PowerPointPresentation-Week3.pptVIP

Week 3: Hemoglobinopathies Hemoglobinopathies Thalassemia genetics Hb synthesis Hb A, A2, F Hb ELP Hb Constant-Spring Hb Bart’s Hb H Hb Lepore Hb E Hb S Hb C Hb SC disease HPFH Hemoglobinopathies Decrease, lack of, or abnormal globin May be severe hemolytic anemia Abnormal Hb with low functionality Mutation may be deletion, substitution, elongation Hb electrophoresis may be helpful Hemoglobin Heme Porphyrin ring and Fe Globins Alpha family on chromosome 16 ????]--//--[??????????? Beta family on chromosome 11 ????]--//--[?]--[????[????????? Thalassemia 1925: Described by Dr. Thomas Cooley and Dr. Pearl Lee of Detroit 1920’s: Osmotic fragility test 1932: Dr. George Whipple of Rochester coined the name “thalassa anemia” from Greek story about Xenophon’s army returning from Persia 1930’s: Familial pattern recognized 1950’s: Alkali denaturation test for Hb F, Hb ELP 1956: Coulter model A 1960’s: RBC indices 1980’s: Histogram, DNA analysis, PCR Signs and Symptoms Hemolytic Bone changes (hair on end) Ethnicity: Mediterranean, Africa, Southeast Asia Hypo-Micro, Poikilocytosis NRBC’s, reticulocytosis, basophilic stippling Siderocytes (with repeated transfusions) ? Thalassemia Deletion of one or more alpha genes from chromosome 16 -a/aa: silent career with little signs --/aa: cis double deletion more common in SEA -a/-a: trans double deletion --/-a: Hb H disease --/--: Hb Bart’s hydrops fetalis Hb Constant-Spring: elongation (discovered in Kingston, Jamaica; 2% of Thai have it) ? Thalassemia Lab Changes High RBC Low HH and indices High RDW May need to rule out IDA Hb ELP not useful except in Hb H BCB prep for Hb H ? Thalassemia Usually point mutation in the control region ?+ has minimal production ?o has no production ?+/?+ or ?o/?o is b thal major or Cooley’s anemia Often not apparent at birth until b chain takes over g chain production High Hb A2, Hb F Related: Hb Lepore (d-b fusion), HPFH Hb S Sickling Hb Autosomal Sickle crisis in low oxygen condition ?6 glutamate to v