Management of age-associated medical complications in patients with β-thalassemia

ABSTRACT

Introduction: β-Thalassemia syndromes are among the most common monogenic disorders worldwide. Clinically, on the basis of the severity of the phenotype, β-thalassemias are classified into two groups: transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). In the last few decades, considerable advances in understanding the pathophysiology of β-thalassemia have significantly improve d patient management, which has led to an increase in the life span of these subjects. However, new complications associated with aging are emerging, and β-thalassemias are becoming a growing concern for the health care systems.

Areas covered: The present review focused on the age-related complications in adults with β-thalassemia. Among the cardiovascular diseases, which remain a major cause of morbidity, pulmonary hypertension and arrhythmias are exhibiting increased prevalence. Adrenal insufficiency and bone disease are emerging as endocrinological complications that require proper treatment. Moreover, age-related complications observed in the general population, including cancers and renal disease, should not be neglected.

Expert opinion: The present study reviews the management of above-stated complications in adults with β-thalassemia based on the experience of a referral center. It is noteworthy that clinical trials in this context are limited, and the expert opinion offered in the present report stems mainly from direct clinical experience.

KEYWORDS:

• Adrenal insufficiency
• anemia
• arrythmias
• bone disease
• cancer
• cardiovascular disease
• iron overload
• pulmonary hypertension
• renal disease
• thalassemia

Article highlights

• Owing to well-established standardized treatment, including transfusions and iron chelation, significant improvement has been observed in the survival of β-thalassemia patients. As a consequence, age-related complications associated with this condition, which were uncommon in the past, are emerging now.

• Cardiovascular diseases remain a significant cause of morbidity, and arrhythmias are becoming more prevalent in adults who have exhibited iron overload in the past. Arrhythmias should be treated as in the general population. Ablation strategy should be considered in selected cases, although specific recommendations for this are missing.

• Bone disease is multifactorial and exerts a significant impact on the patients’ quality of life because of the associated pain and functional limitations. Supplementation of Vitamin D and calcium and bisphosphonates therapy are the most prescribed treatments in this case. Denosumab or Teriparatide may be prescribed for selected patients.

• In the case of low or borderline basal cortisol levels, a stimulation test with Synachten is necessary in order to identify adrenal insufficiency which would require appropriate replacement therapy.

• Hepatocellular carcinoma and the other solid and hematological tumors should be treated as in the general population, considering patient comorbidities and performance status.

• Renal dysfunction should be carefully monitored. Adjustment of the chelation therapy and deprescribing is advised in order to minimize toxicity.

Declaration of interest

I Motta has received honoraria from and is a member of an advisory board for Sanofi-Genzyme. MD Cappellini is a member of Vifor, Sanofi-Genzyme, Celgine, Novartis and Bluebird advisory boards. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.