Snap Shot A 22-year-old Vietnamese female presents for a routine gyn exam. Her menstrual cycle is normal and there is no evidence of other bleeding. Guiac is negative. Her hemoglobin is at 11 (12-16), RBC is 5.8 (3.5-5.5), and an MCV of 70 (80-100) with a normal RDW of 10. WBC and platelets are normal. Hemoglobin electrophoresis shows an increase in amount of Hgb A2 and Hgb F. Introduction Hereditary disease caused by decreased production of hemoglobin chains Most common cause of microcytic anemia in Asian Americans and African Americans There are four alpha genes and two beta genes that make up three forms of hemoglobin (Hgb) Hgb Form Subunits Prevalence Hgb A alpha, alpha, beta, beta 96-98% of adult hemoglobin Hgb A2 alpha, alpha, delta, delta Present in trace amounts in adults Hgb F alpha, alpha, gamma, gamma Declines in the first year of life Evaluation Forms of disease diagnosed through gel-electrophoresis of globin chains Unexplained finding is that although there is a decrease in the Hgb concentration and MCV, there is a normal or slightly increased RBC count Ratio used: Mentzer Ratio = MCV / RBC if it is less than 13 it is highly predictive of thalassemia greater than 13 indicates an iron deficiency or anemia of inflammation Alpha Thalassemia Due to a decrease in alpha globin chain production Seen commonly in Asians less common in Africans and Mediterranean Affected alleles Disease Characteristics Evaluation 1/4 Carrier state Asymptomatic Normal 2/4 Alpha Thal. minor Normal life expectancy Mild microcytic anemia 3/4 Hgb H disease Associated with chronic hemolytic anemia, pallor, and splenomegaly. May require occasional transfusion Hgb H (beta tetramer) and Bart's Hgb (gamma tetramer) on electrophoresis 4/4 Hydrops fetalis Fetal demise with total body edema Bart's beta-4 Hgb precipitations Beta Thalassemia Beta thalasemia is more common in people of Mediterranean or African origin Function of beta chain required at six months when switch from fetal y Hgb to adult beta Hgb occurs Affected alleles Disease Characteristics Evaluation Treatment 1/2 Thalassemia minor Asymptomatic carrier Decreased Hgb A, increased Hgb A2(y) and normal Hgb F Avoid oxidative stress, treat with folate and transfusions during severe anemia and pregnancy 2/2 Thalassemia major Anemia develops at six months as Hgb F declines, frontal bossing from extramedullary hematopoiesis, and splenomegly No Hgb A, increased Hgb A2, and Hgb F on electrophoresis Splenectomy, folate supplementation, and transfusions. Symptoms improve with transfusions, patients usually die from transfusion iron overload (heart and liver failure).