Complications
As life expectancy increases, thrombotic complications are presenting more frequently, particularly in patients with thalassemia intermedia.[89]
Iron overload may lead to arthropathy due to direct iron deposition in joints.
Osteopenia or osteoporosis may occur as a result of multiple factors, such as genetics (e.g., CO-LIA 1 gene polymorphism), bone marrow hyperplasia, and endocrine dysfunction (i.e., secondary to iron overload).[83][84] Bisphosphonates and zinc sulfate supplementation have both been associated with increased bone mineral density when used in patients with beta-thalassemia.[84][85]
A Cochrane systematic review failed to find randomized controlled trials addressing the treatment of dental and orthodontic complications in individuals with thalassemia.[86]
Pigmentation and bronzing from direct iron deposition may occur.
The anterior pituitary is most often involved, resulting in slow growth, delayed sexual maturation, and often infertility, the latter being the result of direct iron deposition in the gonads.[81][82]
The pancreatic islet cells are also susceptible to the toxic effects of iron. Impaired insulin secretion and abnormal glucose tolerance usually precede the development of insulin-dependent (type 1) diabetes and may occur in highly loaded patients at any age.
Patients should be followed regularly by an endocrinologist because of the propensity for all of these complications.
Older males may experience dysfunction in sexual performance, and females may develop secondary amenorrhea related to gonadal iron deposition and disturbances in sex hormone secretion.
Thyroid dysfunction, though uncommon, may also manifest at any age. Parathyroid dysfunction may result in osteopenia or osteoporosis, particularly in patients with a more severe iron overload.[83][84] In patients with beta-thalassemia, bisphosphonates and zinc sulfate supplementation have both been associated with increased bone mineral density.[84][85]
Can be febrile, allergic, or hemolytic.
Variable likelihood, depending on blood-banking and transfusion protocols. Generally low to very low in the developed world and higher in developing countries.
Transmission of transfusion-related pathogens including bacteria, viruses (HIV, hepatitis B virus, hepatitis C virus, parvovirus, CMV), and parasites (malaria).
Patients who have transfusion-acquired hepatitis C should be regularly followed by a hepatologist. Data suggest that although transfusion requirement is substantially increased during therapy with ribavirin, successful treatment is possible for a subset of such patients.[78][79]
Variable likelihood, depending on blood-banking and transfusion protocols (including screening of donors and testing of blood products). Generally low to very low in the developed world and higher in developing countries.
Preventable to some extent with limited phenotype matching of blood products transfused, or programs to limit the number of donor exposures (using a defined cadre of donors for specific patients).
Variable likelihood, depending on blood-banking and transfusion protocols. Generally low to very low in the developed world and higher in developing countries.
Arrhythmias (supraventricular or ventricular tachycardias, ventricular and atrial premature beats, heart block, and atrial fibrillation) and contractile dysfunction leading to congestive heart failure are potential complications associated with iron overload. These may be seen as iron loading becomes progressively more severe. Often, asymptomatic arrhythmias are seen on Holter monitoring only. Separate monitoring of cardiac iron by MRI and regular evaluation by a cardiologist is strongly recommended.[80]
Splenectomized patients may have an increased susceptibility to some bacterial infections, particularly pneumococcal, and may be at risk for development of thromboembolism and pulmonary hypertension, in part as a result of thrombocytosis that usually follows the procedure. Prophylaxis with penicillin and vaccination against pneumococcus is recommended for all splenectomized patients.
The development of gallstones may be more common in beta-thalassemia intermedia than in beta-thalassemia major.[87]
The development of pulmonary hypertension may be more common in beta-thalassemia intermedia than in beta-thalassemia major.[88]
Additional complications include the development of extramedullary masses of erythropoietic tissue, especially related to the spinal column. These masses may cause pressure effects on the spinal cord and intrathoracic and intra-abdominal structures.
Leg ulcers may develop as a result of chronic anemia and hypoxia, and can be a particularly distressing and chronic problem.
Aplastic crises related to parvovirus B19 infection may develop in untransfused beta-thalassemia intermedia patients with a high red cell turnover and low marrow reserve capacity. This may require transfusional support but is generally self-limited.
With mild to moderate iron loading, the liver is not enlarged and liver function is normal. However, hepatomegaly and liver dysfunction with icterus may be seen when iron overload is severe.
Progressive loading leads to fibrosis with scarring, micronodular regeneration, and progression to cirrhosis and hepatocellular carcinoma.[76]
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