Sickle Cell Disease

Question 1

For SCD what is the genotype and associated electrophoresis results?

Answer 1

SS-due to glutamic acid to valine change
Electrohphoresis-HbS>90%, HbA-0

Question 2

For SC disease what does electrophoresis show and what is the symptom severity?

Answer 2

They will have 50% of Sickle hemoglobin and 50% of C hemoglobin. Due to glutamic acid to lysine change. They have mild anemia compared to SS dx and predominantly vasocclusive symptoms.

Question 3

What is the electrophoresis for S beta null disease and what is the symptom severity? What is the MCV?

Answer 3

There will be 90% of Hb S and 0 of HbA. They have severe anemia with a very LOW MCV. They have severe hemolytic anemia and vaso-occlusive dx.

Question 4

What is the electrophoresis for SB+ dx? What is the symptom severity?

Answer 4

They have about 75% HbS and 25% HbA. They mild/moderate anemia. Mostly have vaso-occlusive symptoms.

Question 5

For sickle cell trait what is the electrophoresis and what is the symptom severity? What complications can they experience?

Answer 5

They should have more HbA (60%) compared to HbS (40%). They should have normal hemoglobin and MCV. They can have renal/thrombotic complications.

Question 6

For patients with sickle cell disease with alpha thalssemia what effect does this have on their symptoms and why?

Answer 6

Because this causes less hemoglobin, there is less polymerization which in turn lessens the hemolysis.

Question 7

In those SCD patients with persistence of fetal hemoglobin what effect does this have?

Answer 7

If they have a HbF greater than 20% they have less vaso-occlusive crises. HbF>10% also decreases CVA and AVN.

Question 8

What are the clinical signs of aplastic crisis in sickle cell disease? What should you suspect and what is the tx?

Answer 8

They have a very low reticulocyte count. This is concerning for parvovirus. You treat with IVIG and simple transfusion. Send for IgM and PCR.

Question 9

What are the clinical features to suggest hyperhemolytic syndrome if they received a prior transfusion? What is the time line of symptoms?

Answer 9

Here you will see the typical hemolysis labs, however the reticulocyte will be significantly low. The DAT will be positive. Typically they received a transfusion 2-14 days prior.

Question 10

What is the tx of hyperhemolytic syndrome from transfusion?

Answer 10

IVIG, steroids, Ritxuimab. For severe episodes you can consider giving extended match red cell txn in addition or red cell exchange.

Question 11

What are the clinical features seen with hyperhemolytic syndrome that is non immune mediated (not related to a transfusion)?

Answer 11

All of the hemolysis markers will be positive, in this case the reticulocyte count will be elevated. It is a TMA like process-you can get severe organ dysfunction. The DAT most of the time is negative.

Question 12

What is the treatment of non immune mediated hyperhemolytic syndrome?

Answer 12

You do a red cell exchange. I’m GW lecture he says you can also consider Plasma Exchange if red cell exchange not working.

Question 13

What are the clinical features of hepatic sequestration?

Answer 13

RUQ pain, sudden increase in hepatomegaly w/concomitant drop (2g or more) in Hgb, transaminitis (particularly ALT), liver failure, elevated conjugated bilirubin. Look for low platelets.

Question 14

What is the treatment of hepatic sequestration?

Answer 14

Exchange or simple transfusion

Question 15

What are the clinical features of splenic sequestration? In adults what type of sickle cell does this occur in?

Answer 15

LUQ pain with splenomegaly and thrombocytopenia. It occurs in SC and SB+ disease.

Question 16

How do you treat splenic sequestration?

Answer 16

Really with red cell exchange. You can give a simple transfusion to start. Also have the option of splenectomy

Question 17

What are the clinical features of intra-hepatic cholestasis? What is the tx?

Answer 17

Very high direct bilirubin (greater than 50% of total bilirubin), elevated PT/PTT (bleeding), renal dysfunction, encephalopathy. You give a red cell exchange.

Question 18

What is the treatment for mild-mod acute chest vs severe acute chest?

Answer 18

Mild-Mod: simple transfusion
Severe-exchange txn

Question 19

In pediatric patients with SCD what is primary prevention for CVA.

Answer 19

They get screened with transcranial doppler yearly. If it is high they go on chronic transfusion programs. Reduces risk by over 90%

Question 20

In adult patients with SCD when they are diagnosed with stroke, what is the best next step?

Answer 20

They should be implemented on a chronic transfusion program to keep Hb s<30% and maintain Hb of 10 or higher.

Question 21

If CT head is negative for CVA in a patient presenting with neurological symptoms what study should be ordered next?

Answer 21

MRA/MRV, MRV to rule out cerebral sinus venous thrombosis.

Question 22

What is the tx for CVA in SCD?

Answer 22

Exchange transfusion to maintain Hb>10, Hb S< 30%, and O2 sat>95%.

Question 23

What is the recommendation regarding screening for PAH in SCD?

Answer 23

Only screen patients with TTE who are symptomatic: chest pain, dyspnea, hypoxia, sleep disordered breathing, syncope/presyncope, loud P2

Question 24

For patients with SCD that are found to have albumuniria what is the recommendation per ASH guidelines? How often do you screen for this?

Answer 24

Start a low dose ACE/ARB. Yearly starting at age 10. If positive you check every 3 months.

Question 25

How is priapism managed for events that are less than 3 hours (stuttering priapism)?

Answer 25

Any event lasting over 1 hour requires urological eval. First you want to start IV fluids. For events less than 3 hours you do pseudo-ephedrine.

Question 26

What type of priapism should you consider if the event last for over 4 hours and what is the management?

Answer 26

Remember all patients should be started on IV fluids right away! For over 4 hours you think ischemic priapism and you have to treat with cavernous aspiration +/- irrigation.

Question 27

When should you consider starting iron chelation therapy in SCD? What is the goal ferritin?

Answer 27

With a ferritin greater than 1000. Less than 500.

Question 28

What adhesion molecule does Crizanlizumab target?

Answer 28

P-selectin.

Question 29

So currently the three agents that help reduce VOC in SCD are?

Answer 29

Hydrea, L-glutamine, and Crizanlizumab.

Question 30

How does Voexelotor work? What is the main clinical effect?

Answer 30

It binds to the alpha globin chain to stabilize the oxygenation state to prevent polymerization. It increase the hemoglobin usually by 1g/dl.

Question 31

What is the mechanism of Hydrea?

Answer 31

It inhibits RNA reductase

Question 32

What is the vaccine recommendation for Pneumococcal vaccination?

Answer 32

PPV-23: At least 2 doses 5 years apart, and then every 5 years thereafter. If only two doses were given, then third dose given @ age 65.
PCV 13-one lifetime dose age 18 or after

Question 33

What is the recommendation for Meningiococcal vaccination?

Answer 33

Quadrivalent conjugate vaccine for at least 2 doses followed by booster ever 5 years. Patients will also need serogroup B vaccine.

Question 34

What are the clinical features of acute hepatic sickle crisis? What is the tx?

Answer 34

There will be elevations in ALT/AST. The bilirubin is usually normal or mildly elevated. PT/PTT are normal. No coagulopathy or organ failure. Tx-hydration, pain management.