12-1: 1/5 - Disorders Of Hemoglobin - Thalassemias

Front 1

Epsilon globin is present in ________ until about _____ weeks of gestation.

Back 1

Embryonal hgb, until about 6 weeks

Front 2

Alpha globin is present in ________ beginning at _____ weeks of gestation.

Back 2

Embryonal-->Fetal-->adult beginning around 6 weeks

Front 3

Gamma globin is present in ______ beginning at ______ weeks of gestation.

Back 3

Embryonal-->Fetal-->adult beginning at 6 weeks gestation

DECREASES at/near birth (this is a component of fetal Hgb).

Front 4

Beta globin is present in _____ beginning at ____ weeks of gestation.

Back 4

Present in embryo-->adult, present at 12 weeks, but increases at/near birth (this is a component of adult Hgb).

Front 5

What is a thalassemia?

Back 5

Defect in production of hemoglobin

Front 6

What is a hemoglobinopathy?

Back 6

Defect in Hgb fn

Front 7

Disorders of hemoglobin are due to _______.

Back 7

DNA mutations (GENETIC)

Front 8

alpha-thalassemia:
Pathophys
How does it result in ineffectual erythropoiesis?

Back 8

Genetic defect causing dec'd gene product and thus:

dec'd/abnl alpha chains
excess gamma chains to dimerize (gamma 4) in infant, and extra beta chains in adult (beta 4)
Form 'pseudohgbs' and precipitate in RBC, causing hemolysis
Stimulates marrow to produce RBCs that don't work and die (ineffectual erythropoiesis)

Hemolysis + marrow expansion-->multisystem dz

Front 9

alpha-thalassemia:
Classification based on gene deletion; treatment requirements

Back 9

aa/aa: normal
aa/a-: mild microcytosis, NO anemia
aa/-- or a-/a-: mild microcytosis, mild anemia; NO TX REQD
a-/--: Hgb H dz; sometimes require transfusion
--/--: Hgb Barts - Hydrops fetalis unless transfused in utero

Front 10

Hemoglobin Constant Spring:
What is it?
Effects?

Back 10

alpha globin variant seen in persons of Asian ancestry; results in elongated globin chain and thalassemic phenotype

Front 11

beta-thalassemia:
Pathophys

Back 11

Dec'd or abnl beta chains available to dimerize

alpha chains dimerize then tetramize (alpha4) and combine with gamma and sigma chains (elevated Hgb F and A2)

alpha4 globins bind O2 with high affinity and precipitate within reticulocyte, killing cell before it leaves marrow-->ineffectual erythropoiesis (and hemolysis)

Front 12

Beta-thalassemia:
Classification
Effects, treatment requirements
Degree of effect on beta chains

Back 12

Differs from alpha-thal classification because not based on gene mutations, but rather on clinical severity.

Thal trait: no anemia; 1 beta chain dysfnal

Thal minor: mild microcytic anemia; 1 beta chain dysfnal, 1 beta chain mutated (but still present)

Thal intermedia: mod microcytic anemia, mostly compensated

Thal major: severe anemia, requires transfusion support; neither of beta chains are fnal

Front 13

Homozygous alpha-thal vs homozygous beta-thal:
Presentation

Back 13

homo alpha-thal: present in utero
homo beta-thal: first year of life (6 mos)

Front 14

Clinical presentation of beta-thal.

Back 14

Growth retardation
Pallor
Icterus
Hepatosplenomegaly
Frontal Bossing
Maxillary hyperplasia

Front 15

Why does deletion of all alpha chain genes cause fetal death, but deletion of all beta chain genes do not appear clinically until >4 months of life?

Back 15

Fetuses and newborns have gamma chains to mop up extra alpha chains to maintain balance

Front 16

Iron deficiency vs Thalassemia:
General
Lab values:
Mentzer Index
Serum iron
Ferritin
TIBC

Back 16

Both are microcytic, hypochromic anemias

Range of distribution width more elevated in Fe def bc marrow can make large reticulocytes

Mentzer index (MCV/Red cell count):
<12: thalassemia
>13: Fe def anemia

Fe def:
Low serum iron
Low ferritin (stored iron)
High capacity to bind iron (TIBC)

Front 17

Transfusion therapy:
Effects on beta-thal
AEs

Back 17

Corrects anemia and ineffective erythropoiesis

Consequences:
Time/effort/money
Rxn, infection
Iron overload!!! --liver deposition leads to cirrhosis; CHF,

Front 18

Will a patient with a two alpha-chain deletion and a beta-0 thal have more or less severe disease than beta-0 thal alone?

Back 18

LESS severe due to less of an imbalance of alpha and beta chains

Thalassemia is about imbalance!

Front 19

Back 19

Front 20

Back 20

Front 21

Back 21

Front 22

Back 22

Front 23

Back 23