Approach Considerations
Thalassemia intermedia therapy is aimed not only at treating the anemia, but also at addressing iron overload and inhibiting the clinical consequences of ineffective erythropoiesis.
Clinical Management
The treatment of most cases of thalassemia intermedia involves close monitoring and observation, with pediatric patients being monitored for such characteristics as adequate growth, appropriate development, and skeletal deformities. [1] Clinicians should strive to prevent all patients from suffering complications from extramedullary hematopoiesis and iron overload.
Blood transfusions
Patients undergo transfusions as needed, most often in response to stressors such as illness, pregnancy, surgery, and periods of rapid growth. [1] In later life, some patients become transfusion dependent. When regular transfusions are deemed necessary, many clinicians target a pretransfusion hemoglobin of around 9.5-10 g/dL as a means of suppressing bone marrow activity. [1] Evidence of cardiopulmonary compromise, significant extramedullary hematopoiesis, poor growth and development, and functional impairment all suggest that chronic transfusion therapy is required. In the the OPTIMAL CARE study, transfused thalassemia intermedia patients experienced fewer complications related to chronic anemia, ineffective erythropoiesis, and hemolysis (extramedullary hematopoiesis, pulmonary hypertension, thromboembolic events), while suffering higher rates of iron overload–related endocrinopathy [16] .
Lowering the risk of transfusion complications involves efforts such as extended cross-matching to prevent alloimmunization and leukocyte depletion to reduce febrile nonhemolytic reactions. (See also Transfusion and Autotransfusion, Transfusion-Induced Iron Overload, Alloimmunization From Transfusions, and Transfusion Reactions.)
Chelation therapy
Even without chronic transfusion, iron overload can develop in the presence of beta thalassemia intermedia consequent to increased iron absorption from the gut. [1] Available chelation therapy agents include deferoxamine (parenterally administered) and deferiprone and deferasirox (both orally administered). With the introduction of deferiprone and deferasirox, deferoxamine, due to its cumbersome administration schedule, fell out of favor in North America and Europe.
A 5-year, prospective European study reported on 555 children and adults who were divided into two groups, the first of which was treated with deferasirox for a total of 5 years (deferasirox cohort), and the second of which was started on deferoxamine for the first year and then switched to deferasirox (cross-over cohort). At the end of the treatment period, a liver biopsy was obtained and hepatic iron content (HIC) was measured in the two groups and compared with the initial level before treatment. In the deferasirox cohort, HIC decreased by 7.8 ±11.2 mg Fe/g dry weight. In the cross-over cohort, the decrease was somewhat less, at 3.1 ±7.9 mg Fe/g dry weight. [17]
These findings support the long-term efficacy of this oral chelating agent, which also was proven to be safe with only minimal adverse effects reported, including increased blood creatinine in 11.2%, abdominal pain in 9%, and nausea in 7.4%. No adverse effects on growth in children or sexual development in adolescents were noted. [17]
Patients should be started on chelation therapy under the following circumstances:
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The liver iron concentration is 5 mg Fe/g dry weight or greater
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The serum ferritin level is 800 ng/mL or greater
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In cases when evaluation of the liver iron concentration is not possible, the serum ferritin level is in the range between greater than 300 and less than 800 ng/mL, and other clinical or laboratory measures point to iron overload
Chelation therapy is aimed at obtaining a liver iron concentration of 3 mg Fe/g dry weight or a serum ferritin level of 300 ng/mL. [4]
Paraspinal extramedullary hematopoietic pseudotumors
Prompt evaluation for paraspinal extramedullary hematopoietic pseudotumors should conducted, via spinal MRI, in patients with beta thalassemia in whom the symptoms and signs of spinal cord compression are present. [4] Urgent referrals should be made to neurology, neurosurgery, and radiational oncology so that a multiple disciplinary decision can be made regarding treatment. Stimulation of fetal hemoglobin by way of a short course of hypertransfusion and hydroxyurea can be used to treat mild symptoms. [1] Low-dose radiotherapy and steroids can also be considered. Laminectomy may be required to address severe symptoms that fail to respond to medical therapy. [1] Caution should be taken with a laminectomy, as immediate total resection of extramedullary hematopoietic pseudotumors can result in clinical deterioration due to acute loss of hematopoietic centers.
Thromboprophylaxis
Beta thalassemia intermedia is associated with a hypercoagulable state, with splenectomized patients especially at risk for thrombotic events. Although there are no available results from clinical trials on the use of antiplatelet or anticoagulant therapy for thrombosis prevention, data suggest that aspirin use prevents thrombosis recurrence in splenectomized beta thalassemia intermedia patients. [16]
Surgical Intervention
Splenectomy
Splenectomy should be reserved for patients with massive splenomegaly, worsening pancytopenia, or hypersplenism. Among its many risks, the greatest dangers related to splenectomy are postsplenectomy sepsis and thrombosis, with these being particular hazards in patients with beta thalassemia intermedia. Observational studies suggest that following splenectomy, the risks for venous thromboembolism, pulmonary hypertension, and leg ulcers are raised five-, four-, and four-fold, respectively, in patients with beta thalassemia intermedia, with the likelihood of silent cerebral infarcts also increased. [16, 18, 1]
Bone marrow transplantation
In patients with severe thalassemia intermedia who require aggressive therapy to sustain life, bone marrow transplantation, similar to that performed in patients with thalassemia major, is a reasonable alternative to transfusion and chelation if a matched sibling donor is available.
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Peripheral blood film in thalassemia intermedia.
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Basophilic stippling in thalassemia intermedia.
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Nucleated red blood cell in thalassemia intermedia.
