Sickle Cell Disease

Table of Contents

Sickle cell disease is an inherited red-blood cell disorder which causes the body to produce abnormally shaped red blood cells.

Sickle cell disease is inherited as an autosomal recessive trait. Normal Hb A gets replaced with abnormal Hb S.

Children with this disorder have atypical hemoglobin molecules called hemoglobin S which can distort red blood cells into a sickle or crescent shape.

Red blood cells with normal hemoglobin are smooth, disk-shaped, and flexible, like doughnuts without holes. They can move through the blood vessels easily.

Cells with sickle cell hemoglobin are stiff and sticky. When they lose their oxygen, they form into the shape of a sickle or crescent, like the letter C.

These cells stick together and can’t easily move through the blood vessels. This can block small blood vessels and the movement of healthy, normal oxygen-carrying blood. The blockage can cause pain

Classification of sickle cell disease

Disease is broadly classified into;

Sickle-cell Anaemia (Homozygotes) : Are patients whose Red blood cells only contains abnormal beta chains leading to HbSS (SS). These pts are said to have sickle-cell anaemia and they have S+S of Sickle cell disease. Other names for cell sickle anaemia are;
– “HbSS“ –”SS disease“ – “Haemoglobin S”
Sickle cell trait (Heterozygotes/ carriers: Patients whose Red blood cells contains a mixture of normal beta chains of HbA and abnormal beta chains of HbS. Thus patients have both HbA and HbS (HbAS) .This results in the clinically asymptomatic disease /patients do not have signs and symptoms of Sickle cell disease. Such pts are said to have a sickle cell trait

Possibility of Sickle cell Disease

Problems in sickle cell disease typically begin around 5 to 6 months of age. Sickle-cell disease occurs when person inherits two abnormal copies of the hemoglobin gene, one from each parent. This gene occurs in chromosome 11.

Type of Gene	Normal	Trait	Disease
One Parent with Trait	50%	50%	0%
Both Parents with Trait	25%	50%	25%
One Parent with Disease	50%	50%	50%
Both Parents have Disease	0%	0%	100%

Cause of Sickle Cell Disease

It is caused by a defect in beta chains where a given amino acid is replaced by another (Substitution of valine for glutamic acid) at position 6 of the chain.

This change creates abnormal hemoglobin called HbS.

Pathophysiology of Sickle Cell Disease.

Normally each haemoglobin molecule consist of four molecules of haem folate into one molecule of globin.

But in sickle cell disease this is altered and cell become sickle shaped, glutamine is replaced by valine. The sickle cells elongate under conditions of lower oxygen concentration, Acidosis takes place and dehydration.

When red blood cells (RBCs) containing homozygous HbS are exposed to deoxygenated conditions, the sickling process begins. This distorts the membranes of red blood cells. The cell become easily entangled leading to blood viscosity, vessel occlusion and tissue necrosis.

These cells fail to return to normal shape when normal oxygen tension is restored. As a result, these rigid blood cells are unable to deform as they pass through narrow capillaries, leading to vessel occlusion and ischemia. The actual anemia of the illness is caused by haemolysis, the destruction of the red cells, because of their shape.

Although the bone marrow attempts to compensate by creating new red cells, it does not match the rate of destruction.

Healthy red blood cells typically function for 90–120 days, but sickled cells only last 10–20 days.

Increased sequestration of Red blood cells in the spleen also cause anemia

Clinical Presentation of SCD

Children are rarely symptomatic until late in the first years of life related to increased amount of fetal haemoglobin being cleared from blood. The severity of symptoms can vary from person to person. Sickle-cell disease may lead to various acute and chronic complications, several of which have a high mortality rate.

Fevers
Painful swelling of hands & feet (hand & foot syndrome)
Anaemia & jaundice
Pain in the chest, abdomen, limbs and joints
Priapism: This is a painful obstruction of the blood vessels in the penis by sickle cells. If not promptly treated, it can result in impotence.
Shortness of Breath
Fatigue and weakness
Abdominal swelling and pain.
Unusual headache
Haemoglobin 6g/dl – 9 g/dl.
Loss of appetite.
Paleness.
Irritability.
Jaundice.
Bossing of bones of skull indicating active erythropoiesis
Intercurrent infections like Acute Respiratory Infections ,pneumonia, malaria with severe aneamia
Splenomegaly ; rare if patients is less than 10yrs due to splenic infarction
Growth retardation due to on and off ill health
Stroke. The misshapen cells can block the major blood vessels that supply the brain with oxygen. Any interruption in the flow of blood and oxygen to the brain can result in severe brain damage.
Pain crisis, or sickle crisis. This occurs when the flow of blood is blocked to an area because the sickled cells have become stuck in the blood vessel.

Sickle-cell crisis

Sickle cell crisis is pain that can begin sudden and lasts several hours to several days.

The terms “sickle-cell crisis” or “sickling crisis” may be used to describe several independent acute conditions occurring in patients with Sickle Cell Disease.

It happens when sickled red blood cells block small blood vessels that carry blood to bones. Children may present with pain in the back, knees, legs, arms, chest or stomach. The pain can be throbbing, sharp, dull or stabbing.

Types of Sickle Cell Crisis.

(i) Sickle cell vaso – occlusive crisis: This is the most common form of crisis. Small blood vessels are occluded by the sickle cells causing distal ischemia and infarction.

Extremities. Bone destruction leading to osteoporosis or ischaemic necrosis.
Bone pain and swollen joints.
Foot and hand syndrome due to aseptic infarction of meta carpals and metatarsals causing swelling and pains often this is seen in infants and toddlers.

(ii) Splenic sequestration Crisis: Large amounts of blood become pooled to the spleen. The spleen becomes massively enlarged.

Great decrease in Red blood cells mass occurs with in hours.
Signs of circulatory collapse develop rapidly.
This is the most frequent cause of death in infants with sickle cell disease.

(iii) Aplastic Crisis: The bone marrow ceases to produce RBCs.

There will be low blood cell circulation in blood hence anaemia.
Folic acid deficiency
Ingestion of bone marrow toxins (eg, phenylbutazone)

(iv) Haemolytic Crisis: Hemolytic crisis occurs when large numbers of red blood cells are destroyed over a short time. The loss of red blood cells occurs much faster than the body can produce new red blood cells.

Causes of hemolysis include:

- A lack of certain proteins inside red blood cells
- Autoimmune diseases
- Certain infections
- Defects in the hemoglobin molecules inside red blood cells
- Defects of the proteins that make up the internal framework of red blood cells
- Side effects of certain medicines
- Reactions to blood transfusions.

(v) Acute chest syndrome. This occurs when sickling occurs in the chest. This can be life-threatening. It often occurs suddenly, when the body is under stress from infection, fever, or dehydration.

Precipitating Factors of Crisis

Dehydration.
Infection.
Trauma.
Strainous Physical exercises.
Extreme fatigue.
Extreme exertion
Severe cold that constricts peripheral vessels
Fever Excessive exercise

Hypoxia.
Acidosis.
Extreme temperature
High attitude
Emotional stress
Pregnancy
Asthma
Anxiety
Abrupt changes in temperature

Chronic symptoms of sickle cell Disease.

Chronic organ damage results in organ dysfunction and the patient will present with jaundice.
Gall stones.
Progressive impairment of kidney function.
Growth retardation of the long bones and spine deformities.
Delayed puberty.
Chronic painful leg ulcers related to chronic anaemia.
Decreased lifespan.
Altered body structures (bossing of the head, septic necrosis of bones especially the femur and the head of the humerus.

Investigations / Diagnosis

Family history of sickle cell disease
Full blood count & peripheral film comment : May indicate leukocytosis due to bacterial infection
Hb estimation: The level of Hb is in the range 6-8 g/dL with a high reticulocyte count (10-20%)..
Sicklcell prep (Sickling test):
-Done by finger or heel stick.
-Oxygen removed from a drop of blood. The blood is observed under the microscope for sickle shaped cells.
-The test does not distinguish between the patient with sickle cell trait and disease or other sickle haemoglobins opathies.
Haemoglobin electrophoresis.
-Requires vein puncture, haemoglobin is subjected to an electric current that separates the various types and determines the amount present . It demonstrates the different types of Hb found in RBCs
-This test is used to diagnose both trait and sickle cell disease. It provides definitive diagnosis for the patient.
Sickledex test Sickledex are available for rapid screening to detect the presence of Hb S in the blood.
Peripheral blood smear:
May show;–Sickle cells —Reticulocytes (immature RBCs)
Urinalysis
Liver and renal function tests
Chest radiography (for Acute Chest Syndrome)
Abdominal ultrasound incase of mesenteric crisis.
Sickling test; Used in emergency screening for sicklers before surgery

Differential Diagnosis

Acute Anemia
Carotid-Cavernous Fistula (CCF)
Hemoglobin C Disease
Hemolytic Anemia
Osteomyelitis in Emergency Medicine
Pulmonary Embolism (PE)
Rheumatoid Arthritis Hand Imaging
Septic Arthritis

Management of Sickle Cell Disease.

Management is according to the type of crisis .
Acute painful attacks require supportive therapy with intravenous fluids, oxygen, antibiotics and adequate analgesia.
Crises can be extremely painful and require usually narcotic analgesia. Morphine is the drug of choice. Milder pain can sometimes be relieved by codeine, paracetamol and NSAIDs.
Prophylaxis is with penicillin twice daily, up to 5 years of age due to the immature immune system that makes them more prone to early childhood illnesses is recommended and vaccination with polyvalent pneumococcal and Haemophilus influenzae type B vaccine .
Anemia Transfusions should only be given for clear indications.
Patient with steady state anemia, those having minor surgery or having painful episodes without complications should not be transfused.
Transfusions should be given for heart failure, strokes, acute chest syndrome, acute spleenic sequestration and aplastic crises.
Transfusion and splenectomy may be life-saving for young children with splenic sequestration.
A full compatibility screen should always be performed.
Folic acid 5 mg daily for life is recommended.
Hydroxycarbamide (hydroxyurea)starting dose 20mg/kg is the first drug which has been widely used as therapy for sickle cell anemia. It acts by increasing Hb F concentrations but the reduction in neutrophils may also help. Hydroxycarbamide has been shown in trials to reduce the episodes of pain, the acute chest syndrome and the need for blood transfusions.
Malaria prevention: Since they are more vulnerable to malaria, because the most common cause of painful crises in malarial countries is infection with malaria.
It has therefore been recommended that people with sickle-cell disease living in malarial countries should receive anti-malarial chemoprophylaxis monthly for life i.e sulfadoxine pyrimethamine.
Pain management.

Home management
Paracetamol 1 g every 8 hours
Child: 10-15 mg/kg 6-8 hourly
And/or ibuprofen Child: 5-10 mg/kg 8 hourly.
Adults 400-600 mg 6-8 hourly.
And/or diclofenac 50 mg 8 hourly
Children only >9 years and >35 kg: 2 mg/kg in 3 divided doses.
- If pain not controlled, add:
- Codeine 30-60 mg every 6 hours (only in patients >12 years).
Or tramadol 50-100 mg every 6-8 hours (only in patients >12 years)
- Or Oral morphine at 0.2-0.4 mg/kg every 4 hours and re-assess pain level.
If pain still not controlled, refer to hospital
- At the hospital;
- Morphine oral
- Child and Adult: 0.3-0.6 mg/kg per dose and re-assess
- Morphine Intravenously.
- Child: 0.1-0.2 mg/kg per dose
- Adult: 5-10 mg dose and re-assess
- Use of laxative: bisacodyl 2.5 mg to 5 mg orally to prevent constipation due to morphine intake.
Cure:
The only therapy approved by the FDA that may be able to cure SCD is a bone marrow or stem cell transplant.
Bone marrow or stem cell transplants are very risky and can have serious side effects, including death. For the transplant to work, the bone marrow must be a close match. Usually, the best donor is a brother or sister.

Prevention of Sickle cell crisis.

Drink plenty of water.
Try not to get too hot or too cold.
Try to avoid places or situations that cause exposure to high altitudes (for example, flying, mountain climbing, or cities with a high altitude).
Vaccination
Try to avoid places or situations with exposure to low oxygen levels (for example, mountain climbing or exercising extremely hard, such as in military boot camp or when training for an athletic competition).
Wash your hands often.
Prepare food safely. Bacteria can be especially harmful to children with SCD.
Yearly visits to an eye doctor to look for damage to the retina

Nursing Diagnosis

Acute pain related to tissue hypoxia due to agglutination of sickled cells within blood vessels evidenced by patient verbalization.
Risk for infection related to lowered immunity
Impaired Gas Exchange related to decreased oxygen-carrying capacity of the blood, reduced RBC life span/premature destruction, abnormal RBC structure; sensitivity to low oxygen tension (strenuous exercise, increase in altitude) as evidenced by difficult in breathing.
Ineffective Tissue Perfusion related to vaso-occlusive nature of sickling as evidenced by changes in vital signs: diminished peripheral pulses/capillary refill, general pallor or decreased mentation, restlessness.
Risk for Deficient Fluid Volume related to increased fluid needs, e.g., hypermetabolic state/fever, inflammatory processes.
Acute Pain related to Intravascular sickling with localized stasis, occlusion, and infarction/necrosis as evidenced by generalized pain, described as throbbing, or severe ; affecting peripheral extremities, bones, joints, back, abdomen, or head (headaches)
Risk for Impaired Skin Integrity related to impaired circulation (venous stasis and vasso-occlusion)

Prevention Of Sickle Cell Disease

Genetic counseling is important to prevent passing on the trait or disease to children for those wanting to have them.
Premarital counseling is encouraged. Early recognition/screening of children with low Hb
Periodic comprehensive evaluations, and other disease-specific health maintenance services.

Complications of Sickle Cell Anemia

Stroke. Issues in circulation will result to blockages, therefore predisposing the patient to develop thrombolytic strokes
Acute chest syndrome. This is characterized by chest pain, fever and difficulty breathing requiring emergency medical treatment
Pulmonary hypertension. This type of anemia can cause build-up of unnecessary lung pressure due to problems with circulation as a result of erythrocyte clumping
Organ damage. Due to the chronic inability of the red blood cells to provide essential oxygen for normal organ function, patients with sickle cell anemia may develop organ failure, which can be fatal.
Blindness. One of the potential complications of having abnormal red blood cells circulating in the body is damage to smaller blood vessels, particularly the eye. This in turn will cause eye damage and eventually blindness.
Leg ulcers. Poor wound healing and rampant skin breakdown can be observed for patients suffering from sickle cell anemia.
Gallstones. The build of bilirubin caused by the metabolism of the abnormal erythrocytes will result to gall stones that will block the flow of bile.
Priapism. This is a condition wherein men with Sickle cell anemia will present with painful and long-lasting erections due to the blockages of the tiny blood vessels of the penis.
Pregnancy complications. Sickle cell anemia increases the risk of high blood pressure and the presence of clots that will interfere with the normal development of the fetus