B&l: 7. Turnicky : Hemoglobinopathies

Front 1

What is HbA1c?

Back 1

addition of glucose to the beta chain

Increased levels produced in diabetics with increased blood glucose levels
Tool for monitoring glucose control

Front 2

Why do hemoglobinopathies normally not manifest until 6 months of age?

Back 2

because Hb F is normally active until then

Front 3

The most common disorders are mutations of the globin beta chain and include:

Back 3

HbS
HbC
HbE

Front 4

what are 3 major mechanisms of hemoglobinopathies

Back 4

Altered function
Altered Stability
Altered solubility (seen in Hb S/C)

Front 5

how can you identify abnormal Hb?

Back 5

Hb electrophoresis

each Hb has different weight, so they migrate at different speeds

Front 6

what is the substitution in sickle cell anemia?

Back 6

Nonpolar valine is substituted for polar glutamic acid at the 6th position, in the the beta chain

aka there is a valine instead of a glutamate

Front 7

what precipitates the formation of the crescent shaped RBC in Hb S?

Back 7

Hypoxia, acidosis, hypertonicity and temperatures>37o promote deoxygenation and the formation of HBS polymers

The spleen, kidney retina and BM provide the above microenvironment

Front 8

sickle cells will return to normal shape upon reoxygenation, how do you get irreversible sickled cells? (and thus anemia)

Back 8

With repeated sickling the red cell membrane becomes leaky and rigid leading to irreversible sickled cells
Removed by spleen, liver or BM

Front 9

what is the lifespan for an RBC in sickle cell anemia?

Back 9

14 days

(norm is like 120)

Front 10

how can sickle pts get autosplectomy?

Back 10

their cells clog up the microvasculature leading to fibrosis of the spleen

Front 11

what Accounts for the majority of clinical signs in sickle cell anemia?

Back 11

Blockage of microvasculature by rigid sickled cells

Front 12

Pain, low grade fever, tissue necrosis, and thrombotic problems (stroke, blindness, etc) can all be seen in what?

Back 12

sickle cell anemia

Front 13

what is aplastic crisis? what does it normally follow?

Back 13

temporary cessation of erythropoiesis in the setting of chronic hemolysis leading to worsening of anemia

Follows viral, bacterial infections

Front 14

what type of anemia is sickle cell?

Back 14

Normochromic normocytic

Front 15

Basophilic stippling can make you suspect what in general

Back 15

hemoglobinopathy

Front 16

what is Hydroxyurea? What is it used in?

Back 16

Reduces sickling by reactivating fetal genes and elevating levels of HbF
Fewer vaso-occlusive events
Side effects: cytopenias

Front 17

why do pts with sickle trait not have the signs of anemia?

Back 17

Heterozyous condition

The one normal gene confers enough normal Hb to prevent symptoms or anemia

Front 18

what is the mutation in Hemoglobin C?

Back 18

Beta(6): Glu to Lys

Front 19

in hemoglobin C, what do you see?

Back 19

Target cells and

Intracellular Hb crystals

Front 20

Both sickling and HbC crystal formation leading to vaso-occulsive crisis.
occurs in what hemoglobinopathy?

Back 20

Hemoglobin S/C

Front 21

what is a thalassemia?

Back 21

Decreased globin chain synthesis:

Structural gene delections or
Mutations in controlling sites preventing gene expression.

Front 22

what are the 2 variants of thalassemia?

Back 22

Alpha thalassemia:
Impaired alpha chain synthesis

Beta thalassemia:
Impaired beta chain synthesis
Beta Variant

Front 23

in thalassemia please list the relative levels in a CBC for

RBC count:
MCH
MCHC
MCV
RDW
Peripheral smear

Back 23

RBC count: elevated
MCH: decreased
MCHC: decreased
MCV: DECREASED
RDW: normal or small
Peripheral smear: target cells

Front 24

why is there an elevated RBC count in thalassemia?

Back 24

Diminished synthesis of a globin chain
Too few cells with normal hemoglobin
Marked tissue hypoxia
Compensatory erythropoietin driving marked marrow hyperplasia and even greater ineffective erythropoiesis releasing increased numbers of red cells into the circulation

Front 25

severe anemia with cardiac failure in the 1st decade, pt will have Chronic hemolysis with gallstones, gout and icterus
Splenomegally
Extramedullary hematopoiesis
BM hyperplasia with facial deformities

what does this describe

Back 25

Beta Thalassemia: HomozygousThalassemia Major

Front 26

HomozygousThalassemia Major is a lack of what?

Back 26

Lack of Beta chain production
(for globin)

Front 27

One normal beta gene is present directing nearly normal beta chain synthesis
RBC survival near normal except in stress or pregnancy when moderate Hypo/micro anemia develops.
Usually only a mild Hypo/micro anemia

this describes?

Back 27

Beta Thalassemia:Heterozygous Beta Thalassemia Minor

Front 28

which thalaseemia is a genetic mutation of one or more genes?

Back 28

Alpha Thalassemia

Front 29

Silent Carrier
Alpha Thal Trait
Hemoglobin H Disease
Hydrops fetalis with Hb Bart’s

are forms of what?

Back 29

Alpha Thalassemia

Front 30

no alpha genes =

Back 30

Hydrops fetalis

Front 31

what shifts the O2 curve to the right? what does this mean

Back 31

this is stuff that drops O2 off the RBC

decrease pH
increase 23BPG
increase temp
increase CO2

Front 32

A heterogeneous group of acquired or hereditary disorders characterized by Bone Marrow HYPOCELLULARITY =

Back 32

Hypoproliferative Anemia

Front 33

what are the 2 types of hypoproliferative anemia?

Back 33

Pleuripotent: Aplastic Anemia with decrease in all 3 cell lines with peripheral pancytopenia
Unipotent: only one cell line affected, eg pure red cell aplasia

Front 34

define aplastic anemia

Back 34

BM cellularity <25% plus two of the following:

WBC count <0.5 x 109/L
Platelet count < 20,000
Anemia with corrected reticulocyte count <1%

Front 35

what is pancytopenia?

Back 35

reduction in the number of red and white blood cells, as well as platelets.

Front 36

pancytopenia is typical, Relative reticulocyte count maybe normal but corrected retic count is always low.
Erythropoietin often increased

what do you see this in

Back 36

Aplastic Anemia

Front 37

BM infiltration by tumor, fibrosis or granulomas =

Back 37

Myelophthisic Anemia

aka tumor cells fill the marrow and you can't undergo hematopoesis

Front 38

what is leukoerythroblastic picture? what is it seen in?

***

Back 38

Release of immature cells in peripheral blood: NRBCs, tear drop cells & neutrophilic left shift

Seen with Myelophthisic Anemia (leukemia, carcinoma, etc)

Front 39

abnormal replacement disrupts the normal marrow architecture allowing release of immature cells. Anemia, thrombocytopenia or pancytopenia may be seen

this describes

Back 39

Myelophthisic Anemia

Front 40

tear drop cell is a tip off for what

Back 40

a space occupying bone marrow lesion

like Myelophthisic Anemia

Front 41

Anemia with NRBCs, polychromasia, teardrop cells, aniso/poikilocytosis
Neutrophil shift to the left, but total count variable
Platelets often large (indicating immaturity)

often seen in?

Back 41

Myelophthisic Anemia

Front 42

you have a pt with anemia and no matter what you do you cannot treat it. What do they have?

Back 42

Myelodysplastic Syndrome

Front 43

Clonal pluripotential stem cell disorder
Previously call pre-leukemia
BM maturation abnormalities characterized by BM hypercellularity with peripheral cytopenias, with anemia
Frequent chromosomal abnormalities

this describes what?

Back 43

Myelodysplastic Syndrome

Front 44

Anemia most consistent finding, often macrocytic by indices, but dimorphic on smear review.
Bicytopenia: 30%
Pancytopenia: 20%

this is seen in what?

Back 44

Myelodysplastic Syndrome