Sickle Cell Anemia

Dr. Sabir

What is Sickle Cell Anemia (SCA)? an inherited condition

that results in a decrease in the ability of red blood cells to carry oxygen throughout the body

Sickle red blood cells become hard and irregularly shaped (resembling a sickle)

Become clogged in the small blood vessels and therefore do not deliver oxygen to the tissues.

Lack of tissue oxygenation can cause excruciating pain, damage to body organs and even death.

Pathogenesis

Normal hemoglobin 2 alpha and 2 beta chains form a 4 chain tetramer

HbS: Valine substituted for glutamic acid in both beta chains (HbSS). This occurs due to single point mutation at sixth position of

beta globin chain which has thymine instead of adenine.

PATHOGENESISArterial pO2 oxyHbS(soluble)

Stiff,viscous sickle cell

Venous pO2 deoxyHbSpolymerised)

Membrane changes Ca2+

influx,K+leakage

Capillary venule occlusionShortened red cell survival

MicroinfarctionIschemic tissue painIschemic organic malfn. Anemia, jaundice

Mechanism -HbS

When sickle haemoglobin (HbS) gives up its oxygen to the tissues, HbS sticks together Forms long rods inside RBC RBC become rigid, inflexible, and sickle-shaped Unable to squeeze through small blood vessels,

instead blocks small blood vessels Less oxygen to tissues of body

RBCs containing HbS have a shorter lifespan Normally 120 days Chronic state of anaemia

Sickle Cell Trait

Sickle haemoglobin (S) + Normal haemoglobin (A) in RBC Adequate amount of normal Hb (A) in red blood

cells RBC remain flexible Carrier Do Not have the symptoms of the sickle cell

disorders, with 2 exceptions

1. Pain when Less Oxygen than usual (scuba diving, activities at high altitude (12,000ft), under general anaesthesia)

2. Minute kidney problems

LAB DIAGNOSIS

SICKLE TEST:Red cells with HbS take a sickle shape when mixed with a freshly prepared solution of the reducing agent sodium metabisulphite.(2%) Giving an appearance of turbidity.

SOLUBILITY TEST:Hb added to solution of sodium dithionite(reducing agent) in phosphate buffer.Turbidity shows presence of HbS.

Hb ELECTROPHORESIS

BLOOD PICTURE Hb : 6-9gm%, may be lower

Anemia: normocytic, normochromic

MCV,MCH: Normal

Stained film:Moderate anisopoikilocytosis, sickle cells, oval cells, occ target cells, Howell-Jolly bodies

Reticulocytosis (10-20%)

Screening

1. Haemoglobin Electrophoresis Simple Blood test Routine screening in high risk groups

• During pregnancy• Before anaesthesia

2. Prenatal Testing Amniocentesis

16 and 18 weeks of the pregnancy small risk of causing a miscarriage (1 in 100)

Chorionic villus sampling (CVS) 9th or 10th week of pregnancy very small amount of material from the developing

placenta slightly higher chance of miscarriage

Early Symptoms and Complications

Typically appear during infant's first year 1st symptom: dactylitis and fever (6 mo-2

yrs) Pain in the chest, abdomen, limbs and

joints Enlargement of the heart, liver and spleen

nosebleeds Frequent upper respiratory infections Chronic anemia as children grow older

Over time Sickle Cell sufferers can experience damage to organs such as liver, kidney, lungs, heart and spleen

Can result in death

Medical Complications

1. pain episodes

2. strokes

3. increased infections

4. leg ulcers

5. bone damage

6. jaundice

7. early gallstones

8. lung blockage

9. kidney damage and loss of body water in urine

10.painful erections (priapism)

11.blood blockage in the spleen or liver (sequestration)

12.eye damage

13.low red blood cell counts (anemia)

14.delayed growth

Serious Complications: PAINRecurrent Pain Episodes or Sickling

Crises Occur at any age but appear to be

particularly frequent during late adolescence and early adult life Unpredictable Red Blood Cells get stuck in the small veins

and prevent normal blood flow Characterized by severe severe pain in the back,

chest, abdomen, extremities, and head Highly disruptive to life Most common reasons for individuals to seek

health care

1. Fever

2. Chest pain

3. Shortness of Breath

4. Increasing tiredness

5. Abdominal swelling

6. Unusual headache

Danger Signs of a Crisis

7. Any sudden weakness orloss of feeling

8. Pain that will not go away with home treatment

9. Priapism (painful erection that will not go down)

10.Sudden vision changeSEEK URGENT HOSPITAL TREATMENT IF IN CRISIS

Crises

During a crisis severe pain in the fingers, toes,

arms, joints,legs, back, abdomen, and bones.

Decrease in oxygen to the chest and lungs May lead to acute chest syndrome

Damage to the lungs Severe pain and fever airways narrowing, further reducing O2

Leads to an increased risk of potentially fatal infections

Infections Thirst and dehydration caused by not

drinking enough( even if thirst is not felt ) Over-exertion Over-excitement Cold weather and cold drinks and

swimming Bangs, bumps, bruises and strains Stress triggers pain in adults, but does

not seem to do so in children.

Triggers of Pain

Alleviating Pain

Warmth: increases blood flow Massaging and rubbing Heat from hot water bottles and deep heat creams Bandaging to support the painful region Resting the body Getting the sufferer to relax

deep breathing exercises distracting the attention

Pain-killing medicines (analgesics): paracetamol, codeine non-steroidal anti-inflammatory, morphine if necessary

1. Taking folic acid daily to help make new red cells

2. Daily penicillin until age six to prevent serious infection

3. Drinking plenty of water daily (8-10 glasses for adults)

4. Avoiding too hot or too cold temperatures

5. Avoiding over exertion and stress

6. Getting plenty of rest

7. Getting regular check-ups from knowledgeable health care providers

Daily Preventive Measures

Treating Complications

Pain-killing drugs and oral and intravenous fluids To reduce pain and prevent complications.

Transfusions Correct anemia Treat spleen enlargement in children before the

condition becomes life-threatening Regular transfusion therapy also can help prevent

recurring strokes in children at high risk of crippling nervous system complications.

Hydroxyurea The first effective drug treatment for adults with

severe sickle cell anemia reported in early 1995 Daily doses of the anticancer drug,

hydroxyurea, reduced the frequency of painful crises, acute chest syndrome, needed fewer blood transfusions

Increases production of fetal hemoglobin in the blood Fetal hemoglobin seems to prevent sickling

of red cells cells containing fetal hemoglobin tend to

survive longer in the bloodstream

Developing Treatments

Bone marrow transplantation

Shown to provide a cure for severely affected children with sickle cell disease

Only about 18 percent of children with sickle cell anemia are likely to have a matched sibling.

Developing Treatments

The Ultimate Cure? Gene Therapy

1. Correcting the “defective gene” and inserting it into the bone marrow

2. Turning off the defective gene and simultaneously reactivating another gene that turns on production of fetal hemoglobin.

No real cure for Sickle Cell Anemia at this time.

“In the past 30 years, the life expectancy of people with sickle cell anemia has increased. Many patients with sickle cell anemia now live into their mid-forties and beyond.”