Sickle cell

Question 1

Etiology of sickle cell

Answer 1

Valine substituted for glutamic acid at 6th position of beta globin chain, leading to decreased solubility, overwhelming RBC skeleton, leading to sickling

Question 2

hgb electrophoresis in sickle cell anemia

Answer 2

90% hgb SS
5% hgb A2
3-4% hgb F

Question 3

hgb electrophoresis in sickle cell trait

Answer 3

60% hgb A
40% hgb S
A2 normal
F normal

Question 4

Hgb SC electrophoresis

Answer 4

50% hgb S
0% hgb A
50% hgb C

Question 5

hgb SC specific clinical features

Answer 5

• ocular complications, *sickle cell retinopathy. They have a higher incidence of sickle cell retinopathy than HbSS
• osteonecrosis

Question 6

sickle b0 phenotype

Answer 6

very similar to hgb ss

Question 7

sickle b0 hgb electrophoresis

Answer 7

hgb s at 80%
A2 at 3%
*Just remember very little to no hgb A
hgb F at 17%

Question 8

sickle b+ hgb electrophoresis

Answer 8

hgb s at 80%
A 20%
A2 3%
hgb F at 17%

Question 9

complications sickle cell trait patients are at risk of

Answer 9

• hematuria
• renal papillary necrosis
• pyelo
• VTE during pregnancy
• hypothesthenuria (inability of the kidney to concentrate the urine normally)
• increased UTI’s in pregnancy
• renal medullary carcinoma
• risk of severe splenic infarction at high altitude

Question 10

Malignancy sickle cell patients are at higher risk of

Answer 10

Renal medullary carcinoma

Question 11

Sickle cell additional clinical complications

Answer 11

• developmental delay
• retinal vessel occlusion
• osteomyelitis
• leg ulcers
• biliary stones
• hepatic sequestration crises

Question 12

Encapsulated organisms sickle cell pts are at risk of

Answer 12

Please SHind ME Skis
Pseudomonas
Strep
H flu
Meningitis
E coli
Salmonella
Klebsiella
Group b strep

Question 13

Vaccinations sickle cell patients need

Answer 13

• Strep pneumonia
• H flu
• neisseria meningitis

Question 14

GU complications of sickle cell

Answer 14

• priapism
• renal medullary necrosis

Question 15

indications for exchange in sickle cell

Answer 15

*acute retinal artery occlusion
- CVA
- severe ACS

Question 16

How to reduce risk of alloimmunization in sickle cell patients

Answer 16

Extended red cell phenotyping (looking at kell antigens etc)

Question 17

presentation of splenic sequestration crises

Answer 17

• sudden drop in hgb (RBCs pool in spleen) + left upper quadrant pain + massive splenomegaly
  *can be in hypovolemic shock
  *Typically occurs in children <2. HOWEVER, adults who have milder forms (HbSC or HbS/b+ can happen because spleen is not auto-infarcted

Question 18

hyperhemolytic crisis presentation

Answer 18

• hematuria
• severe hemolysis in the setting of transfusion

Question 19

management of hyperhemolysis in sickle cell

Answer 19

*Suppress the antibody
- steroids
- IVIG
+/- rituxan
**Transfuse compatible blood, not exchange transfusion

Question 20

L glutamine evidence in SCD

Answer 20

• decreased frequency of pain crises

Question 21

crizanlizumab mechanism

Answer 21

antibody against P selectin, which prevents sickled RBC’s from adhering to vascular endothelium

Question 22

crizanlizumab clinical benefit

Answer 22

decreased frequency of pain crises

Question 23

voxelotor mechanism

Answer 23

oxygen-affinity modulator.[7] Voxelotor has been shown to have disease-modifying potential by increasing hemoglobin levels and decreasing hemolysis indicators
*So it’s a polymerization inhibitor

Question 24

voxelotor clinical benefit

Answer 24

Improved hgb, thus reducing transfusion requirements

Question 25

Howell-Jolly Body clinical significance

Answer 25

asplenia or significantly reduced splenic function

Question 26

How to differentiate hgb SS vs. Hgb Sbeta0

Answer 26

Hgb Sbeta0 will have low MCV (<70)

Question 27

Clinical features of hemoglobin S with persistence of fetal hemoglobin

Answer 27

- asymptomatic

Question 28

Management of SCD pt with recurrent ACS

Answer 28

Chronic transfusion

Question 29

1) How to screen for risk of CVA in kids with SCD 2) next steps

Answer 29

transcranial doppler IF abnormal, need regular transfusions to keep hgb S <30% *After 12 months can switch to maximally tolerated hydrea

Question 30

Goal hgb S with exchange in setting of CVA

Answer 30

<20%

Question 31

Regular screening for SCD

Answer 31

- MRI for silent CVA - TTE for pHTN ONLY if signs/symptoms suggestive of pHTN - annual albumin/creatinine ratio monitoring *IF albuminuria, ACEi - annual retinal exam for sickle cell retinopathy (need to see retinal specialist) - ferritin every 3 months for transfusional iron overload

Question 32

Management of splenic sequestration

Answer 32

- transfusion (unplugs the spleen) *1 unit at a time. By unplugging spleen, blood can gush out and lead to volume overload and hyperviscosity.

Question 33

Sickle cell intrahepatic cholestasis clinical features

Answer 33

- sickle cell occlusion in hepatic sinusoids - RUQ pain + very high bili + ALT can be in 1000s

Question 34

Sickle cell intrahepatic cholestasis management

Answer 34

Red cell exchange

Question 35

Renal papillary necrosis management

Answer 35

- hydration, urinary alkalization, relieve obstruction

Question 36

Presentation of orbital infarction in SCD

Answer 36

- protrusion of eye + eye pain + lid/orbital edema

Question 37

Management of orbital infarction in SCD

Answer 37

IV fluids, pain control, steroids

Question 38

acute aplastic crisis presentation

Answer 38

Rapid drop in hgb with reticulocytopenia

Question 39

Goal ferritin for SCD pts with transfusional iron overload

Answer 39

Less than 1000

Question 40

hydroxyurea counciling for patients

Answer 40

IF child-bearing age, pregnancy test before starting **contraception to avoid pregnancy Men → discuss low sperm count and mobility IF planning on conceiving, stop for 1-2 months IF pregnant, STOP

Question 41

L-glutamine mechanism of action in SCD

Answer 41

anti-oxidant which may increase availability of reduced glutathione, reducing susceptibility to oxidative stress

Question 42

Management of elective surgery in SCD

Answer 42

High risk surgery (prolonged surgery or prolonged impaired blood supply, hypothermia, pulmonary or cardiac disease): exchange transfusion Intermediate risk surgery: simple transfusion to target hgb 10 Low risk surgery no transfusions

Question 43

approved gene therapy products for SCD

Answer 43

- Lovotibeglogene autotemcel (lovo-cel) (gene addition using viral vector) - Exagamglogene autotemcel (exa-cel) (CRISPR gene edited)

Question 44

SE's/sequelae of gene therapy for SCD

Answer 44

Primarily related to busulfan conditioning - secondary malignancies from busulfan conditioning - loss of fertility from busulfan conditioning

Question 45

Management of priapism in SCD

Answer 45

- Emergent urology consult (exchange transfusion does not help in data, and urologists can do faster bedside interventions)

Question 46

Hgb S/alpha thal trait vs. hgb s trait

Answer 46

Hbs 25% with alpha thal trait vs 35% w/ hgb s disease (less alpha to pair with hgb s so reduces severity/phenotype of disease)