Sickle Cell Disease Core Concepts for the Emergency Physician and Nurse Epidemiology, Genetics, Pathophysiology Spring 2013 Paula Tanabe, PhD, RN, FAEN, FAAN Associate Professor Duke University, Schools of Nursing and Medicine

Epidemiology of SCD SCD is a genetic disease affecting 70,000 – 100,000 Americans, primarily of African descent (Hassell, 2010) Most common genetic disease among blacks SCD occurs in 1 of every 500 black births 1:1,100 Hispanics (eastern states) 1:32,000 Hispanics (western states) SCD occurs in many other ethnic groups, including Northern Europeans and those that live in the Middle Eastern Countries 1:12 African-Americans are carriers (trait) for the disorder

Comparison of Life Expectancy US Population vs. Sickle Cell Disease

Changes in Life Expectancy National Center for Health Statistics (CDC) Compared with Largest declines in ages 0-4 Smaller but significant declines up to age 19 – Due to prophylactic treatment with penicillin and vaccinations – Transcranial doppler screening identifies children at risk of stroke; placed on chronic transfusion therapy to prevent stroke No differences in the age group Increase in death rate ages: 45-54, 55-65, and 65-75

What is the pathophysiology?

Normal Vs. Sickle Red Cells Normal Biconcave disc-shaped Deformable Life span of 120 days Sickle Sickle-shaped Rigid Live for 20 days or less Sticky surface, abnormal properties

Prolonged Sickling of RBC’s After recurrent episodes of sickling – membrane damage occurs – cells not capable of resuming biconcave shape upon re-oxygenation Deformed sickle cells adhere to endothelium & macrophages – induces hemolytic process

Hemolysis and Vaso-occlusion Vaso-occlusion: Complex process initiated by rigid and abnormally shaped sickled RBC’s Abnormal adhesion occurs to the endothelium Activation of WBC’s, RBC’s and the endothelial surface which enhances the VOC process Results in tissue damage, hypoxia, necrosis and organ dysfunction Hemolysis: ▪ Anemia in SCD is caused by red cell destruction, or hemolysis ▪ The degree of anemia varies widely between patients ▪ Red cell production by the bone marrow increases dramatically, but is unable to keep pace with the destruction

Chronic Manifestations: Anemia Jaundice Splenomegaly Functional asplenia Cardiomegaly and functional murmurs Hyposthenuria and enuresis Proteinemia Cholelithiasis Delayed growth and sexual maturation Restrictive lung disease* Pulmonary hypertension* Avascular necrosis Proliferative retinopathy Leg ulcers Transfusional hemosiderosis* Acute Manifestations: Bacterial sepsis or meningitis* Recurrent vaso-occlusive pain (dactylitis, musculo-skeletal or abdominal pain) Splenic sequestration* Aplastic crisis* Acute chest syndrome* Stroke* Priapism Hematuria, including papillary necrosis Acute and Chronic Manifestations *Potential cause of mortality

Sickle Cell Disease (SCD) Common Genotypes Sickle cell anemia (SS, most severe form) Sickle/Hb C disease (SC, lesser severity, but can still have pain episodes, and life-threatening complications) Sickle/Beta plus thalassemia (Sβ + thalassemia, similar to SC) Sickle/Beta zero thalassemia (Sβ° thalassemia, similar to SS) 65 % 25 % 8 % 2 % Genotype Approximate % of US Patients

References Hassell KL. Population estimates of sickle cell disease in the U.S. Am J Prev Med. 2010;38(4S):S512-S521. Platt et al. Mortality in sickle cell disease, life expectancy and risk factors for early death. NEJM : Hamideh, D. Trends in Mortality Among Patients with SCD in the United States. Is there any change in the past 10 years? th Annual Sickle Cell Disease Research and Educational Symposium & Annual National SCD Scientific Meeting

Post-Test 1.Which genotype is associated with the most severe symptoms? a)SS b)SC c)SB 0 d)SB +

Post-Test 2. What is the median lifespan for most individuals with SCD? a)20’s b) 30’s c) 40’s d) 50’s

Post Test Answers 1.A – Patients with SS have the most severe form of the disease which is associated with more complications. However, all patients can experience pain and multiple other complications. 2.C – The median lifespan continues to be 48 for females and 42 for males.