Associate Professor of pediatrics at Zucker School of Medicine at Hofstra/Northwell.

Abena Appiah-Kubi, MD, MPH

Sickle Cell Disease: Problems, Progress, and Potential

Over the past few decades, major progress has been made in recognizing and treating 

. Despite its relative rarity, SCD has gone from an underacknowledged and underdiagnosed condition to a critical focus of hematology. Clinicians have overcome the significant rates of adolescent mortality due to the disease, allowing hundreds of thousands of newborns with SCD to survive to adulthood.

SCD is a hereditary condition that affects roughly 100,000 individuals in the US and >3 million globally. Mutations in the βb globin gene result in sickle hemoglobin production, which can lead to chronic hemolysis and vaso-occlusion. Acute and chronic pain are common throughout the lifespan of patients living with the condition, as well as end-organ damage, which can lead to significant disease morbidity and a substantially lower median life expectancy.

Most patients affected by SCD are of African descent, with estimates from 2021 suggesting 1 in 365 Black births and 1 in 16,300 Hispanic births are affected. Recent improvements in screening and management of acute complications have, however, allowed >95% of newborns with SCD in medium- to high-resource countries to survive to adulthood. Unfortunately, this only shifted the burden of SCD to adults, where it has taken on the characteristics of a chronic disorder with substantial morbidity.

Physiological aging conditions also add to SCD-related complications, and life expectancy is reduced by >2 decades compared to the general population. A report on SCD-related deaths showed most patients dying in their mid-thirties to mid-fifties. Roughly 70% of these deaths occurred in inpatients, and the main causes included arrhythmias, myocardial infarction, and pulseless electrical alternans.

The shifting burden to adult patients and lingering issues with access to and disparities in healthcare for underserved communities have grown into substantial roadblocks for treatment. To that end, in honor of Sickle Cell Awareness Month, the editorial team of 

 spoke with Claudia Morris, MD, professor of pediatrics and emergency medicine at Emory University and pediatric emergency medicine physician at Children’s Health Care of Atlanta, and Abena Otema Appiah-Kubi, MD, a pediatric hematologist with Northwell Health, to discuss the recent strides made in sickle cell treatment and care – and highlight how far we still have to go.

 approved the first cell-based therapies for SCD – exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia). Exagamglogene autotemcel was approved for SCD in patients ≥12 years with recurrent vaso-occlusive crises, and is the first FDA-approved therapy using CRISPR/Cas9. This genome editing technology modified patients’ hematopoietic stem cells by cutting DNA in targeted areas, which allows clinicians to remove, add, or replace DNA where it was cut. The modified stem cells are then transplanted back into the patient, where they engraft within bone marrow and increase the production of fetal hemoglobin to prevent red blood cells from sickling.

Lovotibeglogene autotemcel utilizes a lentiviral vector for genetic modification and is approved in the same patient group. With this treatment, the patient’s blood stem cells are modified to produce HbA^T87Q, a gene-therapy derived hemoglobin with a similar function to hemoglobin A. Red blood cells containing HbA^T87Q have a lower risk of sickling and occluding blood flow.

“So far with both of these, we’ve had great, great results,” Appiah-Kubi told 

. “There are criteria that make you eligible or ineligible for these therapies, so that has to be said, but it’s very exciting that we can actually offer these treatments to individuals living with sickle cell disease today.”

Despite these medical advancements, significant issues still prevent many patients from accessing the care they need. Given its status as an orphan disease, SCD still does not receive the research funding and pharmaceutical investment of other diseases with higher public profiles. Individuals with SCD have less access to comprehensive care as a result.

Additionally, most people living with SCD are publicly insured, so the high cost of managing the disease is often out of reach. Coupled with a limited supply of healthcare providers with expertise in SCD treatment, the options for any given patient to receive treatment are limited.

While major overhauls to pediatric care have resulted in a significant increase in survival rates for children with SCD, with 94% of patients surviving to adulthood, mortality rates among young adults have risen in response. With a limited number of SCD specialists to respond to the increasing number of patients, mortality rates often rise 2.3-fold as patients transition from childhood to adulthood.

SCD patients also have significant issues in obtaining pain treatment, despite the severe chronic organ damage and pain typically accompanying the disease. Many patients who enter the hospital seeking pain relief are stigmatized, with many assuming they are simply seeking to fuel drug addictions. In 2014, the National Heart, Lung, and Blood Institute expert panel recommended opioid analgesia for SCD pain; however, given the heavily publicized and ongoing opioid abuse crisis in the US, access to the drugs is limited both by government policy and individual perceptions.

“Depending on the environment and whether or not there’s a lot of education of the clinicians on sickle cell disease, [patients] are often seen as drug seeking when they come in with acute pain,” Morris told 

. “And studies have shown that patients who frequently come to the emergency department actually have more severe disease; they have more hemolysis, they have more inflammation and signs of greater disease severity, and this is why they’re coming to our emergency department.”

To that end, multidisciplinary action and more complete education are needed to afford patients the care they need. Appiah-Kubi and Morris both agreed that a broader approach to SCD could provide a much-needed revitalization of care for patients. Given the disease’s impact on almost every organ in the body, just about every specialty can be called upon to pitch in for care.

“You just have to be aware that, for instance, sickle cell disease can actually lead to blindness; this individual should probably go see an ophthalmologist,” Appiah-Kubi said. “Have I checked out this individual’s heart? Maybe we need a cardiologist to look at that. What about the lungs?”

Ultimately, both Appiah-Kubi and Morris expressed their excitement about the ongoing advancements in the disease, highlighting the significant progress made and the promise the field still holds.

“We can only get better, right?” Appiah-Kubi said. “It’s a really exciting time to be caring for individuals living with sickle cell disease. And so I really hope that the future continues to be as great and as bright, and that we continue to do the best we can to make sure that individuals living with sickle cell disease can live the best life.”

Brandow AM, Liem RI. Advances in the diagnosis and treatment of sickle cell disease. J Hematol Oncol. 2022;15(1):20. Published 2022 Mar 3. 

Sachdev V, Rosing DR, Thein SL. Cardiovascular complications of sickle cell disease. Trends Cardiovasc Med. 2021;31(3):187-193. 

FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease.

 December 8, 2023. Accessed September 21, 2025. 

https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease

Lee L, Smith-Whitley K, Banks S, Puckrein G. Reducing Health Care Disparities in Sickle Cell Disease: A Review. Public Health Rep. 2019;134(6):599-607. 

Videos

This Sickle Cell Awareness Month, HCPLive draws attention to recent advancements made in SCD treatment and how much still needs to be done to address it.

Appiah-Kubi also noted that despite elevated HbF levels, very young children with SCA already had anemia and reticulocytosis.

Achieving Quick Responses in Sickle Cell Anemia With Early, Appropriate Hydroxyurea Dosing, with Abena Appiah-Kubi, MD, MPH

Early initiation and appropriate titration of hydroxyurea led to quick fetal hemoglobin (HbF) responses in children with sickle cell anemia (SCA).

These findings, from the Hydroxyurea Optimization through Precision Study (HOPS, NCT03789591), were presented at the

 66th American Society of Hematology (ASH) Annual Meeting and Exposition

, held December 7-10, 2024, in San Diego, California, by Abena Appiah-Kubi, MD, MPD, Associate Professor of pediatrics at Zucker School of Medicine at Hofstra/Northwell.

Appiah-Kubi and colleagues found that overall, early initiation of hydroxyurea with dose escalation resulted in significant hematologic improvement, with increases in hemoglobin from 9.0 g/dL (standard deviation [SD], 1.1) to 10.1 (SD, 1.4; 

<.001), Absolute Reticulocyte Count from 265 (SD, 123) to 185 (SD, 110; 

<.001), and HbF from 27.4% (SD, 11.2) to 34.3% (SD, 10.3; 

<.001). Most (74%) participants achieved HbF levels of at least 30% and 31% had HbF levels of at least 40% at month 6, compared to 46% and 13%, before treatment initiation.

“We recommend that we can start children with SCA on hydroxyurea even at a young age, despite whatever their HbF levels are, because… in these very young children, they actually already had anemia and reticulocytosis, so they were already showing us evidence of hemolysis with the illness, even at that very young age. Their HbF levels were around 27% in both arms and despite that, we still had these findings. And so don't be afraid to start it early. Even if the HbF level is elevated, we see remarkable improvement in all hematologic markers,” Appiah-Kubi told 

Appiah-Kubi A, Jacob SA, Heeney MM, et al. Individualized, PK-Guided Dosing of Hydroxyurea for Young Children with Sickle Cell Anemia: Final Results from the Hydroxyurea Optimization through Precision Study (HOPS). Presented at: ASH Annual meeting; December 7-10; San Diego, California. Abstract 175.

Abena Appiah-Kubi, MD, MPH

Articles