RBC I, Thalassemias and hemolytic anemias Putthoff Flashcards Preview

Year 2 Heme lymph > RBC I, Thalassemias and hemolytic anemias Putthoff > Flashcards

Flashcards in RBC I, Thalassemias and hemolytic anemias Putthoff Deck (64):
1

where are alpha chain encoded

chromosome 16

2

where are the beta chains encoded

chromosome 11

3

where are thalassemias endemic to

mediterranean basin
tropical africa, indian continent and asia

4

how do thalassemias cause anemia (generally)

decreased production and lifespan
not destruction

5

What are the B0 mutations

no beta globin synthesis

6

what are the B+ mutation

reduced beta globin synthesis

7

most common cause of beta+ mutations

splicing mutations that affect the RNA

8

common mutations with B0 thalassemias

prevention mRNA
chain terminator mutations (new stop codon)

9

how does beta thalassemia cause anemia

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

10

how does beta thalassemia lead to bony abnormalities

ineffective erythropoiesis leads to erythroid hyperplasia and extensive EMH

11

why do thalassemia patients suffer from hemochromatosis

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

12

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

chain production is more in balance

13

what is beta thalassemia major

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

14

what is beta thalassemia intermedia

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

15

what is beta thalssemia minor

heterozygous b0 B b+B

16

what is clinical presentation of beta thalassemia minor

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

17

when does anemia manifest in beta thalassemia major in newborns

6-p mo when HbF switches over to HbA

18

What do RBC look like in beta thalassemia major

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

19

clinical cours of beta thalassemia major

brief unless receiving blood transfusions

20

signs of beta thalssemia major

anemia
enlarged and distorted boney prominences
HSM
cardiac disease from hemochromatosis

21

how do you Tx patients with beta thalassemia major

transfusion but must also give iron chelators to prevent hemochromatosis

22

what will PS look like in beta thalssemia minor

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

23

what will Hb electrophoresis show in beta thalassemia minor

increase HbA2 and normal or slightly increased HbF

24

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

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

25

severity of alpha thalssemia depends on what

how many alpha globin genes are affected

26

what is Hb barts

gamma globin tetramers in newborns with alpha thalassemia

27

how does alpha thalassemia present in older children and adults

HbH
beta tetramers

28

why in HbH is anemia less severe

the beta tetramers are more soluble than alpha

29

what is most common cause of reduced alpha chain synthesis

gene deletion

30

what is silent carrier state alpha thalassemia

-/a a/a
no RBC abnormality

31

what are the alpha thalassemia trait varieties

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

32

what are signs of alpha thalassemia trait

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

33

What is genotype for HbH disease

-/- -/a

34

HbH most common in what population

asian

35

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

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

36

clinical signs HbH

severe anemia

37

what is hydrops fetalis

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

38

clinical signs of fetus with hydrops fetalis

pallor, generalized edema, massive HSM

39

What is Paroxysmal nocturnal Hbinuria

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

40

what is the only hemolytic anemia caused by acquired genetic defect

PNH

41

what are PNH blood cells deficient in

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

42

what is inheritance of PNH

X linked

43

RBC in PNH are prone to what

injury by C' or lysis
intravascular from MAC attack

44

typical presentation PNH

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

45

what is leading cause of deat in individuals with PNH

thrombosis
venous- hepatic or cerebral

46

what neoplasias are PNH assoc with

myelodysplastic syndrome and acute myeloid leukemia

47

What do we detect on flow cytometry for PNH

CD59

48

Tx for PNH

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

49

eculizumab increases risk for what

serious or fatal meningococal infections

50

what characterizes immunohemolytic annemias

Ab that bind to RBC leading to premature destruction

51

Describe warm Ab type immunohemolytic anemia

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

52

describe cold agglutinin type immunohemolytic anemia

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

53

describe cold hemolysin type immunohemolytic anemia

IgG active below 37
rare- children after viral infection

54

how do you Dx immunohemolytic anemia

direct Coombs antiglobulin test

55

what is indirect Coombs antiglobulin test used for

to charcterize the Ag target and temperature dependence of Ab

56

what is most common form immunohemolytic anemia

warm Ab type

57

types of drug induced warm hemolytic anemia

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

58

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

alpha methlydopa

59

clinical symptoms of cold agglutinin hemolytic anemia

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

60

what is paroxysmal cold hemoglobinuria

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

61

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

cardiac valve prostheses and microangiopathic disorders

62

what is microangiopathic hemolytic anemia seen in

DIC
TTP
HUS
malignant HTN
SLE
disseminated cancer

63

cause of RBC damage in microangiopathic disorders

luminal narrowing form fibrosis or other stuff causing damage to RBC

64

what do rBC look like after damage

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