Mark D. Browning, M.D. March 10, 2016

Presentation on theme: "Mark D. Browning, M.D. March 10, 2016"— Presentation transcript:

1 Mark D. Browning, M.D. March 10, 2016
Hemoglobinopathies Mark D. Browning, M.D. March 10, 2016

2 Hemoglobin

3 Normal Hemoglobin 2 alpha chains 2 beta chains
141 amino acids 2 beta chains 146 amino acids These 4 polypeptide chains form a helical structure Hydrophobic pockets…holding four heme groups Central cavity…between…2 beta globin chains houses 2-3 DPG

4

5

6 Hemoglobin Electrophoresis

7 *Hemoglobinopathies > 400 Hemoglobin variants defined
> ½ are clinically silent Heterozygotes present with mild effect Homozygotes present with moderate to severe effect Hemolytic anemia High oxygen affinity…erythrocytosis Low oxygen affinity…cyanosis

8 Hemoglobinopathies Thalassemias Sickle Cell Disease & Hgbs C, D, & E
Quantitative defect in globin synthesis involving gene mutation or defect Sickle Cell Disease & Hgbs C, D, & E Qualitative (structural) defect in amino acid substitution in the globin chain

9 *Hemoglobinopathies Most Common
Hgb S, C, D & E Present in their homozygote form, results in severe disease…SS, CC, DD, EE Present in their heterozygous form, results in mild disease…AS, AC, AD, AE Hemoglobin electrophoresis Confirms diagnosis (Figure 7-2) Confederate States of America (CFSA)…all but A2 hemoglobin on cellulose acetate at alkaline pH

10 Hemoglobin EE

11 Hemoglobin CC

12 Hemoglobin E

13 *Microcytic Hypochromic Anemia

14 *Hypochromic Mirocytic RBCs Differential: Iron Def. vs. Thal.

15 *Thalassemia Abnormal production of globin chain proteins
Gene mutations associated with quantitative failure in chain production Diagnosis is based on changes in intracellular levels of major hemoglobin types (normal-below) Hgb A = 97.5% = alpha (2) + beta (2) Hgb A2 = 2% = alpha (2) + delta (2) Hgb F = 1%= alpha (2) + gamma (2)

16 ***Thalassemia Alpha Thal
4 alpha genes Missing 1 to 4 genes Missing one alpha…silent carrier…normal phenotype…no anemia & normal MCV **Missing 2 alphas *Mild anemia & decreased MCV *Alpha+/alpha-//alpha+alpha- African/American *Alpha-/alpha-//alpha+alpha+ Asian Inheritance of more severe form of alpha thal…Hgb H or Hydrops fetalis Eg…Holy Land Patient

17 Holy Land Patient *Diagnosis Alpha Thal Minor Missing 2 alphas
Hgb 11.5 MCV 70 RBC 5.85 million Hgb A=97 *Hgb A2=2% …normal Hgb F =1% *Diagnosis by exclusion

18 **Thalassemia Minor vs. Iron Deficient Anemia (Last 5)

19 *Thalassemia Alpha Thal (Hemoglobin H)
Missing 3 alpha genes Hemoglobin H disease Patient has 5-30% Hgb H (4 betas) on electrophoresis Mild to moderate anemia (Hgb 7 to 10)f Reticulocytosis, microcytosis, hypochromia & targeting….hemolysis….splenomegaly

20 Alpha Thalassemia ** ** ** ##

21 Thalassemia Alpha Thal…Hydrops Fetalis ##
Missing 4 alpha genes ## More common in Asians Stillborn Less common in Blacks

22 **Thalassemia Beta Thal Minor
Gene deletion(Beta 0) or mutation(Beta +) Heterozygous form **Increase in Hgb A2 to 4-7% Slight increase in Hgb F Confusion with iron deficiency Can lower A2 to normal Iron studies to exclude iron deficiency

23 **Globin Chain Development A2 Increased in Beta Thal minor
Decreased in Beta Thal Minor Increased in Beta Thal Minor

24 Thalassemia—Differential Dx Alpha, Beta or Iron Deficiency
Anemia, decreased MCV (75) in all 3 Thalassemia RDW is not increased because uniform red cells Targets present because hemoglobin does not match the membrane synthesis Beta Thalassemia…increased Hgb A2 ** Iron deficiency Anisocytosis, poikilocytosis, pencil cells & increased RDW (red cell distribution width)