Sickle cell disease

• Genetic disease where RBC take the shape of a crescent. Caused by defective haemoglobin - B globin becomes misshapen.
• It decreases the severity of plasmodium falciparum malaria. It is called heterozygote advantage.
• It is a missense mutation, valine instead of glutamic acid in the B globin gene.
• Acidosis and low flow vessels causes sickling of RBCs.
• Low haptoglobin is a sign of intravascular haemolysis. Free haemoglobin in the plasma becomes bound to haptoglobin, so when RBCs die the haemoglobin needs to attach itself to a protein (haptoglobin). Haemoglobin gets recycled by haptoglobin which increases levels of unconjugated bilirubin leading to jaundice.
• To counteract the anemia caused by sickle cells disease, the bone marrow increases the production of reticulocytes. This leads to new bone formation which expands the medullary cavities in the skull causing enlarged cheeks and hair on end sign on skull x-ray.
• RBCs get stuck in capillaries which clog up blood flow to bones of hands and feet eading to dactylitis and other bones leading to pain crisis and avascular necrosis. They can cause an infarct in the spleen causing a splenic sequestration (backup of blood). The spleen can become fibrosed and becomes susceptible to encapsulated bacteria.
• Howell-jolly bodies are present on peripheral blood smear in sickle cell disease. They are basophilic nuclear remnants in RBCs.
• Sickle cells can get stuck in the cerebral vasculature leading to stoke or moya-moya disease.
• Sickle cells can get stuck in the blood vessels of the lungs leading to acute chest syndrome. This prevents other red blood cells from becoming oxygenated.
• Sickle cells can clog up the renal papillae which can lead to necrosis and manifests as haematuria and proteinuria.
• Diagnosis is included in the newborn blood spot screen.
• Sickle cell is treated with oxygen and fluids. Opiods are used to manage pain. Antibiotics can help in treating underlying bacterial infection from acute chest syndrome. Blood transfusions are sometimes used but there is a risk of iron overload and antibodies against future transfusions. Children get prophylactic treatment with penicillin and polysaccharide vaccine to prevent sepsis and meningitis.
• Treatment with hydroxyurea increases gamma globin which increases foetal haemoglobin. This prevent sickling.
• Other treatments include bone marrow transplants and gene therapy.
• RBCs 'sickle' when they are deoxygenated.