RBC Function And Disorders Of Iron Metabolism

1.

A 25-year-old female with transfusion-dependent thalassemia presents to clinic. She recently read an article on the Internet concerning thalassemia and iron overload. She asks how to prevent iron overload and liver problems.

Which of the following is the most common treatment of iron overload in patients with transfusion-dependent thalassemia?

Phlebotomy

Iron-chelating medications

Vitamin C

No treatment

Severe iron deposition resulting in cardiac, hepatic, and endocrine damage is generally seen in patients who have received 100 or more units of blood (about 20 to 25 g of iron). Obviously, phlebotomy is not an option, and the only way to prevent or treat iron overload is treatment with a chelating agent capable of complexing with iron and permitting its excretion. In sickle cell patients, exchange transfusion, or erythrocytapheresis, can limit increases in iron loading; however, chelation is still required to decrease iron stores. Three iron-chelating agents are potentially available: only two (deferoxamine and desferasirox) are approved for use in the United States.

Explanation

Severe iron deposition resulting in cardiac, hepatic, and endocrine damage is generally seen in patients who have received 100 or more units of blood (about 20 to 25 g of iron). Obviously, phlebotomy is not an option, and the only way to prevent or treat iron overload is treatment with a chelating agent capable of complexing with iron and permitting its excretion. In sickle cell patients, exchange transfusion, or erythrocytapheresis, can limit increases in iron loading; however, chelation is still required to decrease iron stores. Three iron-chelating agents are potentially available: only two (deferoxamine and desferasirox) are approved for use in the United States.

2.

A 60-year-old man with a medical history significant for diabetes mellitus and congestive heart failure presents to clinic for a routine examination. He is currently without complaint. Physical examination illustrates hepatomegaly. Routine laboratory evaluation reveals an elevated alanine aminotransferase (four times the upper limit of normal). Additional laboratory evaluation illustrates a transferrin saturation > 60% and ferritin 650 ng/mL.

What is the most likely diagnosis in this patient?

Congestive hepatopathy

Nonalcoholic steatohepatitis

Medication-related hepatopathy

Hemochromatosis

Patients present to medical attention for evaluation of chemical abnormalities of liver function or hepatomegaly, for evaluation of diabetes or hypogonadism, for arthropathy in the young, or because evaluation for nonspecific fatigue led to measurement of iron levels (usually while looking for iron deficiency anemia). This sort of nonspecific presentation is now more common than the classic tetrad of clinical signs of liver disease, diabetes mellitus, skin pigmentation, and gonadal failure. Although the combination of pancreatic dysfunction and skin pigmentation is referred to as "bronze diabetes," the skin color is more typically a faint bluish gray. Measurement of the serum transferrin saturation is usually recommended as the initial biochemical screening assay. Although individual laboratories may have their own reference ranges, a repeated value greater than 45% in women or 50% in men is usually accepted as the threshold value for further investigation. The serum ferritin concentration is then measured as a biochemical indicator of iron overload, and in the absence of complicating factors, a ferritin concentration greater than 300 µg/L suggests increased iron stores. Some advocate using a ferritin concentration of 1,000 µg/L, arguing that it is a more specific indicator of patients at risk for clinical disease.

Explanation

Patients present to medical attention for evaluation of chemical abnormalities of liver function or hepatomegaly, for evaluation of diabetes or hypogonadism, for arthropathy in the young, or because evaluation for nonspecific fatigue led to measurement of iron levels (usually while looking for iron deficiency anemia). This sort of nonspecific presentation is now more common than the classic tetrad of clinical signs of liver disease, diabetes mellitus, skin pigmentation, and gonadal failure. Although the combination of pancreatic dysfunction and skin pigmentation is referred to as "bronze diabetes," the skin color is more typically a faint bluish gray. Measurement of the serum transferrin saturation is usually recommended as the initial biochemical screening assay. Although individual laboratories may have their own reference ranges, a repeated value greater than 45% in women or 50% in men is usually accepted as the threshold value for further investigation. The serum ferritin concentration is then measured as a biochemical indicator of iron overload, and in the absence of complicating factors, a ferritin concentration greater than 300 µg/L suggests increased iron stores. Some advocate using a ferritin concentration of 1,000 µg/L, arguing that it is a more specific indicator of patients at risk for clinical disease.

3.

A 65-year-old man with hypertension presents to clinic with a complaint of fatigue and dizziness. Physical examination demonstrates conjunctival pallor and tachycardia. Routine laboratory evaluation reveals hemoglobin 10 mg/ dL, hematocrit 30%, and mean corpuscular volume 72 fL. Additional laboratory evaluation illustrates iron defi ciency anemia.

Which of the following is the next best step in the management of the patient's iron deficiency anemia?

Gastrointestinal evaluation for blood loss

Oral ferrous sulfate

Intravenous iron dextran

Dietitian consultation

It is important to recognize that management of iron defi ciency includes investigation of the etiology of iron loss. In young menstruating or recently postpartum women without clinical evidence of blood loss elsewhere, it is reasonable to attribute iron deficiency to menses or childbirth. For other patients, gastrointestinal investigation (including endoscopy) is usually required. Therapy for iron deficiency anemia should both correct the hemoglobin deficit and replace storage iron.

Explanation

It is important to recognize that management of iron defi ciency includes investigation of the etiology of iron loss. In young menstruating or recently postpartum women without clinical evidence of blood loss elsewhere, it is reasonable to attribute iron deficiency to menses or childbirth. For other patients, gastrointestinal investigation (including endoscopy) is usually required. Therapy for iron deficiency anemia should both correct the hemoglobin deficit and replace storage iron.

4.

A 22-year-old African-American male comes to clinic for a routine examination. He is currently without complaint. His physical examination is unremarkable. Routine laboratory evaluation reveals hemoglobin of 10 mg/dL, hematocrit 30%, and mean corpuscular volume 66 fL. Upon further questioning, he denies bleeding. Additional testing reveals normal mean corpuscular hemoglobin concentration, red cell distribution width, and ferritin. Review of his previous records illustrates anemia throughout his childhood.

Which of the following is the most likely cause of the patient's anemia?

Iron deficiency anemia

Sickle cell anemia

Thalassemia

Vitamin B12 deficiency

Traditional red cell indices such as the mean corpuscular volume, mean corpuscular hemoglobin concentration, and red cell distribution width have some utility in the diagnosis of iron deficiency but may be abnormal in other disorders and so are not specific. A low mean corpuscular volume with a normal mean corpuscular hemoglobin concentration and normal red cell distribution width favors a diagnosis of thalassemia rather than iron deficiency anemia. Other red cell indices that can be derived by the newer generations of automated hematology analyzers, such as the proportion of hypochromic red cells and reticulocyte corpuscular hemoglobin, appear to have some utility in the identifi cation of iron deficient erythropoiesis even before iron deficiency anemia develops. Their role in practice is still evolving. Free erythrocyte protoporphyrin, also called zinc protoporphyrin, is elevated in iron deficiency but is rarely used in practice.

Explanation

Traditional red cell indices such as the mean corpuscular volume, mean corpuscular hemoglobin concentration, and red cell distribution width have some utility in the diagnosis of iron deficiency but may be abnormal in other disorders and so are not specific. A low mean corpuscular volume with a normal mean corpuscular hemoglobin concentration and normal red cell distribution width favors a diagnosis of thalassemia rather than iron deficiency anemia. Other red cell indices that can be derived by the newer generations of automated hematology analyzers, such as the proportion of hypochromic red cells and reticulocyte corpuscular hemoglobin, appear to have some utility in the identifi cation of iron deficient erythropoiesis even before iron deficiency anemia develops. Their role in practice is still evolving. Free erythrocyte protoporphyrin, also called zinc protoporphyrin, is elevated in iron deficiency but is rarely used in practice.

5.

A 60-year-old man, recently diagnosed with hemochromatosis, presents to discuss treatment options. He has heard of iron supplementation, herbal medications, and phlebotomy.

Which of the following is the best treatment option in this patient?

Plasmapheresis

Iron-chelating agents

Weekly to biweekly phlebotomy until the patient nears iron deficiency

Iron

Iron removal therapy is always indicated for patients with hereditary hemochromatosis, even when cirrhosis or organ damage is already present, because further progression of the disease can be slowed or arrested, and alleviation of some organ dysfunction is possible. The treatment of choice for hereditary hemochromatosis is phlebotomy to reduce the body iron levels to normal or near-normal and maintain them in that range. The use of iron-chelating agents instead of phlebotomy in patients with hereditary hemochromatosis and severe hemodynamically unstable heart failure in lieu of phlebotomy has been reported. Phlebotomy therapy should be started as soon as the diagnosis of the homozygous state for hereditary hemochromatosis has been established; postponement only increases the risk of organ damage from iron overload. The phlebotomy program should remove 500 mL of blood (containing 200 to 250 mg of iron) once weekly or, for heavily loaded patients, twice weekly until the patient approaches iron deficiency. Before each phlebotomy, the hematocrit or hemoglobin concentration should be measured.

Explanation

Iron removal therapy is always indicated for patients with hereditary hemochromatosis, even when cirrhosis or organ damage is already present, because further progression of the disease can be slowed or arrested, and alleviation of some organ dysfunction is possible. The treatment of choice for hereditary hemochromatosis is phlebotomy to reduce the body iron levels to normal or near-normal and maintain them in that range. The use of iron-chelating agents instead of phlebotomy in patients with hereditary hemochromatosis and severe hemodynamically unstable heart failure in lieu of phlebotomy has been reported. Phlebotomy therapy should be started as soon as the diagnosis of the homozygous state for hereditary hemochromatosis has been established; postponement only increases the risk of organ damage from iron overload. The phlebotomy program should remove 500 mL of blood (containing 200 to 250 mg of iron) once weekly or, for heavily loaded patients, twice weekly until the patient approaches iron deficiency. Before each phlebotomy, the hematocrit or hemoglobin concentration should be measured.