NAPLEX: Blood Disorders - Sickle Cell Disease

sickle cell disease

group of inherited RBC disorders that results from a genetic mutation that encode Hgb → have RBC that contain abnormal hemoglobin (hemoglobin S) which causes RBC to be rigid with a concave "sickle" shape → RBC cannot transport O2 effectively + stick together → block smaller blood vessels → complications + RBC hemolyze after 10-20 days → anemia

when do sx of SCD develop

~2-3 mo after birth

acute sickle cell crises

Acute chest syndrome

Anemia

Cholescystitis (gallbladder infection)

Infection

Multiorgan failure (kidneys, liver, lung)

Priapism (painful and prolonged erection)

Splenic sequestration

Stroke

Vaso-occlusive crisis (acute pain crisis)

chronic sickle cell crises

Avascular necrosis (bone death)

Depression and stress

Gallstones

Leg ulcers

Pain

Pregnancy complications (including fetal death)

Pulmonary HTN

Recurrent priapism

Renal impairment

Retinopathy

females with SCD contraception practices

d/t risk of stroke avoid estrogen

use progestin only contraceptives, levonorgestrel intrauterine devices (IUD) and barrier methods as preferred methods of contraception

non drug treatment SCD

- blood transfusions

- bone marrow transplant

goal hgb level following blood transfusions

no higher than 10 g/dL

to prevent iron overload

SCD drug treatment

- immunizations + ppx abx

- chelation therapy: deferasirox, deferiprone

- analgesics

- disease modifying therapy: hydroxyurea, L-glutamine, voxelotor, crizanlizumab

routine childhood vaccinations for SCD

Haemophilus influenzae type B (Hib)

PCV15 or PCV20

additional vaccines for functional asplenia

MenACWY + routine boosters (Menveo, MenQuadfi)

Meningococcal serogroup B (Bexsero, Truenba) at age >10

Pneumococcal vaccines - if never received as a child give one of the following regimens at age >19

- PCV20 x1 or

- PCY15 x1 followed by PPSV23 >8 wks later

prophylactic abx for SCD

oral penicillin

Infants who screen positive for SCD at birth should be started on BID penicillin and treated until 5 y/o

Continue indefinitely if pt undergoes surgical removal of spleen or invasive pneumococcal infection develops despite ppx

hydroxyurea indications

all adults >1 moderate severe pain crises

peds patients age 9 mo - 18 y/o

hydroxyurea counseling

Contraception required during treatment and for 6-12 mo after discontinuation

Do not breastfeed during treatment

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

Folic acid supplementation is recommended to prevent macrocytosis

Clinical response can take 3-6 mo

hydroxyurea monitoring

CBC q2-4 wks during treatment initiation + titration, then q2-3 mo when stable dose is achieved

If toxicity (ANC <2000 cells/mm3, PLT <80,000 cells/mm3) hold until bone marrow recovers then restart dose at 2.5-5 mg/kg/day lower

HgbF

LFTs

Uric acid

Renal fxn

Baseline pregnancy test

how does L-glutamine (endari) help SCD

Reduces acute complications of SCD

has better safety profile than hydroxyurea

L-glutamine counseling (endari)

Mix each dose in 8 oz of a cold or room temperature beverage or 4-6 oz of food - drug does not need to completely dissolve before administration

how does voxelotor help SCD

Prevents RBC sickling

how does crizanlizumab (adakveo) help SCD

Reduces frequency of VOC

hydroxyurea warnings

- myelosuppression

- malignancy

- embryo fetal toxicity (contraception required; 12 mo for M, 6 mo for F after discontinuation)

- no live vaccines

hydroxyurea SE

photosensitivity

iron chelation treatment options

oral deferasirox

exjade

jadeno