Thalassemia is a prevalent hereditary hemoglobinopathy affecting an estimated 4.4 in 10,000 live births worldwide.1 Although improvements in the understanding and management of the disease have increased life expectancy for these patients, they require close monitoring to detect potential complications such as iron overload, erythrocyte alloimmunization, infections, and allergic or hemolytic transfusion reactions.2

However, recent findings suggest that adherence to this recommended practice is suboptimal. In a study published in Scientific Reports in June 2021,3 researchers compared patterns in the monitoring of thalassemia complications at a tertiary hospital in Thailand during the 3 years before and after the Thalassemia International Federation (TIF) clinical practice guidelines4 were released in 2014.

“Thailand has one of the largest thalassemia populations in the world with a prevalence of more than 600,000, while the estimated prevalence in the United States is far lower,” according to American Society of Hematology expert Alexis Thompson, MD, MPH, chief of the division of hematology at the Children’s Hospital of Philadelphia.3 Although the true prevalence of thalassemia in the United States is unknown, researchers have found that 1 in 10,000 newborns in California has an alpha-thalassemia syndrome.5 “The spectrum of thalassemia complications is similar in the US, though the burden in Thailand is much greater with individuals who have more advanced complications.”

Continue Reading

Based on medical records from 524 adult patients treated in 3 different types of clinical practices at the same hospital, the most commonly observed complications in the 2021 study were osteopenia/osteoporosis (69.8%), gallstones (67.6%), and low vitamin D levels (67.6%).

Although iron overload (93.1%) and liver function (82.3%) were frequently evaluated, most other complications were assessed less often, including diabetes mellitus or impaired fasting glucose (70.6%). Hepatitis B and C, hypothyroidism, and gallstones were evaluated in roughly 45% of cases, and cortisol, vitamin D, and osteopenia/osteoporosis were assessed in less than 25% of cases.

The results also demonstrated that monitoring for these various complications increased in thalassemia clinics after publication of the TIF guidelines, but not in private hematology and internal medicine clinics.

“I think this paper highlights the need to increase awareness of thalassemia, especially focusing on the needs of this population for consistent, high-quality care and compliance with guidelines in order to avoid preventable morbidity,” Dr Thompson said. “Awareness includes physician training and patient education, but also advocacy for governmental agencies to provide more resources to improve access to treatment.”

For additional insights regarding the state of care for this patient population, we interviewed Srila Gopal, MBBS, hematologist and medical director of the Adult Sickle Cell Program at UC San Diego Health.

A recent study identified significant gaps in monitoring for complications in patients with thalassemia in Thailand.3 Are you aware of similar issues in the United States?

Dr Gopal: Yes, unfortunately the gaps are quite similar in the United States. When any individual needs chronic transfusions, there is a risk of iron overload and iron starts to deposit in the liver, kidneys, pancreas, and heart. The main complications we see in addition to iron overload include gallstones, enlarged spleen, and blood clots, issues with bone health, and then later in the disease course we may see pulmonary hypertension and cardiovascular issues like atrial fibrillation.

Due to advances in the management of thalassemia, these patients are living longer,6 but we just don’t have enough adult hematologists trained with expertise in managing thalassemia, so there are gaps in transition of care.

At the same time, we know very little about the disease in adults — we need more longitudinal data regarding the natural history of the disease. What we do know is that, when these patients become adults, they end up in private practice where the doctor has maybe seen one patient with thalassemia. These individuals need a lot of organized care to monitor and treat complications, and many private practices don’t have the resources.

What are few of the resources that you’ve found most helpful in managing these patients?

Dr Gopal: I’m very fortunate that we have a pediatric thalassemia program at UC San Diego Health, and the team has taught me a lot. Also, my state has the Thalassemia Western Consortium, which is mostly pediatric providers who care for thalassemia patients. They have an annual meeting where we discuss cases, and it has been very helpful to be educated by this group.

Cooley’s Anemia Foundation offers numerous resources for both patients and providers.7 I’ve started to include the link on my treatment plan or visit summary after seeing patients.

In terms of medically caring for these patients, I recommend referring to a site that offers a yearly screening program, a thalassemia focused-program, or a site that has clinical trials, as well as working closely with blood banks and identifying appropriate transfusion therapies. The most important need is access to a good transfusion program and blood banking program.

Some of these individuals need blood transfusions every 3 to 4 weeks to keep them going, and you have to know their original blood type so they won’t form antibodies to the blood they receive. The blood bank needs to know this so they can match the patient’s blood to the donor’s blood.

What are some recent and emerging treatment approaches for thalassemia?

Dr Gopal: Luspatercept, the one treatment approved by the US Food and Drug administration for beta thalassemia, has been shown to decrease the need for transfusions.8

In addition, gene therapy is being studied as a potentially curative option for beta thalassemia, with very promising thus far. In an open-label Phase 3 study published in the New England Journal of Medicine, over 90% of patients receiving this treatment became transfusion independent.9

Two other therapies being studied for transfusion-dependent and non-transfusion-dependent thalassemia are mitapivat and benserazide. Clinical trials of these medications are underway, so it will be interesting to see the results of those.10,11

References

  1. Kadhim KA, Baldawi KH, Lami FH. Prevalence, incidence, trend, and complications of thalassemia in Iraq. Hemoglobin. 2017;41(3):164-168. doi:1080/03630269.2017.1354877
  2. Patterson S, Singleton A, Branscomb J, Nsonwu V, Spratling R. Transfusion complications in thalassemia: Patient knowledge and perspectives. Front Med (Lausanne). 2022;9:772886. doi:10.3389/fmed.2022.772886
  3. Ekwattanakit S, Hantaweepant C, Khuhapinant A, Siritanaratkul N, Viprakasit V. An urgent need for improving thalassemia care due to the wide gap in current real-life practice and clinical practice guidelines. Sci Rep. 2021;11(1):13283. doi:10.1038/s41598-021-92715-w
  4. Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V, eds. Guidelines for the management of transfusion dependent thalassaemia (TDT). 3rd ed. Thalassaemia International Federation; 2014. 
  5. Bender MA, Yusuf C, Davis T, et al. Newborn screening practices and alpha-thalassemia detection – United States, 2016. MMWR Morb Mortal Wkly Rep. 2020;69(36):1269-1272. doi:10.15585/mmwr.mm6936a7
  6. Farmakis D, Giakoumis A, Angastiniotis M, Eleftheriou A. The changing epidemiology of the ageing thalassaemia populations: A position statement of the Thalassaemia International Federation. Eur J Haematol. 2020;105(1):16-23. doi:10.1111/ejh.13410
  7. Cooley’s Anemia Foundation. About thalassemia. Accessed April 24, 2022.
  8. Cappellini MD, Taher AT. The use of luspatercept for thalassemia in adults. Blood Adv. 2021;5(1):326-333. doi:10.1182/bloodadvances.2020002725
  9. Locatelli F, Thompson AA, Kwiatkowski JL, et al. Betibeglogene autotemcel gene therapy for non-β0/β0 genotype β-thalassemia. N Engl J Med. 2022;386(5):415-427. doi:10.1056/NEJMoa2113206
  10. A study evaluating the efficacy and safety of mitapivat in participants with non-transfusion-dependent alpha- or beta-thalassemia (α- or β-NTDT) (ENERGIZE). ClinicalTrails.gov Identifier: NCT04770753. Updated April 11, 2022. Accessed April 24, 2022. https://clinicaltrials.gov/ct2/show/NCT04770753
  11. The BENeFiTS trial in beta thalassemia Iintermedia (PB04-001). ClinicalTrails.gov Identifier: NCT04432623. Updated April 15, 2022. Accessed April 24, 2022. https://clinicaltrials.gov/ct2/show/NCT04432623

Topics:

Health Disparity Thalassemias