Sickle Cell Anemia

SICKLE CELL ANEMIA

What Is Sickle Cell Anemia? Sickle cell disease is a grp of haemoglobin disorders in which the sickle Beta-globin gene is inherited

• The sickle Beta-globin abnormality is caused by substitution of valine for glutamic acid in position 6 in the Beta chain • Homozygous sickle cell anamia (Hb SS) is most common while the doubly heterozygote conditions of Hb SC and Hb SBthal also cause sickling disease.

• Hb S is insoluble and forms crystals when exposed to low oxygen tension. • Deoxygenated sickle haemoglobin polymerizes into long fibers, each consisting of seven intertwined double strands with cross-linking.

• Sickle cell anemia is a serious condition in which the red blood cells can become sickle-shaped (that is, shaped like a “C”). • Normal red blood cells are smooth and round like a doughnut without a hole. They move easily through blood vessels to carry oxygen to all parts of the body. • Sickle-shaped cells don’t move easily through blood. They’re stiff and sticky and tend to form clumps and get stuck in blood vessels. • The clumps of sickle cells block blood flow in the blood vessels that lead to the limbs and organs. Blocked blood vessels can cause pain, serious

MICROSCOPIC EXAMINATION

What Causes Sickle Cell Anemia? • Sickle cell anemia is an inherited condition. People with sickle cell anemia inherit two copies of the sickle cell gene, one from each parent. • The sickle cell gene makes abnormal hemoglobin.

Inheritance Pattern for Sickle Cell Trait

CLINICAL FEATURES • Severe haemolytic anemia punctuated by crises. • Crises may be vaso-occlusive, visceral, aplastic or haemolytic. • The clinical expression of Hb SS is very variable, some has normal life, free of crises but others develop severe crises.

• anemia occurs as abnormal RBC have a shortened life span of only about 15 days compared to the usual 120 days. • The RBC are also fragile and lack flexibility leading to veno-occlusion and resulting pain crises ~ Sudden episodes of pain throughout the body (common symptom of sickle cell anemia) and are often referred to as “sickle cell crises.”

Sickle cell crises - can cause acute or chronic pain. Acute pain is the most common type. This is sudden pain that can range from mild to very severe. The pain usually lasts from hours to a few days. Chronic pain usually lasts for weeks to months. Chronic pain can be hard to bear and mentally draining. This pain may severely limit daily activities.

Painful vaso-occlusive • Most frequent • Precipitated by factors such as acidosis, dehydration or deoxygenation • Infracts can occur in a variety organs including bones • Most serious vaso-occlusive--brain

Aplastic crises • Result of infection with parvovirus or folate deficiency • Sudden fall in haemoglobin---require transfusion

Haemolytic crisis • Increase rate of haemolytic with fall in haemoglobin but rise in reticulocytes • Usually accompany by a painfull crises

Other clinical features • Ulcers of the lower legs (common) • Spleen enlarged in infancy and early childhood but later reduced in size as a result of infarcts • Pigment gallstones are frequent

How Is Sickle Cell Anemia Diagnosed?

• Complete Blood Cell count showing anemia, adult sickle cell anemia patient usually has elevated WBC and platelet count, elevated reticulocytes, elevated bilirubin • Hgb electropheresis shows abnormal Hgb SS (more severe disease) or SC or S-beta Thalassemia. Sickle hemoglobin moves differently than normal hemoglobin. • Electrophoresis is usually used to diagnose older children and adults.

• Electrophoresis - It’s also possible to identify sickle cell anemia before birth. This is done using a sample of amniotic fluid or tissue taken from the placenta. (Amniotic fluid is the fluid in the sac surrounding a growing embryo). • It identifies the sickle gene, rather than the hemoglobin it makes.

TREATMENT • No cure for sickle cell disease other than allogeneic bone marrow transplant which carries significant risk for morbidity and mortality. • Management of this chronic disease includes avoidance of known triggers of venoocclusive crisis • daily folic acid. • Analgesics for painful crisis

• Vaccination with pneumococcal vaccine q5 years in adults is recommended. • Blood transfusions with exchange transfusion is used in serious cases of acute chest syndrome or priapism

New medicines being studied are: • Butyric acid. This is a food additive that may increase normal hemoglobin in the blood. • Clotrimazole. This is used now to treat fungus infections. This medicine helps prevent the loss of water from a red blood cell and can keep the cell from turning into a sickle cell. • Nitric oxide. This may make sickle cells less sticky and keep blood vessels open. People with sickle cell anemia have low levels of nitric acid in their blood.

How Can Sickle Cell Anemia Be Prevented? • Sickle cell anemia is an inherited condition. Children who inherit the genes for sickle cell anemia can’t prevent developing the condition, although they can take steps to reduce complications. • People who are in groups that are at high risk for sickle cell anemia and who are planning to have children may want to consider genetic

A procedure called pre-implantation genetic diagnosis can improve the chance that two people with sickle cell trait will have a child with normal hemoglobin. Eggs from the mother and sperm from the father are mixed together in a laboratory dish. The eggs that become fertilized are checked for sickle cell anemia. Fertilized eggs that don’t have sickle cell genes are then implanted in the mother’s womb. This is a complex procedure done only in a few places,