Sickle Cell Disease - Dr. Smith

What is sickle cell disease?

A group of inherited blood disorders

What blood disorders are inherited in sickle cell disease?

Sickle cell anemia (most common)

Erythrocytes change into crescent/sickle shape

Sickle hemoglobin (HbS)

In healthy individuals beta-globin combines with alpha-globin to make a red blood cell. How does this differ in SC?

Beta-globins stick together and form long fibers

What is the lifespan of a RBC in SC?

10-20 days

What is the primary hemoglobin at gestation and birth?

HbF

In those without sickle cell disease, what replaces HbF?

HbA

What replaces HbF in SCD?

HbS

When should SCD neonatal screening occur?

Before 2 months old

Anemia usually appears how long after birth in those that are HbSS?

4-6 months

Is reticulocyte count elevated or decreased in SC?

Elevated

What is a common clinical feature seen with sickle cell disease?

Dactylitis (hand and foot syndrome)

Pain and swelling of the hands and feet

What are acute complication of SC? (7)

VOC

Acute chest syndrome

Splenic sequestration

Stroke

Priapism

Aplastic crisis

Cholelithiasis

What are chronic complications of SC? (7)

Chronic pain

Pulmonary HTN

Avascular HTN

Nephropathy

Hepatopathy

Cardiomyopathy

Depression

HbSS

Sickle cell anemia

HbSC

Sickle cell disease

HbAS

Sickle cell trait

T/F: Damaged RBCs contain abnormalities that lead to hemolytic anemia and block small blood vessels?

TRUE

Obstruction of blood flow to the spleen via SCD can result in what?

Functional asplenia and increased susceptibility to infection

Mean survival age of HbSS?

42-48 (males, females)

Mean survival age of HbSC?

60-68 (males, females)

SCD has increased morbidity d/t _______ _________.

Chronic manifestations

Goals of treatment in SC?

- Reduce/eliminate sxs

- Decrease sickle cell crisis

- Prevent development of complications

- Maintain/improve QoL

- Decrease hospitalizations/morbidity

- Improve mortality

What are the three general treatments for SC?

Prevention of infection

Blood transfusion

Hydroxyurea

How is Penicillin VK given for SC?

Twice daily at least until the age of 5

How are pneumococcal vaccines given in SC?

Every 5 years starting at age 2, lifelong

How is malaria prophylaxis used in SC?

Daily, weekly, or intermittent and lifelong in a malarious area

What is the frequency and duration of blood transfusions for treatment of anemia in SC?

Acute care/Simple transfusion (?), target Hgb 10, limited

What is the frequency and duration of blood transfusion for primary and secondary stroke prevention in SC?

Target HbS

What is hydroxyurea used for in SC?

Prevention of acute complications and primary stroke prevention

Frequency/dose/duration of hydroxyurea?

15-35mg/kg/day, indefinite

What is the dose of Penicillin VK for kids 2 mo - 3 y/o?

125 mg po BID

What is the dose of Pen VK in kids 3-5y?

250 mg po BID

What antibiotic to use if child is penicillin allergic?

Erythromycin

What bacteria needs to be covered by immunization in asplenia?

S. pneumo (pneumococcus)

H. flu (Hib)

N. meningititties (meningococcus)

What pneumococcal vaccines are used in SC?

Prevnar 15 or 20

Pneumovax (PPSV23)

What Hib vaccines to use?

Pentacel

PedavacHIB/COMVAX

Hiberix

What meningococcus vaccines are used in SC?

Menactra

Menveo

What baseline vaccines should be given in SC (with or without asplenia)?

yearly flu vaccine >6 mo

COVID-19

All recommended childhood vaccines

What do blood transfusion do to HbS?

LOWER (want

What are the risks of of blood transfusions?

limited availability of blood

iron overload

Tranfusion reactions

Alloimmunization

Hyperviscosity

Viral transmission

What is the range of onset for alloimunization?

usually 7-10d, can be 2-20d

How is alloimmunization treated?

steroids and IV immunoglobulin

What are indications for transfusions? (8)

Acute stroke

Acute bleeding

Acute chest syndrome (symptomatic)

Acute symptomatic anemia

Acute multi-organ failure

Prior to surgical procedures w/ gen anesthesia

Hepatic or splenic sequestration

Aplastic crisis

When is a transfusion NOT indicated?

Uncomplicated painful crisis

Priapism

Asymptomatic anemia

AKI w/o organ failure

When is chelation therapy needed?

Chronic iron overload

What are markers of iron overload?

Transfusion of packed RBCs PLUS serum ferritin consistently > 1000 mcg/L

How is deferasirox taken?

po daily

How is deferiprone taken?

po 2-3x daily

How is deferoxamine taken?

IV/SQ over 8-24hr 5-7 days/week

ADE of iron chelators?

GI, HA, back pain, infusion site rxn, visual changes, high frequency hearing loss

Drug interactions with iron chelators?

Aluminum-containing antacids

Counseling for iron chelators?

Pink, red, or orange colored urine

Take on an empty stomach (or w/ light meal like yogurt or applsauce)

What is the standard of care for pts >2 y/o?

Hydroxyurea

When to initiate hydroxyurea in adults?

> moderate to severe pain crisis during 12 month period

Pain or severe symptomatic chronic anemia that interferes with QoL

H/o severe or recurrent ACS

Pre-treatment labs for hydroxyurea?

CBC w/ diff, retic count, MCV

HbF quantitative measurement

Renal/Liver function tests

Pregnancy test

Adult dosing for hydroxyurea?

15 mg/kg/d - round to nearest 500

Pediatric dose for hydroxyurea?

20 mg/kg/d - round to nearest 50 or 100

How to titrate hydroxyurea?

5 mg/kg/d every 8 weeks to 35 mg/kg/d

ADEs of hydroxyurea?

Bone marrow suppression

Dry skin

Leg ulcerations

Hyperpigmentation of skin/nails

Rash

Counseling for hydroxyurea?

Use contraception

Skip dose if missed

Take for 6 months before discontinuing

Clinical response takes 3-6 months

MCV correlates with adherence

T/F: MCV levels are increased on hydroxyurea bc it interferes w/ DNA synthesis which leads to macrocytosis

TRUE

What is the only brand/formulation of L-glutamine that should be used in SCD?

Endari

Is L-glutamine helpful in a crisis?

NO

ADE of L-glutamine?

HA

Flatulence

Constipation

Abdominal pain

Back pain

Cough

Chest pain

Dosing for L-glutamine?

>65 kg = 15 gm PO BID

Administration of L-glutamine?

mix packet with 8 oz cold or room temp drink

Indication for L-glutamine?

Prevention/reduction of acute SCD complications

Indication for crizanlizumab?

Reduced frequency of VOC

Dosing for crizanlizumab?

5 mg/kg IV over 30 mins

0, 2, and 4 weeks thereafter

ADE of crizanlizumab?

Fever, chills, nausea, vomiting, fatigue, dizziness, pruritis, urticaria,, sweating, SOB/wheezing

How should an acute pain crisis be managed?

Nonopioids, opioids, supportive care

What type of supportive care is used in acute pain crisis?

Hydration

Oxygen

Heat compress

Oral antihistamine for itching

What labs should be monitored for acute pain crisis?

Hemoglobin, retic count, total bilirubin, lactose dehydrogenase, BMP

Should disease modifying therapy be initiated during a crisis?

NO

What causes VOC?

Muscle or bone infarction due to vaso-oclusion

T/F: In VOC, pain may localized or all over

TRUE

What is treatment for VOC?

Pain management and IV hydration

How should mild pain in VOC be treated?

•NSAIDs: ketorolac (Toradol) IV, ibuprofen (Motrin) PO

•Acetaminophen (Tylenol)

How should moderate pain in VOC be managed?

Opioids:

•Oxycodone (immediate release, CR) PO

•Hydrocodone/APAP PO

+/- NSAIDs

How should severe pain in VOC be managed?

Opioids

•Morphine PO or IV

•Hydromorphone (Dilaudid) PO or IV

•Patient controlled analgesia (PCA) IV

+/- NSAIDs

When a person with SCD has a fever and acute infection, what should be empirically covered?

•Pneumonia

•Osteomyelitis

•Meningitis

•Bacteremia

How is acute chest syndrome diagnosed?

•New infiltrate on chest x-ray

•Pulmonary edema

•Fever

•Cough

•Chest pain

•Oxygen saturation < 90%

•Increased work of breathing

•Wheezing

What are empiric antibiotic regimens for acute chest syndrome?

•Ceftriaxone + azithromycin

•Moxifloxacin

What are supportive treatments for acute chest syndrome?

•Bronchodilators

•Pain management

•IV hydration

•Oxygen

•Incentive spirometry

•Transfusions if Hgb < 9 gm/dL

How is an aplastic crisis managed?

Trasnfusions

How is splenic sequestration managed?

Transfusions, hydration, splenectomy (immunizations)