Sickle Cell Disease FAQ: Subtypes, Current Therapies, and Access Challenges

Sickle cell disease (SCD) is a complex inherited blood disorder that disproportionately affects Black and African American communities in the US and millions of others worldwide.

This FAQ explores the major subtypes of SCD, current FDA-approved therapies, and emerging treatment strategies. Experts also highlight how cost, provider awareness, and systemic inequities continue to shape access to care.

What Is Sickle Cell Disease?

SCD is an inherited hemoglobin (Hb) disorder caused by a point mutation in the β-hemoglobin gene, resulting in the polymerization of hemoglobin (HbS) that distorts, injures, and sickles red blood cells. Sickle cell disease is the umbrella term that encompasses various subtypes of the disease that vary in severity and symptoms.

Sickle cell anemia (HbSS) is the homozygous dominant variant and the most common and severe form of the disease. Patients who only inherited 1 gene encoding for abnormal HbS and a different type of abnormal hemoglobin called “C” have a milder form of the disease, known as HbSC disease.

Another form of the disease is HbS beta thalassemia, where patients inherit one gene encoding for HbS and another encoding for beta thalassemia. There are 2 types of beta thalassemia: zero (HbS beta⁰) and plus (HbS beta⁺). Patients with the zero variant of beta thalassemia often have the more severe form of the disease like HbSS, while those who have the plus variant have a milder form of SCD.¹

Patients with SCD experience acute vasoocclusive episodes (VOEs), hemolytic anemia, organ damage and failure, and a reduced life span by 20 years compared with the median life span.²

Who Is Most Affected by SCD and Why?

SCD affects approximately 100,000 people in the US as of 2024 but disproportionately impacts non-Hispanic Black or African American individuals, who make up more than 90% of cases.³ However, the disease is much more common in Africa, India, and parts of the Middle East and is not isolated to the US.

Research suggests that the genetic disorder originated in malaria-endemic regions of sub-Saharan Africa and the subcontinent of India, where more than 200,000 infants are born with SCD each year.⁴ The sickle cell trait is present in nearly 30% of some African populations and 40% of “tribal” populations in India.

The high prevalence of SCD carriers is frequently attributed to the evolutionary benefits it provided against malaria in these regions.⁴

What Current Therapies or Treatments Exist to Treat SCD?

In 1994, hydroxyurea (Droxia; Bristol-Myers Squibb) was the first therapy to treat SCD to receive FDA approval. For nearly a decade, it was the only approved therapy to treat SCD. Hydroxyurea increases the amount of fetal hemoglobin (HbF) in patients with SCD. Patients with SCD have a natural concentration of HbF that switches into adult hemoglobin, and patients with more HbF experience milder SCD symptoms due to the reduction in HbS and hemoglobin polymerization.⁵

Although hydroxyurea continues to serve as a first-line therapy, experts say it’s not quite enough to reduce adverse events in patients, especially when started later in life. However, when combined with anti-inflammatory therapies, its benefits might be enhanced.

“I think other drugs that are developed that might affect inflammation or the interaction of sickle cells with endothelial cells are nice drugs to have at the moment, because hydroxyurea, which is the drug that's most available for treating sickle cell disease, doesn't work well enough,” Martin H. Steinberg, MD, a hematologist and internal medicine specialist at Boston University Chobanian & Avedisian School of Medicine, said in an interview with The American Journal of Managed Care^® (AJMC^®).

Other drugs that target VOEs in patients with sickle cell disease include L-glutamine (Endari; Emmaus Medical, Inc), voxelotor (Oxbryta; Global Blood Therapeutics), and crizanlizumab (Adakveo; Novartis). However, voxelotor was discontinued due to safety concerns, and crizanlizumab was discontinued in the European Union but is still approved by the FDA.⁵

Thromboinflammatory-targeting therapies for SCD have increased in popularity. Although none have been FDA approved, Steinberg said they’re more likely efficacious when used adjunctively with hydroxyurea.

“They're not primary therapies,” he said. “Treating sickle cell disease with anti-inflammatory agents alone doesn't make sense to me, because while there is inflammation, it's not primary inflammation; it's a consequence of these damaged sickle red blood cells.”

How Has Cost Disproportionately Impacted Equitable Access to Treatments?

Although there are approved therapies to treat SCD, cost remains a barrier for patients.

“There are many steps and challenges all the way from systems to practitioners who are familiar with hydroxyurea and how to use it to resistance by or concerns with patients, some of it very legitimate, but a lack of understanding,” Ted Wun, MD, chief of hematology and oncology at UC Davis Health, said in an interview with AJMC. “There was very low uptake of those in the community, partially because of access to a practitioner who is even aware of them or doesn't know really how to use the drugs.”

The American Society of Hematology has invited practitioners and physicians to participate in workshops that improve awareness and promote continuing education programs. Many of these resources are now sponsored by national organizations dedicated to SCD, like the Sickle Cell Disease Foundation, Wun said.

“[They] train teams to take care of patients with sickle cell disease. And they're not just physicians, but nurse practitioners, social workers, nurses, and pharmacists,” Wun said. “Over the 4 or 5 years, those operating 58 new teams throughout the country were trained in optimal care for patients with SCD.”

Steinberg and Wun both agree that equitable access is a progressive goal with a lot of work still needed to ensure patients with SCD receive the care they need.

“Equitable health care is a laudable goal, which we're really far from in this country, not just for the patients with sickle cell, but for everybody,” Steinberg said.

References

1. About sickle cell disease. CDC. February 21, 2025. Accessed February 16, 2026. https://www.cdc.gov/sickle-cell/about/index.html

2. Solovieff N, Hartley SW, Baldwin CT, et al. Ancestry of African American with sickle cell disease. Blood Cells Mol Dis. 2011;47(1):41-45. doi:10.1016/j.bcmd.2011.04.002

3. Data and statistics on sickle cell disease. CDC. May 15, 2024. Accessed February 16, 2026. https://www.cdc.gov/sickle-cell/data/index.html

4. Pendharker D, Niraml G. Tracing the origin of sickle cell disease back to 50,000 years. Blood Glob Hematol. 2026;2(1):100041. doi:10.1016/j.bglo.2025.100041

5. Ball J, Bradley A, Le A, Tisdale JF, Uchida N. Current and future treatments for sickle cell disease: from hematopoietic stem cell transplantation to in vivo gene therapy. Mol Ther. 2025;33(5):2172-2191. doi:10.1016/j.ymthe.2025.03.016