MKSAP Quiz: Evaluation for worsening fatigue
A 76-year-old woman is evaluated for worsening fatigue. She reports no additional symptoms. Medical history is significant for myelodysplastic syndrome diagnosed 3 years ago. Following a physical exam and lab studies, what is the most appropriate management?
A 76-year-old woman is evaluated for worsening fatigue. She reports no additional symptoms. Medical history is significant for myelodysplastic syndrome diagnosed 3 years ago, which has required the transfusion of 1 to 2 units of blood every 5 to 6 weeks to maintain a hemoglobin level of approximately 8 g/dL (80 g/L); she has exertional dyspnea when the hemoglobin level drops below 7 g/dL (70 g/L).
On physical examination, vital signs are normal. The abdomen is soft. Conjunctival pallor is noted. The examination is otherwise noncontributory.
Laboratory studies show a hemoglobin level of 7.5 g/dL (75 g/L) and a serum ferritin level of 1638 ng/mL (1638 µg/L).
Which of the following is the most appropriate management?
A. Begin deferasirox
B. Begin succimer
C. Perform therapeutic phlebotomy
D. Withhold transfusion until hemoglobin level is 6 g/dL (60 g/L)
MKSAP Answer and Critique
The correct answer is A. Begin deferasirox. This content is available to MKSAP 18 subscribers as Question 32 in the Hematology and Oncology section. More information about MKSAP is available online.
This patient should begin deferasirox for treatment of secondary iron overload. In most cases, secondary iron overload occurs in patients with severe anemia who require chronic transfusion therapy. Because iron excretion has no regulated mechanism, multiple transfusions (for anemias not stemming from blood loss or iron deficiency) lead to iron overload, with subsequent secondary organ damage. If these anemias resolve (either from hematopoietic stem cell transplantation or remission of leukemias), phlebotomy should be initiated. When anemia is ongoing, such as in this patient, iron chelation is required, for which deferoxamine or deferasirox may be used. These agents are relatively toxic, leading to potential kidney and liver damage, agranulocytosis, or ocular and ophthalmic disorders; therefore, careful monitoring is required. Serum ferritin level correlates with iron burden in patients receiving chronic transfusion, and levels greater than 1000 ng/mL (1000 µg/L) are generally considered an indication for therapy. Deferoxamine is only available for parenteral administration, which is much less convenient in the long-term outpatient setting than oral iron chelation. The availability of oral iron chelation with deferasirox has increased medication adherence for patients who develop secondary iron overload from chronic transfusions for hemoglobinopathies or myelodysplastic syndrome. Deferasirox commonly causes gastrointestinal side effects. The medication is often better tolerated in the evening, before the evening meal.
Succimer is used to chelate lead and enhance excretion in patients with chronic lead intoxication. It would not be used to treat iron overload.
Therapeutic phlebotomy is the management of choice for hereditary (primary) hemochromatosis. It effectively removes 200 mg of iron with each pint of blood removed. However, therapeutic phlebotomy is not suitable for patients with symptomatic anemia who require chronic transfusion, as is the case with this patient.
Withholding transfusion is not appropriate because of this patient's age and her symptomatic anemia.
Key Point
- Secondary iron overload from chronic transfusions can be effectively treated with oral chelation agents, such as deferasirox.