RBC I, Thalassemias and hemolytic anemias Putthoff

Question 1

where are alpha chain encoded

Answer 1

chromosome 16

Question 2

where are the beta chains encoded

Answer 2

chromosome 11

Question 3

where are thalassemias endemic to

Answer 3

mediterranean basin

tropical africa, indian continent and asia

Question 4

how do thalassemias cause anemia (generally)

Answer 4

decreased production and lifespan

not destruction

Question 5

What are the B0 mutations

Answer 5

no beta globin synthesis

Question 6

what are the B+ mutation

Answer 6

reduced beta globin synthesis

Question 7

most common cause of beta+ mutations

Answer 7

splicing mutations that affect the RNA

Question 8

common mutations with B0 thalassemias

Answer 8

prevention mRNA

chain terminator mutations (new stop codon)

Question 9

how does beta thalassemia cause anemia

Answer 9

deficit in HbA synthesis
hypochromic microcytic RBC with subnormal O2
diminished survival of RBC and precursors
unpaired alpha chains make insoluble inclusions

Question 10

how does beta thalassemia lead to bony abnormalities

Answer 10

ineffective erythropoiesis leads to erythroid hyperplasia and extensive EMH

Question 11

why do thalassemia patients suffer from hemochromatosis

Answer 11

the erythroid drive suppresses hepcidin so no neg feedback on Fe absorption. absorb more leads to iron accumulation

Question 12

why is a defect in beta and alppha chain not as severe as say 2 defects in beta or 2 defects in alpha

Answer 12

chain production is more in balance

Question 13

what is beta thalassemia major

Answer 13

homozygou so could be B0B0 or b+b+ or b+b0

Question 14

what is beta thalassemia intermedia

Answer 14

B0B+ b+b+ B0B b+B
variable
severe but does not require blood transfusions

Question 15

what is beta thalssemia minor

Answer 15

heterozygous b0 B b+B

Question 16

what is clinical presentation of beta thalassemia minor

Answer 16

asymptomatic with mild or absent anemia, red cell abnormalities seen.

Question 17

when does anemia manifest in beta thalassemia major in newborns

Answer 17

6-p mo when HbF switches over to HbA

Question 18

What do RBC look like in beta thalassemia major

Answer 18

anisocytosis poikilocytosis, microcytosis, hypochromic
target cells
basophilic stippling and fragmented cells
inclusions are aggregates of alpha chains

Question 19

clinical cours of beta thalassemia major

Answer 19

brief unless receiving blood transfusions

Question 20

signs of beta thalssemia major

Answer 20

anemia
enlarged and distorted boney prominences
HSM
cardiac disease from hemochromatosis

Question 21

how do you Tx patients with beta thalassemia major

Answer 21

transfusion but must also give iron chelators to prevent hemochromatosis

Question 22

what will PS look like in beta thalssemia minor

Answer 22

RBC abnormalities like hypochromia, microcytosis, basophilic stippling and target cells
mild erythroid hyperplasia in BM

Question 23

what will Hb electrophoresis show in beta thalassemia minor

Answer 23

increase HbA2 and normal or slightly increased HbF

Question 24

Wgat dies beta thalssemia minor look like and how do you diferentiate

Answer 24

iron deficiency anemia
look at iron panel
also increase in HbA2 helpful

Question 25

severity of alpha thalssemia depends on what

Answer 25

how many alpha globin genes are affected

Question 26

what is Hb barts

Answer 26

gamma globin tetramers in newborns with alpha thalassemia

Question 27

how does alpha thalassemia present in older children and adults

Answer 27

HbH | beta tetramers

Question 28

why in HbH is anemia less severe

Answer 28

the beta tetramers are more soluble than alpha

Question 29

what is most common cause of reduced alpha chain synthesis

Answer 29

gene deletion

Question 30

what is silent carrier state alpha thalassemia

Answer 30

-/a a/a | no RBC abnormality

Question 31

what are the alpha thalassemia trait varieties

Answer 31

- /- a/a (asian) | - /a -/a (black, asian)

Question 32

what are signs of alpha thalassemia trait

Answer 32

microcytosis minimal or no anemia no abnormal physical sings low HbA2 or normal

Question 33

What is genotype for HbH disease

Answer 33

-/- -/a

Question 34

HbH most common in what population

Answer 34

asian

Question 35

why is there hypoxia when there are tetramers of beta globins HbH

Answer 35

because has extremely high affinity for O2, does not release | leads to oxidation and promotes RBC sequestration and phagocytosis

Question 36

clinical signs HbH

Answer 36

severe anemia

Question 37

what is hydrops fetalis

Answer 37

-/- -/- no alpha globin chain synthesis lethal in utero distress in 3rd trimester

Question 38

clinical signs of fetus with hydrops fetalis

Answer 38

pallor, generalized edema, massive HSM

Question 39

What is Paroxysmal nocturnal Hbinuria

Answer 39

disease from mutations in PIGA enzyme essential for synthesis of MAC regulatory proteins

Question 40

what is the only hemolytic anemia caused by acquired genetic defect

Answer 40

PNH

Question 41

what are PNH blood cells deficient in

Answer 41

3 GPI-linked proteins that regulate C' activity | CD55 CD59 and C8

Question 42

what is inheritance of PNH

Answer 42

X linked

Question 43

RBC in PNH are prone to what

Answer 43

injury by C' or lysis | intravascular from MAC attack

Question 44

typical presentation PNH

Answer 44

chronic hemolysis without dramatic Hburia | at night because blood pH drops at night which increases C' activity

Question 45

what is leading cause of deat in individuals with PNH

Answer 45

thrombosis | venous- hepatic or cerebral

Question 46

what neoplasias are PNH assoc with

Answer 46

myelodysplastic syndrome and acute myeloid leukemia

Question 47

What do we detect on flow cytometry for PNH

Answer 47

CD59

Question 48

Tx for PNH

Answer 48

eculizumab to prevent conversion of C5 to C5a | reducing thrombosis by 90%

Question 49

eculizumab increases risk for what

Answer 49

serious or fatal meningococal infections

Question 50

what characterizes immunohemolytic annemias

Answer 50

Ab that bind to RBC leading to premature destruction

Question 51

Describe warm Ab type immunohemolytic anemia

Answer 51

IgG can be primary (idiopathic) secondary (SLE) (drugs lymphoid neoplasms)

Question 52

describe cold agglutinin type immunohemolytic anemia

Answer 52

IgM (active below 37C) acute (mycoplasmal infection, infectious mononucleosis) chronic: idiopathic, lymphoid neoplasms

Question 53

describe cold hemolysin type immunohemolytic anemia

Answer 53

IgG active below 37 | rare- children after viral infection

Question 54

how do you Dx immunohemolytic anemia

Answer 54

direct Coombs antiglobulin test

Question 55

what is indirect Coombs antiglobulin test used for

Answer 55

to charcterize the Ag target and temperature dependence of Ab

Question 56

what is most common form immunohemolytic anemia

Answer 56

warm Ab type

Question 57

types of drug induced warm hemolytic anemia

Answer 57

antigenic drugs that promote extravascular hemolysis by acting like opsonins tolerance breaking drugs that create autoAb

Question 58

example of tolerance breaking drug that can lead to autoAb against RBC

Answer 58

alpha methlydopa

Question 59

clinical symptoms of cold agglutinin hemolytic anemia

Answer 59

pallor cyanosis and raynaud phenomenon | exposed areas like finger toes, nose etc

Question 60

what is paroxysmal cold hemoglobinuria

Answer 60

rare disorder that can cause fatal intravascular hemolysis | type of cold hemolysin type hemolytic anemia

Question 61

most significant hemolysis caused by trauma to rBC is seen in what individuals

Answer 61

cardiac valve prostheses and microangiopathic disorders

Question 62

what is microangiopathic hemolytic anemia seen in

Answer 62

``` DIC TTP HUS malignant HTN SLE disseminated cancer ```

Question 63

cause of RBC damage in microangiopathic disorders

Answer 63

luminal narrowing form fibrosis or other stuff causing damage to RBC

Question 64

what do rBC look like after damage

Answer 64

``` schistocytes RBC fragments "burr cells" "helmet cells" "triangle cells" ```