Chronic anemia is present in all individuals with sickle cell disease. It is generally asymptomatic, though patients report chronic fatigue and exercise intolerance. Vaso-obstruction and pain are the major presenting symptoms of the disease. The precipitating cause of the vaso-occlusive crisis is often not clear but include the following [5]:

• Hypoxia
• Infection
• Dehydration
• Acidosis
• Emotional stress
• Extremes in environmental temperature
• Pregnancy
• Alcohol ingestion

Mandatory neonatal screening in the United States identifies new cases. Symptoms do not occur in the first 6 months of life because of the persistence of fetal hemoglobin (HbF). After 6 months of age as fetal hemoglobin levels decrease and the percentage of sickle hemoglobin increases, symptoms begin to appear. Hand and foot syndrome is often the presenting sign (6 mo.-5 yr.). The bone marrow of the small bones of the hands and feet is very active in infancy and early childhood. This activity level increases the risk of ischemia and infarct. It results in acute swelling, erythema, and severe pain of the hands and feet. Onset is sudden and duration short [6].

• Splenomegaly

  In two mouse SCD models, Berkeley and SAD, inhibition of red blood cell dehydration and sickling was achieved with correction of hematological parameters, splenomegaly, and prevention of the characteristic urine concentration defect. [ncbi.nlm.nih.gov]

  In two mouse SCD models, Berkeley and SAD, inhibition of red blood cell dehydration and sickling was achieved with correction of hematological parameters, splenomegaly, and prevention of the characteristic urine concentration defect. ↵ * To whom correspondence [doi.org]

  Splenomegaly is often present in older children and adults. The peripheral blood smear shows many target cells and Hb C crystals, but no irreversibly sickled cells. [clinicaladvisor.com]

• Pain

  Vaso-obstruction and pain are the major presenting symptoms of the disease. [symptoma.com]

  Acute pain: assess all patients with sickle cell disease who present with acute pain to determine whether their pain is being caused by an acute painful sickle cell episode or whether an alternative diagnosis is possible, particularly if pain is reported [patient.info]

  Painful vaso-occlusive crisis causes severe pain in long bones, the hands and feet, back, and joints. Hip pain may result from avascular necrosis of the femoral head. [msdmanuals.com]

  Pain crises Pain crises in persons with sickle cell anemia are intermittent painful episodes that are the result of inadequate blood supply to body tissues. [medicinenet.com]

• Anemia

  From What treatments manage symptoms of fatigue and anemia? Fatigue is a common symptom in persons with sickle cell anemia. Sickle cell anemia causes a chronic form of anemia, which can lead to fatigue. [medicinenet.com]

  Some hemoglobinopathies result in anemias that are severe in patients who are homozygous but mild in those who are heterozygous. Some patients are compound heterozygotes for 2 different hemoglobinopathies and have anemia of varying severity. [msdmanuals.com]

  To learn more about Sickle Cell Anemia, see these other NetWellness features: Sickle Cell Anemia Overview Chronic Complications of Sickle Cell Treatments for Sickle Cell Sickle Cell Anemia: Not a Black Disease Sickle Cell Classroom and Workplace Guides [netwellness.org]

• Fever

  We determined practice variation for children with SCD presenting with fever to the emergency department (ED). [ncbi.nlm.nih.gov]

  Acute chest syndrome is characterized by sudden onset of fever, chest pain, and pulmonary infiltrates. It may follow bacterial pneumonia. Hypoxemia may develop rapidly, causing dyspnea. [msdmanuals.com]

  Fever may be present as well. Do not assume an infectious cause in Sickle Cell Patients who present with fever. Physical exam may reveal lethargy, rapid heart rate and occasionally frank heart failure. [emergencymedicinecases.com]

• Severe Pain

  Abstract Patients with sickle-cell disease (SCD) can experience recurrent vaso-occlusive episodes (VOEs), which are associated with severe pain. [ncbi.nlm.nih.gov]

• Fatigue

  What treatments manage symptoms of fatigue and anemia? Fatigue is a common symptom in persons with sickle cell anemia. Sickle cell anemia causes a chronic form of anemia, which can lead to fatigue. [medicinenet.com]

  Sickled cells lose their normal functioning and hemodynamic properties, leading to chronic fatigue as well as to episodes of painful crises. [ncbi.nlm.nih.gov]

  Red blood cells in people affected by SCD do no last as long as cells with healthy haemoglobin, which can lead to a lower number of red blood cells than normal and resulting symptoms of anaemia, such as fatigue. [news-medical.net]

  People who have sickle cell disease may also have trouble coping with pain and fatigue, as well as with frequent medical visits and hospitalizations. [nhlbi.nih.gov]

• Dyspnea

  He presented with progressive severe dyspnea on exertion and lower extremity edema. [ncbi.nlm.nih.gov]

  Acute chest syndrome: Inquire about shortness of breath or dyspnea, fever, and cough. Stroke: Ask about aphasia, paresthesias, limb weakness, and change of level of consciousness. [web.archive.org]

  Echocardiography should be performed on all patients with dyspnea. The goal of treatment is two-fold; symptom control and prevention and management of complications. [symptoma.com]

  Hypoxemia may develop rapidly, causing dyspnea. DNA testing (prenatal diagnosis) Peripheral smear Solubility testing Hemoglobin electrophoresis (or thin-layer isoelectric focusing) The type of testing done depends on the age of the patient. [msdmanuals.com]

• Abdominal Pain

  Despite testing negative for malaria by both smear and PCR 2 weeks after arrival in the USA, the patient developed fever and diffuse bilateral lower rib cage and upper abdominal pain 2 weeks later and subsequently tested positive for Plasmodium falciparum [ncbi.nlm.nih.gov]

  Common side effects of Endari include constipation, nausea, headache, abdominal pain, cough, pain in the extremities, back pain and chest pain. [web.archive.org]

• Severe Abdominal Pain

  Abdominal crisis: The pain associated with the abdominal crisis of sickle cell disease is constant and sudden. It becomes unrelenting. The pain may or may not be localized to any one area of the abdomen. [emedicinehealth.com]

  Severe abdominal pain may develop with or without vomiting and is usually accompanied by back and joint pain. Acute chest syndrome is characterized by sudden onset of fever, chest pain, and pulmonary infiltrates. It may follow bacterial pneumonia. [msdmanuals.com]

  Other serious warning signs that signal a need for immediate medical treatment are: Pain that doesn’t go away with home treatment Severe abdominal pain (stomachache) or swollen belly Chest pain Sudden vision problems Headache that’s different from usual [med.umich.edu]

• Failure to Thrive

  The hallmark presentations are failure to thrive and repeated infections and repeated attacks of painful hand-foot syndrome, termed dactylitis. [themedicalbiochemistrypage.org]

  Children affected with thalassaemia show no symptoms at birth, but anaemia emerges in the first few months of life, becoming progressively severe and leading to pallor, easy fatigability, failure to thrive, a delay in maturity and fever. [cochranelibrary.com]

• Acute Abdomen

  It often involves the abdomen, bones, joints, and soft tissue, and it may present as dactylitis (bilateral painful and swollen hands and/or feet in children), acute joint necrosis or avascular necrosis, or acute abdomen. [30] With repeated episodes in [emedicine.medscape.com]

  Pain crisis can involve the abdomen, bones, joints, and soft tissue, and it may present as dactylitis (bilateral painful and swollen hands and/or feet in children), acute joint necrosis, or acute abdomen. 4 With repeated episodes in the spleen, infarctions [web.archive.org]

• Chest Pain

  Children with SCD presenting to the ED with fever and shortness of breath, tachypnea, cough, rales, or chest pain should receive a CXR due to high ACS rates. [ncbi.nlm.nih.gov]

  Someone with sickle cell disease needs medical care right away if any of these problems happen: a fever of 101°F (38°C) or higher pain that isn't getting better with medicine chest pain severe headaches or dizziness severe stomach pain or swelling shortness [kidshealth.org]

  Common side effects of Endari include constipation, nausea, headache, abdominal pain, cough, pain in the extremities, back pain and chest pain. [web.archive.org]

• Tachycardia

  Common symptoms include: Labored breathing Tachycardia (rapid heartbeat) Fever Changes in mental status (i.e. confusion) Tests for Diagnosing and Monitoring for Sickle Cell Disease At the UPMC Adult Sickle Cell Disease Program, we will obtain a complete [upmc.com]

  […] dose, if possible) and folic acid Surgical history (helps rule out other causes of abdominal pain) Previous hemoglobin levels and previous transfusions Vaccination Consanguinity, family history of similar episodes Physical Vital signs Hypotension and tachycardia [web.archive.org]

  Assess for signs and symptoms of dehydration, such as dry skin and mucous membranes, decreased skin turgor, hypotension, and tachycardia. [journals.lww.com]

  […] thoracic; jaundice; dark urine; fever; elevated white blood cell (WBC) count; lethargy; fatigue; sleepiness Sequestration crisis: Occurs in infants between 8 and 24 mo; massive pooling of RBCs in the liver and spleen Lethargy, pale skin, hypovolemia, tachycardia [medical-dictionary.thefreedictionary.com]

• Jaundice

  Jaundice and gallstones Jaundice is indicated by a yellow tone in the skin and eyes, and alone it is not a health concern. Jaundice may occur if bilirubin levels increase, which can occur with high levels of red blood cell destruction. [medical-dictionary.thefreedictionary.com]

  Jaundice, or yellowing of the skin, eyes, and mouth. Jaundice is a common sign and symptom of sickle disease. Sickle cells do not live as long as normal red blood cells and, therefore, they are dying faster than the liver can filter them out. [hopkinsmedicine.org]

  Jaundice, or yellowing of the skin, eyes, and oral mucosa. Jaundice is a common sign and symptom of sickle disease. [stanfordchildrens.org]

• Hepatomegaly

  Additional autopsy findings included cardiomegaly with a heart weight of 450 gm (312±78), right atrial and right ventricular chamber dilatation, and hepatomegaly with a liver weight of 2650 gm (1475±362). [ncbi.nlm.nih.gov]

  Hepatomegaly was seen in 28.6% of the subjects. On evaluation of the hematological parameters, hemoglobin of SCD constitutes amongst the commonest of the hemoglobinopathies, reported from the Indian subcontinent with varied incidence. [doi.org]

  […] occur in up to 50% of children.54 Prompt transfusion can be life saving.55 Hepatic sequestration is a rare but severe complication of SCD caused by the obstruction of hepatic sinusoidal blood flow by sickled erythrocytes and is characterised by painful hepatomegaly [adc.bmj.com]

  […] following factors with the log-rank test 22 : the patient's age and sex, the donor's sex, the genotypes of both patient and donor, the number of transfusions received, the incidence of red-cell alloimmunization, previous chelation therapy, the presence of hepatomegaly [oadoi.org]

• Scleral Icterus

  Enlarged liver, with jaundice and yellowing of the whites of the eyes (scleral icterus) Marked enlargement of bone marrow and possible significant deformities of some bones actively involved in producing red blood cells Other complications of sickle cell [labtestsonline.org]

• Arthritis

  Tumor necrosis factor α plays a key role in multiple inflammatory conditions, including psoriatic arthritis, rheumatoid arthritis, and hidradenitis suppurativa. [ncbi.nlm.nih.gov]

  The inflammation from dactylitis and arthritis can be reduced by anti-inflammation medications, such as ibuprofen and aspirin. [medicinenet.com]

  In reactive arthritis, sausage fingers occur due to synovitis.[2] Dactylitis may also be seen with sarcoidosis. [en.wikipedia.org]

• Swelling of Hand

  Swelling in hands and feet. Joint pain that resembles arthritis. Chronic neuropathic pain (nerve pain). Life-threatening infections. Anemia (decrease in red blood cells). [my.clevelandclinic.org]

  They may include: Anemia (looking pale) Dark urine Yellow eyes Painful swelling of hands and feet Frequent pain episodes Stunted growth Stroke back to top Treatment There are no standard treatments that cure sickle cell anemia. [web.archive.org]

  They may include: Anemia (looking pale) Dark urine Yellow eyes Painful swelling of hands and feet Frequent pain episodes Stunted growth Stroke back to top Treatment There are no standard treatments that cure sickle cell disease. [hematology.org]

• Hip Pain

  Endpoints should focus on participants' subjective experience (e.g. quality of life and pain) as well as more objective 'time-to-event' measures (e.g. mortality, survival, hip longevity). [ncbi.nlm.nih.gov]

  pain for the past two years. [orthobullets.com]

  This can be very painful. The bones usually affected are the thigh bones at the hip joint and the arm bones at the shoulder joint. The aim of treatment is to stop the pain and maintain a mobile joint. [doi.org]

  Painful vaso-occlusive crisis causes severe pain in long bones, the hands and feet, back, and joints. Hip pain may result from avascular necrosis of the femoral head. [msdmanuals.com]

• Foot Pain

  The erythrocyte sedimentation rate, if done to exclude other disorders (eg, juvenile rheumatoid arthritis causing hand and foot pain), is low. [msdmanuals.com]

• Knee Pain

  It can be asymptomatic or cause chronic pain. AVN of the hips causes knee and/or hip pain with walking or climbing. This chronic pain syndrome needs to be differentiated from the acute pain of VOC. [clinicaladvisor.com]

• Kidney Failure

  Failure Mar. 10, 2017 — Sickle cell trait, a common hemoglobin variant in African Americans, is associated with a twofold higher risk of developing kidney failure requiring dialysis, concludes a team of researchers. [sciencedaily.com]

  kidney failure, leg ulcer, eye failure, joint disease, chronic pain, psychosocial strain, anemia, lung disease, and more). [dmpi.duke.edu]

  Review Topic QID: 2907 3 Patients with sickle cell disease 4 Patients with chronic kidney failure requiring dialysis 5 Patients with puncture wounds through athletic shoes ML 1 Select Answer to see Preferred Response PREFERRED RESPONSE 3 (OBQ06.42) A [orthobullets.com]

  When blood flow is blocked, your symptoms depend on what body parts are affected: Bones: Pain (painful crisis), damage to the hip joints Heart: Enlarged heart, heart failure Kidneys: Kidney failure, kidney pain Lungs: Acute chest syndrome Penis: Priapism [merckmanuals.com]

• Hematuria

  These findings are illustrated with a case of a 9-year old girl with sickle cell disease who was referred with painless gross hematuria. [ncbi.nlm.nih.gov]

  Case-control analysis showed that ineffective erythropoiesis with increasingly severe anemia, hypertension, proteinuria, the nephrotic syndrome, and microscopic hematuria were significant pre-azotemic predictors of chronic renal failure. [doi.org]

  Unilateral hematuria (by unknown mechanisms and usually from the left kidney) can occur but is self-limited. [msdmanuals.com]

• Stroke

  The majority of strokes in this population occur between ages 3 and 14. [strokecenter.org]

  Fourteen patients (93.3%) had strokes before diagnosis of MMS, with an average age at first stroke of 6.6 ± 3.9 years. [ncbi.nlm.nih.gov]

  No cases of stroke occurred in the PPG. In the SPG, one patient with a history of stroke and severe cerebrovascular disease had a recurrence after 11 yr of chronic transfusion, when the HbS level was 20%. [doi.org]

• Headache

  We present a case of an 18-year-old male with a history of sickle cell disease, who was transferred to our emergency department with progressively severe headache and jaw pain for one-week. [ncbi.nlm.nih.gov]

  Signs can include headache,, weakness of the arms and legs, speech problems, a facial droop, or loss of consciousness. [kidshealth.org]

• Dizziness

  She presented with a 2-month history of headache, dizziness, personality and behavioral changes, and vomiting. Initial clinical evaluation raised the suspicion of brain tumor. [ncbi.nlm.nih.gov]

  Signs of anemia include: paleness, often seen in the skin, lips, or nailbeds tiredness dizziness being short of breath feeling lightheaded being irritable trouble paying attention a fast heartbeat People with sickle cell anemia may have jaundice (skin [kidshealth.org]

  Symptoms can vary in form and severity, depending on patient, but typically include Serious pain Fatigue Shortness of breath Headaches Dizziness How Is Sickle Cell Disease Diagnosed? Sickle cell disease is diagnosed by a blood test. [pfizer.com]

A complete history and review of symptoms should be completed at each visit. This should include the history of:

• Infection and exposure to infection
• Pain (frequency, duration, location, severity, medication)
• Adherence to the medication regime, efficacy, and side effects
• Difficulty or interference with activities of daily living
• Emotional status and support systems

Physical exam

A comprehensive physical examination should pay particular attention to indicators of vaso-obstruction and infection, as well as evidence of complications of the disease.

Management

Diagnosis of sickle cell disease is confirmed by the presence of homozygous HbS through hemoglobin electrophoresis. The presence of heterozygous HbS indicates a carrier of the sickle cell trait. Prenatal diagnosis may be made using DNA analysis with chorionic villus sampling at 8 to 12 weeks gestation or amniotic fluid testing at 6 weeks gestation.

Baseline blood studies should be done on all patients. Management of sickle cell disease should include regular routine blood work. The following schedule is suggested [7]:

• CBC (WBC, diff, reticulocyte count): Every 3 month
• Percentage of HbF: Annually
• Renal function (BUN, creatinine, urinalysis): Annually
• Secretory phospholipase A2: Every 3 month (in infancy)

Other suggested testing:

• Pulmonary function test (PFT): Every 6 month
• Transdoppler ultrasound (TCD): Annually - abnormal results repeat within 2-4 weeks (Transdoppler ultrasound measures cerebral blood flow and is a good predictor of stroke risk [6])

Imaging

Magnetic resonance imaging (MRI) is the best method for detecting early signs of osteonecrosis and osteomyelitis. It can distinguish between osteomyelitis and bony infarction and can detect changes in the bone marrow early. It can also identify the presence of silent cerebral infarcts, helpful for stroke prevention [6]. An abdominal ultrasound should be used whenever patients present with abdominal pain to rule out cholecystitis, cholelithiasis, or ectopic pregnancy. Routinely the procedure can be used to measure and monitor spleen and liver size [7]. Ultrasonography of the kidneys can detect causes of obstructive uropathy, nephrolithiasis, and papillary necrosis. Echocardiograms can identify pulmonary hypertension. Adults should be tested annually. Echocardiography should be performed on all patients with dyspnea [7].

• Reticulocytosis

  Nucleated RBCs frequently appear in the peripheral blood, and reticulocytosis ≥ 10% is common. Dry-stained smears may show sickled RBCs (crescent-shaped, often with elongated or pointed ends). [msdmanuals.com]

  […] increasingly anemic when the body cannot keep up with the rapid RBC destruction, resulting in a condition known as hemolytic anemia, smaller than normal red cells ( microcytosis ), and an increased number of newly produced red cells called reticulocytes (reticulocytosis [labtestsonline.org]

  The condition is self-limited, with bone marrow recovery occurring in 7-10 days, followed by brisk reticulocytosis. [emedicine.medscape.com]

  […] complication, seen in the first few years of life and resulting in circulatory collapse and death from anemia and hypovolemic shock, is defined as a sudden enlargement of the spleen with a decrease in Hb concentration (2 g/L at least) and substantial reticulocytosis [web.archive.org]

• Normocytic Anemia

  Patients with symptoms or signs suggesting the disorder or its complications (eg, poor growth, acute and unexplained bone pain, aseptic necrosis of the femoral head, unexplained hematuria), and black patients with normocytic anemia (particularly if hemolysis [msdmanuals.com]

  Patients with Hb SS and Hb SC have a normocytic anemia, unless they have coinherited α-thalassemia. Patients with Hb Sβ + and Hb Sβ 0 have a microcytic anemia. Table II. [clinicaladvisor.com]

• Hemoglobin Decreased

  A reticulocyte count 1% suggests aplastic crisis, particularly when hemoglobin decreases below the patient’s usual level. [msdmanuals.com]

  A reticulocyte count < 1% suggests aplastic crisis, particularly when hemoglobin decreases below the patient’s usual level. [merckmanuals.com]

• Reticulocytes Increased

  With each course, fetal reticulocytes increased within 48-72 h, peaked in 7-11 d, and fell by 18-21 d. [doi.org]

• Neutrophilia

  Chronic hemolytic anemia leads to decreased RBCs WBCs: 4,500–11,000/μL Chronic neutrophilia is often present with leukocytosis Elevation in the WBC count (> 20,000 per mm3) with left shift indicates infection Platelets: 150,000–400,000/μL Often increased [medical-dictionary.thefreedictionary.com]

• Leukocytosis

  The clinical signs, consisting of swelling, tenderness, fever, and leukocytosis, were self-limiting and resolved in five to thirty-one days. [ncbi.nlm.nih.gov]

  Leukocytosis or erythema does not accompany the swelling. Acute chest syndrome In young children, the acute chest syndrome consists of chest pain, fever, cough, tachypnea, leukocytosis, and pulmonary infiltrates in the upper lobes. [emedicine.medscape.com]

  […] associated with older age, low steady state hemoglobin, low steady state leukocytes count, 3 transfusion within 2 weeks, and treatment with corticosteroids or nonsteroidal anti-inflammatory drugs within 2 weeks. 4 Silent infarcts are associated with leukocytosis [ahajournals.org]

The goal of treatment is two-fold; symptom control and prevention and management of complications. Treatment is aimed at [7]:

• Decreasing the number and frequency of vaso-obstructive crises
• Controlling chronic pain
• Management of chronic hemolytic anemia
• Prevention and treatment of pulmonary hypertension
• Prevention and treatment of infarcts
• Prevention and management of organ damage
• Identification of stroke risk and prevention of acute episodes

Routine immunizations

Pneumococcal pneumonia vaccine is of greatest importance as pneumococcal pneumonia is a leading cause of morbidity and mortality in individuals with sickle cell disease. Recommended vaccines are:

• Routinely scheduled childhood/adult vaccinations
• Influenza
• Meningococcal vaccine
• Pneumococcal conjugate vaccine (PCV7) or pneumococcal polysaccharide vaccine (PPV23)

Medications

Hydroxyurea therapy: Hydroxyurea is currently the only drug approved by the US Food and Drug Administration for the treatment of sickle cell disease. It increases the total fetal hemoglobin which retards the formation of polymers and sickling of red blood cells. It also reduces circulating leukocytes, decreasing inflammation [8]. Hydroxyurea therapy has proven to decrease the frequency and severity of crises. It has been shown to reduce the number of hospitalizations and to limit the need for transfusions. Patients should be monitored for leukopenia and thrombocytopenia. Complications from long-term usage are not yet known. Efficacy in children has not been proven.

Other medications used in controlling symptoms include:

• Opioid analgesics are given to control acute pain crises. Morphine sulfate is the recommended drug.
• Non-narcotic analgesics may be effective in combination with opioids. These include ketorolac, aspirin, acetaminophen, and non-steroidal anti-inflammatory drugs.
• Antibiotics are used to treat infections. The antibiotic of choice is dependent on the causative agent. Prophylactic penicillin helps to prevent the occurrence of pneumonia.
• Vitamins: Individuals with sickle cell disease need additional folic acid.
• Bronchodilators are used for the treatment of acute chest syndrome

Non-pharmacologic therapy

Vigorous hydration is needed to prevent acidosis, maintain circulating volume, and prevent venous stasis. This intervention decreases the incidence of sickling episodes. There are no dietary restrictions associated with the disease. However, a well-balanced diet is essential to maintaining health and preventing infection.

Oxygen therapy may be necessary during acute episodes to prevent hypoxia. It is not recommended for routine use to treat chronic anemia. It is imperative in acute chest syndrome, congestive heart failure and severe pneumonia. Incentive spirometry may be helpful in patients with respiratory complications or acute respiratory illness.

Transfusions are reserved for the treatment of sudden severe anemia due to acute splenic sequestration, para-virus B19 infection, hyper-hemolytic crises, and acute chest syndrome. They are also necessary peri-operatively and during pregnancy. Complications of transfusions include:

• Alloimmunization – an adverse reaction to differences in minor red blood cell antigens between donor and recipient.
• Infection
• Iron overload – inevitably occurs with recurrent transfusions and can lead to heart failure and embolism. It must be treated with chelating agents to remove excessive iron [9].

Erythrocytaphoresis is an automated red blood cell exchange procedure. The process exchanges blood containing HbS while replacing it with HbS free blood [8].

Alternative therapies that may be of help in the control of chronic pain include:

• Physical therapy
• Heat and cold application
• Acupuncture and acupressure

Bone marrow transplantation can be a cure for sickle cell disease. After the destruction of defective HbS bone marrow with radiation or chemotherapy, normal bone marrow replaces it. The use of this therapy is limited because it requires a matching sibling donor who is free of the disease or trait.

Stem cell transplantation is still experimental but has hopes of being a more realistic cure for the disease.

Sickle cell disease is a life–long progressive disorder marked by episodic vaso-obstructive crises resulting in chronic morbidity and early mortality. Morbidity varies from individual to individual. Symptomatology and complications increase with age. Life expectancy has been extended in the past twenty years and is now estimated to be >50 years. This change is due to the development of the vaccine for pneumococcal pneumonia, increasing use of Hydroxyurea therapy, and improved monitoring and control of complications [3].

Sickle cell disease originated in West Africa where it has the highest prevalence still. Through migration and dispersion, the genetic mutation spread and is now seen worldwide. The distribution is related to the collocation of endemic malaria and sickle cell disease. The heterozygous form (Sickle cell trait) seems to have Malaria inhibiting qualities. Individuals who carry the HbS trait have a lower incidence and severity of the disease.

The incidence rate for sickle cell disease in the United States is approximately 8,000 annually or 1 per 500 African American births [4]. Prevalence is about 72,000 Americans. While 2 million people or 1 in 12 African Americans carry the sickle cell genetic trait.

Sickle cell disease arises from a gene mutation which substitutes thymine for adenine on the 6th beta-globin chain of the hemoglobin molecule (GAG to GTG) [2]. The resulting sickle hemoglobin (HbS) forms a gel-like polymer when deoxygenated. This polymer gradually forms parallel filament strands which cause the red blood cells to sickle. Sickled cells have antigen-4 (VLA-4) on their surfaces which causes them to adhere to the vascular endothelium obstructing the microvasculature.

Vaso-obstruction is responsible for the symptoms and complications associated with the disease [2]. Inflammation of the endothelium occurs secondary to ischemia. There is a sudden influx of leukocytes to the area causing swelling, narrowing and eventual obstruction of the microvasculature. Acute pain crises are a directed result of ischemia and infarct of tissues and organs following an acute vaso-obstructive episode. Deprived of oxygen, cells in the affected area are damaged. Inflammation, swelling, erythema, and eventually necrosis occur.

There are no guidelines for prevention of sickle cell disease.

Sickle cell disease is an autosomal recessive hemolytic anemia. It is a genetic disorder affecting primarily Africans (African Americans) [1]. It is the most common genetic blood disorder in the United States. Sickle cell disease is caused by a mutation of the gene responsible for hemoglobin production. Red blood cells carrying the defective hemoglobin (HbS) change shape when deoxygenated forming the characteristic sickle shape. These cells become ridge and friable, leading to increased hemolysis. This alteration in the red blood cells is responsible for the major symptoms and complications of the disease.

The cardinal signs of sickle cell disease are [2]:

• Chronic hemolytic anemia
• Severe acute and/or chronic pain
• Increased susceptibility to infection
• Recurrent episodic vaso-obstructive crises

Additional symptoms:

• Hand-foot syndrome
• Priapism
• Leg ulcers
• Acute chest syndrome
• Acute bone pain crises
• Splenic sequestration
• Aplastic anemia crises
• Growth retardation
• Central nervous system involvement
• Stroke
• Focal neurologic deficits
• Ophthalmic involvement
• Ptosis
• Retinal hemorrhage
• Vision loss
• Cardiac involvement
• Dilation of both ventricles and left atrium
• Congestive heart failure
• Cholelithiasis and/or cholangitis
• Nephropathology
• Liver involvement

What is sickle cell disease?

Sickle cell disease is an inherited/genetic disorder that affects the body’s red blood cells. It is passed from both parents who carry the sickle cell trait to their child. In this disease, defective hemoglobin, which carries oxygen in the blood, causes the red blood cells to change shape into the characteristic sickle shape.

Normal red blood cells are round and are able to move through small blood vessels in the body to deliver oxygen. The sickle-shaped cells are rigid and adhere to the walls of the small blood vessels. The defective red blood cells obstruct the vessels and clog the flow of blood and oxygen to the tissues and organs of the body.

Sickle cell disease is found most often in African-Americans and Africans. However, other ethnic groups can have sickle cell disease.

Sickle cell disease is diagnosed by hemoglobin electrophoresis, which determines the type of hemoglobin one has.
People who inherit only one sickle cell gene are carriers, but people who inherit two sickle cell genes have sickle cell disease.

What are the symptoms of sickle cell disease?

Newborn screening in the United States identifies babies with the disease at that time. In those individuals who have not been identified at birth, the following symptoms might indicate the need for testing for the disease.

• Chronic anemia with associated fatigue and exercise intolerance.
• Acute or chronic episodes of pain which can occur in any part of the body.
• Swelling and inflammation of the long bones and joints.
• Enlargement and tenderness of the spleen and live.

What are the medical problems of sickle cell disease?

Medical problems associated with sickle cell disease include:

• Respiratory illness known as acute chest syndrome
• Pain episodes due to ischemia, lack of oxygen supply, of tissues and organs
• Stroke resulting from blockage of blood supply to the brain
• Priapism, a persistent, painful, erection that lasts for more than four hours
• Increased susceptibility to infections
• Damage to any organ of the body and to bones and joints

How is sickle cell disease treated?

Currently, there is no cure for sickle cell disease. Treatment of sickle cell disease depends upon the symptoms a person is experiencing. Some medicines that can be used to treat sickle cell disease-related pain include:

• Pain medications, including opioids and anti-inflammatory medicines
• Antibiotics
• Hydroxyurea (e.g., Hydrea and Droxia)
• Iron overload therapy
• Tricyclic antidepressants such as amitriptyline
• Anticonvulsants such as gabapentin

New treatments for sickle cell disease are improving life expectancy and quality of life.

What can you do to prevent complications of the disease?

If you or a member of your family has sickle cell disease you can go a long way toward preventing the complications associated with the disease. The following guidelines are important.

• Stay well hydrated – Dehydration can be a trigger that causes acute sickling episodes.
• Contact your healthcare provider immediately if you have any symptoms of infection.
• Get routine and preventive health care, including immunizations.
• Get emergency healthcare for severe chest pain, difficulty breathing, or signs of a stroke (confusion, numbness, paralysis, or loss of consciousness).
• Take medications as ordered and report any adverse effects.
• Avoid alcohol, non-prescription drugs, and over-exertion.

1. Taber’s Online Medical Dictionary, accessed Jan. 24, 2014
2. Chiang EY, Frenette PS. Sickle cell vaso-occlusion. Hematol Oncol Clin North Am. Oct 2005;19(5):771-84, v.
3. Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. Jun 9 1994;330(23):1639-44.
4. National Institutes of Health. Introduction to Genes and Disease: Anemia, Sickle Cell. National Center for Biotechnology Information. Accessed Jan 20, 2014.
5. Zen Q, Batchvarova M, Twyman CA, et al. B-CAM/LU expression and the role of B-CAM/LU activation in binding of low- and high-density red cells to laminin in sickle cell disease. Am J Hematol. Feb 2004;75(2):63-72.
6. Miller ST, Sleeper LA, Pegelow CH, et al. Prediction of adverse outcomes in children with sickle cell disease. N Engl J Med. Jan 13 2000;342(2):83-9
7. Rees DC, Olujohungbe AD, Parker NE, Stephens AD, Telfer P, Wright J. Guidelines for the management of the acute painful crisis in sickle cell disease. Br J Haematol. Mar 2003;120(5):744-52.
8. Adams RJ, Brambilla D. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med. Dec 29 2005;353(26):2769-78.
9. Rienhoff HY Jr, Viprakasit V, Tay L, et al. A phase 1 dose-escalation study: safety, tolerability, and pharmacokinetics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload. Haematologica. Apr 2011;96(4):521-5.