SICKLE CELL ANEMIA

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Dr Deepa Gupta Basu Moderated by – Dr Harsha Soni Dr AshokMohato SICKLE CELL ANAEMIA

STRUCTURE OF HAEMOGLOBIN : 

STRUCTURE OF HAEMOGLOBIN Hb is a conjugated protein molecule consist of two pairs of polypeptide chain. (alpha & beta) Each globin chain bears a haem group whose central iron atom is the site to which O2 attaches to haemoglobin. Molecular weight of Hb is 64000

TYPES OF HAEMOGLOBIN : 

TYPES OF HAEMOGLOBIN Hb A1- 97% of adult haemoglobin, consists of 2 alpha & 2 beta chains. Hb A2- Consists of 2 alpha & 2 delta chains. Hb F - 70 – 90% at birth, 25% by 1 month and 5% by 6months of age, consists of 2 alpha & 2 gamma chains. Hb Gower 1-Confined to embryonic stage, consists of 2 alpha & 2 epsilon chains. Hb Gower 2-Consists of 2 alpha & 2 zeta chains. Hb Portland- Found in trace in neonates and intrauterine life. Hb –Brat’s –Found in small amount in cord blood of neonates with thalasseamia.

Types Of Haemoglobinopathies : 

Types Of Haemoglobinopathies Sickle Cell Traits (HbAS) Adequate amount of normal haemoglobin is present, they are carriers, do not have symptoms of sickle cell disorder. Sickle Cell Anemia (HbSS) Most severe form of disease Haemoglobin C (HbSC) Haemoglobin E (HbSE) Haemoglobin S beta Thalasseamia-This is a mild form of sickle disorder.

HISTORY : 

HISTORY In the year 1904 cardiologist and professor of medicine James B Herrick found peculiar elongated cells in blood of a 20 years old dental student who was suffering from anemia. Veron Mason in 1922 named SICKLE CELL ANAEMIA. Linus Pauling in 1940 demonstrated that sickling occurs as a result of abnormality in haemoglobin molecule. Sickle cell disease is the first genetic disorder whose molecular basis was known. June 19th is celebrated as World Sickle Cell Day

PATHOPYSIOLOGY : 

PATHOPYSIOLOGY Sickle cell anemia is a autosomal recessive genetic disease that results from the substitution of Valine from Glutamic acid in position 6 of beta globin gene leading to production of defective form of haemoglobin.(Hb S) Hb S is a structurally defective haemoglobin.

Change in properties of Sickle Cell RBC : 

Change in properties of Sickle Cell RBC Deoxygenation leads to hydrophobic interaction between adjacent Hb S molecules. Distortion of RBC into sickle form cells Rapid haemolysis Decreased elasticity of cell wall of RBC Decreased life span 10 – 20 days. Clogging of RBC in microcirculation.

TRAITS & DISEASE : 

TRAITS & DISEASE

Prevalence in Chattisgarh : 

Prevalence in Chattisgarh Sickle Cell Anemia is found among the tribal population of Chattisgarh Bhils of Jabua district Tribal group of Bastar. Halbas of Rajnandgaon district Prevalence of sickle cell disease is as high as 30% Prevalence of Sickle haemoglobin varies from 15-30% among non tribal scheduled caste and backward class communities of Chattisgarh.

Sickle Cell Disorders in India : 

Sickle Cell Disorders in India

Chattisgarh & MP : 

Chattisgarh & MP

CLINICAL MANIFESTATION : 

CLINICAL MANIFESTATION Vasooclusive crisis Haematological crisis Aplastic crisis Sequestration crisis Infectious crisis

Vasooclusive crisis : 

Vasooclusive crisis Obstructed microcirculation leading to ischemic injury to organ Avascular necrosis Acute chest syndrome Acquired asplenia Splenic sequestration Hand foot syndrome Papillary necrosis in kidneys Hyposthenuria and enuresis Cerebral infarction Skin ulceration Retinal hemorrhage and retinopathy Priaprism

Clinical features : 

Clinical features

Haematological crisis : 

Haematological crisis Acute splenic sequestration, pooling of blood in the engorged spleen Aplastic crisis – Seen in patients with parovrus B-19 infection or folic acid deficiency leading to decreased marrow erythropoiesis Anemia Pigmented gallstone Jaundice Delayed growth

Infectious crisis : 

Infectious crisis Infectious crisis is due to functional asplenia and decreased level of serum immunoglobulin M (IGM) increasing susceptibility to infections. Haemophilius influenzae, streptococcus pneumoniae, mycoplasma pneumoniae, salmonella typhimurium, staphylococcus aureus, and escherichia coli are the common causative microbes. Common infections include pneumonia, bronchitis, pyelonephritis, cystitis, osteomyelitis, meningitis, and sepsis

Complications effecting organ system : 

Complications effecting organ system CVS-Anemia and vasooclusive phenomena causing myocardial ischemia and myocardial infarction, repeated blood transfusion leading to restrictive cardiomyopathy. Pulmonary-Acute chest syndrome CNS-25% patient have TIA, strokes, cerebral hemorrhage Hepato biliary system-Gall stone recurrent abdominal pain, autosplenectomy Urinary system- Haematuria, hyposthenurea and renal failure Ocular complication- Proliferative retinopathy, vitreous hemorrhage and retinal detachment Orthopedic – Hand foot syndrome, avascular necrosis of hip, osteomyelitis

FISH MOUTH APPREANCE : 

FISH MOUTH APPREANCE

Proliferative retinopathy : 

Proliferative retinopathy

Sea fan appearance in retina : 

Sea fan appearance in retina

Avascular necrosis : 

Avascular necrosis

CT scan : 

CT scan

Paediatric manifestation : 

Paediatric manifestation Young infants have recurrent edema of the dorsum of hands and feet. Infarction of cortex of long bones lead to prominent signs of local inflammation. Repeated infarction in the joints of large and small bones lead to abnormal angled digits, malformed and frozen joints, particularly at the knee and ankle. Chronic leg ulcer is common in adolescent patients. Abdominal examination may reveal splenomegaly if sequestration is occurring otherwise the spleen is small in size due to autoinfarction Evidence of cholilethiasis is seen in patients as young as 3 years old. By mid childhood most patients are underweight as compared to children of their same age and height.

Pregnancy and sickle cell disease : 

Pregnancy and sickle cell disease There is a higher rate of spontaneous abortion. A miscarriage may happen up to 25% of the time. There is ahigher 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 sickle cell disease during pregnancy, especially bladder infection. Increased chance of PIH and preeclampsia Increased incidence of PPH.

INVESTIGATIONS : 

INVESTIGATIONS Hb-6-8gm% Reticulocytes high Peripheral smear may show sickle cells Features of hyposplenism :Target cells and Howell- Jolley bodies seen Sickle solubility test Sickling test with reducing agent Sodium metabisulphide Hb electrophoresis High performance liquid chromatography(HPCL) WBC may be elevated Bilirubin may be elevated Urinarary cast may be seen or trace of RBC in urine

TREATMENT : 

TREATMENT Oxygenation Pain Management (NSAID, OPIODS) Hydroxyurea, Folic acid Hydration Blood Transfusion Antibiotics (Penicillin group) Steroids Bone marrow transplantation Gene therapy

Blood Transfusion : 

Blood Transfusion Blood transfusion is currently the most effective and proven treatment for severe anemia of SCD, it significantly reduces crisis. Blood transfusion reduces pain by increasing the number of functioning RBC and by increasing the oxygen caring capacity of blood

Bone Marrow Transplant : 

Bone Marrow Transplant Bone marrow transplant is the closest thing possible to the cure of SCA. 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 SCA, in which a defective mutants alleles is replaced with a functional one. Gene therapy would be the best cure for SCA in future, as of now it is on it’s experimental stage.

Other treatment of complications : 

Other treatment of complications Dialysis or kidney transplant for renal failure. Cholecystectomy for pigmented cholelitheasis. Hip replacement for avascular necrosis. Surgery for eye problem. Irrigation surgery for Priapism. Wound care for leg ulcer.

How Can Sickle Cell Anemia Be Prevented? : 

How Can Sickle Cell Anemia Be Prevented? Genetic counseling Pre implantation genetic diagnosis Perenatal testing -amniocentesis (16 – 18 wks) and chorius villus sampling ( 9 -10 wks)

PRECAUTIONS : 

PRECAUTIONS Regular health check up & good hydration. Vaccination for pneumonia, meningitis, influenza, and hepatitis Preventing infection – daily dose of penicillin Preventing strokes – Transcranial doppler ultrasound every 3 months. Preventing eye damage – Fundus examination every 3 months. Avoid alcohol, smoking, cold climate, high altitude exposure. THERE ARE 4 MILLION SICKLE CELL DISEASED PATIENTS WORLDWIDE

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THANK YOU

Electrophoresis : 

Electrophoresis