SICKLE CELL ANEMIA
- Prajwal Sidrampurmath
Introduction
Why exactly there’s hemolysis in SCA?
• Any shape other than biconcave of RBC, is not flexible to withstand the stress posed by the smallest of the microcirculation (especially that of the Billroth cords, diameter 2-3microns).
• Hence they get stuck in these microcirculation and phagocytosed by the splenic macrophages (extra vascular hemolysis)
PATHOGENESIS:
It’s an AUTOSOMAL RECESSIVE DISORDER.
NON CONSERVATIVE MISSENSE MUTATION,
In the beta-chain of Hb, (DNA codon GAG—GUG), hence the beta-globin will have a Valine in place of Glutamate in the 6th position.
Primarily affected Hb in SCA is – HbA (adult type Hb)
EFFECTS:
Two possible things can happen ,
Homozygous., the diseased state, it is seen since Valine (hydrophobic) whereas glutamate (hydrophilic) thereby changing the property of the protein globin. 
• Due to this change, Hb still retain its ability of oxygen carriage.
• But has attained the capacity of changing shape when deoxygenated, this is called as SICKLING. Producing Sickled Hb / HbS
• Preferable conditions are, 1. Acidosis – decreased O2 affinity. 2. Low flow vessels – since Hb gets more time to release O2 and becomes deoxygenated.
• This repeated sickling weakens the RBC membrane leading to intravascular hemolysis.
Heterozygous, it’s a carrier state called as SICKLE TRAIT.
• No problems are seen untill exposed to extreme conditions like high altitude or severe dehydration.
This SCA can considered to be an example of Herd immunity especially in some malaria endemic regions, since malarial parasite is intracellular parasite therefore this SCA decreases disease severity and probability of acquiring it also.
THE DISORDER : CLINICALLY
Briefly speaking, about the disorder and some special features
• ANEMIA: Raised Reticulocytes, increased extramedullary hematopoiesis (Hepatomegaly),
• Decreased free haptoglobin levels in plasma, due free Hb released from intravascular hemolysis.
• ACHOLURIC JAUNDICE.
• Sickled RBC'S may occulde the microvasculature, leading to Dactylitis, splenic infarct + sequestration leading to increased susceptibility to infection from encapsulated bacteria.(since they are phagocytosed by splenic macrophages), strokes, acute chest syndrome – having a vicious cycle that further worsens the disease clinically, necrosis of renal papillae – hematuria and proteinuria, in case of males PRAIPISM (painful and prolonged erection) can also be seen.
• On the peripheral smear, HOWEL JOLLY BODY – basophilic nuclear remnant of RBC are seen.
DIAGNOSIS:
• Newborn blood spot serum test (in some developed countries)
• Blood smear – Sickled RBC’S
• Protein electrophoresis for HbS identication
TREATMENT:
• Improve oxygenation and fluid intake especially when the risk factors are present.
• Opoids for inflammatory pains.
• Antibiotics for underlying bacterial infections.
• Blood transfusion, but not very frequently since it may increase the iron overload and Antibodies may develop against future transfusions.
• In children, Prophylaxis with Penicillin and vaccine against Strept.pnuemoniae to prevent sepsis and meningitis. HYDROXYUREA is given, which increases gamma globin (part of HbF), so that HbF interferes with HbS polymerization and prevents sickling—so there are no symptoms of HbS in infants untill HbA doesn’t predominantly formed.
• Rarely bone marrow transplantation.
• Gene therapy for the mutant gene.
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