What is Sickle Cell Trait?
Sickle cell trait is a genetic condition where a person has one normal hemoglobin gene (A) and one sickle hemoglobin gene (S), resulting in the genotype (AS). On the other hand, sickle cell disease happens when a person inherits two abnormal sickle genes (SS). There are various forms of sickle cell disease, including hemoglobin SS (HbSS), hemoglobin SC (HbSC), and hemoglobin S beta-thalassemia. These cause vaso-occlusive crises, which are events that block blood vessels. HbSS is the most common and severe type.
HbSC happens when a person inherits HbS from one parent and HbC from the other. HbS beta-thalassemia is a rare mutation that happens when a person inherits beta-thalassemia hemoglobin from one parent and HbS from the other. But the presence of sickle hemoglobin alone doesn’t lead to vaso-occlusion; it occurs due to other factors like deformed red blood cells and increased cell fragility.
First described in 1910, sickle cell disease is a significant health issue, causing lifelong health problems and early death due to chronic anaemia and damage to organs. Unlike sickle cell disease, sickle cell trait is usually harmless as it doesn’t typically lead to vaso-occlusive crises. People with sickle cell trait have a better quality of life and the same mortality rate as the general population. However, they can experience the same symptoms as sickle cell anemia under certain conditions that favor cell sickling, such as severe hypoxia and dehydration.
Sickle cell trait is usually diagnosed through initial screening tests followed by confirmatory tests or genetic analysis. Since the US introduced the Sickle Cell Anemia Act in 1972, nationwide newborn screening has increased. After a positive screening test, doctors use a technique called hemoglobin electrophoresis to confirm the diagnosis. Treatment is necessary if the person experiences conditions that cause cell sickling (e.g., dehydration or hypoxia) or other medical conditions related to sickle cell trait. Therefore, doctors must be able to recognize the complications associated with sickle cell trait to provide prompt treatment.
What Causes Sickle Cell Trait?
Sickle cell trait is a condition that develops due to an abnormal type of hemoglobin, referred to as sickle hemoglobin or Hb S. This abnormality results from a minor change in a protein chain called beta-globin. This change swaps one element for another at a specific point (codon 6) in the beta hemoglobin chain, causing a shift from one type of amino acid (glutamic acid) to another (valine). When this valine-type hemoglobin is exposed to low levels of oxygen, it causes the red blood cells to take on a sickle shape.
People with sickle cell trait inherit two different types of hemoglobin. They get the sickle hemoglobin (HbS) from one parent and normal hemoglobin (HbA) from the other parent. Because of this, they are referred to as heterozygous.
Risk Factors and Frequency for Sickle Cell Trait
Sickle cell trait (SCT) is more commonly found in people of African descent or whose ancestors lived in regions where malaria is common. In the United States, SCT affects about 9% of African Americans and only 0.2% of Caucasians. It is estimated that around the world, 300 million people have SCT, and a large portion (one-third) live in sub-Saharan Africa. Places where malaria is common, such as some areas in Africa and Saudi Arabia, can have SCT rates as high as 25% and 60% respectively. Due to people moving from high SCT regions like Africa and the Middle East to other parts of the world, the prevalence of SCT and sickle cell disease is expected to rise in the western world.
Signs and Symptoms of Sickle Cell Trait
If a family member suffers from sickle cell disease (HbSS), it is important for medical professionals to ask about this during medical history taking, as it may affect you. While those who have sickle cell disease may suffer from symptoms like body pain and fatigue due to blockage of blood vessels, red blood cell destruction, and infection, individuals with sickle cell trait usually don’t have any symptoms. Most of the time, individuals with sickle cell trait exhibit no symptoms if their HbS levels are less than 35%. So, they present just like those with normal hemoglobin.
However, when symptoms do occur for people with sickle cell trait, they may experience blood in their urine and muscle breakdown as a result of exertion. Conditions like hot climates, lack of water in the body, or high altitudes may make these symptoms worse. Symptoms linked to sickling, such as those found in heat stroke or heart rhythm problems, require a comprehensive medical evaluation to make the right diagnosis. This involves gaining a detailed medical history of the present illness and conducting a thorough physical examination.
The type of discomfort often reported by individuals with sickle cell trait is usually described as cramping, weakness, and a dull ache that starts a few minutes after physical activity. This is due to decreased blood flow to the muscles. In cases where an athlete with this trait reports such symptoms, medical professionals should consider it as a possible sickling event until proven otherwise. Other symptoms might include pain on the left side of the abdomen or chest, chest tightness, and breathing abnormalities. Loss of consciousness or confusion is generally not associated with this condition.
In a physical examination, the large muscles (like the calves, quads, hamstrings, or glutes) usually look normal when compared to the cramping caused by heat exertion. However, patients with sickle cell trait can show signs of large muscle weakness. Dehydration, commonly reported in patients with sickle cell trait who have suddenly passed away, is also a usual finding. Signs of other conditions that are more commonly seen in patients with sickle cell trait (like pulmonary embolism, deep vein thrombosis, or chronic kidney disease) can also be found during the examination.
Testing for Sickle Cell Trait
In the US, unlike in many other countries, pregnant women are offered tests to find out if their unborn babies have sickle cell disease. After the baby is born, they are tested for the sickle cell trait before leaving the hospital. This is called a sickling test and involves checking a blood drop under a microscope.
If the blood cells appear ‘sickled’ or crescent-shaped, doctors will carry out a secondary test called hemoglobin electrophoresis to confirm the diagnosis. This test gives a percentage of the different types of hemoglobin in the blood sample. In people with the sickle cell trait, their blood contains a mix of normal hemoglobin A and abnormal hemoglobin S.
As having the sickle cell trait can increase the chance of other health conditions, like chronic kidney disease, it’s crucial for doctors to check for these regularly. For people with the sickle cell trait and signs of kidney disease, doctors recommend annual testing that checks kidney function (like creatinine and urinalysis tests, as well as blood pressure checking). If these people also have blood in their urine, further tests like an ultrasound or CT scan of the kidneys and urinary tract should be done. This is because having the sickle cell trait increases the risk of a kind of kidney cancer called renal medullary cell carcinoma.
Treatment Options for Sickle Cell Trait
People who carry the sickle cell trait (SCT) but have no symptoms don’t usually need treatment. However, if certain conditions trigger ‘sickling’ (an abnormal shape) of their red blood cells, or if they have other health problems linked to the SCT, treatment may be necessary. Doctors need to be aware of complications linked to SCT, like a certain type of kidney damage, small blood vessel disease, and deep vein blood clots. This way, they can start suitable treatment quickly if a patient comes in with symptoms such as blood in their urine or pain in their side.
It’s also useful for people with SCT to take steps to prevent problems. If they take part in sports or go to areas at moderate or high altitudes, getting used to these situations gradually might help. It’s important for them to avoid becoming dehydrated, lacking oxygen, or overheating. For children with SCT, annual health checks are recommended, including tests for levels of iron, folic acid, and vitamin D.
There are also special guidelines if you’re pregnant and carry SCT. These women should have urine tests every three months to check for silent bladder infections because they’re more prone to a more severe kidney infection. If a kidney infection is suspected, treatment needs to be given early and thoroughly. Due to common blood problems like anemia, taking folic acid and iron during pregnancy and while breastfeeding is suggested. If you’re looking to become pregnant or already are, and you have either small red blood cells, a family history of hemoglobin diseases, or are from a region where sickle cell disease or thalassemia are common, screening for these diseases is recommended by experts.
What else can Sickle Cell Trait be?
When diagnosing sickle cell trait, doctors may also consider other conditions that have similar symptoms. These include:
- Various forms of sickle cell disease
- Beta-thalassemia major, a severe blood disorder
- Beta-thalassemia minor, a milder form of blood disorder
It’s essential for the doctor to evaluate these possibilities before making a diagnosis.
What to expect with Sickle Cell Trait
Even though people with the sickle cell trait may experience various complications like damage to the inner part of the kidney (papillary necrosis), symptomless urinary infections (asymptomatic bacteriuria), sudden tissue death in the spleen (splenic infarction), and even death triggered by strenuous physical activity, their overall health outlook is generally positive. According to one study, despite these complications, individuals with the sickle cell trait tend to live as long as the average person without the trait.
It’s worth noting that people with sickle cell disease generally have a higher risk of dying while in hospital care, but this increased risk doesn’t apply to those with just the sickle cell trait.
Possible Complications When Diagnosed with Sickle Cell Trait
Although people with sickle cell trait are often thought to have no health risks, they can actually be prone to a number of medical issues. These may include blood in the urine due to kidney damage, spleen damage, kidney cancer, chronic kidney disease, sudden death during intense physical activity, and in women, bacteria in the urine without symptoms. Additionally, the risk of severe illness and death from COVID-19 can be higher in these individuals.
Papillary Necrosis
This is a condition that has been noted in several case studies. Research has shown that individuals with sickle cell trait and higher levels of a certain type of hemoglobin called HbS are more prone to this problem. This is due to the abnormal hemoglobin causing blockages in small blood vessels, leading to damage of the kidney tissues. Symptoms usually include visible blood in urine and abdominal pain. Management typically involves intravenous fluids, bed rest, and managing pain. Thankfully, the overall prognosis is generally good as typically only a part of the kidney is affected and there is enough healthy tissue left.
Splenic Infarction
Splenic infarction, or damage to the spleen, can occur under certain conditions like low oxygen levels, dehydration, increased acidity, or if the individual is at high altitude. Even resting at low altitudes may lead to spleen complications in some cases. The higher the altitude, the greater the risk. Lab tests showing an increase in bilirubin or LDH can indicate significant spleen issues. That said, removal of the spleen was necessary in very few cases in one study.
Renal Medullary Carcinoma
One of the serious complications connected with sickle cell trait is renal medullary carcinoma, a type of kidney cancer. This type of cancer is often aggressive and may have already spread at the time of diagnosis.
Chronic Kidney Disease
Studies have identified a link between sickle cell trait and an increase in chronic kidney disease, especially in African American males. This is thought to be due to insufficient oxygen supply to the kidneys leading to repeated damage and release of substances that contribute to kidney disease.
Sudden Death
Intense physical activity has been related to sudden death in some cases, especially in athletes, police, and military recruits with sickle cell trait. The risk of sudden death during high-intensity activity was found to be 37 times higher in one study of Division I football players. As a result, it was proposed that all athletes be screened for sickle cell trait to prevent such occurrences.
Exertional Rhabdomyolysis
Exertional rhabdomyolysis, a condition where muscle breaks down during physical activity leading to harmful substances in the urine, has also been linked with sickle cell trait. A tragic instance of a college athlete with sickle cell trait dying during severe football training led to proposed screening for this condition.
COVID-19
There is evidence to suggest that individuals with sickle cell trait have a higher risk of severe illness and death from COVID-19.
Preventing Sickle Cell Trait
About 9% of the African American community carries the sickle cell trait. Despite this, only 16% of people in their childbearing years who have the trait are aware of it. Most people discover they have the trait when they are newborns, but later screenings are uncommon and can lead to people not knowing about their condition. Furthermore, misunderstandings and language differences can also prevent people from becoming aware of their sickle cell status.
A research study led by Creary S and his team found something interesting. Before teaching caregivers about the sickle cell trait, only 38.1% had some knowledge of it. However, after providing education, an impressive 90.3% had a better understanding of the trait. This shows the importance of education in tackling such health-related issues.
Both the sickle cell trait and the disease itself can be complex topics for patients and their families to understand. It is crucial for healthcare professionals to provide education and genetic counseling to them to ensure they have a clear understanding.
