Sickle cell Flashcards
Etiology of sickle cell
Valine substituted for glutamic acid at 6th position of beta globin chain, leading to decreased solubility, overwhelming RBC skeleton, leading to sickling
hgb electrophoresis in sickle cell anemia
90% hgb SS
5% hgb A2
3-4% hgb F
hgb electrophoresis in sickle cell trait
60% hgb A
40% hgb S
A2 normal
F normal
Hgb SC electrophoresis
50% hgb S
0% hgb A
50% hgb C
hgb SC specific clinical features
- ocular complications, *sickle cell retinopathy. They have a higher incidence of sickle cell retinopathy than HbSS
- osteonecrosis
sickle b0 phenotype
very similar to hgb ss
sickle b0 hgb electrophoresis
hgb s at 80%
A2 at 3%
*Just remember very little to no hgb A
hgb F at 17%
sickle b+ hgb electrophoresis
hgb s at 80%
A 20%
A2 3%
hgb F at 17%
complications sickle cell trait patients are at risk of
- 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
Malignancy sickle cell patients are at higher risk of
Renal medullary carcinoma
Sickle cell additional clinical complications
- developmental delay
- retinal vessel occlusion
- osteomyelitis
- leg ulcers
- biliary stones
- hepatic sequestration crises
Encapsulated organisms sickle cell pts are at risk of
Please SHind ME Skis
Pseudomonas
Strep
H flu
Meningitis
E coli
Salmonella
Klebsiella
Group b strep
Vaccinations sickle cell patients need
- Strep pneumonia
- H flu
- neisseria meningitis
GU complications of sickle cell
- priapism
- renal medullary necrosis
indications for exchange in sickle cell
*acute retinal artery occlusion
- CVA
- severe ACS
How to reduce risk of alloimmunization in sickle cell patients
Extended red cell phenotyping (looking at kell antigens etc)
presentation of splenic sequestration crises
- 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
hyperhemolytic crisis presentation
- hematuria
- severe hemolysis in the setting of transfusion
management of hyperhemolysis in sickle cell
*Suppress the antibody
- steroids
- IVIG
+/- rituxan
**Transfuse compatible blood, not exchange transfusion
L glutamine evidence in SCD
- decreased frequency of pain crises
crizanlizumab mechanism
antibody against P selectin, which prevents sickled RBC’s from adhering to vascular endothelium
crizanlizumab clinical benefit
decreased frequency of pain crises
voxelotor mechanism
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
voxelotor clinical benefit
Improved hgb, thus reducing transfusion requirements
Howell-Jolly Body clinical significance
asplenia or significantly reduced splenic function
How to differentiate hgb SS vs. Hgb Sbeta0
Hgb Sbeta0 will have low MCV (<70)
Clinical features of hemoglobin S with persistence of fetal hemoglobin
- asymptomatic
Management of SCD pt with recurrent ACS
Chronic transfusion
1) How to screen for risk of CVA in kids with SCD 2) next steps
transcranial doppler
IF abnormal, need regular transfusions to keep hgb S <30%
*After 12 months can switch to maximally tolerated hydrea
Goal hgb S with exchange in setting of CVA
<20%
Regular screening for SCD
- 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
Management of splenic sequestration
- transfusion (unplugs the spleen)
*1 unit at a time. By unplugging spleen, blood can gush out and lead to volume overload and hyperviscosity.
Sickle cell intrahepatic cholestasis clinical features
- sickle cell occlusion in hepatic sinusoids
- RUQ pain + very high bili + ALT can be in 1000s
Sickle cell intrahepatic cholestasis management
Red cell exchange
Renal papillary necrosis management
- hydration, urinary alkalization, relieve obstruction
Presentation of orbital infarction in SCD
- protrusion of eye + eye pain + lid/orbital edema
Management of orbital infarction in SCD
IV fluids, pain control, steroids
acute aplastic crisis presentation
Rapid drop in hgb with reticulocytopenia
Goal ferritin for SCD pts with transfusional iron overload
Less than 1000
hydroxyurea counciling for patients
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
L-glutamine mechanism of action in SCD
anti-oxidant which may increase availability of reduced glutathione, reducing susceptibility to oxidative stress
Management of elective surgery in SCD
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
approved gene therapy products for SCD
- Lovotibeglogene autotemcel (lovo-cel) (gene addition using viral vector)
- Exagamglogene autotemcel (exa-cel) (CRISPR gene edited)
SE’s/sequelae of gene therapy for SCD
Primarily related to busulfan conditioning
- secondary malignancies from busulfan conditioning
- loss of fertility from busulfan conditioning
Management of priapism in SCD
- Emergent urology consult (exchange transfusion does not help in data, and urologists can do faster bedside interventions)
Hgb S/alpha thal trait vs. hgb s trait
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)
