SIGNS AND SYMPTOMS

The signs and symptoms of sickle cell anemia vary. Some people have mild symptoms. Others have very severe symptoms and often are hospitalized for treatment.

Sickle cell anemia is present at birth, but many infants don't show any signs until after 4 months of age.

The most common signs and symptoms are linked to anemia and pain. Other signs and symptoms are linked to the disease's complications.

Signs and Symptoms Related to Anemia

The most common symptom of anemia is fatigue (feeling tired or weak). Other signs and symptoms of anemia include:

  • Shortness of breath
  • Dizziness
  • Headaches
  • Coldness in the hands and feet
  • Paler than normal skin or mucous membranes (the tissue that lines your nose, mouth, and other organs and body cavities)
  • Jaundice (a yellowish color of the skin or whites of the eyes)

Signs and Symptoms Related to Pain

Sudden pain throughout the body is a common symptom of sickle cell anemia. This pain is called a sickle cell crisis. Sickle cell crises often affect the bones, lungs, abdomen, and joints.

These crises occur when sickled red blood cells block blood flow to the limbs and organs. This can cause pain and organ damage.

The pain from sickle cell anemia can be acute or chronic, but acute pain is more common. Acute pain is sudden and can range from mild to very severe. The pain usually lasts from hours to as long as a week or more.

Many people who have sickle cell anemia also have chronic pain, especially in their bones. Chronic pain often lasts for weeks or months and can be hard to bear and mentally draining. Chronic pain may limit your daily activities.

Almost all people who have sickle cell anemia have painful crises at some point in their lives. Some have these crises less than once a year. Others may have crises once a month or more. Repeated crises can damage the bones, kidneys, lungs, eyes, heart, and liver. This type of damage happens more often in adults than in children.

Many factors can play a role in sickle cell crises. Often, more than one factor is involved and the exact cause isn't known.

You can control some factors. For example, the risk of a sickle cell crisis increases if you're dehydrated (your body doesn't have enough fluids). Drinking plenty of fluids can lower the risk of a painful crisis.

You can't control other factors, such as infections.

Painful crises are the leading cause of emergency room visits and hospital stays for people who have sickle cell anemia.

DIAGNOSIS

Sickle cell disease is detected by blood tests. There are three types of blood tests which can be done.

  • Solubility test (test tube method)
  • Sickling test (slide method)
  • Electrophoresis test: Above two tests cannot determine the patient whether Carrier (AS) or sufferer (SS).

If any of the two tests are positive, electrophoresis should be done.

In HbSS, the complete blood count reveals haemoglobin levels in the range of 6–8 g/dl with a high reticulocyte count (as the bone marrow compensates for the destruction of sickled cells by producing more red blood cells). In other forms of sickle-cell disease, Hb levels tend to be higher. A blood film may show features of hyposplenism (target cells and Howell-Jolly bodies).

Sickling of the red blood cells, on a blood film, can be induced by the addition of sodium metabisulfite. The presence of sickle haemoglobin can also be demonstrated with the "sickle solubility test". A mixture of haemoglobin S (Hb S) in a reducing solution (such as sodium dithionite) gives a turbid appearance, whereas normal Hb gives a clear solution.

Abnormal hemoglobin forms can be detected on hemoglobin electrophoresis, a form of gel electrophoresis on which the various types of hemoglobin move at varying speeds. Sickle-cell hemoglobin (HgbS) and hemoglobin C with sickling (HgbSC)—the two most common forms—can be identified from there. The diagnosis can be confirmed with high-performance liquid chromatography. Genetic testing is rarely performed, as other investigations are highly specific for HbS and HbC.

An acute sickle-cell crisis is often precipitated by infection. Therefore, a urinalysis to detect an occult urinary tract infection, and chest X-ray to look for occult pneumonia, should be routinely performed.

People who are known carriers of the disease often undergo genetic counseling before they have a child. A test to see if an unborn child has the disease takes either a blood sample from the fetus or a sample of amniotic fluid. Since taking a blood sample from a fetus has greater risks, the latter test is usually used. Neonatal screening provides not only a method of early detection for individuals with sickle-cell disease, but also allows for identification of the groups of people that carry the sickle cell trait. 

PROBLEMS AND COMPLICATIONS

Sickle- cell disease may lead to various acute and chronic complications, several of which have a high mortality rate.

  • Sickle cell crisis

The terms "sickle-cell crisis" or "sickling crisis" may be used to describe several independent acute conditions occurring in patients with SCD. SCD results in anemia and crises that could be of many types including the vaso-occlusive crisis, aplastic crisis, sequestration crisis, haemolytic crisis, and others. Most episodes of sickle-cell crises last between five and seven days. "Although infection, dehydration, and acidosis (all of which favor sickling) can act as triggers, in most instances, no predisposing cause is identified."

  • Vaso-occlusive crisis

The vaso-occlusive crisis is caused by sickle-shaped red blood cells that obstruct capillaries and restrict blood flow to an organ resulting in ischemia, pain, necrosis, and often organ damage. The frequency, severity, and duration of these crises vary considerably. Painful crises are treated with hydration, analgesics, and blood transfusion; pain management requires opioid administration at regular intervals until the crisis has settled. For milder crises, a subgroup of patients manage  on NSAIDs (such as diclofenac or naproxen). For more severe crises, most patients require inpatient management for intravenous opioids; patient-controlled analgesiadevices are commonly used in this setting. Vaso-occlusive crisis involving organs such as the penis or lungs are considered an emergency and treated with red-blood cell transfusions. Incentive spirometry, a technique to encourage deep breathing to minimise the development of atelectasis, is recommended.

  • Splenic sequestration crisis

Because of its narrow vessels and function in clearing defective red blood cells, the spleen is frequently affected.[6] It is usually infarcted before the end of childhood in individuals suffering from sickle-cell anemia. This autosplenectomyincreases the risk of infectionfrom encapsulated organisms; preventive antibiotics and vaccinations are recommended for those with such asplenia.

Splenic sequestration crises are acute, painful enlargements of the spleen, caused by intrasplenic trapping of red cells and resulting in a precipitous fall in hemoglobin levels with the potential for hypovolemic shock. Sequestration crises are considered an emergency. If not treated, patients may die within 1–2 hours due to circulatory failure. Management is supportive, sometimes with blood transfusion. These crises are transient, they continue for 3–4 hours and may last for one day.

ØAcute Chest Syndrome

Acute chest syndrome is a life-threatening condition linked to sickle cell anemia. This syndrome is similar to pneumonia. An infection or sickle cells trapped in the lungs can cause acute chest syndrome.

People who have this condition often have chest pain, shortness of breath, and fever. They also often have low oxygen levels and abnormal chest x ray results.

  • Aplastic crisis

Aplastic crises are acute worses of the patient's baseline anemia, producing pallor, tachycardia, and fatigue. This crisis is normally triggered by parvovirus B19, which directly affects production of red blood cells by invading the red cell precursors and multiplying in and destroying them. Parvovirus infection nearly completely prevents red blood cell production for two to three days. In normal individuals, this is of little consequence, but the shortened red cell life of SCD patients’results in an abrupt, life-threatening situation. Reticulocyte counts drop dramatically during the disease (causing reticulocytopenia), and the rapid turnover of red cells leads to the drop in hemoglobin. This crisis takes 4 days to one week to disappear. Most patients can be managed supportively; some need blood transfusion.

 

ØPulmonary Hypertension

Damage to the small blood vessels in the lungs makes it hard for the heart to pump blood through the lungs. This causes blood pressure in the lungs to rise.

Increased blood pressure in the lungs is called pulmonary hypertension (PH). Shortness of breath and fatigue are the main symptoms of PH.

  • Delayed Growth and Puberty in Children

Children who have sickle cell anemia often grow more slowly than other children. They may reach puberty later. A shortage of red blood cells causes the slow growth rate. Adults who have sickle cell anemia often are slender or smaller in size than other adults.

ØStroke

Two forms of stroke can occur in people who have sickle cell anemia. One form occurs if a blood vessel in the brain is damaged and blocked. This type of stroke occurs more often in children than adults. The other form of stroke occurs if a blood vessel in the brain bursts.

Either type of stroke can cause learning problems and lasting brain damage, long-term disability, paralysis (an inability to move), or death.

ØEye Problems

Sickle cells also can affect the small blood vessels that deliver oxygen-rich blood to the eyes. Sickle cells can block these vessels or cause them to break open and bleed. This can damage the retinas—thin layers of tissue at the back of the eyes. The retinas take the images you see and send them to your brain.

This damage can cause serious problems, including blindness.

ØGallstones

When red blood cells die, they release their hemoglobin. The body breaks down this protein into a compound called bilirubin. Too much bilirubin in the body can cause stones to form in the gallbladder, called gallstones.

Gallstones may cause steady pain that lasts for 30 minutes or more in the upper right side of the belly, under the right shoulder, or between the shoulder blades. The pain may happen after eating fatty meals.

People who have gallstones may have nausea (feeling sick to the stomach), vomiting, fever, sweating, chills, clay-colored stools, or jaundice.

ØMultiple Organ Failure

Multiple organ failure is rare, but serious. It happens if you have a sickle cell crisis that causes two out of three major organs (lungs, liver, or kidneys) to fail. Often, multiple organ failure occurs during an unusually severe pain crisis.

Symptoms of this complication are fever, rapid heartbeat, problems breathing, and changes in mental status (such as sudden tiredness or confusion).

TREATMENT

Sickle cell anemia has no widely available cure. However, treatments can help relieve symptoms and treat complications. The goals of treating sickle cell anemia are to relieve pain; prevent infections, organ damage, and strokes; and control complications (if they occur).

Blood and marrow stem cell transplants may offer a cure for a small number of people who have sickle cell anemia. Researchers continue to look for new treatments for the disease.

Infants who have been diagnosed with sickle cell anemia through newborn screening are treated with antibiotics to prevent infections and receive needed vaccinations. Their parents are educated about the disease and how to manage it. These initial treatment steps have greatly improved the outcome for children who have sickle cell anemia.

Specialists Involved

People who have sickle cell anemia need regular medical care. Some doctors and clinics specialize in treating people who have the disease. Hematologists specialize in treating adults and children who have blood diseases or disorders.

Treating Pain

ØMedicines and Fluids

Mild pain often is treated at home with over-the-counter pain medicines, heating pads, rest, and plenty of fluids. More severe pain may need to be treated in a day clinic, emergency room, or hospital.

The usual treatments for acute (rapid-onset) pain are fluids, medicines, and oxygen therapy (if the oxygen level is low). Fluids help prevent dehydration, a condition in which your body doesn't have enough fluids. Fluids are given either by mouth or through a vein. Your doctor may prescribe antibiotics if you have an infection.

If pain continues or becomes severe, stronger medicines called opioids might be needed. Talk with your doctor about the possible benefits and risks of taking strong pain medicine, especially if the medicine will be used for a long period.

  • Folic acid and penicillin

Children born with sickle-cell disease will undergo close observation by the pediatrician and will require management by a hematologist to assure they remain healthy. These patients will take a 1 mg dose of folic acid daily for life. From birth to fiveyears of age, they will also have to take penicillin daily due to the immature immune system that makes them more prone to early childhood illnesses.

  • Hydroxyurea

The first approved drug for the causative treatment of sickle-cell anemia, hydroxyurea, was shown to decrease the number and severity of attacks in a study in 1995 (Charache et al.) and shown to possibly increase survival time in a study in 2003 (Steinberg et al.). This is achieved, in part, by reactivating fetal haemoglobin production in place of the hemoglobin S that causes sickle-cell anemia. Hydroxyurea had previously been used as a chemotherapy agent, and there is some concern that long-term use may be harmful, but this risk has been shown to be either absent or very small and it is likely that the benefits outweigh the risks.

  • Transfusion therapies

Blood transfusions are commonly used to treat worsening anemia and sickle cell complications. A sudden worsening of anemia due to an infection or enlarged spleen is a common reason for a blood transfusion.

Some, but not all, people who have sickle cell anemia need regular blood transfusions to prevent life-threatening problems, such as stroke, spleen problems, or acute chest syndrome.

Having routine blood transfusions can cause side effects. Examples include allergic reactions and a dangerous buildup of iron in the body (which must be treated). However in general, the blood supply has a risk of infections such as hepatitis and HIV.

§  Infections

Infections can be a major complication of sickle cell anemia throughout life, but especially during childhood. Often, infections can be prevented or treated.

To prevent infections in babies and young children, treatments include:

  • Daily doses of antibiotics. Treatment may begin as early as 2 months of age and continue until the child is at least 5 years old.
  • All routine vaccinations (including a yearly flu shot), plus the pneumococcal vaccine.

If your child has sickle cell anemia and shows early signs of an infection, such as a fever, you should seek treatment right away.

Adults who have sickle cell anemia also should have flu shots every year and get vaccinated against pneumonia.

§  Treating Other Complications

Acute chest syndrome is a severe and life-threatening complication of sickle cell anemia. If acute (sudden) failure of the liver and kidneys also occurs, it's called acute multiple organ failure.

Treatment for these complications usually occurs in a hospital and may include oxygen therapy, blood transfusions, antibiotics, pain medicine, and balancing body fluids.

Leg ulcers (sores) due to sickle cell anemia can be very painful. Ulcers can be treated with cleansing solutions and medicated creams or ointments.

Skin grafts might be needed if the leg ulcers are ongoing. Bed rest and keeping the legs raised to reduce swelling are helpful. If you have a lot of pain from leg ulcers, your doctor may recommend a strong pain medicine.

Your doctor might recommend gallbladder surgery if the presence of gallstones leads to gallbladder disease.

Priapism (a painful erection in males) can be treated with fluids, medicines, or surgery.

New Treatments

Research on blood and marrow stem cell transplants, gene therapy, and new medicines for sickle cell anemia is ongoing. The hope is that these studies will provide better treatments for the disease. Researchers also are looking for a way to predict the severity of the disease.

ØBlood and Marrow Stem Cell Transplant

A blood and marrow stem cell transplant can work well for treating sickle cell anemia. This treatment may even offer a cure for a small number of people.

The stem cells used for a transplant must come from a closely matched donor. The donor usually is a close family member who doesn't have sickle cell anemia. This limits the number of people who may have a donor.

The transplant process is risky and can lead to serious side effects or even death. However, new transplant approaches may improve treatment for people who have sickle cell anemia and involve less risk.

Blood and marrow stem cell transplants usually are used for young patients who have severe sickle cell anemia. However, the decision to give this treatment is made on a case-by-case basis.

Researchers continue to look for sources of bone marrow stem cells—for example, blood from babies' umbilical cords. They also continue to look for ways to reduce the risks of this procedure.

ØGene Therapy

Gene therapy is being studied as a possible treatment for sickle cell anemia. Researchers want to know whether a normal gene can be put into the bone marrow stem cells of a person who has sickle cell anemia. This would cause the body to make normal red blood cells.

Researchers also are studying whether they can "turn off" the sickle hemoglobin gene or "turn on" a gene that makes red blood cells behave normally.

ØNew Medicines

Researchers are studying several medicines for sickle cell anemia. They include:

  • Decitabine. Like hydroxyurea, this medicine prompts the body to make fetal hemoglobin. Fetal hemoglobin helps prevent red blood cells from sickling and improves anemia. Decitabine might be used instead of hydroxyurea or added to hydroxyurea.
  • Adenosine A2a receptor agonists. These medicines may reduce pain-related complications in people who have sickle cell anemia.
  • 5-HMF. This natural compound binds to red blood cells and increases their oxygen. This helps prevent the red blood cells from sickling.