19.0 - THALASSEMIA INTERMEDIA
Thalassemia intermedia is a severe disease, and special care needs to be made to assure proper treatment and care. Thalassemia intermedia is difficult to diagnose, and there are many variants which need to be considered.
Thalassemia intermedia is a more serious thalassemia syndrome than previously thought and frequently does not receive the attention it deserves. It is vital that people with thalassemia intermedia be monitored closely throughout life. Unlike thalassemia major, where the level of anemia makes transfusion mandatory, thalassemia intermedia patients may not have hemoglobin levels low enough to warrant mandatory blood transfusion and regular care. However, progression of both the anemia and ineffective erythropoiesis may eventually result in serious complications. This important group of patients suffers immeasurably due to an unpredictable degree of anemia and course of treatment; therefore, following standards of care is of utmost importance.
Many of the complications noted in thalassemia major occur in thalassemia intermedia. These complications result from ineffective erythropoiesis, anemia, dietary iron absorption, and inadequate transfusion. Patients with thalassemia intermedia experience bone changes, endocrinopathies, osteoporosis, cardiac disease, pulmonary hypertension, and chronic bone and joint pain. The extent of these complications affects intervention and initiation of treatment. Beyond supportive treatment, treatment modalities involve transfusions, splenectomy, and medications that increase hemoglobin F synthesis. Occasionally, attention should be given to treatment of specific complications, including iron overload, pulmonary hypertension, osteoporosis, and gallstones.
19.1 Nontransfused thalassemia intermedia
A baseline red blood cell phenotype should be obtained from patients, who should then be seen at a thalassemia center every three to six months, with attention to overall clinical well-being, anthropometrics as described for thalassemia major, changes in exercise tolerance, complaints of pain and/or shortness of breath, CBC, reticulocyte count, and ferritin levels.
A low-iron diet and drinking tea with meals to decrease absorption of iron is recommended. If zinc level is low, patients should be put on supplementation. Daily supplementation of 1 mg folic acid should also be taken. Patients should receive immunizations as outlined for thalassemia major patients.
19.1.1 Growth and development
Look for changes in facial bone structure. For growing children, obtain biannual skull X-rays and facial photographs: anterior/posterior and lateral. Pay attention to growth velocity, especially in young children and in adolescents. Patients should have annual dental and orthodontic evaluations and be observed for delayed or arrested puberty. Some patients have excessive growth of their heads even with only mild anemia. This in itself could be an indicator for transfusion therapy. Therefore, close monitoring of the head circumference is necessary.
19.1.2 Extramedullary erythropoiesis
Tumor masses of extramedullary erythropoietic tissue are a common complication of the nontransfused thalassemia patient. These often occur in the paraspinal areas, and are asymptomatic. However, some cases lead to spinal cord compression and acute neurologic complications. Transfusion therapy often decreases their size and prevents further growth. Rarely, emergency intervention is necessary.
Osteopenia and osteoporosis should be assessed annually or every two years via DXA scan. Bone pain and fractures should be an emphasis.
Fertility should be assessed on an individual basis. Transfusion support during pregnancy should also be considered.
19.1.4 Cardiopulmonary assessment
Adults should have an annual echocardiogram for early detection of left heart decompression, and TR jet, which detects pulmonary hypertension. Those with existing pulmonary hypertension should have an annual pulmonary function test and a six-minute walk test.
19.1.5 Considerations for transfusions
The decision to start regular transfusions depends on clinical and laboratory assessment. This decision is not necessarily a permanent commitment to lifelong transfusion. Such decisions are difficult and best made at a thalassemia center.
Indications that might be considered before starting chronic transfusion include the following:
- In childhood, growth failure, delayed puberty, or poor school performance
- Symptomatic anemia
- Skeletal malformation or bone disease
- Pulmonary hypertension with or without left heart decompression
Transient transfusions may also be considered during pregnancy or times of infection.
19.1.6 Considerations for splenectomy
Splenectomy is reserved for cases of massive splenomegaly or hypersplenism, or instances where patients are unable to be transfused. The benefits and complications of transfusions and splenectomy need to be discussed with the family.
The general recommendations for endocrine and iron-status monitoring outlined for thalassemia major should be applied to patients with thalassemia intermedia. After the initial evaluations, the frequency of monitoring can be modified based on the degree of iron loading or growth failure.
19.1.7 Assessment of iron overload
Ferritin and iron saturation levels should be monitored annually. If the ferritin levels are persistently greater than 1,000 ng/mL or the iron saturation is greater than 60 percent, obtain a quantitative assessment of liver iron. Use the guidelines in Section 5 for the administration of deferasirox or deferoxamine. When a thalassemia intermedia patient does not get transfused, the iron burden develops from increased gastrointestinal absorption only, so drug dosing may need to be modified. Consultation with an iron chelation specialist is recommended.