Sickle Cell Disease (exam 3) Flashcards
sickle cells are RBCs that become
sickle shaped and inflexible
normal Hgb
HbA
consists of 2 normal alpha and 2 mortal beta chains
patients with normal Hgb are homozygous for normal hemoglobin
HbAA
sickle cell Hgb is an abnormality in
the beta chain
most patients with SCD are
homozygous for HbS
one HbS and one HbA results in
sickle cell trait (SCT)
does a person with sickle cell trait have sickle cell disease?
no
HbSS
2 genes for HbS
most severe form of SCD
HbSC
1 gene for HbS and 1 gene for HbC
HbS/B+ thalassemia
1 gene for HbS
reduced amounts of beta globin
HbS/B0 thalassemia
1 gene for HbS
no beta global production
similar severity to HbSS
Sickle cell anemia
2 of the most severe forms of SCD (HbSS and HbS/B0 thalassemia)
patient with SCA also have
SCD
SCD shortens the lifespan by
20-30 years
if first neonatal screening test is positive, then what is done?
a second test is done by 2 months of age to confirm diagnosis
vasoocclusion
rigid, sticky cells clog blood vessels
vasoocclusion causes
ischemia
pain
organ damage
hemolysis
abnormal RBCs get destroyed in the spleen
sickle RBC life span
10-20 days
functional asplenia
sickle cells obstruct blood flow to spleen
increased risk for infection
most common infection due to functional asplenia
streptococcus pneumonia
anemia begins to develop
4-6 months after birth
initial presentation of SCA in infants
develop hemolytic anemia and vasoocclusion
swelling and pain of hands and feet (dactylitis)
guidelines available on management of SCD complications
cardiopulmonary and kidney disease
cerebrovascular disease
management of acute and chronic pain
stem cell transplantation
transfusion support
possible cure for SCD
hematopoietic stem cell transplantation
HSCT carries many risk, but optimal outcomes are with
matched sibling donor (95-98%)
consider with matched unrelated donor in patients ____________ with severe complications
under age 16
Casgevy increases production of
HgF
Lyfgenia increases production of
HgA
Casgevy and Lyfgenia are approved for patients
age 12 and older with episodes of vasoocclusive crises
Casgevy and Lyfgenia MOA
stem cells are modified and transplanted back to the patient where they multiply in the bone marrow
most common cause of death in children with SCD is
sepsis due to S. pneumonia
prevention of infection in SCD patients
immunizations
penicillin prophylaxis
Immunization recommendations in SCD
influenza yearly over 6 months of age
meningococcal vaccine at 8 weeks
2 types of pneumococcal vaccines
2 types of pneumococcal vaccines given in SCD
PV15 or 20 (4 dose series)
PPSV23 (at age 2 and 5 years later)
PPSV23 does not need to be given if the patient already received
PV20
Penicillin decreases the risk of pneumococcal infection by
84%
if the patient has a penicillin allergy give
erythromycin 20mg/kg/day
continue prophylaxis at age 5 only if the patient has high risk for infection such as
splenectomy
history of invasive pneumococcal infection
consider withholding penicillin prophylaxis in children with
less severe forms of SCD unless they’ve had a splenectomy
screening is recommended for
renal disease
pulmonary HTN
ophthalmologic complications
stroke
Hydroxyurea
stimulates HbF production
decreases HbS polymer formation and RBC sickling
Hydroxyurea MOA
causes stress erythropoiesis
rapid erythroid regeneration
shift of erythrocyte Hgb production to HbF
indications for hydroxyurea therapy
children and infants over 9 months with SCA
adults with SCA
consider in patients with HbSC or HbS/B+ thalassemia with recurrent sickle cell pain
Hydroxyurea is recommended for adults with SCA who have
3 or more moderate-severe pain crises within a year
SCD associated pain interfering with daily activity/QOL
Severe symptomatic chronic anemia
history of severe and/or recurrent acute chest syndrome
history of stroke (but can’t give chronic transfusion)
Hydroxyurea brand names used for sickle cell anemia
droxia
siklos
droxia target population
approved for adults
guidelines recommend for children
skills target population
children over 2
adolescents
adults
Hydrea is used for
leukemia
head and neck cancers
droxia requires renal dose adjustment when creatinine clearance is
less than 60 ml/min
adverse effects of hydroxyurea
bone marrow suppression
dry skin
hyperpigmentation of skin/nails
acute leukemia and chronic opportunistic infections (chronic use)
when is improvement observed when taking hydroxyurea?
3-6 months
WAIT FULL 6 MONTHS!!
bone marrow suppression from hydroxyurea results in
neutropenia
thrombocytopenia
anemia
dec reticulocyte count
bone marrow suppression from hydroxyurea usually resolves on its own ________________________
2 weeks after discontinuation
can hydroxyurea be used in pregnancy?
is it safe for males when getting pregnant?
no! can cause fetal harm
no! may damage spermatozoa and testicular tissue; genetic abnormalities
before women start hydroxyurea, what needs to be tested?
pregnancy
women should avoid pregnancy for at least ______________ post hydroxyurea therapy
6 months
men should use effective contraceptives for at least _______________ after Siklos and ______________ after Droxia
6 months
1 year
what should be monitored for toxicity when taking hydroxyurea?
serum creatinine
ALT/AST
neutrophils
platelets
hemoglobin
reticulocytes
what do we monitor for adherence in patients taking hydroxyurea?
HgF and MCV are expected to increase
___________ supplementation is recommended when taking hydroxyurea since low levels can be based by high ___________ level
folic acid
MCV
if toxicity from hydroxyurea does not recur after __________ then the dose can be increased
12 weeks
Parameters to check when deciding to hold hydroxyurea
neutrophils
platelets
hemoglobin
reticulocytes
L-glutamine adverse effects
constipation
pain in stomach area
nausea
cough
headache
pain in hands, feet, back and chest
L- glutamine MOA
precursor to NAD+
improves and restores the ratio of NADH to NAD+ which may help sickle RBCs to tolerate increased oxidative stress
L-glutamine target populations
5 years and older
prevents vasoocclusive pain in patients with 2 or more episodes in the prior year
why was Voxelotor withdrawn from the market?
higher rates of vasooclussive crisis and fatal events compared to placebo
Crizanlizumab (adakveo) indication
reduces vaso-occlusive crises frequency in SCD
given IV
Crizanlizumab (adakveo) target population
16 years and older
common ADRs of Crizanlizumab (adakveo)
nausea
arthralgia
back pain
fever
Crizanlizumab (adakveo) MOA
binds to P-selectin and inhibits interactions with RBCs, platelets, endothelial cells, etc
Crizanlizumab (adakveo) results in decreased ______________ and reduced _____________
platelet aggregation and vasoocclusion
painful SCD crises
Transfusion therapy provides SCD patients with
normal RBCs containing HgA
simple transfusion
transfuses blood
exchange transfusion
removes volume of blood from patient then transfuse
allows transfusion of extra blood
less change of iron overload
higher % of HgA transfused
risks of transfusion
alloimmunization
non hemolytic transfusion reactions
hyperviscosity
viral transmission
volume overload
iron overload
alloimmunization is when ______________ gets activated against the transfused blood and can result in ____________
the immune system
hemolysis
iron overload
iron levels increase with transfusions
liver, heart, and pancreas can be damaged
how to manage iron overload
minimize excess dietary iron
iron chelating agents
how to diagnose iron overload
liver biopsy
MIR of liver (Q1-2 years)
serum ferritin level
in iron overload, consider chelation therapy when
ferritin > 1500-2000 mcg/L
patient received over 1 year of chronic infusions
Deferasirox black box warning
acute renal failure
hepatic failure
GI hemorrhage
Deferasirox is contraindicated in patients
with platelets under 50,000
Deferasirox MOA
binds iron in the gut for fecal elimination
Deferasirox (exjade) administration
dissolve in water, OJ, apple juice
take on empty stomach - 30 minutes before a meal
what to monitor when on Deferasirox
SCr
LFTs
Ferritin
auditory/ophthalmic testing
Deferasirox (Jadenu) administration
swallow whole or crush and mix with soft foots
empty stomach or light meal
Desforoxamine (desferal) ADRs
ocular and auditory effects
red/pink/orange discoloration of urine
Deferiprone (Ferriprox) black box warning
what to monitor because of this
neutropenia
monitor ANC weekly and hold in patients with ANC < 1,500
Deferiprone (Ferriprox) ADRs
discoloration of urine
GI effects
increased liver enzymes
SCD patients often have
vitamin and nutrient deficiencies
nutritional management recommendations
folic acid 1 mg qd
daily multivitamin without iron
vitamin d and calcium when needed
Acute sickle cell pain (vasoocclusive crisis)
result from infarction due to vasoocclusion
most common reason for hospitalization in SCD
can affect multiple sites
when there is mild Acute sickle cell pain use ____________ management
when there is moderate to severe acute sickle cell pain use _____________ management
outpatient
inpatient
components of therapy for acute sickle cell pain
consider causes and if infection present
fluid hydration
analgesics
non pharmacological therapy (ex: heating pad)
Analgesic therapy for mild-moderate pain
NSAIDs or APAP
if pain persists add opioids
analgesic therapy for moderate-severe pain
parenteral opioids (morphine, hydromorphone)
consider adding NSAIDs
should people with acute sickle cell pain be started on scheduled doses?
Yes!
change from _______ to _______ opioid therapy when pain improves
IV
oral
patients with SCD have an increased risk of sepsis and infection because of
functional asplenia
if a patient comes in with a temperature above ___________, evaluate immediately
101.3
acute chest syndrome
new pulmonary infiltrate associated with dyspnea, cough, tachycardia, chest pain, fever, wheezing and hypoxia
acute chest syndrome is most commonly caused by
infection
acute chest syndrome can develop into
respiratory failure and can involve many organs
management of acute chest syndrome
incentive spirometry
manage pain
antibiotic therapy similar to community acquired pneumonia
when managing pain for ACS, avoid _____________ with excessive opioid use
respiratory depression
antibiotics for ACS
IV CEPHALOSPORIN and macrolide
alt: respiratory floroquinolone
if a patient with ACS is wheezing or has a history of asthma
provide bronchodilators
if a patient with ACS is hypoxic or is in acute distress
provide oxygen therapy
Priapism
sustained, unwanted painful penile erection lasting 4 or more hours
stuttering priapism
shorter episode, minutes to 2 hours, that resolve spontaneously
Priapism results from
low blood flow to penis due to stasis and sickling of RBCs
when does priapism require prompt medical attention?
when it lasts over 2-3 hours
in patients with priapism, it is recommended to start
IV/PO hydration and IV/PO analgesics
if hydration and analgesics are insufficient in patients with priapism, use
vasoconstrictors (phenylephrine, pseudoephedrine)
vasodilators (terbutaline, hydralazine)
there is high risk of ___________ in SCD due to vasoocclusion in the brain
stroke
when there is acute stroke, use
exchange transfusion
for secondary stroke prevention use
chronic transfusion therapy (simple or exchange)
splenic sequestration
sudden enlargement of spleen due to trapping of sickled RBCs in spleen
splenic sequestration results in a drop in
hemoglobin
hematocrit
circulating blood volume
splenic sequestration can lead to
hypovolemia, shock and death
treatment for splenic seqestration
IV fluids
transfusion
splenectomy
antibiotics (if febrile)
aplastic crisis
acute decrease in hemoglobin with decreased reticulocyte count
suppression of RBC production due to infection
aplastic crisis from infection is most commonly caused by
parvovirus B19 infection
aplastic crisis management
supportive care – most resolve spontaneously
provide blood transfusions if severe/symptomatic anemia
