported to reverse sideroblastic changes by itself in some patients.[69] It is advisable to replace folate in pyridoxine-responsive cases to ensure adequate supplies of ingredients during a period of increased hemoglobin synthesis.


Transfusion is the mainstay of treatment for those whose sideroblastic anemia does not respond to pyridoxine therapy.[70] It is problematic and should be avoided if the anemia is mild to moderate and the patient asymptomatic.

Even in the absence of transfusion, patients with sideroblastic anemia are prone to develop iron overload.[71] Transfusion in sideroblastic anemia has been known to worsen iron overload and lead to secondary hemochromatosis and cirrhosis. Iron overload in sideroblastic anemia can be fatal.[72]

Management of iron overload

Deferoxamine (desferrioxamine; Desferal) can be used if iron overload develops from repeated blood transfusions.[73] Although effective, it must be administered by a subcutaneous pump for several hours a day.

Deferasirox (Exjade) is a relatively new oral iron chelator that has been used instead of deferoxamine and appears to be effective. First used in Europe, it has been introduced in United States and is a once-daily pill. Renal toxicity and allergic reactions are a concern.

Phlebotomy can be performed for iron overload.[74] In some patients who do not tolerate deferoxamine therapy, this procedure is an option, but the limiting factor may be anemia.

Other Agents

Heme arginate as an infusion has been used with mixed results and is not a first-line drug.[75]

Erythropoietin (EPO) has been tried and does not appear to reverse sideroblastic anemia[76] ; it has also been reported to cause neutropenia in this setting.[77] EPO in combination with granulocyte colony-stimulating factor (G-CSF) appears to have a better response rate than EPO alone (50%).[78, 79]

Lenalidomide may reduce transfusion needs in some patients with refractory anemia with ring sideroblasts (RARS).[80]

Prednisone and danazol have not been effective,[81] except for some patients with active connective tissue disease (eg, systemic lupus erythematosus (SLE),[82] ) in whom sideroblastic changes disappear with prednisone when the SLE flare subsides.

Cytotoxic therapies such as cyclophosphamide have been tried with some success in patients with erythropoietin inhibitors, resulting in ineffective erythropoiesis.[83]

Chloroquine has been successfully used to treat pyridoxine-resistant sideroblastic anemia, but no large study has been done, and thus only limited data are available.[84] The drug affects heme metabolism and is also used in certain porphyrias.

Ubidecarenone (coenzyme Q10) has been used with mixed results in the treatment of sideroblastic anemia and is not recommended as standard of care.[85, 86]

Azacitidine and other newer agents being used for myelodysplastic syndrome (MDS) have not been specifically studied or approved for sideroblastic anemias in general.


Bone marrow

Bone marrow transplantation is a treatment of last resort and is best saved for young patients whose conditions are pyridoxine resistant[87] and transfusion dependent[88] and who have a human leukocyte antigen (HLA)-matched sibling. Even then, the response ranges from cure to death within weeks.[58] Severe graft versus host disease has been reported even with HLA-identical sibling donors.[59] The evidence is limited to a few case reports in the literature.[89, 90, 91]


Surgical intervention in cases of sideroblastic anemia may include liver transplantation for cirrhosis and iron overload that is not responsive to chelation and phlebotomy.


Transfer to the care of a hematologist is recommended, especially for cases of pyridoxine-resistant sideroblastic anemia and for patients who become transfusion dependent. Consider consultations with a neurologist for mitochondrial myopathy-anemia syndromes.



Medication Summary

In cases of sideroblastic anemia, the goals of pharmacotherapy are to reduce morbidity and prevent complications. Medications used include vitamins and antidotes to toxic metal ions.


Class Summary

Antidotes are used to decrease toxic blood levels of metal ions such as iron.

Deferoxamine mesylate (Desferal)

Deferoxamine (desferrioxamine) is usually administered as a slow subcutaneous infusion through a portable pump. It is freely soluble in water. Approximately 8 mg of iron is bound by 100 mg of deferoxamine. Deferoxamine promotes renal and hepatic excretion in urine and bile in feces. It gives urine a red discoloration.

Deferoxamine readily chelates iron from ferritin and hemosiderin but not transferrin. It does not affect iron in cytochromes or hemoglobin. It is most effective when provided to the circulation continuously by infusion. It helps prevent damage to the liver and bone marrow from iron deposition.

Deferoxamine may be administered either by intramuscular (IM) injection or by slow intravenous (IV) infusion. It does not effectively chelate other trace metals of nutritional importance. It is provided in vials containing 500 mg of lyophilized sterile drug. Two mL of sterile water for injection should be added to each vial, bringing the concentration to 250 mg/mL. For IV use, this may be diluted in 0.9% sterile saline, 5% dextrose solution, or Ringer solution.

The IM route is the preferred route of administration, except in the presence of hypotension and cardiovascular collapse, when the IV route should be considered.

Deferasirox (Exjade)

Deferasirox is supplied as a tab for oral suspension. It is an oral iron chelation agent demonstrated to reduce liver iron concentration in adults and children who receive repeated red blood cell (RBC) transfusions. It binds iron with high affinity in a 2:1 ratio.

Deferasirox is approved for treatment of chronic iron overload due to multiple blood transfusions. Treatment initiation is recommended with evidence of chronic iron overload (ie, transfusion of about 100 mL/kg packed RBCs [about 20 U for a 40-kg person] and a serum ferritin level consistently higher than 1000 µg/L).


Class Summary

Vitamins are used to meet necessary dietary requirements and are used in metabolic pathways, as well as DNA and protein synthesis.

Folic acid

Folic acid is a water-soluble vitamin used in nucleic acid synthesis. It is required for normal erythropoiesis.

Pyridoxine (Aminoxin)

Pyridoxine is necessary for normal metabolism of proteins, carbohydrates, and fats. It is also involved in the synthesis of gamma-aminobutyric acid (GABA) within the central nervous system.