Sickle Cell Anaemia: Types, Symptoms, Causes, Diagnosis & Treatment

Sickle cell anaemia is a serious, inherited blood condition that affects the shape and functions of red blood cells. Usually, red blood cells (RBCs) are disc-shaped and flexible, permitting them to move easily through blood vessels to deliver oxygen to the body's organs and tissues. In sickle cell anaemia, the red blood cells become rigid and shaped like sickles or crescent moons. This abnormal shape can cause the cells to get stuck in blood vessels, leading to episodes of pain, infections, delayed growth, and, in some cases, stroke.

The prime cause of this condition is a mutation in the gene that tells the body how to make haemoglobin—the protein in red blood cells that carries oxygen. The abnormal haemoglobin causes RBCs to become misshapen. Living with sickle cell anaemia involves managing the condition's symptoms and complications, as there is no widely available cure for most people.

Sickle cell anaemia is a lifelong illness that can significantly affect a person's quality of life. Early diagnosis and regular care can help manage the symptoms and reduce the possibility of complications. 

Sickle cell anaemia is part of a group of disorders known as sickle cell disease. Sickle cell disorder is determined by the genes inherited from one's parents. The most common types include:

• Sickle cell anaemia (HbSS): HbSS is the most severe form of sickle cell disease. It develops when a child inherits two sickle cell genes, one from each parent.
• Sickle Haemoglobin C Disease (HbSC): HbSC is a milder form of sickle cell disease. Individuals with HbSC inherit one sickle cell gene from one parent and one gene for an abnormal type of haemoglobin ("C") from the other parent.
• Sickle Beta Thalassemia (HbSβ-Thalassemia): HbSβ-Thalassemia combines a sickle cell gene with a gene for beta thalassemia, another type of anaemia. The severity of HbS beta thalassemia varies and depends on the amount of normal beta-globin produced.

Each type affects the body differently, with varying degrees of severity. However, all types share some common symptoms and complications.

People with sickle cell anaemia experience various symptoms and complications due to their sickle cells' irregular shape and rigidity. The most common symptoms are:

• Sickle cell crises are episodes of severe pain often felt in the chest, abdomen, joints and bones. The severity of pain varies and can last from a few hours to several days.
• Fatigue or feeling tired
• Difficulty breathing, especially during physical activity
• Anaemia 
• Frequent infections
• Delayed growth in children and teenagers
• Vision problems
• Swelling in the hands and feet
• Yellowish discoloration of the skin and eyes (jaundice)

The frequency and severity of symptoms can differ from person to person. Some may have occasional pain crises, while others may experience more frequent and severe episodes. Additionally, the risk of complications such as stroke, acute chest syndrome, and organ damage increases with the severity of the disease.

The Importance of Early Detection

Early diagnosis of sickle cell anaemia is crucial for managing the condition effectively. Newborn screening programs in many countries now include tests for sickle cell disease, allowing for early intervention. Prompt initiation of treatments such as penicillin prophylaxis, vaccinations, and pain management strategies can significantly enhance the quality of life for affected people and reduce the risk of severe complications.

Understanding genetic risk: 

This condition is inherited in an autosomal recessive (AR) pattern, meaning both parents must carry a sickle cell gene to pass the disease to their children. Understanding one's genetic risk through family history and genetic counselling can provide critical information for prospective parents.

The role of genetic counselling:

Genetic counselling for people with a family history of sickle cell anaemia or those identified as carriers of the sickle cell trait is crucial. It provides a platform for discussing the possibility of having a child with sickle cell anaemia and exploring reproductive options. Genetic counsellors can offer advice on preventive measures such as pre-implantation genetic diagnosis (PGD) for couples undergoing in vitro fertilization (IVF), which allows embryos to be tested for the sickle cell gene before implantation.

Prenatal screening:

Prenatal screening is another preventive strategy, offering early diagnosis of sickle cell anaemia in unborn babies. Pregnant women can undergo blood tests to check for sickle cell trait and other abnormal haemoglobin types. Additionally, various diagnostic procedures, such as amniocentesis and chorionic villus sampling (CVS), can diagnose sickle cell anaemia in the fetus, giving parents time to make informed decisions or prepare for the medical management of the condition.

• Genetic mutation: The HBB gene provides instructions for making the beta-globin subunit of haemoglobin, and a mutation in this gene can cause sickle cell anaemia. This mutation produces abnormal haemoglobin, or haemoglobin S, which can deform red blood cells into a sickle shape. To develop sickle cell anaemia, an individual must inherit two copies of the HBB gene mutation, one from each parent.
• Genetic inheritance: The autosomal recessive inheritance pattern means that both parents must carry the sickle cell trait for their child to have a chance of inheriting sickle cell anaemia. If both parents are carriers, there is a 25% chance with each pregnancy that the child will have sickle cell anaemia, a 50% chance that the child will be a carrier and a 25% chance that the child will neither have the disease nor be a carrier.
• Environmental and lifestyle factors: While the underlying cause of sickle cell anaemia is genetic, environmental and lifestyle factors can influence the severity of the disease and the occurrence of pain crises. Various factors, such as temperature extremes, dehydration, high altitudes, and strenuous exercise, can trigger sickle cell crises. 

The diagnosis of sickle cell anaemia typically consists of a combination of medical history, physical assessment, and laboratory test results. Here's an overview of the diagnostic process:

• Newborn screening: In many countries, newborn screening for sickle cell anaemia is part of routine neonatal care. This test includes taking a blood sample from the baby's heel to test for sickle haemoglobin. Early diagnosis through newborn screening allows for immediate intervention, which can significantly improve the child’s health outcomes and quality of life.
• Medical history and family history: The healthcare provider will inquire about symptoms and family medical history, as sickle cell anaemia is an inherited ailment. During the physical examination, the doctor will analyze the signs of this condition, such as pale skin, jaundice, swelling of hands and feet, and an enlarged spleen.
• Blood tests: Various blood tests can diagnose sickle cell anaemia at any age. The most common is the haemoglobin electrophoresis test, which measures the different types of haemoglobin in the blood. This test can identify sickle haemoglobin (HbS) and other abnormal haemoglobin types. Complete blood count (CBC) tests can also provide valuable information by revealing anaemia, a common symptom of sickle cell anaemia.
• Differential diagnosis: It is crucial to distinguish sickle cell anaemia from similar conditions, such as thalassemia. Both are genetic blood disorders that can cause anaemia and have overlapping symptoms, but their management and prognosis differ. Various tests can confirm sickle cell anaemia, including:

a. Genetic testing can verify the presence of specific gene mutations associated with sickle cell anaemia.

b. Haemoglobin solubility test is used as a rapid screening method to detect the presence of sickle haemoglobin.

c. High-Performance Liquid Chromatography (HPLC) is a highly accurate method for quantifying haemoglobin S and other haemoglobin types in the blood. 

Treatment and management of sickle cell anaemia aim to relieve symptoms, prevent complications, and enhance quality of life. Here are the different modalities to manage this condition:

Pain management:

Pain episodes, also known as sickle cell crises, are a hallmark of sickle cell anaemia. They occur when sickled RBCs block blood flow through the blood vessels, resulting in tissue ischemia and pain. Effective pain management strategies include over-the-counter pain relievers, prescription medications, and sometimes hospitalization for more severe pain. Hydration and warmth can also help alleviate pain.

Preventing and managing complications:

Regular medical care is crucial for preventing and managing the complications of sickle cell anaemia. This includes vaccinations to prevent infections, regular eye exams to monitor for retinopathy, and taking penicillin or other antibiotics to prevent pneumonia and other infections. 

Hydroxyurea therapy:

Hydroxyurea medication can reduce the frequency of pain crisis episodes and the need for blood transfusions in people with sickle cell anaemia. It works by stimulating the production of foetal haemoglobin, a type of haemoglobin that helps prevent the sickling of red blood cells. 

Blood transfusion: 

Healthcare providers may advise blood transfusions in people with severe anaemia or complications such as stroke.

Bone marrow transplantation: 

Hematopoietic stem cell, or bone marrow transplantation, is a curative treatment option for sickle cell anaemia. It includes replacing the diseased bone marrow with healthy bone marrow from a compatible donor. Matched sibling donor is best option. However in case matched sibling donor is unavailable then alternate donor transplant from half-matched (parent or sibling) can also be offered.

Additional treatments: 

According to the symptomatic presentation, the doctor may recommend other treatments, such as oxygen therapy, pulmonary hypertension medications, or therapy for specific organ complications.

• Long-term health monitoring: People with sickle cell anaemia require lifelong monitoring and care to control their condition. Regular check-ups with a healthcare provider experienced in sickle cell anaemia are essential. These visits allow for the monitoring of the patient’s haemoglobin levels and kidney function and allow for the adjustment of treatment plans as needed.
• Lifestyle management: Adopting a healthy lifestyle can help mitigate some of the manifestations of sickle cell anaemia and improve overall well-being. It includes eating a balanced diet, staying hydrated, avoiding temperature extremes, and getting regular exercise tailored to the individual's capabilities and health status. 
• Community and support: Living with sickle cell anaemia can be challenging, but support from family, friends, and the wider community can make a significant difference. Educational programs can raise awareness and understanding of the condition, leading to better support for those affected. Additionally, connecting with others through support groups or online forums can provide emotional support, practical advice, and a sense of community.

What is sickle cell anaemia?

Sickle cell anaemia is a severe, inherited haemoglobin disorder that causes RBCs to take a sickle or crescent shape. These abnormally shaped cells can cause blockages in blood vessels, leading to various health issues, including pain episodes, serious infections, and chronic anaemia.

What causes sickle cell anaemia?

This condition is caused by a mutation in the gene that controls the production of haemoglobin. When someone has two copies of this mutated gene, they produce abnormal haemoglobin known as haemoglobin S, which can disfigure red blood cells into a sickle shape.

How common is sickle cell anaemia?

Sickle cell anaemia affects millions of people worldwide, with a higher prevalence among those of African, Mediterranean, Middle Eastern, and Indian ancestry. It is a significant health concern in areas where malaria is common, as the sickle cell trait provides some protection against this disease.

Is sickle cell anaemia genetic?

Sickle cell anaemia is a genetic disorder. It follows an autosomal recessive pattern, meaning both parents must bear a sickle cell gene for their child to be affected. If both parents carry one sickle cell gene and one normal haemoglobin gene, their child has a 25% possibility of having sickle cell anaemia.

What are the manifestations of sickle cell anaemia?

Symptoms of sickle cell anaemia can vary and may include anaemia, episodes of pain, susceptibility to infections, delayed growth, and vision problems. The severity of symptoms can differ significantly from one individual to another.

How is sickle cell anaemia diagnosed?

Diagnosis typically involves blood analysis to check for haemoglobin S—the defective form of haemoglobin that causes sickle cell anaemia. Newborn screening, haemoglobin electrophoresis, and genetic testing are some methods used to diagnose this condition.

Can sickle cell anaemia be cured?

Yes, Bone marrow transplant from an unaffected or carrier donor can cure sickle cell disease permanently. Other exciting option is gene therapy which is as yet not available in India.

What is the difference between sickle cell trait and sickle cell disease?

Sickle cell disease encompasses disorders that include sickle cell anaemia, while sickle cell trait refers to individuals who carry one gene for sickle cell and one for normal haemoglobin. Those with the trait usually do not have disease symptoms but can pass the gene to their children.

Can people with sickle cell trait have symptoms?

Most people with sickle cell trait do not experience symptoms of sickle cell disease. However, under extreme conditions such as high altitude or severe dehydration, they might experience health issues related to the trait.

Is sickle cell anaemia preventable?

As a genetic condition, sickle cell anaemia itself is not preventable. However, genetic counselling and screening can help at-risk individuals understand their chances of having a child with the condition.

Can sickle cell anaemia be detected before birth?

Prenatal tests can detect sickle cell anaemia in the foetus. Various tests, such as amniocentesis and chorionic villus sampling (CVS), can be performed during pregnancy to diagnose this and other genetic conditions.

What are the treatment modalities for sickle cell anaemia?

Treatment focuses on managing its manifestations and preventing complications. It may include medication for pain and to reduce complications, blood transfusions, and hydroxyurea, a drug that can lower the frequency of pain episodes. Bone marrow or stem cell transplants from a healthy unaffected or carrier donor can cure sickle cell disease permanently.

What complications can arise from sickle cell anaemia?

Complications can be severe and life-threatening. They include acute chest syndrome, stroke, organ damage, and increased susceptibility to infections. Regular medical care is crucial to manage the disease and its complications.

What is a sickle cell crisis?

A sickle cell crisis or vaso-occlusive crisis is a severe pain episode that occurs when sickled red blood cells block blood flow to limbs and organs. These crises can cause acute pain and organ damage and are a common manifestation of the disease.

How does sickle cell anaemia affect red blood cells?

Sickle cell anaemia causes RBCs to become rigid, sticky, and misshapen, resembling a crescent or sickle. This abnormal shape prevents the cells from flowing smoothly through blood vessels, leading to blockages, reduced oxygen delivery to tissues, and premature destruction of red blood cells, causing anaemia.

What is the life expectancy for people with sickle cell anaemia?

Advances in treatment have refined the outlook for individuals with sickle cell anaemia, with many living into their 40s, 50s, and beyond. However, life expectancy can vary widely based on access to care, the severity of the disease, and individual health factors.

Can sickle cell anaemia cause organ damage?

Chronic blood flow blockage can damage organs such as the spleen, liver, kidney, and heart, impairing their function. Regular medical monitoring and treatment are necessary to manage this risk.

Can sickle cell anaemia affect pregnancy?

Sickle cell anaemia can increase the risk of complications during pregnancy for both the mother and the baby. Women with sickle cell anaemia should seek care from a healthcare team experienced in managing high-risk pregnancies.

What is hydroxyurea, and how is it used to treat sickle cell anaemia?

Hydroxyurea is a medication that can lower the incidence of sickle cell crises and the need for blood transfusions. It works by stimulating the production of foetal haemoglobin, a type of haemoglobin not affected by the sickle cell mutation.

Can sickle cell anaemia cause strokes?

Sickle cell anaemia can elevate the possibility of stroke, particularly in children. This risk is due to the blockage of blood vessels in the brain by sickled red cells, which can decrease blood flow and oxygen.

Can sickle cell anaemia cause heart problems?

Sickle cell anaemia can lead to heart problems due to the increased workload on the heart and the chronic anaemia associated with the condition, resulting in conditions such as arrhythmias and heart failure.

Can sickle cell anaemia cause lung problems?

Acute chest syndrome, a serious lung condition, can occur in people with sickle cell anaemia. It develops when sickled cells are trapped in the lungs, leading to infection, inflammation, and decreased oxygen levels.

Can Sickle Cell Anaemia Cause Kidney Problems?

Sickle cell anaemia can indeed affect kidney function. The abnormal shape of the sickle cells can damage the nephrons — the tiny filtering units within the kidneys. Nephron damage can lead to a condition known as sickle cell nephropathy, which may progress to kidney failure in severe cases. People with sickle cell disease are also at a high risk of developing haematuria (blood in the urine) and proteinuria (protein in the urine), both indicators of kidney damage.

Can Sickle Cell Anaemia Cause Liver Problems?

The blockages caused by sickled cells can slow or block blood flow to the liver, leading to sickle cell hepatopathy. This condition encompasses a range of liver complications, from mild liver enzyme elevations to acute hepatic sequestration crises, where a large volume of blood is trapped in the liver, causing sudden and severe liver enlargement, pain, and potential liver failure.

Chronic liver disease and gallstones are also more common in individuals with sickle cell anaemia due to the increased disintegration of red blood cells and the subsequent high levels of bilirubin, a byproduct of this process.

Can Sickle Cell Anaemia Cause Joint Pain?

Pain in various joints is a common complaint among people with sickle cell anaemia, often resulting from vaso-occlusive crises. Over time, repeated crises can lead to avascular necrosis, particularly in the hip and shoulder joints, where the lack of blood flow causes the death of bone tissue.

Can Sickle Cell Anaemia Cause Vision Problems?

Vision problems in individuals with sickle cell anaemia arise from the blockage of blood vessels in the eye. The retina can be damaged due to insufficient oxygen supply, leading to proliferative sickle retinopathy. This condition can cause new, fragile blood vessels to grow on the retina, which can bleed into the eye and cause vision loss or even blindness if not treated promptly.

Can Sickle Cell Anaemia Cause Infections?

People with sickle cell anaemia are more prone to infections due to the spleen damage caused by recurrent sickling of red blood cells. The spleen is crucial in filtering bacteria from the blood and producing antibodies. When it's damaged or removed (splenectomy), patients are at an increased risk of bacterial infections, particularly from pneumococcus, Haemophilus influenzae, and Salmonella species.

Can Sickle Cell Anaemia Cause Delayed Growth and Development in Children?

Children with sickle cell anaemia often experience delayed growth and development. The chronic anaemia associated with the condition means their bodies may not receive enough oxygen-rich blood to support normal growth. Additionally, the energy expenditure for maintaining body functions in the face of ongoing sickle cell complications can divert resources away from growth.

Can Sickle Cell Anaemia Cause Bone Problems?

Beyond joint pain, sickle cell anaemia can cause other bone problems. The interruption of blood supply to bones (bone infarction) can lead to bone tissue's weakening and eventual death, a condition known as avascular necrosis. Children may also suffer from dactylitis, or hand-foot syndrome, where the small bones in the hands and feet swell due to blocked blood flow.

Can Sickle Cell Anaemia Cause Fatigue?

Fatigue is a hallmark symptom of sickle cell anaemia, stemming directly from the anaemia. People often feel tired or weak as fewer RBCs carry oxygen to the body's tissues. This fatigue can significantly impact daily life, limiting individuals' ability to perform physical activities or maintain concentration.

Can Sickle Cell Anaemia Cause Jaundice?

Yellowing of the skin and eyes (jaundice) is common in individuals with sickle cell anaemia. It results from the high bilirubin levels produced by the rapid breakdown of sickled red blood cells. 

Can Sickle Cell Anaemia Cause Priapism?

Priapism, a painful and prolonged erection of the penis, can occur in males with sickle cell anaemia. The sickled cells can block the venous outflow from the penis, leading to priapism. If not treated promptly, it can result in erectile dysfunction due to damage to the penile tissue.

Can Sickle Cell Anaemia Cause Leg Ulcers?

Leg ulcers are a painful and often persistent complication of sickle cell anaemia. They typically develop in the lower part of the leg and are thought to result from blocked blood flow and chronic inflammation in the skin. 

Can Sickle Cell Anaemia Cause Infertility?

Sickle cell anaemia can impact fertility in both men and women. In men, sickle cell crises can damage the penis and lead to priapism, potentially causing erectile dysfunction. In women, irregular menstrual cycles and complications with the reproductive organs may occur. Moreover, the stress and complications associated with sickle cell anaemia can affect sexual health and fertility indirectly.

Can Sickle Cell Anaemia Cause Skin Ulcers?

Similar to leg ulcers, skin ulcers in other body parts can occur due to impaired circulation and chronic inflammation associated with sickle cell anaemia. These ulcers require careful management to prevent infection and promote healing, often involving specialized wound care and pain management strategies.

Can Sickle Cell Anaemia Cause Neurological Problems?

Sickle cell anaemia can lead to neurological complications, including stroke. The blockage of blood vessels by sickled red cells can diminish blood flow to the brain, resulting in stroke or transient ischemic attacks (TIAs). 

Can Sickle Cell Anaemia Cause Seizures?

Seizures in individuals with sickle cell anaemia may result from stroke or other neurological complications. Managing seizures involves controlling the underlying cause, such as preventing future strokes, and may require anti-epileptic medications.

Can Sickle Cell Anaemia Cause Anemia?

Sickle cell anaemia is, fundamentally, a form of anaemia. The sickled cells are fragile and prone to breaking apart easily, leading to a lower number of red blood cells in the bloodstream. This intrinsic anaemia can worsen during sickle cell crises or infections, requiring careful monitoring and management.

Can Sickle Cell Anaemia Cause Blood Clots?

People with sickle cell anaemia are at an increased risk of developing blood clots. The abnormal shape of the sickled cells can lead to increased blood viscosity and the formation of clots, which can cause blockages in veins and arteries, leading to complications like pulmonary embolism.

Can Sickle Cell Anaemia Cause Immune System Problems?

The damage to the spleen caused by recurrent sickling of red blood cells can impair the immune system, making individuals with sickle cell anaemia more susceptible to infections. 

Can Sickle Cell Anaemia Cause Complications During Surgery?

Surgery poses additional risks for individuals with sickle cell anaemia, including increased risk of sickle cell crises and infections. Preoperative and postoperative management tailored to the needs of individuals with sickle cell disease is essential to minimize these risks.

Can Sickle Cell Anaemia Cause Memory Problems?

Cognitive issues, including memory problems, can occur in individuals with sickle cell anaemia, possibly due to micro-infarctions in the brain from blocked blood flow.

Can Sickle Cell Anaemia Cause Social Challenges?

The impact of sickle cell anaemia extends beyond the physical symptoms and complications. The chronic nature of the disease can lead to social isolation, difficulties in school or work, and challenges in maintaining relationships. Support groups, counselling, and educational interventions can help individuals and families navigate these challenges.