Pathology > Basic Hematology > Red Cell Disorders > Sideroblastic Anemia

Sideroblastic Anemia

Sideroblastic anemias are usually associated with microcytosis and hypochromia and thus must be distinguished from the anemias of iron deficiency and thalassemia.

Although adequate iron is present, a mitochondrial defect (decreased activity of D-ALA or ferrochelatase) prevents the incorporation of iron into hemoglobin.

Instead iron accumulates in mitochondria ringing the red cell nucleus forming "ringed sideroblasts".

Most sideroblastic anemias are acquired and are associated with drugs (alcohol*, isoniazid, chloramphenicol, cytotoxic agents, and other Vit B6 antagonists), heavy metals (lead), and various hematologic, neoplastic and inflammatory diseases.

*Ethanol abuse is the most common cause.

Non-heme iron accumulates in RBC mitochondria surrounding the nucleus instead of cytoplasmic ferritin. A ring of iron is seen as opposed to the normal situation where only a few (<4) small aggregates of iron (ferritin) are present.

Sideroblastic anemias may be either hereditary or acquired.

The hereditary form is an X-linked recessive trait with variable expression.

Hereditary sideroblastic anemias are usually microcytic/hypochromic and thus must be distinguished from iron deficiency and thalassemia.

Anisocytosis (increased RDW) due to microcytic and normocytic RBCs and basophilic stippling are common.

Because iron is not being used transferrin saturation is elevated (>80%) and serum LDH is increased (ineffective erythropoiesis).

Acquired sideroblastic anemia is often the earliest evidence of a myelodysplastic syndrome (MDS) - refractory anemia with ringed sideroblasts. The ringed sideroblasts of MDS are accompanied by dysplasia of myeloid and megakaryoctic cell lines and should be classified as one of the myelodysplastic syndromes. See White Cell Disorder Section.

Acquired sideroblastic anemia frequently demonstrates a "dimorphic" RBC population [microcytic and macrocytic RBCs (increased RDW)], basophilic stippling, ovalocytes, and other evidence of poikilocytosis.

Hereditary sideroblastic anemia often responds to pyridoxine (Vitamin B6) therapy, but the acquired form rarely responds.

In pyridoxine responsive sideroblastic anemia D-ALA synthetase is impaired, probably a result of D-ALA synthetase destruction by mitochrondrial proteases.

Blood transfusions may be necessary because of the ineffective erythropoiesis of sideroblastic anemia. In time iron overload can be a problem.

Would you expect a high or a low reticulocyte count in sideroblastic anemia ?

 

Lead poisoning inhibits porphobilinogin synthetase. Coproporphyrin and ALA spill into the urine (not porphobilinogin as in congenital porphyrias). Globin synthesis is also inhibited by lead.

The anemia is usually microcytic; with basophilic stippling; ringed sideroblasts; increased serum Fe, but may be hemolytic.

Symptoms include abdominal pain with constipation; metabolic acidosis, and may lead to shock, coma and death.

Pb is a common cause of poisoning in children.

Pb poisoning is treated with the chelating agent desferrioxamine.

What causes the basophilic stippling shown above

 

 

HEMATOPATHOLOGY

A 26-year-old black man comes to you because of intermittent right upper quadrant abdominal pain. He has a fever and you note jaundice. You order an ultrasound of his abdomen and find multiple gallstones. Lab results:

Hct = .36 L/L; Hgb = 120 g/L. PBS at right.

Your most likely diagnosis:

A. Autoimmune hemolytic anemia
B. Sickle cell anemia
C. Sickle cell trait
D. G-6-PD deficiency
E. Pyruvate kinase deficiency

Continue with the next question before checking the answer

 

 

One year later he (same man as in the previous question) returns because of extreme lethargy. His laboratory results at this time:

Hct = .13 L/L; Hgb = 4.3 g/L; WBC 5,500 /mL;

plts 275,000/mL; retics 0.2%.

At this point the most likely complication is:

A. Acute cholecystitis
B. Parvovirus infection
C. Expansion of his lymphoma
D. Sickle cell vaso-occlusive crisis
E. Exposure to antioxidant drugs/chemicals

 

A 55 year old man is brought to the ER because of abdominal cramping. He is belligerent. He complains of weight loss and has not been eating. You note pallor of his conjuctiva and skin. His Hct = .22L/L; Hgb = 72g/L; MCV = 105 fL. The PBS shows a basophilic stippling and hypochromia. The bone marrow aspirate Fe stains is at right.

Based on the history and findings what should you be considering in your differential?

A. Lead posioning
B. Megaloblastic anemia
C. Pyridoxine deficiency
D. Myelodysplasia - refractory anemia with ringed sideroblasts
E. All of the above are likely

 

You order Pb levels on this patient (from previous question) which come back normal. At a followup visit you should be especially curious about his history of:

A. Hepatitis
B. Alcohol use
C. Dietary Fe intake
D. Fava bean ingestion
E. Recent blood transfusions

 

A 60 year-old Italian woman with a 35 pack year history of cigarette-smoking. Following onset of a cough productive of sputum she is started on a course of ampicillin. She does not improve, becoming increasingly weak and SOB.

Her Hct = .28L/L; Hgb = 92g/L; MCV = 118fl;
Plts = 350 x 109/L; WBC=9.2 x 109/L.
The PBS is at right.

Based on the history and findings what is your is your most likely diagnosis?

A. B-thalassemia
B. Hypothyroidism
C. G-6-PD deficiency
D.Small cell carcinoma
E. Mycoplasma pneumonia

 

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