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.
1. Sickle Cell Traits (HbAS) Adequate amount of normal haemoglobin is present, they are carriers, do not have symptoms of sickle cell disorder.2. Sickle Cell Anemia (HbSS) Most severe form of disease3. Haemoglobin C (HbSC)4. Haemoglobin E (HbSE)5. Haemoglobin S beta Thalasseamia-This is a mild form of sickle disorder.
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 at chromosome 11 leading to production of defective form of haemoglobin.(Hb S) Hb S is a structurally defective haemoglobin.
Deoxygenation leads to hydrophobic interaction between adjacent Hb S molecules. This leads to hydrophobic polymerization of red cell membrane The red cell cytosol becomes viscous gell as HBs aggregates form and become needle with continued deoxygination distortion of RBC into sickle form cells Rapid haemolysis Decreased elasticity of cell wall of RBC Decreased life span 10 – 20 days. From 120 days Clogging of RBC in microcirculation
SICKLE CELL TrAIT 40% hbS 60% hbA . hbA prEvENTS SICKLINg uNTILLprofouNd hypoxIAhbf vS hbS hbf INhIbIT poLyMErISATIoN , No SyMTEMS upTo 6MoNThS hErEdITAry pErSISTENT hbf SICKLE CELL dISEASELESS SEvErEhbC vS hbS IN hbSC hbS 50% + dEhydArTIoN of hbSC INCrEASEdhbS poLyMErISATIoN CAuSE hbSC dISEASE
MCHC INTrA CELLuLAr dEhydrATIoN INCrErSES MChC fACILITATES SICKLINgPh dECrEASE IN ph INCrEAS dEoxygINATEd hbS AugMENTINg SICKLINgTransit time of blood cells through micro vascularbed ShorT TrANSIT TIME LEAdS To AggrEgATIoN of dEoxygENATEd hbS-SICKLINg TrANSIT TIME IS NorMAL IN SpLEEN ANd boNE MArrow SoproMINENTLy AffECTEd INfLAMEd vESSELS INfLAMEd TISSuE ArE proNE for dECrEASINgTrANSIT TIME ANd proNE for SICKLINg
Obstructed microcirculation leading to ischemic injury to organ1. Avascular necrosis2. Acute chest syndrome3. Acquired asplenia4. Splenic sequestration5. Hand foot syndrome6. Papillary necrosis in kidneys7. Hyposthenuria and enuresis8. Cerebral infarction9. Skin ulceration10. Retinal hemorrhage and retinopathy11. Priaprism
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 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
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
1. Young infants have recurrent edema of the dorsum of hands and feet.2. Infarction of cortex of long bones lead to prominent signs of local inflammation.3. 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.4. Chronic leg ulcer is common in adolescent patients.5. Abdominal examination may reveal splenomegaly if sequestration is occurring otherwise the spleen is small in size due to autoinfarction6. Evidence of cholilethiasis is seen in patients as young as 3 years old.7. By mid childhood most patients are underweight as compared to children of their same age and height.
1. There is a higher rate of spontaneous abortion. A miscarriage may happen up to 25% of the time.1. There is ahigher rate of babies not surviving to birth or being stillborn. 8-10% . 1. Birth weight is lower than average. 2. Infection is more common in women with sickle celldisease during pregnancy, especially bladder infection. 3. Increased chance of PIH and preeclampsia 4. Increased incidence of PPH.
Medical Complications1. pain episodes 9. kidney damage and loss of body water in urine2. strokes 10. painful erections in men3. increased infections (priapism)4. leg ulcers 11. blood blockage in the spleen5. bone damage or liver (sequestration)6. yellow eyes or 12. eye damage jaundice 13. low red blood cell counts7. early gallstones (anemia)8. lung blockage 14. delayed growth
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 Howell-Jolly bodies
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 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 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.
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.