Slide 1: Sickle Cell Anemia Dr Ashok Mahato What is Sickle cell anemia ? : What is Sickle cell anemia ? It is a type of Haemoglobinopathy.
Inherited as an autosomal recessive genetic
disease & result from substitution of aminoacid
valine from glutamic acid in position 6 of Beta
globin chain leading to production of defective
form of haemoglobin [ HbS ]
HbS is a structurally & qualitatively defective Hb. Slide 3: SC Hb affects the normal O2 carrying capacity of RBC’s . When these Sickle cells are de-oxygenated under stress , the RBC’s change from round flexible disc-like cells to elongated sickle / crescentic moon shape. Effect is that the cells do not pass freely through small capillaries & form clusters, which block the blood vessels. This blockage prevents oxygenation of the tissues in the affected areas resulting in tissue hypoxia & consequent pain known as sickle cell crisis/pain The Proteins of Hemoglobin A : The Proteins of Hemoglobin A There are 4 protein subunits of Hemoglobin A
There will be different forms of Hemoglobin when there is a mutation in the beta subunit. Slide 5: Homozygotes only produce abnormal beta
chains & make haemoglobin S [ HbS, termed SS ]
& this result in clinical syndrome of sickle cell
Heterozygotes produce a mixture of normal &
abnormal beta chains that make normal HbA
& HbS [ termed AS ] & results in clinically
asymptomatic Sickle cell trait. Slide 6: AS AS SS AS AS AA Normal Sickle – cell trait Sickle - cell
disease Possible genotype of offspring of parents with Sickle – cell trait Pathogenesis : Pathogenesis Deoxygenation leads to hydrophobic interaction between adjacent Hb S molecules.
Distortion of Red cell membrane produce
sickle shaped cells
Decreased elasticity of cell wall of RBC
Decreased life span 10 – 20 days.
Clogging of RBC in microcirculation. Red blood cells Going through Vessels : Red blood cells Going through Vessels Clinical features : Clinical features Sickling is precipitated by hypoxia , acidosis
dehydration & infection.
Irreversibly sickled cells have a shortened
survival & plug vessels in microcirculation.
Acute syndrome of plugging of RBC’s in
1. Vaso-occlusive crisis. 2. Aplastic crisis
3. Sequestration crisis. 4. Sic kle chest synd. Acute crisis : Acute crisis Vaso-occlusive crisis – plugging of small
vessels in bone produces severe pain in
humerus , femora, ribs, spine. Plugging in
hands & feet of children causes dactylitis.
It is most common crisis.
Sickle chest syndrome – common cause of
death in adult. Bone marrow infarction
results fat emboli to lungs which causes
pulmonary infartion & ventilatory failure. Acute crisis : Acute crisis Sequestration crisis – Thrombosis of
venous outflow of organ causes acute
painful enlargement & loss of function.
In children massive enlargement of spleen
result in severe anemia & circulatory
collapse with death. Recurrent sickling &
infarction of spleen in adults may have
no functional spleen & is called
autosplenectomy. Acute crisis : Acute crisis Aplastic crisis – Infection of adult sicklers
with human erythrovirus 19 result in
severe but self limiting red cell aplasia.
This produces very low Hb which may
cause heart failure. Clinical manifestation of SCD : Clinical manifestation of SCD Ocular- Background retinopathy, Proliferative
retinopathy, Vitreous bleed.
Renal – Enuresis, haematuria, papillary
Bone -- Dactilytis, arthropathy, osteomyelitis
avascular necrosis, vertebral collapse
CNS – CVA, Fits, Subarachnoid bleed.
Cardiac – Sickle myocardium, cardiomegaly
transfusional iron overload. Clinical manifestation : Clinical manifestation Priapism.
Pulmonary infarction Slide 15: X-ray of a hand of young baby swollen from dactylitis Enlarged & unhealthy spleen
with SCD Slide 16: Adolescents and adults can develop ulcers
on their legs Why Sickle Cell Trait are resistant to Malaria ? : Why Sickle Cell Trait are resistant to Malaria ? When Hb of Sickle Cell carriers come in contact with the Malaria parasite they become sickled. When sickled cell pass through the spleen, the cells are eliminated with the Malaria parasite.
Sickle Cell trait causes the parasite to stay in the body for an extended period of time, so it is able to build up a defense to it. 3. As O2 concentration is low in the spleen, infected trapped cells in the spleen are destroyed
4. Malaria parasite produces lactic acid in RBC . This causes the RBC to polymerize & sickling. sickled cells are then destroyed in the spleen. Investigation : Investigation Screening test – Demonstrated by exposing RBC to a
reducing agent such as Sodium dithionte ; HbA
gives clear solution but HbS polymerises to produce
a turbid solution.
Hb electrophoresis – Gives a definitive diagnosis.
HPLC [ High performance liquid chromatography]
to quantify the amount of sickled cell.
Blood film shows compensated anemia with
Hb % 6-8gm. Features of Hyposlenism – target cell
Howell- jelly bodies. Slide 19: Screening Haemoglobin Electrophoresis
Simple Blood test
Routine screening in high risk groups
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 Slide 20: Early Symptoms & Complication Typically appear during infant's 1st Yr
1st symptom: dactylitis & fever
[6 mo - 2 yrs ]
Pain in the chest, abdomen, limbs &
Enlargement of the heart, liver & spleen
Frequent upper respiratory infections
Chronic anemia as children grow older Slide 21: Recurrent Pain Episodes / Sickling Crises Occur at any age but appear to be particularly frequent during late adolescence & early adult life.
RBC get stuck in the small veins & prevent normal blood flow.
Characterized by severe pain in the back, chest, abdomen, extremities, & head.
Highly disruptive to life
Most common reasons for individuals to seek health care Slide 22: Infectious complications
Prominent early in life
Leading cause of morbidity and mortality
Good prognosis in newborn if screening for SCD is early with vaccination for childhood illnesses, use of prophylactic antibiotics, & aggressive diagnosis & T/t of febrile events.
Acute splenic sequestration
Episodes of rapid increase in splenic size & decrease in Hb . High morbidity & mortality early in life for children with SCA & at any age for those with SCD. Serious Complications Slide 23: Strokes
Up to 15% of children may have overt or silent strokes during childhood
Chronic transfusion therapy reduces the recurrence rate of overt stroke & keeping HbS level below 30%.
Painful inflammatory disease of bone,often bacterial
in origin & may result in death of bony tissues.
Avascular necrosis of the femur & humerus
Death of bone tissue due to disrupted blood supply Marked by severe pain in the affected region & by weakened bone that may flatten & collapse. Serious Complications Serious Complications : Serious Complications Leg ulcers
Seen in patients older than 10 years of age
Resistant to therapy and cause significant morbidity
Proliferative retinopathy, vitreous hemorrhage, & retinal detachment
Distressing complication, occurs at all ages,difficult to treat &
Causes a high incidence of impotence.
Associated with fatigue, irritability, jaundice, pain, delayed puberty, leg sores, Pregnancy & SC disease : Pregnancy & SC disease Higher rate of spontaneous abortion. A miscarriage may happen up to 25% of the time.
Higher rate of babies not surviving to birth or being stillborn. 8-10% .
Birth weight is lower than average.
Infection is more common in women with SCD during pregnancy, especially bladder infection.
Increased chance of PIH and preeclampsia
Increased incidence of PPH. Slide 26: Fever
Shortness of Breath
Unusual headache Danger Signs of a Crisis 7. Sudden diminished vision.
8. sudden weakness of
Priapism [ painful erection that will not go down ] SEEK URGENT HOSPITAL T/t IF IN CRISIS Slide 27: Infections
Thirst & dehydration caused by not drinking enough water even if thirst is not felt.
Cold weather & cold drinks & swimming
Laceration ,bruises , strains & sprains .
Stress triggers pain in adults, but does not seem to do so in children. Triggers of Pain Management of VOC : Management of VOC All voc are managed by aggressive rehydration
O2 therapy , adequate analgesia [ opiates]
antibiotics & BT where ever possible.
Regular transfusion programme to supress HbS level
below 30% is indicated in CVA in children.
Prophylaxis with daily Folic acid & Penicillin V to
protect against pneumococcal infection.
Vaccination against Pneumococcus, Haemophilus
influenzae B & Hepatitis B. Slide 29: Alleviating Pain Warmth: increases blood flow
Massaging and rubbing
Heat from hot water bottles & deep heat creams
Bandaging to support the painful region
Resting the body to relax.
Getting the sufferer to relax
deep breathing exercises
distracting the attention.
Analgesics : NSAIDs / Morphine if necessary. Slide 30: Folic acid daily to help make new red cells
Daily penicillin until age six to prevent serious infection
Drinking plenty of water daily (8-10 glasses for adults)
Avoiding too hot or too cold temperatures
Avoiding over exertion and stress
Getting plenty of rest . Daily Preventative Measures Slide 31: Child encouraged to participate in sports, but not pushed passed their limitations
If they are in pain or feel tired they should be allowed to rest and keep warm.
They should have access to drinks.
Strenuous exercise, dehydration and cold can induce a crisis.
Strenuous outdoor activities should be avoided in cold or wet weather
Should only swim if the water is warm and care is taken to keep warm when leaving the water
If develops a crisis despite these precautions he or she should avoid swimming all together Psychosocial Issues Slide 32: Hydroxyurea
Effective drug T/t for adults with severe SCA.
Daily doses of the anticancer drug, hydroxyurea, reduces the frequency of painful crises, acute chest syndrome & need fewer Bld trasfn .
Increases production of Fetal Hb in the blood.
Fetal Hb seems to prevent sickling of RBCs.
Cells containing Fetal Hb tend to survive longer in the bloodstream Long term T/t Bone Marrow Transplant : Bone Marrow Transplant Bone marrow transplant is the closest thing possible to the cure of SSA.
Helps in production of healthy RBC from transplanted bone marrow
The success rate is 90 – 95% Gene Therapy : Gene Therapy Gene therapy is a relatively new idea of inserting genes into the cells of an individual in order to treat hereditary disease such as SSA, in which a defective mutants alleles is replaced with a functional one.
Gene therapy would be the best cure for SSA in future, as of now it is on it’s experimental stage. Slide 35: Thank You