A 35-year-old man is evaluated during a routine visit for β-thalassemia intermedia. One year ago, he began requiring erythrocyte transfusions every 4 to 6 months for symptomatic anemia. He has no other symptoms or medical problems, and his only medication is folic acid.
On physical examination, vital signs are normal. Frontal bossing, macrocephaly, scleral icterus, and splenomegaly are present and unchanged from previous examination. The remainder of the physical examination is unremarkable.
Laboratory studies show a hemoglobin level of 7.9 g/dL (79 g/L), leukocyte count of 6400/μL (6.4 × 109/L), and platelet count of 110,000/μL (110 × 109/L). Iron studies were at the higher limit of normal one and a half years ago.
Which of following is the most appropriate additional management?
A. Abdominal ultrasonography
B. Iron studies
C. Prophylactic anticoagulation
MKSAP Answer and Critique
The correct answer is B. Iron studies. This content is available to MKSAP 19 subscribers as Question 38 in the Hematology section. More information about MKSAP is available online.
Iron studies are the most appropriate additional management (Option B). In patients with thalassemia, iron overload–related heart failure and/or arrhythmias are the major cause of death. Baseline iron studies should be obtained, and serial measurements of serum ferritin can monitor iron stores, particularly if transfusion requirements increase. In addition to standard cardiac assessment with electrocardiography and echocardiography, MRI is used to monitor cardiac and hepatic iron stores. This patient has many of the manifestations of β-thalassemia, including anemia, extramedullary hematopoiesis, hepatosplenomegaly, and bone marrow space expansion with characteristic skeletal changes. Patients often remain transfusion independent during childhood and young adulthood but require transfusions beginning in the third and fourth decades of life. Heightened gastrointestinal absorption of iron that accompanies ineffective erythropoiesis adds to the transfusion-related iron overload. Excess iron deposition in the organs can lead to arrhythmia and heart failure, cirrhosis and portal hypertension, and endocrinopathies (diabetes, hypopituitarism, hypogonadism). Patients should avoid iron supplementation, and transfusions should be performed judiciously. Patients with secondary iron overload require chelation therapy with parenteral desferrioxamine or oral iron chelators (deferasirox or deferiprone) before the onset of end-organ damage.
Like patients with chronic hemolytic anemias, patients with thalassemia are at increased risk for pigment gallstones. For patients without symptoms attributable to gallstones, neither routine screening with abdominal ultrasonography nor prophylactic cholecystectomy is recommended (Option A). For patients undergoing splenectomy, cholecystectomy is an option that can be discussed with the surgical team.
Patients with thalassemia are at increased risk for venous thromboembolism, and the risk increases following splenectomy. However, no evidence-based recommendations support prophylactic anticoagulation or antiplatelet therapy in asymptomatic patients with thalassemia (Option C). Physicians and patients should be aware of the increased risk and have a low threshold to investigate suspicious symptoms.
In select adult patients with thalassemia, splenectomy may be indicated (Option D). Generally agreed upon indications include severe anemia resulting from thalassemia, sudden and dramatic increase in transfusion requirements, hypersplenism-related cytopenias, and symptomatic splenomegaly (abdominal fullness, pain, early satiety). This patient has no indication for splenectomy at this time.
- Iron overload–related heart failure and arrhythmias are the major causes of death in patients with thalassemia.
- In patients with thalassemia, iron stores can be monitored with serial serum ferritin measurements, and MRI can monitor cardiac and hepatic iron stores.