PRESENTED BY ZOE DANIELS SICKLE CELL DISEASE PRESENTED BY ZOE DANIELS

WHAT IS IT? Sickle cell disease is a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. Normal RBC are round and flexible, which enables them to travel through small blood vessels to deliver oxygen to all parts of the body . Sickle cell disease causes red blood cells to form into a crescent shape like a sickle; the sickle shape RBC break apart easily causing anemia.

Etiology Sickle cell anemia is an autosomal recessive genetic, lifelong disease. People who have the disease are born with it. They inherit two genes from sickle hemoglobin—one from each parent. People who inherit a sickle hemoglobin gene from one parent and a normal gene from the other parent have a condition called sickle cell trait.

Genetics

The gene related to sickle cell anemia is HBB, that is symbol for hemoglobin Beta. HBB gene is in the region of 15.5 on the short arm of human chromosome 11. Mutations in the HBB gene cause sickle cell disease. Hemoglobin consists of four protein subunits, typically, 2 subunits called alpha- globin and 2 subunits called beta-globin. The HBB gene provides instructions for making beta-globin. Various versions of beta-globin result from different mutations in the HBB gene.

One particular HBB gene mutation produces an abnormal version of beta- globin known as hemoglobin S (HbS). Hemoglobin S is produced when amino acid at position 6 of the HBB gene, GAG codon (glutamic acid) that is hydrophilic substitutes by GTG codon (valine) which is hydrophobic.

Types There are 3 main types of sickle cell disease: Hemoglobin SS disease: Individuals have received two copies of the hemoglobin S gene. Hemoglobin SC disease: Individuals have received one copy of the hemoglobin S gene and one copy of the hemoglobin C gene. Hemoglobin SB (beta)

Diagnosis Sickling test- SICKLE-CELL ANEMIA Cell Blood Count/ Peripheral Blood Smear HbS Electrophoresis & Isoelectric focusing Chorionic villus Sampling -antenatal screening Total and Direct Bilirubin

Complications Pain Infections A stroke Hand-Foot Syndrome Anemia Acute Chest Syndrome

Clinical features of sickle cell disease Hematological Hemolytic anemia; typical base line hemoglobin levels are 6 – 9 in sickle cell disease Orthropedic Osteonecrosis Osteomyelitists Dactylitis early onset is a marker of disease severity 50% adults are affected

Clinical features cont’d Vascular Leg ulcers - 20 % of adults get this Neurological Pain crisis 70% of patients Stroke 10 % childern; cause 20% of deaths Proliferative retinopathy – 50 % SC adults Chronic pain syndrome – small subset of patients

Clinical features cont’d Pulmonary Acute chest syndrome 40% patients Airway hyperactivity 35% children Restrictive lung disease 10 – 15 % patients Genitourinary Chronic renal insufficiency 5 – 20 % of adults Priapism 10 – 40 % of men

Signs & symptoms Blockage of blood flow to the spleen or liver Shortness of breath Dizziness Coldness in hands and feet Jaundice Severe pain throughout the body (sickle cell crises) often affect : bones, lungs, abdomen and joints Strokes

Comparison of RBC

Pathophysiology Sickle cell anemia is caused by the ß- globin chain of hemoglobin, causing the hydrophilic amino acid glutamic acid to be replaced with the hydrophobic amino acid valine the sixth position. Red blood cells typically live 90 – 120 days but sickle cells only survive 10 – 20 days. The induction of sickling is susceptible erythrocytes requires exposure to oxygen tensions less than 40 mmHg for 2 – 4 minutes.

Pathophysiology cont’d The de- oxygenation of hemoglobin S leads to polymerization of insoluble hemoglobin S strands. The initiation of polymerization may be incomplete and reversible if re- oxygenation ocurs early in the process. Repetitive exposure to alternating de- oxygenated and oxygenated states can lead to membrane distortion, oxidative damage and irreversible sickling.

Summary of pathophysiology

Prevention No prevention, because it’s an inherited disease. Persons born with it, necessary steps should be taken to reduce complications. People who are at high risk of having a child with sickle cell anemia and are planning to have children may want to consider genetic counseling

Treatment Daily dose of penicillin to prevent potentially deadly infections. Patients also take folic acid, which helps build new red blood cells. Bone marrow transplant. Antibiotics, pain management and blood transfusions. A new drug treatment, hydroxyurea

Treatment cont’d

References http://www.nhlbi.nih.gov/health/health- topics/topics/sca/ http://ghr.nlm.nih.gov/condition/sickle-cell- disease http://www.chg.duke.edu/diseases/sicklecell.html http://learn.genetics.utah.edu/content/disorders/si nglegene/sicklecell/ https://www.genome.gov/10001219

References cont’d https://www.nhlbi.nih.gov/health/health-topics/topics/sca/diagnosis.html https://www.clinicalkey.com/topics/hematology/sickle-cell-disease.html http://emedicine.medscape.com/article/205926-differential http://www.chop.edu/service/hematology/our-programs/sickle-cell-center/diagnosing-and-treating-sickle-cell-disease.html