SCD

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Most common cause of death for people with SCD is infection

Early sign
Dactylitis
o Splenic sequestration
Acutely enlarged spleen
May require ED services
May require splenectomy
o Aplastic crisis
More common in children
Period of profound anemia often caused by infection
The already taxed RBC production is temporarily compromised
o Sickle Cell Crisis
Vaso-occlusive episode of pain
Can include infection, hypoxia, and dehydration
o Acute chest syndrome
Often caused by a vaso-occlusion
o Cerebrovascular events
Stroke, hemorrhage cerebral, cerebral microvascular disease
o Hemolysis-related issues
Leg ulcers, priapism, pulmonary artery hypertension, chronic
anemia
o Increased risk for infection
Splenic damage in SCD impairs organs ability to remove bacteria
from blood
SC disease
o More severe than sickle cell trait or HbC Trait
Sickle cell trait has SA so its better genetically
o RBC in the disease live longer than those in SCA
Live about 40 days ***
Regular live to about 120 days
o Still see acute chest syndrome but it occurs much later and is less
frequent
o Retinopathy is more common in this disease
Can cause visual loss
Increased cell density and viscosity which can cause more
retinopathy in the disease
o Avascular necrosis
Not enough bone tissue to keep up with the blood supply
Often shows up in the hips or shoulders
Sickle Cell trait
o Hetero are usually asymptomatic
Impact of fetal hemoglobin
o Primary in fetal Hb until birth
o Fetal Hb can delay the polymerization
Does not have the hydrophobic pocket
o Hydroxyurea

Stimulates the production of fetal Hb

B-Thalassemia
o Cause by ineffective erythropoiesis
o Not making enough RBC
o Cooleys anemia
Presents at a young age
Pale appearance
o In Major
Need regular transfusion
o Intermediate
Presents later
Transfusions are not normally required or as needed
Can also have iron overload
Due to increased intestinal absorption of iron
o Minor
Carrier state
Transfusions are not normally required
DDx
o Non-SCD related anemia
o Leukemia
o PE
o Septic arthritis
o Some connective tissue disease
DDx for B-Thalassemia
o Hemolytic anemia
o SCD
o Congenital dyserythropoietic anemia
SCD diagnosis
o Newborn screening
o Need to start prophylactic antibodies
o Positive IEF diagnostics
o Gene testing
Targeted mutational analysis
Sequence analysis
o Important to be accurate with Hb status
B-Thalassemia
o Gene testing is available
Can do primer PCR
o Sequence analysis
Management
o Once diagnosed you need to have pneumococcal vaccine and penicillin
prophylaxis
o Lifestyle approaches
Stay well hydrated
Avoid physical exertion
Avoid high elevation
Treatment

o Episodes of pain is opiods

o Acute chest syndrome will usually include transfusions
o Rapid treatment is advised
Management Pain episodes
o Episodes are difficult to predict
o Mild to moderate pain episodes
Stay at home and take oral pain medications
o More severe
Go to the ER
Get IV or IM pain medications
Might need to be hospitalized
Management ACS
o Main goal is to not allow the pt to go into acute respiratory failure
o Treatment is expedient
o Supplemental oxygen
o IV ABx is given if infection is suspected
o Frequent ACS shortens lifespan
Management of splenic sequestration
o Leading cause of death in children
o Sudden weakness
o Can be fatal if not treated quickly
o Immediate RBC transfusions are needed
Hopefully will remobilize trapped RBC in the spleen
o Survival of the episode can have reoccurrence
o Chronic transfusion therapy
Fetal Hb Management
o Disrupts polymerization of Hb S
o Hereditary persistence of fetal Hb
Point mutation can cause this
Increased production of fetal Hb throughout adulthood
Can have a deletion in gama and beta globin region
Hydroxyuria Management
o Leads to rapid erythropoiesis
o Leads to more hemoglobin F production
o Reduces vascular inflammation
o Do not know long term affects
Other drugs can promote HbF
o 5-azacytidine
Older drug
Inhibits gama globin methylation
o Butyrate derivatives
Inhibit HDAC (wants to remove acetyl group) which can maintain
an open chromosome structure
In a study, HbF was increased when this was given
Chronic RBC transfusion
o Goal is to maintain a HbS below 30%
o Possible iron overload

Stem cell transplant

o Usually performed in patients tha exhibit sever phenotype
Done through a sibling
o 80% survival
o No pain crisis afterwards
As well ass
Recovery of splenic function
Come chimerism but do not present symptoms from SCD
SCD and pregnancy
o Pregnancy is not contraindicated
Increased risk for preeclampsia, preterm delivery, intrauterine
growth, and retardation
Hydroxyurea must be stopped prior to contraception
Possible opiod withdrawl
Management of B-Thalassemia
o Transfusions
Careful of iron overload
o Use of chelation therapy
This is usually done after 10-12 transfusions
Desferal
Normally given over a span of 24 hours and through a
pump
o Bone marrow transplant
Disease free survival in children is about 90%
Found though if you have liver issues then your disease free
survival drops to 60%
o Option to use umbilical cord blood transplant
Gene therapy is possible for both
o Lentiviral mediated delivery
Integration of a random location could result in a region of
heterochromatin and become silenced
If this happens the silencing could be permanent or
transition to progeny
Attempts have been made to combat this event
Insulator element
Consider the size of the region youre repairing
SCA
Deliver the gama gene instead but the locus control
region is still needed
Correct the RNA but the need to manipulate splicing is
important
BsBs is Sickle cell anemia ***