Hemoglobinopathies and Thalassemia

Question 1

clinical manifestations thalessemia

Answer 1

anemia, chronic hemolysis, microcytic hypochromic, ineffective erythropoesis. Splenomegaly, functional hyposplenism.

Question 2

extramedullary erythropoesis in thal causes

Answer 2

masses large enough to cause compression syndromes.

Question 3

lab findings thal

Answer 3

decreased MCV, hemoglobin, MCH, MCHC, microcytic hypochromic, presence high affinity hemoglobins, increased EV hemolysis, extramedullary hematopoeisis.

Question 4

Mentzer index

Answer 4

differentiate thal from IDA. Divide MCV / RBC #. If < 13 favors thal. If > 13 favors IDA. Iron studies should also be performed. Perform hemoglobin electrophoresis. Sequencing for hemoglobin types, dot blot assays first.

Question 5

alpha gene genetics

Answer 5

2 a genes located on each of chromosome 16. A2 located upstream and produces 2-3 times more mRNA than A1 downstream.

Question 6

all 4 alpha genes mutated

Answer 6

hydrops fetalis

Question 7

3 alpha chains mutated

Answer 7

HBH disease

Question 8

deletion 2 genes

Answer 8

thalassemia minor.

Question 9

deletion 1 gene

Answer 9

silent carrier.

Question 10

difference hemoblobinopathies thal

Answer 10

thal RBC count increased over what is expected, opathies normocytic normochromic, thal microcytic microchromic. sickles cells and crystals in opathies. Solubility test + in opathies, - in thal. Retic increased more in opathies. `HBH HB barts present.

Question 11

Gamma clobin tetramers

Answer 11

barts

Question 12

Deletional more common in

Answer 12

alpha genes

Question 13

non deletional more common in

Answer 13

beta chains. ie promoter nonsense, stop codon, splice site.

Question 14

beta gene genetics

Answer 14

located on chromosome 11 only one beta gene from each parent

Question 15

target cells

Answer 15

increase in beta thalassemia major. anemia is also more severe.

Question 16

A and F hemoglobin relationship in thalassemia

Answer 16

as aanemia sd severity increases from minor to major, A decreases F increases. Can be seen on electrophoresis.

Question 17

increase in F

Answer 17

increased oxygen affinity for F decreases delivery to tissues.

Question 18

Beta thalassemia

Answer 18

increased alpha chains cause precipitation, damage rbc membrane, cause ineffective erythropoeisis and IV EV destruction, SPLENOMEGALY, INCREASE EPO, EXTRAMEDULLARY ERYTHROPOEISIS. INCREASE IRON, TOXICITY.

Question 19

target cells in thal due to

Answer 19

decrease in hemoglobin without corresponding decrease in membrane.

Question 20

reticulocyte count lower than expected in thal due to:

Answer 20

ineffective erythropoeisis

Question 21

hb constant spring

Answer 21

alpha chain elongated by 31 amino acids. homozygs mild anemia hetero asymptomatic.

Question 22

hb lepore

Answer 22

hybrid beta-delta chain fusion. Alpha chains have nothing to associate with cause hemolysis like beta thal.

Question 23

Hereditary persistence of fetal hemoglob

Answer 23

increase in gamma chains to compensate for absence of beta dlta chains. HBF common. Mostly asymptomatic.

Question 24

HBS Pathology

Answer 24

GLU-> Val mutation on surface causes less polar and less soluble in deoxy state. Reversible on oxygenation. Delays means most blood cells do not sickle, but sickle in spleen kidney and other hypoxic acidic

Question 25

HBA

Answer 25

A2B2 normal adult

Question 26

Gower 1

Answer 26

psi epsilon embryonic

Question 27

Gower II

Answer 27

A epsilon embryonic

Question 28

Portland

Answer 28

Psi2 gamma 2 embryonic

Question 29

HBF

Answer 29

alpha 2 gamma 2

Question 30

HBA2

Answer 30

alpha2 delta 2

Question 31

Hemoglobin chain ovef maturation

Answer 31

switch from psi to alpha, and epislon (E) to gamma (F) to B(adult)

Question 32

test for hemoglobinopathies:

Answer 32

electrophoresis, HPLC PCR, solubility test, heat precipitation test, tests for Heinz bodies.

Question 33

Mutation for HB S, C and E

Answer 33

ALL GLUTAMIC ACID NEGATIVE CHARGE. S IS NON POLAR VAL, WHILE E AND C ARE POSITIVELY CHARGED LYS.

Question 34

HBS BLOOD SMEAR

Answer 34

NORMOCYTIC NORMOCHROMIC, SICKLE CELLS

Question 35

HBE BLOOD SMEAR

Answer 35

MICROCYTIC MICROCHROMIC, TARGET CELLS

Question 36

HBC

Answer 36

NORMOCYTIC AND CHROMIC RETICULOCYTOSIS TARGET CELLS

Question 37

SICKLE CELL DISEASE ASSOCIATED WITH

Answer 37

EV HEMOLYSIS. RPI 3-5 X TO COMPENSATE.

Question 38

HBS OXYGEN AFFINITY

Answer 38

LOWER. BUT POLYMERIZES LEADING TO PREMATURE DESTRUCTION.

Question 39

SICKLING HAPPENS UPON

Answer 39

DEOXYGENATION, REVERSES ON OXYGENATION. MORE PRONE TO OXIDATION. LEADS TO LOSS OF WATER, DESTRUCTION OF MEMBRANE LATTICE PROTEINS, DECREASES DEFORMABILITY, CATION PROTEINS, EV HEMOLYSIS.

Question 40

VASO OCCLUSIVE CRISIS

Answer 40

DEOXYGENATION, BLOCKAGE, REPEATED DEOXYGENATION FROM ANEMIC TISSUE AHEAD OF BLOCKAGE.

Question 41

AUTOSLPENECTOMY

Answer 41

EXTENSIVE EV HEMOLYSIS DECREASES OXYGEN TO SPLEEN, LEADING TO DECREASED FUNCTION.

Question 42

HYDROXYUREA BOOSTS

Answer 42

HBF PRODUCTION

Question 43

HEMOGLOBIN CRYSTAL

Answer 43

MILD TO MODERATE, NO VASOOCCLUSIVE CRISIS. HEMOGLOBIN CRYSTALS FORM. HB S / C HETEROZYGOUS IIS INTERMEDIATE BETWEEN BOTH DISEASES. mORE S BECAUSE S IS MORE NEGATIVELY CHARGED.

Question 44

HEMOGLOBIN E

Answer 44

MILD ASYMPTOMATIC ANEMIA.

Question 45

METHHEMOGLOBINEMIA

Answer 45

OXIDIZED HEMOGLOBIN IS METHHEMOGLOBIN, CANNOT BIND OXYGEN. kEPT REDUCED BY METHHEMOGLOBIN REDUCTASE.>1%.

Question 46

CAUSES METHHEMOGLOBINEMIA

Answer 46

ACQUIRED, REDUCTION PATHWAY OVERWHELMED. | OR CONGENITAL. DEFECT IN PATHWAY, OR STRUCUTURAL ABNORMALITY, HBM.

Question 47

HBM CAUSES

Answer 47

PSUEDOCYANOSIS.

Question 48

HBH

Answer 48

BETA TETRAMERS

Question 49

HB BARTS

Answer 49

GAMMA TETRAMERS

Question 50

CHRONIC HEMOLYSIS IN HBH

Answer 50

PRECIPITATES OF HBH TRIGGER HEMOLYSIS

Question 51

BETA+

Answer 51

PARTIAL BLOCK OF BETA CHAIN SYNTHESIS

Question 52

BETA0

Answer 52

FULL BLOCK OF BETA CHIAN SYNTHESIS.

Question 53

BETA THALASSEMIA BLOOD PICTURE

Answer 53

TARGET CELLS SCHISTOCYTES, RETICS LOWER THAN EXPECTED DUE TO INEFFECTIVE ERYTHROPOESIS