sickle cell disease

background

RBCs have a lifespan of ~120 days

SCD is a group of inherited RBC disorders that most commonly affects the African American population

SCD results from a genetic mutation in the genes that encode hemoglobin

patients have RBCs that contain abnormal hemoglobin, called hemoglobin S --> this causes RBCs to be rigid with a concave "sickle" shape

sickled RBCs hemolyze after 10-20 days, which causes anemia

symptoms of SCD develop 2-3 months after birth --> this is because infants have fetal hemoglobin (HgbF), which blocks the sickling of RBCs

acute and chronic complications

vascular occlusion prevents oxygen from reaching the tissues, causing them to become ischemic --> can lead to different types of sickle cell crisis --> most common is vasoocclusive crisis (VOC), or acute pain crisis

if there is chest pain and evidence of a pulmonary infection, it is called acute chest syndrome

the most common chronic complication is chronic pain

acute SCD complications

acute chest syndrome

anemia

cholecystitis

infection

multiorgan failure

priapism

splenic sequestration

stroke

VOC

chronic SCD complications

avascular necrosis (bone death)

depression and stress

gallstones

leg ulcers

pain

pregnancy complications

pulmonary hypertension

recurrent priapism

renal impairment

retinopathy

infection risk

the spleen aids in immune function by clearing bacteria, particularly the encapsulated organisms --> S. pneumoniae, H. flu, and N. meningitidis

in SCD, the spleen becomes fibrotic and shrinks --> functional asplenia (absent spleen function)

patients with functional asplenia are at increased risk for severe infections --> require immunizations and prophylactic antibiotics

non-drug treatment

blood transfusions

goal Hgb level should be no higher than 10

a risk of transfusion is iron overload --> can use chelation therapy to remove excess iron

the only cure for SCD is bone marrow transplantation

drug treatment

immunizations and antibiotics to reduce infection risk

chelation therapy to manage iron overload

analgesics to control pain

hydroxyurea is the primary disease-modifying therapy for SCD

immunizations and antibiotics

sepsis and meningitis due to s. pneumoniae, H. flu, and N. meningitidis can occur --> vaccinations are essential

prophylactic oral penicillin reduces the risk of death from invasive pneumococcal infections --> infants who screen positive for SCD at birth should be initiated on twice daily penicillin and treated until 5 years old

key vaccines in SCD

routine childhood series -->

- HIB

- pneumococcal conjugate vaccine (PCV15 or PCV20)

additional vaccines for functional asplenia -->

- meningococcal ACWY

- meningococcal B (at age 10 or older)

- pneumococcal if not received as a child (at age 19 or older)

iron chelation treatment

used to treat iron overload from chronic blood transfusions

chelation therapy is used to remove excess iron

oral chelating drugs, such as defarasirox and deferiprone are commonly used

analgesics

patients with severe pain and VOC will require IV admin of opioids or patient-controlled analgesia (PCA)

hydroxyurea

stimulates the production of HbgF

indicated for all adults with 1 or more moderate-severe pain crisis

round doses to the nearest capsule size

hydroxyurea BBW

myelosuppression

hydroxyurea warnings

fetal toxicity

avoid live vaccines

hydroxyurea monitoring

CBC with differential

if toxicity occurs (ANC <2,000), hold hydroxyurea until bone marrow recovers

hydroxyurea notes

contraception required

hazardous drug --> wear gloves and wash hands before and after contact

folic acid supplementation

hydroxyurea drug interactions

additive risk of myelosuppression if used with other immunosuppressants

other drug options

L-glutamine --> reduces acute complications of SCD

voxelotor --> inhibits HgbS polymerization, which prevents RBC sickling

crizanlizumab --> reduces the frequency of VOC

hydroxyurea counseling points

anyone handling the medication should wear disposable gloves to reduce the risk of exposure

can cause infections

avoid in pregnancy

live vaccines must be avoided