Comprehensive Guide to Sickle Cell Disease Symptoms and Treatment

According to Dr. Richard Steingart, a hematologist with Baystate Hematology Oncology, roughly 100,000 Americans live with an inherited blood disorder known as sickle cell disease (SCD). Often referred to as sickle cell anemia, SCD is progressive and incurable. It can cause periods of extreme pain throughout the body and contributes to a shortened lifespan for those affected by it. But, as Dr. Steingart notes, there are promising treatment options for successfully managing SCD.

What is Sickle Cell Disease?

Sickle cell disease occurs when a person inherits abnormal hemoglobin genes from both parents. Hemoglobin is a protein in red blood cells that carries oxygen throughout the body. In SCD, the abnormal hemoglobin causes normally round, flexible, red blood cells to become crescent or "sickle" shaped. In addition, these sickle-shaped cells are stiffer and stickier than normal red blood cells.

As a result, they can block the flow of blood in small blood vessels. Starved of oxygen, the tissues and organs beyond the blockage become damaged, leading to sudden and severe pain referred to as pain crises. A pain crisis can last several hours or several days. Very often, a person in pain crisis needs to go to the hospital for treatment.

In addition, sickled cells are also very fragile. While a normal red blood cell lives about 120 days, the lifespan of a sickled cell is 10 to 20 days. This high die-off rate frequently leads to anemia, which can cause an individual to tire easily and feel sluggish.

What Causes Sickle Cell Disease?

As Dr. Steingart explains, there are three types of hemoglobin:

• Hemoglobin A, which creates healthy, round, pliable blood cells
• Hemoglobin S, which creates sickle-shaped blood cells
• Hemoglobin F, which is produced by a fetus in the womb and by infants in their early months of life. As the child grows, the body stops producing F and the volume of hemoglobin S or A increases.

“People who inherit a hemoglobin S gene from one parent and a hemoglobin A gene from the other are considered to have a sickle cell trait,” says Dr. Steingart. “In most cases, these individuals usually don’t have medical issues or experience pain crises. However, because they carry the S gene, they can pass it on to their children.”

He adds, “Now, in instances where both parents have hemoglobin S, their children will be born with sickle cell disease versus the less-concerning sickle cell trait.”

While SCD is most common in people of African descent (1 in 12), it’s also found in individuals of Hispanic, Indian, European, and Mediterranean descent and exists in most countries.

How is Sickle Cell Disease Diagnosed?

In the United States, every baby born in a hospital is tested for sickle cell shortly after birth. The results are shared with the family and the child’s doctor, typically one to two weeks after testing.

Early detection is important as infants and children with SCD frequently suffer from more infections. As a child with SCD grows, they may also experience:

• Dactylitis, a severe swelling of the fingers or toes brought on by blockages in the small blood vessels as well as the lining of the bones
• Delayed growth and puberty
• Stroke, often first occurring around 7 to 10 years of age with a high probability for recurrence

How Does Sickle Cell Disease Affect the Body?

As Dr. Steingart notes, “From head to toe, there’s really no part of the body that can fully escape the effects of SCD. As mentioned, a crisis can happen at any time. Patients often describe it as a feeling of intense pressure or being stabbed by multiple knives. But even when you’re not experiencing a crisis, SCD can be causing damage throughout the body.”

Here a just a few of most common the impacts Dr. Steingart regularly sees:

• Eyes: SCD can damage the retina in the back of the eye, which is why it’s important for all patients to see an eye doctor annually even if their vision seems fine.
• Chest and Lungs: In addition to higher rates of pneumonia, SCD patients often experience acute chest syndrome. A very common cause of hospitalization and even death, this syndrome can cause chest pain, cough, fever, and low oxygen levels. Over time, patients may experience pulmonary hypertension due to the ongoing death of lung tissue. This condition places a lot of stress on the heart and contributes to a number of heart issues.
• Abdomen: Located in the upper left side of your belly, the spleen filters out any germs in the blood and helps prevent infection. When the spleen is repeatedly scarred by sickled cells, its ability to filter is compromised. Some patients may also experience a spleen crisis when red blood cells get trapped in the spleen. This leads to severe anemia and is considered a medical emergency.
• Gallbladder: SCD patients have a higher incidence of gallstones.
• Hips: Death of the bones in the hip (asceptic necrosis) is common with SCD. Many patients require full hip replacement as early as their 20s and 30s.
• Blood clots: Sickled red blood cells can lead to increased blood clotting and, in turn, increase a patient's chance of developing a blood clot in the leg, thigh, pelvis, or arm. In some cases, a clot can break off and travel to the lungs where it causes a serious and frequently disabling or fatal illness called pulmonary embolism.
• Pregnancy: Women with SCD experience higher rates of miscarriage and often birth smaller-than-average babies.

What Treatments Are Available for Sickle Cell Disease?

The aim of SCD management is avoiding crises, pain relief, and preventing complications.

Dr. Steingart notes that crises are frequently brought on by the following, all of which can lead to the narrowing of blood vessels:

• Exposure to cold temperatures
• Dehydration
• Illegal drug use, especially cocaine
• Excessive alcohol consumption

By abstaining from these behaviors and keeping the body warm, patients can reduce their risk of a crisis.

When crises do occur, pain management is typically accomplished with medication.

“In the best cases, over-the-counter drugs, like Tylenol, can provide the needed relief,” Dr. Steingart says, “But, for severe crises, narcotics are often required.”

And because people with SCD are more prone to infections, daily antibiotic treatment, often penicillin, is often recommended. In addition, routine vaccinations, including annual flu shots, are strongly encouraged.

In terms of treatment, Dr. Steingart notes that patients of today have more options and hope than ever. “For decades, there were very few options for SCD patients other than hydration and pain medication. But beginning in the late 80s and through to today, some advances have been made that significantly improve quality of life and even work to cure the disease.”

Current sickle cell disease treatment options include:

Hydroxyurea

A cornerstone of SCD treatment since 1988, hydroxyurea works by increasing the production of hemoglobin F, which helps prevent the formation of sickled red blood cells. Hydroxyurea has been shown to reduce the frequency of pain crises, acute chest syndrome, and the need for blood transfusions.

Blood Transfusions

Regular blood transfusions are used to:

• Increase the number of healthy red blood cells
• Reduce the risk of stroke in high-risk patients
• Manage severe anemia

New FDA-Approved Medications for Sickle Cell Disease

Recently, several new medications have been approved for SCD treatment:

• Voxelotor (Oxbryta): This drug works by increasing hemoglobin's oxygen uptake, which reduces the sickling of red blood cells.
• Crizanlizumab (Adakveo): An antibody administered by infusion, crizanlizumab helps prevent blood cells from sticking to blood vessel walls, reducing pain crises.
• L-glutamine (Endari): An oral powder mixed into juice twice a day, Endari helps reduce the frequency of pain crises.

Advanced Therapies

Stem Cell or Bone Marrow Transplantation: As promising as transplantation is as potential cure for SCD, it’s also fraught with risk and challenges. The first challenge is finding a suitable donor. The best option is a family member but even so, only 10-15% of family members will be a match.

In the fortunate cases where a match is found, patients must also be prepared to undergo chemotherapy, which works to wipe your system clean of “faulty” red blood cells. However, it also works to reduce immunity, meaning patients are more susceptible to illness and infection, and it also renders patients infertile.

Gene Therapy: Recently, some exciting developments in gene therapy have emerged as an option for treating SCD. Unlike transplants, gene therapy uses only the patient’s blood, eliminating the obstacle of finding a suitable match.

As Dr. Steingart explains, “Gene therapy involves modifying a patient's own stem cells to produce healthy hemoglobin.” Here’s what’s involved:

Stem Cell Collection: The patient's blood stem cells are collected from their bone marrow or blood and taken to a lab for modification.

Genetic Modification Options:

• Gene Addition: A hemoglobin A gene is added to the stem cells to generate a sickle cell trait, which allows for a better quality of life than the patient experienced with just hemoglobin S. The modified stem cells are then infused back into the patient.
• Gene Editing: Referred to as CRISPR technology, gene editing involves editing hemoglobin F into a patient's DNA directly to reactivate the production of hemoglobin F. Again, the modified gene is infused back into the patient where it triggers the creation of healthy, non-sickled hemoglobin.

Dr. Steingart adds, “Both options require the patient to undergo chemotherapy prior to being infused with the modified genes but both aim to provide a long-lasting or potentially curative treatment by addressing the cause of SCD at the genetic level. At this point, research shows gene therapy has an encouraging success rate of 90%.”

He adds, “As research continues, there is hope for even more effective treatments and potential cures in the future.”