Hemoglobinopathies, ASPHO Flashcards
beta globin on chrom?
11
alpha globin on chrom?
16
hgb a2 made of?
alpha 2 delta 2
fetal hgb made of?
alpha 2 gamma 2
hgb barts made of?
gamma 4
hgb H made of?
beta4
prenatal hgb?
gower
alpha globin starts early in the ___ period, as does ____. the latter starts to decrease ___ birth and is very low by __ weeks postnally
fetal; gamma; before; 12
when does beta globin start being made? really becomes prominent when?
early in fetal life, but rises much more slowly than alpha….prominent at 12 weeks of life
delta globin:low levels, mostly present when?
postnatal life
under what circumstances does Hgb S polymerize?
deoxygenated state
most common type of sickel cell diseae?
hgb SS, also most severe
other than hgbss, 3 other types of SCD…which one is most severe?
hgb SC, hgb SBeta +, hgbSBeta null…hgb S Beta null= most severe
what’s common in hgb SC?
retinopathy! splenic infarction
life expectancy for hgb SS?
50s
dx scd how?
- hgb electrophoresis
- isoelectric focusing
- high perforamnce liquid chromatogrpahy
hgb S point mutation?
glutamine-> valine
3 places where Hgb S seen?
africa, india, mediterranean
hgb E seen wehre?
southeast asia
list 7 complciations of SCD
hemolysis juandice gall stones pain priapism stroke ACS splenic seq spleen damage brain damage kidney damage etc
list 5 neuro complications in scd
overt stroke silent cerebral infraction TIA cognitive impairemnt reversible posterior luekoencephalopathy occlusive cerebral vasculopathy
recurrence rate of overt stroke in SCD?
50-90%
primary prevention of stroke in SCD?
chronic transfusion (STOP I and II trials)–> HU (twitch trial)
secondary prevention of stroke in SCD?
chronic transfusion only (swtich trila)
silent stroke 2ndry prevention?
chronic transfusion= SIT trial
do TCD when?
yearly age 2-16
TCD results?
normal <170 cm/s2; conditional 170-<200; abnoraml 200+
risk of stroke for abN TCD?
10% per year for next 3 years
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)
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
secondary stroke prevention?
chronci transfusion therapy
stem cell transplant
what did switch trial show?
chronci transfusions adn cheleation better than HU adn phlebotomy for secondary stroke prevnetion
hyposplenism starts when in hgbss?
3 months of age
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!
splenic sequestration: do what iwth parents? possible tx?
- teach them to palpate spleen
- splenectomy may be needed for severe and/or recurrent episodes
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
if discharging SCD with fever from Er do what?
- observation x 30 min after ceftriaxone
- ensure follow up of pt and culture
ddx for acute anemia in SCD?
splenic seq, aplastic crisis
aplstic crisis in SCD caused by?
parvovrius
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
pain triggers in SCD?
infection
inflamm
cooling of skin
stress
prevent pain crises how?
avoid dehydration, cooling of skin, overexterion, over-heating
- HU
- crizanlizumab
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
causes of ACS? (4)
infection pulm vasc occ hypoventilation/atelectasis pulm edema bronchospasm
antibiotics for ACS?
ceftriaxone + azithromycin
role of transfusion for ACS?
simple if hypoxic
exhcnage if severe
pre-op role for prevention
other than antibiotics and transfusion how else to tx ACS?
O2 maintain normal hydration pain control bronchodilators for wheezing support vent
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
avoid priapisim how?
nightly psuedoephedrine
leuprolide
bicalutamide
long term complciations of SCD? 5
retinopathy AVN cardiomyopathy pulm htn CLD renal failure/insuff progressively severe anemia in adults
5 renals complications in SCD?
polyuria proteinuria renal tubular acidosis gross hematuria ESRD hypothesnuria
indications for HU?
HbSS/Sbeta null from age 9mos
HU dose?
20 mg/kg adn increase over 2-3 mos
what is endari?
l-glutamine…fro SCD pts 5. yrs +…BID dosing..decreases pain crises
what’s oxbryta?
voxelotor…for pts with SCD aged 12+: inhibits HbS polymerizataion by incrasing its O2 affinity–> increase hgb
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
avoid transfusing hgb over what in SCD? hct?
hgb>100; hct>30
indications for exchange transfusion in SCD?
acute stroke
severe ACS
rapid clinical deterioation
high hgb concetnraion (>90)
indications for chronic transfuiosn in scd? (3)
stroke
recurrent ACS
frequent pain
chronic transfusions done how often in SCD?
q4-6 weeks x 6 months +
main complicatins fo CTs in SCD?
iron overload
alloimmunization
infection- transfusion related, vasc access
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
sickle cell trait: how much hgb S?
<50%
issues in sickel cell trait?
- splenic infarct at high altitutde
- increase risk of PE
- inceasesed CKD
- renal medullary carcinoma
hgb C =?
homozyg hb cc
- no sickling
- chronic hemolytic anemia, no transfusions
hgb E=? common where?
glu-> lys
SE Asia
Hb E trait: main hgb? features?
A>E
low MCV, targte cells
Hb E diseae: main hgb? features?
E; mild microcytic anemia, target cells
Hb E/Beta + thal: main hgb, features?
E>A; beta thal minor to intermed
Hb E/beta 0thal: main hgb, features?
E; beta thal intermedia to major
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)
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
thal seen wehre?
africa, mediterranean, SE asia
beta thal trait: hgb F level? hgb A2 level?
f: normal or high
a2: increased (because excess alpha)
alpha thal trait: hgb F level? A2 level?
F: normal (0-2)
A2: normal or decreased (0-2.5%)
iron def aenmai: hgb f? a2?
f normal
a2 normal or low
normal a2 level?
2-3%
aa/a- = ?
silent carrier
–/aa and a-/a TRANS-=?
thal trait
–/a-?
hgb h disease
–/aCSa
hgb h constant spring
–/–?
hydrops fetalis
diff between having 2 parents with trans a-/a- vs cis deletions –/aa?
with cis, chance of –/–= thal major
features of alpha thal trait?
mcv low
mild anemia 110-110
hypochromia
Hb H hgb level?
60-90…not tranfusion dep but intermittently
beta null inndicates
large mut
bta + indicates
point mutations
genotypes in beta thal trait?
b/b+or b/b0
hgb level in beta thal trait?
midl to no anemia: 100-120
MCV 65-75
hb a2 in beta thal trait? hgb f?
a2 increased
f sometimes increased
genotypes in beta thal intermedia?
b+/b+.B+/b0, be/b+, be/b0
see waht in neoantes with beta thal intermedia?
gamma is the predom beta-like globin
mcv in beta thal intermed?
50-65
hb a2 in beta thal intermed?
f in beta thal intermed?
both increased
beta thal major: genotype?
b0b/0
see waht in neonates with beta thal major?
normal counts but hgb F only
what’s delta beta thal?
if you have del of delta nd beta, won’t be able to make A2 (or A).
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.
delta beta 0-HPFH vs. delta beta0?
if HPFH version, normal peripheral phenotype: no low MCV, no hypochromia
Hb H/Cs is __ than Hb H alone
worse
beta thal pts: tx?
SCT
chronic transfusions to keep hb 9-10
iron chelation
organs taht accum iron?
liver heart pituitary (hypogonad, hypot4) pancrase (DM) parathyroid gland--> low ca skin: hpyerpigm
ways to dx fe overload?
serum ferritin
liver bx
MRI
manage Fe overlaod how?
chelation
red cell exchange
phlebotomy
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
3 fe chelators?
deferasirox
deferiprone
deferoxamine
deferasirox:
admin route?
main tox?
monitor how?
oral
GI, hepatic, renal
monthly ferritin, LFTs, BUN/creat, urine prot: creat
deferiprone:
admin route?
main tox?
monitor how?
oral
neutropenia
baseline adn weekly ANC, montly ferritn, LFTs
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
