Sickle cell is a serious disease in which unusually shaped red blood cells obstruct smaller blood vessels, preventing blood flow and leading to pain, especially in the bones. Important organs like the brain, heart and kidneys need constant blood flow to work properly; the lack of oxygen can lead to severe complications and even death.
Sickle cell (SC) is named after a C-shaped farming tool called a "sickle," with a curved, sharp edge for cutting wheat, reflecting the shape of the affected cells.
When the cells become sickle-shaped, this is called "sickling."
A person with sickle cell disease (SCD) will have symptoms; other people have sickle cell trait (SCT). They will have no symptoms but be carriers of the disease.
The symptoms range from being mildly affected and largely free from pain, to frequent and severe pain. Until now, doctors cannot predict who will be severely affected.
Although the SCT carrier is not affected in everyday life, the presence of SCT must be considered when individuals are planning to have children.
History of SCD awareness
The sickle cell shape was first noted in patients in the US in 1910, although the condition had existed in Africa for at least 5,000 years. The pain was then understood to be caused by blockage in the blood vessels. In 1949, SCD was found to be caused by abnormal hemoglobin, referred to as "hemoglobin S."
SCD was one of the first diseases to be understood fully at the biochemical level, when researchers learned that the abnormal hemoglobin was changing shape due to a single amino acid error in hemoglobin S.
In the early 1970s, SCD was already of some interest to the biomedical community, but there was little practical help for those afflicted. Prominent in textbooks, it was virtually absent in the consciousness of US health care professionals.
Despite early discovery of the underlying molecular cause of the disease, progress in patient care remained slow, partly due to the difficulty of treating it, and partly for social reasons.
Civil rights movement raises awareness
In the US, SC mostly affects black people, for whom health research and treatment were long neglected.
In the 1960s-70s, a civil rights journal noted that 50,000 black people had SCD and 2 million had SCT. They pointed out that money raised for SC in the US was far less than for, say, cystic fibrosis, which mainly affects white populations.
In 1970, the Black Panther group claimed that neglect of SC by white, middle-class scientists, doctors and government bureaucrats amounted to genocide by white America against its black population.
They announced the creation of a free testing program and a research foundation, with the aim of finding a cure.
In the summer of 1971, President Richard M. Nixon reacted by announcing that he would request $6 million from Congress to combat the disease.
As the need for improved treatment became recognized, the Sickle Cell Disease Association of America was founded, which later helped establish the Sickle Cell Anemia Control Act of 1972. This allotted government health funds for screening, research and treatment programs.
In 1983, the federal government recognized National Sickle Cell Awareness Month, now held annually in September.
Stigma of SCD
Despite progress since the 1970s, stigmatization of patients with SCD has continued, due to multiple challenges, not only socioeconomic, but also because of the difficulties of managing the chronic illness while accessing and navigating the health care system.
In 2010, Coretta Jenerette and colleagues investigated the stigma faced by young adults in the US with SCD.
The authors define health-related stigma as a form of devaluation, judgment or social disqualification of individuals, based on a health-related condition, resulting in discrimination in work, at schools and within families. It impacts all aspects of life, whether physiological, psychological or social.
Since people with SCD often come from disadvantaged backgrounds, even timely, quality health care may be restricted. For example, there are reports of physicians withholding pain control treatment, due to suspicions of drug abuse. The impact of the stigma can be lifelong, instilling a sense of exile from the healthier world and disgrace due to health encounters and lack of support.
The researchers called for more interventions to tackle this problem.
Myths and misconceptions about SC
The Sickle Cell Association of Ontario, Canada, lists a number of myths and misconceptions that contribute to the stigmatization of people with SCD. We will look at some of them.
Myth #1: SCD affects only Africans and their descendants
SC affects millions of people worldwide, not only Africans. Some 60-80% of people affected in the US are estimated to be black, but other races are affected.
- The exact number of people living with SC in the US is unknown
- The CDC put the figure at around 3 million, with many unaware of their status
- SCD is believed to affect 90,000-100,000 Americans.
People whose ancestors came from sub-Saharan Africa are more likely have it, and it occurs among Hispanics, Asians, Indians and people of Mediterranean and Middle Eastern descent.
Interestingly, the Centers for Disease Control and Prevention (CDC) note that SC is more common among people from places with high malaria prevalence; people with SCT are believed to be less likely to develop severe forms of malaria.
SCD is thought to affect 1 in 500 black people and 1 in 36,000 Hispanic-Americans. SCT could be present in 1 in 12 black people.
The CDC and National Institutes of Health (NIH), together with seven states, are now cooperating on a Registry and Surveillance System for Hemoglobinopathies (RuSH) to establish how many people are living with SC and how the disease impacts their health.
Myth #2: SC skips a generation
Sickle cell can only be passed on from parents to children. It is not contagious and it cannot skip a generation. The likelihood of having it depends on how many SC genes one or both parents have.
Normal hemoglobin is known as HbA; sickle hemoglobin can be called HbS.
Apart from in a sperm or an egg, every cell normally has two copies of each gene.
A person who has SCD has two copies of the HbS gene; a person who has SCT has one copy of HbS and one of HbA.
For a child to have SCD, both parents must have either SCD or SCT.
According to Penn State Hershey Medical Center, the chances of a child being born with SCD or SCT are:
- If neither parent is affected, the child has 0% chance of having SC
- If one parent has SCT, there is a 50% chance of the child having SCT, 50% chance of not having SCT, and 0% chance of having SCD
- If two parents have SCT, there is a 50% chance of their child having SCT, 25% chance of the child having SCD, and 25% chance of having neither
- If one parent has SCT and the other has SCD, there is a 50% chance of their child having SCT and 50% chance of the child having SCD. No child will be completely unaffected
- If one parent has SCD and the other has neither SCD nor CST, there is a 100% chance of their child having SCT, and 0% chance of having SCD
- If two parents have SCD, the chance of their child having it is 100%.
For this reason, genetic testing is strongly recommended for people in high-risk groups who are planning to have children, especially as it is possible to have SCT without knowing it.
Myth #3: People with SC will not reach adulthood
In the past, patients with SCD often died early from organ failure, infection and other complications. Chronic illness and pain also reduce quality of life dramatically.
Advances in medicine and better care now mean that people can live to 50 and beyond. Treatment of symptoms has improved quality of life, and bone marrow transplants offer some the chance of a cure. In time, genetic processes may even enable prevention.
SCD does not have to limit life, or even achievement, as proven by a number of high-profile celebrities and campaigners who live with SC:
- Actor Larenz Tate and his siblings created the Tate Brothers Foundation, dedicated to raising awareness of SC and educating people with SCD about how to avoid iron overload with the "Be Sickle Smart: Ask About Iron" campaign
- TLC's Tionne "T-Boz" Watkins revealed that she had SCD after releasing two multi-platinum selling albums. Using her celebrity status as a platform, she speaks out courageously for the Sickle Cell Disease Association of America, despite lengthy periods of hospitalization
- Tiki Barber of the New York Giants, who retired in 2006 with the team record for all-time rushing and receptions leader, spearheaded "Be Sickle Smart: Ask Tiki About Iron," in a campaign aimed at helping fellow sufferers to take a more active and informed role in their health.
Other high achievers with SC include veteran rapper Prodigy; Paul Williams, one of the original Temptations; and legendary jazz musician Miles Davis, one of the most influential musicians of the 20th century, who passed away from combined effects of a stroke, pneumonia and respiratory failure aged 65.
Myth #4: There is no cure for sickle cell disease
There is no single treatment for SCD, partly due to the variability of symptoms. Most treatments focus on managing symptoms, especially pain. There is a cure, and there are hopes of more on the horizon, but let us look at treatment first.
In the mid-1980s, penicillin was found to help prevent death related to serious infections, if given while patients were healthy.
In the 1990s, the US Food and Drug Administration (FDA) approved a new treatment therapy called hydroxyurea for the complications of SCD.
Hydroxurea works by stimulating the body to produce fetal hemoglobin, a normal hemoglobin in the fetus that prevents sickling.
It is also believed to affect leukocyte count, red cell adhesiveness and other parameters of SCD. It can reduce the blockage of small blood vessels and acute chest syndrome, which prevents blood flow to the lungs. It may improve survival rates and appears to be effective at all ages.
However, hydroxyurea can increase the risk of dangerous infections and other potentially serious side effects, so patients must be carefully monitored.
Apart from pain, which can be severe, the complications of SCD include anemia, a high risk of infection including pneumonia, blindness, organ failure, deep vein thrombosis and stroke, which kills some 10% of children with SCD. Patients are urged to keep all immunizations up to date to prevent infections.
Strategies for preventing pain crises include:
- Drinking plenty of water
- Avoiding getting too hot or cold
- Avoiding high altitudes, for example, through flying or mountain climbing
- Avoiding situations or activities involving low oxygen levels, such as mountain climbing or extreme exercise, as in military boot camp or training for an athletic competition.
People with SCT or SCD can become athletes, as a number of famous cases prove. Precautions such as frequent hydration and not training in high temperatures can help, as recommended by Dr. John Kark, of the Center for Sickle Cell Disease at Howard University School of Medicine in Washington, DC.
Cures and possible cures
Over the last 30 years, hematopoietic stem cells (HSCs) from the bone marrow of a healthy donor have provided long-term and often permanent treatment for patients with SCD, especially children.
The donor is usually a sibling with the same bone marrow type as the patient; unfortunately, only 1 in 10 patients are able to find a matching donor, and transplant can cause life-threatening side effects for some patients.
In 2011, Medical News Today reported on a possible new technique to boost fetal hemoglobin levels by modulating TR2 and TR4 expression. This is considered a potential improvement on hydroxyurea, because of the long-term effects of that drug. More studies are still needed on this.
Next on the horizon is gene therapy, in which a defective gene is replaced with a copy of a normal one. Advances in carrying out gene transfer safely and efficiently have already led to development of early phase clinical trials.
Problems include delivering the replacement gene to the right place in the body and getting it expressed correctly.
However, emerging research on strategies to repair defective genes has the potential to correct fundamental genetic and physiologic processes in SCD; research using reprogrammed cells is evolving rapidly, and experts hope that it could be applicable to SCD.
The outlook overall
In recent years, outpatient programs for pain control have improved, pulmonary hypertension has been identified as a common life-threatening complication, new ways have been developed to identify genetic risk factors for other disease complications, and there are hopes that gene therapy may provide a total cure.
Currently, however, the only real way to reduce incidence is genetic testing prior to marriage or having children, or testing of children in utero. These are difficult questions with profound ethical and social ramifications.
If steps can be made to successfully apply gene therapy to SC, maybe eventually it will be a thing of the past.