Hemoglobinopathies, ASPHO Flashcards
1
Q
beta globin on chrom?
A
11
2
Q
alpha globin on chrom?
A
16
3
Q
hgb a2 made of?
A
alpha 2 delta 2
4
Q
fetal hgb made of?
A
alpha 2 gamma 2
5
Q
hgb barts made of?
A
gamma 4
6
Q
hgb H made of?
A
beta4
7
Q
prenatal hgb?
A
gower
8
Q
alpha globin starts early in the ___ period, as does ____. the latter starts to decrease ___ birth and is very low by __ weeks postnally
A
fetal; gamma; before; 12
9
Q
when does beta globin start being made? really becomes prominent when?
A
early in fetal life, but rises much more slowly than alpha….prominent at 12 weeks of life
10
Q
delta globin:low levels, mostly present when?
A
postnatal life
11
Q
under what circumstances does Hgb S polymerize?
A
deoxygenated state
12
Q
most common type of sickel cell diseae?
A
hgb SS, also most severe
13
Q
other than hgbss, 3 other types of SCD…which one is most severe?
A
hgb SC, hgb SBeta +, hgbSBeta null…hgb S Beta null= most severe
14
Q
what’s common in hgb SC?
A
retinopathy! splenic infarction
15
Q
life expectancy for hgb SS?
A
50s
16
Q
dx scd how?
A
- hgb electrophoresis
- isoelectric focusing
- high perforamnce liquid chromatogrpahy
17
Q
hgb S point mutation?
A
glutamine-> valine
18
Q
3 places where Hgb S seen?
A
africa, india, mediterranean
19
Q
hgb E seen wehre?
A
southeast asia
20
Q
list 7 complciations of SCD
A
hemolysis juandice gall stones pain priapism stroke ACS splenic seq spleen damage brain damage kidney damage etc
21
Q
list 5 neuro complications in scd
A
overt stroke silent cerebral infraction TIA cognitive impairemnt reversible posterior luekoencephalopathy occlusive cerebral vasculopathy
22
Q
recurrence rate of overt stroke in SCD?
A
50-90%
23
Q
primary prevention of stroke in SCD?
A
chronic transfusion (STOP I and II trials)–> HU (twitch trial)
24
Q
secondary prevention of stroke in SCD?
A
chronic transfusion only (swtich trila)
25
silent stroke 2ndry prevention?
chronic transfusion= SIT trial
26
do TCD when?
yearly age 2-16
27
TCD results?
normal <170 cm/s2; conditional 170-<200; abnoraml 200+
28
risk of stroke for abN TCD?
10% per year for next 3 years
29
what did twitch trail show?
HU is non inferior to chronic transfusion therapy...so for pts with abnormal TCD velocities, can transiton to HU from CT after 12 months (if no severe vasculopathy on MRA)
30
how to manage overt stroke?
O2
avoid delays to transfusion
erythrocytapheresis likely better than simple transfusion
can give reg transfusoin if hgb <90 while waiting fro erythrocytapehresis
31
secondary stroke prevention?
chronci transfusion therapy
| stem cell transplant
32
what did switch trial show?
chronci transfusions adn cheleation better than HU adn phlebotomy for secondary stroke prevnetion
33
hyposplenism starts when in hgbss?
3 months of age
34
4 things to say when counseling parent re: hyposplenism in SCD?
- starts young (3 months of age)
- risk of bacterial sespsis (encapsulated orgs)
- reason for newborn screening
- reason for ppx penicillin
- immunizations important!
- empiric maangement for fever!
35
splenic sequestration: do what iwth parents? possible tx?
- teach them to palpate spleen
| - splenectomy may be needed for severe and/or recurrent episodes
36
do waht for SCD patient presenting with fever?
focused hx and phys
CBC, retic, blood culture
IV antibiotics (ceftriaxone)
admission if toxic, altered mental status, temp>39.5, age<1 yr, recent missed PCN, pulm infiltrates, WBC >30, plts<150, hgb<60, history of sepsis, non-adherence
37
if discharging SCD with fever from Er do what?
- observation x 30 min after ceftriaxone
| - ensure follow up of pt and culture
38
ddx for acute anemia in SCD?
splenic seq, aplastic crisis
39
aplstic crisis in SCD caused by?
parvovrius
40
diffs between aplastic crsisi and splenic seq?
- splenomeg in splenic seq
- low retics for aplastic vs high in seq
- nucleated RBCs in seq
- low plts in seq
- decreaesd jaudncie in aplastic
41
pain triggers in SCD?
infection
inflamm
cooling of skin
stress
42
prevent pain crises how?
avoid dehydration, cooling of skin, overexterion, over-heating
- HU
- crizanlizumab
43
5 pts for managing pain crisis?
- NSAIDs, opiates
- warm crompresses, relax, massages
- correct dehydration (avoid over hydration)
- incentive spirometry to prevent ACS
- vigilance for fever adn ACS
- laxatives for opaites
- anti-pruritcs for opiates
44
causes of ACS? (4)
```
infection
pulm vasc occ
hypoventilation/atelectasis
pulm edema
bronchospasm
```
45
antibiotics for ACS?
ceftriaxone + azithromycin
46
role of transfusion for ACS?
simple if hypoxic
exhcnage if severe
pre-op role for prevention
47
other than antibiotics and transfusion how else to tx ACS?
```
O2
maintain normal hydration
pain control
bronchodilators for wheezing
support vent
```
48
manage priapism how?
```
oral pain meds
oral hydration
warm bath/shower
urination
oral pseudoephedrine
```
```
if prolonged:
IV pain meds
IV hydration
oral pseudoephedrine
rapid aspiration adn irrigiation
avoid transfusions
```
49
avoid priapisim how?
nightly psuedoephedrine
leuprolide
bicalutamide
50
long term complciations of SCD? 5
```
retinopathy
AVN
cardiomyopathy
pulm htn
CLD
renal failure/insuff
progressively severe anemia in adults
```
51
5 renals complications in SCD?
```
polyuria
proteinuria
renal tubular acidosis
gross hematuria
ESRD
hypothesnuria
```
52
indications for HU?
HbSS/Sbeta null from age 9mos
53
HU dose?
20 mg/kg adn increase over 2-3 mos
54
what is endari?
l-glutamine...fro SCD pts 5. yrs +...BID dosing..decreases pain crises
55
what's oxbryta?
voxelotor...for pts with SCD aged 12+: inhibits HbS polymerizataion by incrasing its O2 affinity--> increase hgb
56
adakveo is waht?
crizanlizumab..for scd pts 16+...inhibits p-selectin on endothelial cells--> keeps WBC, RBC and plts from sticking together...has to be given IV...at first q2 weeks--> then q4 weeks...less pain crises
57
avoid transfusing hgb over what in SCD? hct?
hgb>100; hct>30
58
indications for exchange transfusion in SCD?
acute stroke
severe ACS
rapid clinical deterioation
high hgb concetnraion (>90)
59
indications for chronic transfuiosn in scd? (3)
stroke
recurrent ACS
frequent pain
60
chronic transfusions done how often in SCD?
q4-6 weeks x 6 months +
61
main complicatins fo CTs in SCD?
iron overload
alloimmunization
infection- transfusion related, vasc access
62
indications for SCT in SCD?
Hb SS or S beta 0 <16 years
- stroke or CNS event >24 h
- impaired neuropsych function with abN brain MRI
- recurrent ACS
- Stage I or II sickle lung disease
- recurrent painful episdoes
63
sickle cell trait: how much hgb S?
<50%
64
issues in sickel cell trait?
- splenic infarct at high altitutde
- increase risk of PE
- inceasesed CKD
- renal medullary carcinoma
65
hgb C =?
homozyg hb cc
- no sickling
- chronic hemolytic anemia, no transfusions
66
hgb E=? common where?
glu-> lys
| SE Asia
67
Hb E trait: main hgb? features?
A>E
| low MCV, targte cells
68
Hb E diseae: main hgb? features?
E; mild microcytic anemia, target cells
69
Hb E/Beta + thal: main hgb, features?
E>A; beta thal minor to intermed
70
Hb E/beta 0thal: main hgb, features?
E; beta thal intermedia to major
71
hbconstant spring?
qual alpha globin mut...like hgb h diseaes (missing 3 normal alphas, but here 2 gene deletion and 1 gene abnormal with constant spring)
72
pathophys of thal?
decreased production of alpha or beta globins--> imbalance between alpha and beta--> glboins in excess precipitate and damange the RBC membrane--> ineffective erythropoieisis-->anemia, BM explanstion, extramedullary hematopoesisi, increased intestinal Fe abs
73
thal seen wehre?
africa, mediterranean, SE asia
74
beta thal trait: hgb F level? hgb A2 level?
f: normal or high
a2: increased (because excess alpha)
75
alpha thal trait: hgb F level? A2 level?
F: normal (0-2)
A2: normal or decreased (0-2.5%)
76
iron def aenmai: hgb f? a2?
f normal
| a2 normal or low
77
normal a2 level?
2-3%
78
aa/a- = ?
silent carrier
79
--/aa and a-/a TRANS-=?
thal trait
80
--/a-?
hgb h disease
81
--/aCSa
hgb h constant spring
82
--/--?
hydrops fetalis
83
diff between having 2 parents with trans a-/a- vs cis deletions --/aa?
with cis, chance of --/--= thal major
84
features of alpha thal trait?
mcv low
mild anemia 110-110
hypochromia
85
Hb H hgb level?
60-90...not tranfusion dep but intermittently
86
beta null inndicates
large mut
87
bta + indicates
point mutations
88
genotypes in beta thal trait?
b/b+or b/b0
89
hgb level in beta thal trait?
midl to no anemia: 100-120
| MCV 65-75
90
hb a2 in beta thal trait? hgb f?
a2 increased
| f sometimes increased
91
genotypes in beta thal intermedia?
b+/b+.B+/b0, be/b+, be/b0
92
see waht in neoantes with beta thal intermedia?
gamma is the predom beta-like globin
93
mcv in beta thal intermed?
50-65
94
hb a2 in beta thal intermed?
| f in beta thal intermed?
both increased
95
beta thal major: genotype?
b0b/0
96
see waht in neonates with beta thal major?
normal counts but hgb F only
97
what's delta beta thal?
if you have del of delta nd beta, won't be able to make A2 (or A).
98
what's hgb lepore?
DNA between delta and beta gone--> get delta beta fusion
Hemoglobin (Hb) Lepore is composed of two normal α chains and two δβ fusion globins that arise from unequal crossover events between the δ- and β-globin genes. The Hb Lepore is widespread all over the world and in many ethnic groups.
99
delta beta 0-HPFH vs. delta beta0?
if HPFH version, normal peripheral phenotype: no low MCV, no hypochromia
100
Hb H/Cs is __ than Hb H alone
worse
101
beta thal pts: tx?
SCT
chronic transfusions to keep hb 9-10
iron chelation
102
organs taht accum iron?
```
liver
heart
pituitary (hypogonad, hypot4)
pancrase (DM)
parathyroid gland--> low ca
skin: hpyerpigm
```
103
ways to dx fe overload?
serum ferritin
liver bx
MRI
104
manage Fe overlaod how?
chelation
red cell exchange
phlebotomy
105
start chelation wehn?
120-200 ml/kg has been transfused...LIC >5-7 mg/g and/or ferriting >1500-2000...often wait til pt >2 yrs
106
3 fe chelators?
deferasirox
deferiprone
deferoxamine
107
deferasirox:
admin route?
main tox?
monitor how?
oral
GI, hepatic, renal
monthly ferritin, LFTs, BUN/creat, urine prot: creat
108
deferiprone:
admin route?
main tox?
monitor how?
oral
neutropenia
baseline adn weekly ANC, montly ferritn, LFTs
109
deferoxamine: admin route?
main tox?
montiroing?
- SC or IV, 5-7 nigths/week
- ocular, otic, bony
- mnthly ferriting, LFts, BUN/creat, urine prot: creat; yearly eye exam and audiogram, consdier yearly bone density
