Hemoglobinopathies

Question 1

hemoglobinopathy definition

Answer 1

disorder involving hemoglobin

Question 2

disorder involving heme

Answer 2

porphyria

Question 3

globins expressed embryonically

Answer 3

epsilon

Question 4

globins expressed fetally

Answer 4

gamma, alpha (HbF)

Question 5

globins expressed in adults

Answer 5

alpha, beta (HbA) & alpha, gamma (HbA2)

Question 6

what types of deletions tend to affect the alpha globin?

Answer 6

deletional mutations leading to zero condition (no production)

Question 7

what types of deletions tend to affect the beta globin?

Answer 7

nondeletional mutations which tend to lead to plus mutations (decreased production)

Question 8

types of nondeletional mutations

Answer 8

transcription, mRNA processing, transport, translation, mRNA stability, protein function mutations

Question 9

composition of typical adult hemoglobin

Answer 9

two alpha, two beta globins and heme

Question 10

structural hemoglobinopathies

Answer 10

qualitative defects in hemoglobin function

Question 11

examples of structural hemoglobinopathies

Answer 11

sickle hemoglobins, low/high O2 affinity, unstable hemoglobins, methermoglobins

Question 12

thalassemia definition

Answer 12

quantitative defects in hemoglobin production (Hb made is normal, just not enough is made)

Question 13

types of thalassemias

Answer 13

alpha, beta, hereditary persistence of fetal, fusion hemoglobins

Question 14

most important thing to know about severity of thalassemia****

Answer 14

the degree of alpha/beta chain imbalance predicts the severity of the phenotype***

Question 15

characteristics of thalasemmia anemia

Answer 15

microcytic, hypochromic

Question 16

alpha thalassemia

Answer 16

deficiency in HbA (alpha/beta) with excess HbH (beta/beta)

Question 17

HbH

Answer 17

beta homotetramer hemoglobin corresponding with alpha thalassemia. soluble and nontoxic

Question 18

alpha thalassemia trait

Answer 18

-a/-a or –/aa. quite mild (slightly low levels of Hb, and slightly small MCV)

Question 19

HbH disease

Answer 19

–/-a. high levels of HbH present. still quite mild symptoms

Question 20

hydrops fetalis

Answer 20

–/–. complete alpha thalassemia. fatal before birth

Question 21

most common alpha thalassemia in blacks

Answer 21

-a/-a. common but not an issue for offspring

Question 22

most common alpha thalassemia in asians

Answer 22

aa/– common, which can lead to hydrous fetalis in offspring

Question 23

beta thalassemia

Answer 23

deficiency in Hb (alpha/beta) and excess alpha homotetramers, which precipitate and are toxic!

Question 24

beta thalassemia minor (trait)

Answer 24

B/B* (one of two genes is defective). decreased Hb & MCV. Increase HbA2 as compensation

Question 25

beta thalassemia intermedia

Answer 25

B+/B* (two defective genes with one mutation being milder) or B+/B+ (two mild mutations). vast phenotypes, anemia, low MCV

Question 26

beta thalassemia major

Answer 26

B*/B* (two defective genes). very anemic, very low MCV, 10% HbA2, 90% HbF as compensation.

Question 27

characteristic most indicative of beta thalassemia?

Answer 27

increased HbA2 levels!

Question 28

clinical presentation of severe beta thalassemia

Answer 28

family history, ethnic background, poor growth/development, jaundice, frontal bossing, splenomegaly, hypochromic/microcytic anemia with targeting, normal iron levels, INCREASED HBA2

Question 29

consequences of alpha homotetramer precipitation

Answer 29

erythroid progenitor membrane damage=ineffective erythropoiesis & RBC membrane damage=accelerated removal=hemolytic anemia --->both lead to profound anemia

Question 30

consequence of ineffective erthyroid mass due to profound anemia in beta thalassemia?

Answer 30

compensatory erythropoiesis (marrow from atypical locations, frontal bossing) & extra medullary erythropoiesis (splenomegaly)

Question 31

most common causes of microcytic anemia

Answer 31

iron deficiency & thalassemia

Question 32

distinguish iron deficiency vs beta thalassemia

Answer 32

TEST IRON LEVELS

Question 33

DIAGNOSE: Hb=9, MCV=74, Ferritin=2

Answer 33

Iron deficient anemia

Question 34

DIAGNOSE: Hb=11, MCV=65, Ferritin=Nl

Answer 34

thalassemia

Question 35

DIAGNOSE: A=94%, A2=5%, F=0%

Answer 35

increased A2=beta thalassemia minor (major would have higher A2, like 10% and increased F)

Question 36

DIAGNOSE: Hb=3.5, MCV=57, Ferritin=1822

Answer 36

thalassemia

Question 37

DIAGNOSE: A=0, A2=10%, F=90%

Answer 37

beta thalassemia major

Question 38

treatment for thalassemia

Answer 38

PRBC transfusion or chelating agents (remove iron), bone marrow transplant

Question 39

genetic basis of sickle cell disease

Answer 39

single missense mutation that results in Glu-->Val substitution in beta globin

Question 40

cause of sickle shape?

Answer 40

when deoxygenated, Hb assembles into long polymer fibers that destroy RBC membrane structure.

Question 41

theories on pathophysiology of sickle disease

Answer 41

log jam model, RBC dehydration, cellular adhesion, reduced NO bioavailability

Question 42

treatment for chronic sickle cell disease

Answer 42

hydroxyurea=inducer of fetal gamma glob in (no hydrophobic site for polymerization). bone marrow transplant

Question 43

blood characteristics of sickle cell disease

Answer 43

moderate anemia, normocyti/normochromic RBCs, drepanocytes (sickle)

Question 44

AA Hb electrophoresis

Answer 44

A=97, A2=<3, F=0, S=0

Question 45

AS Hb electrophoresis

Answer 45

A=60, A2<3, F=0, S=40 (40/60 RULE)

Question 46

SS Hb electrophoresis

Answer 46

A=0, A2<10, S=90

Question 47

DIAGNOSE: A=40, A2=5, F=0, S=60

Answer 47

co inherited beta thalassemia with sickle cell (B+ reducing levels of A, Bs increasing levels of S)

Question 48

DIAGNOSE: A=80, A2=1.5, F=0, S=20

Answer 48

co inherited alpha thalassemia with sickle cell

Question 49

DIAGNOSE: Hb=14, MCV=85, A=59, A2=2, F=0, S=39

Answer 49

sickle cell trait

Question 50

DIAGNOSE: Hb=8, MCV=88, A=0, A2=2.5, F=2, S=96

Answer 50

sickle cell disease

Question 51

DIAGNOSE: Hb=11, MCV=72, ferritin=477, A=10, A2=7, F=7, S=76

Answer 51

coinherited beta thalassemia and sickle cell in beta globin (Bs/B+)