36. Sickle Cell Disease

Question 1

RBCs have a lifespan of ___. Sickled RBCs hemolyze after ____, which causes anemia and fatigue.

Answer 1

90-120 days
10-20 days

Question 2

Sickle cell disease (SCD) is a group of inherited RBCs disorders that most commonly affects the ____ population

Answer 2

African American

Question 3

What is the most common type of sickle cell crisis?

Answer 3

Vaso-occlusive crisis (VOC) or acute pain crisis

Question 4

If pain is in the chest and there is evidence of pulmonary infection in a sickle cell pt, it is called ____ (life-threatening and leading cause of death in SCD)

Answer 4

acute chest syndrome

Question 5

D/t risk of acute stroke, females with sickle cell disease should not use ____

Answer 5

Estrogen
Preferred contraceptives: progestin-only contraceptives, IUDs, and barrier methods

Question 6

What are the most common chronic complications of SCD?

Answer 6

Pulmonary HTN
Chronic pain
Avascular necrosis (bone death)
Renal impairments

Question 7

A healthy spleen has several physiologic roles, including the removal of old or damaged RBCs. It aids in immune function making and storing WBCs and clearing some types of bacterial pathogens (particularly encapsulated organisms such as ___, ___, and ___)

Answer 7

Streptococcus pneumoniae
Haemophilus influenzae
Neisseria meningitidis

Question 8

In SCD, what happens to the spleen?

Answer 8

Spleen becomes fibrotic and shrinks in size d/t repetitive sickling and infarctions
Causes functional asplenia (decreased or absent spleen function), typically within first year of life&raquo_space; increased risk for serious infections (require immunizations and ppx abx)

Question 9

____ protect against many of the life-threatening complications of SCD by providing RBCs with HgbA

Answer 9

blood transfusions

Question 10

When administering chronic (monthly) blood transfusions in SCD pts, the goal Hgb should be no higher than ____

Answer 10

Hgb 10g/dL

Question 11

One of the risks of blood transfusions is ___ which can lead to hemosiderosis

Answer 11

iron overload
Hemosiderosis = excess iron that impairs organ function

Question 12

The only cur for SCD is ___

Answer 12

bone marrow transplantation

Question 13

____ is the primary disease-modifying thearpy for SCD

Answer 13

Hydroxyurea

Question 14

____ (given orally) reduces risk of death from invasive pneumococcal infection in young children with SCD

Answer 14

Ppx penicillin

Question 15

Infants who screen positive for SCD at birth should be initiated on ___ given ___ daily and treated until age ___ (unless surgical removal of spleen or if invasive pneumococcal infection develops despite ppx abx&raquo_space; use ppx abx indefinitely)

Answer 15

penicillin, twice daily
treat until age 5yo

Question 16

Key vaccines in SCD

Answer 16

Routine childhood series
- Hib (H. influenzae type B)
- Pneumococcal (PCV13 (Prevnar 13) or PCV15 (Vaxneuvance)

Additional Vaccines for Functional Asplenia
- Meningococcal conjugate series + routine boosters
- Meningococcal serogroup B (Bexsero, Trumenba)
- Pneumococcal vaccines (Prevnar 20 x1 OR Vaxneuvance (PCV15) x1 + Pneumovax 23 (PPSV23) ≥ 8 weeks later)

Question 17

SCD pts with severe pain and VOC will require IV administration of ____ for analgesia

Answer 17

opioids or patient-controlled analgesia (PCA)

Question 18

____ is a disease-modifying drug that stimulates production of ____ in SCD pts

Answer 18

Hydroxyurea
HgbF

Question 19

Indication of hydroxyurea in select SCD pts

Answer 19

Adults with ≥3 moderate-to-severe pain crises in 1 year

Others: pts with severe or recurrent acute chest syndrome, chronic symptomatic anemia or disability
Consider in all children > 9 mo of age regardless of disease severity

Question 20

Boxed warning for hydroxyurea

Answer 20

Myelosuppression (Decreased WBC, platelets), malignancy (leukemia, skin cancer)

Question 21

Warnings for hydroxyurea

Answer 21

Fetal toxicity, avoid live vaccinations

Others: skin ulcers, macrocytosis, pulmonary toxicity
increased risk of pancreatitis, hepatotoxicity, and peripheral neuropathy when used with antiretroviral drugs

Question 22

Monitoring for hydroxyurea

Answer 22

CBC with differential every 2-4 weeks during treatment initiation and titration, then 2-3 months once stable
Hold if ANC < 2,000 or platelets <80,000 until bone marrow recovers

Question 23

Dosing for hydroxyurea

Answer 23

Weight based (IBW or TBW, whichever is less)&raquo_space; round doses up to nearest capsule size

Question 24

If a pt is on hydroxyurea, contraception is required during treatment and after d/c (____ for females, and ___ for males)

Answer 24

6 months for females
12 months for males

Question 25

Notes for Handling Hydroxyurea

Answer 25

Hazardous drug - wear gloves when dispensing and wash hands before and after contact

Question 26

____ supplementation is recommended to prevent macrocytosis for pts on hydroxyurea

Answer 26

Folic acid supplementation

Question 27

Hydroxyurea can cause myelosuppression. What are some drugs that can cause myelosuppression to avoid when on hydroxyurea?

Answer 27

Pimecrolimus, tacrolimus (topical)
Clozapine, deferipone, leflunomide, natalizumab, tofacitinib

Question 28

Voxelotor (Oxbryta) is the first FDA-approved drug that works by _____ which is the cause of SCD (approved for pts ≥4 yo with SCD with or without hydroxyurea)

Answer 28

Inhibiting HgbS polymerization

Question 29

Chronic blood transfusions can cause iron overload. ___ is used to remove excess iron.

Answer 29

Chelation therapy

Question 30

Historically ____ (antidote for iron toxicity) was used as chelation therapy for iron overload but it has significant toxicities, not available in PO formulation, and requires long infusions (>8-12 hrs).
Oral chelating drugs such as ___ and ___ are now more commonly used.

Answer 30

Deferoxamine (antidote for iron toxicity)
Deferasirox (Exjade, Jadenu)
Deferiprone (Ferriprox)