A 9-year-old boy with beta thalassemia major comes to the office for a routine red blood cell transfusion. He was diagnosed at age 6 months and has since received numerous blood transfusions and chelation therapies. The patient has tolerated each transfusion and chelation therapy well with no immediate reactions or side effects. Vital signs are normal. On physical examination, the boy has mild frontal bossing, hepatosplenomegaly, and jaundice. A recent liver biopsy showed Kupffer cells containing coarse, yellowish-brown cytoplasmic granules. The granules are most likely composed of which of the following?

Question

A 9-year-old boy with beta thalassemia major comes to the office for a routine red blood cell transfusion.  He was diagnosed at age 6 months and has since received numerous blood transfusions and chelation therapies.  The patient has tolerated each transfusion and chelation therapy well with no immediate reactions or side effects.  Vital signs are normal.  On physical examination, the boy has mild frontal bossing, hepatosplenomegaly, and jaundice.  A recent liver biopsy showed Kupffer cells containing coarse, yellowish-brown cytoplasmic granules.  The granules are most likely composed of which of the following?

Quizplus · Accepted Answer

Patients with chronic hemolytic anemia (eg, beta thalassemia major) depend on recurrent red blood cell (RBC) transfusions to maintain an adequate hemoglobin level. Iron overload (hemosiderosis) from increased iron absorption is a common complication resulting from both the primary condition (eg, hemolysis) and its treatment (frequent RBC transfusions). Circulating iron is carried by transferrin. Once deposited in cells, iron binds to apoferritin to form ferritin micelles. Because iron is utilized poorly in patients with thalassemia and cannot be excreted actively, the ferritin micelles accumulate in macrophages of the reticuloendothelial system. The resulting iron-storage complex is known as hemosiderin and microscopically appears as brown or yellowish-brown pigments in either granular or crystalline form. Hemosiderin can be identified histologically with a Prussian-blue stain. In the liver, hemosiderin is typically seen in Kupffer cells (hepatic macrophages that line the walls of the sinusoids and participate in RBC breakdown). Patients receiving regular transfusions should undergo routine iron chelation therapy to reduce the overall iron load within the body and improve survival. Eventually, the iron burden will overwhelm the reticuloendothelial cells' capacity to sequester iron, resulting in parenchymal iron overload in the liver, myocardium, skin, and pancreas (eg, "bronze diabetes"). (Choice A) Amyloid protein has a pale rose color after Congo red staining. Accumulation of amyloid fibrils can result in a variety of sequelae (eg, cardiomyopathy, nephrotic syndrome). (Choice B) Bilirubin is the primary pigment found within bile and is a byproduct of hemoglobin breakdown. Hemolytic anemia commonly results in indirect hyperbilirubinemia and jaundice. (Choice C) Copper accumulation is seen in Wilson disease, an autosomal recessive disease characterized by cirrhosis and neurologic complications. (Choice D) Glycogen appears as clear cytoplasmic vacuoles and stains pinkish purple with the periodic acid-Schiff reaction. Glycogen is abundant in the liver shortly after a meal. (Choice E) Patients with Gaucher disease (glucocerebrosidase enzyme deficiency) have pancytopenia, hepatosplenomegaly, and pathologic fractures. The cardinal histologic finding are Gaucher cells (black arrows), which are macrophages laden with cerebrosides and other glycolipids. (Choice G) Lipofuscin is an insoluble yellow-brown pigment composed of lipids and phospholipids complexed with proteins. This pigment accumulates with age and "wear and tear" of multiple organs. Educational objective: Iron overload (hemosiderosis) is a common and serious complication of chronic hemolytic anemia and frequent blood transfusions. Hemosiderin accumulation is the cardinal histologic finding. Chelation therapy is indicated to reduce parenchymal iron deposition. __________ References: Iron overload syndromes and the liver. (http://www.ncbi.nlm.nih.gov/pubmed/17486050) Iron overload in Beta thalassaemia major and intermedia patients. (http://www.ncbi.nlm.nih.gov/pubmed/24790662)

A 9-Year-Old Boy with Beta Thalassemia Major Comes to the Office