Case 1 Sickle Cell Anemia

Question 0

What genotype causes Sickle Cell Anemia?

Answer 0

HbSS

Question 1

What was the phenotype of the family?

Answer 1

one HbSA (father) - carrier
one HbAbeta+ (mother) - has thalassemia

Question 2

What genotypes cause Sickle Cell Disease?

Answer 2

HbSbeta+, HbSS and HbSC

Question 3

How prevalent is Sickle Cell Anemia?

Answer 3

> 90,000 Americans, 1/500 African American births have the disease

Question 4

What are appropriate tests for diagnosis?

Answer 4

Universal newborn screening with isoelectric focusing hemoglobin electrophoresis monitoring protein

• confirm results with DNA testing
• CBC (complete blood count) - looking for how many RBCs, WBCs and platelets- how much hemoglobin

Question 5

Hemoglobin electrophoresis. . .

Answer 5

looks at speed of hemoglobin protein movement - and uses different charge to separate the molecules

Question 6

When looking at a western blot (DNA test), what indicates sickle cell disease?

Answer 6

The presence of HbSS or HbC and HbS (Hb,something not A and HbS) - HgF level can indicate sickle cell trait

Question 7

Sensitivity

Answer 7

percentage of true positives/(true pos+false negatives=all positives), we want a high sensitivity percentage when doing diagnostic tests/SCREENING

Question 8

Specificity

Answer 8

true negatives, we want a high percentage of true negatives/(true negatives +false positives =all negatives)when doing confirmatory tests

Question 9

Thalassaemia

Answer 9

disorder of hemoglobin synthesis

Question 10

Sickle cell disease

Answer 10

disorder of hemoglobin structure

Question 11

Sickle cell anemia

Answer 11

HbSS, most common and severe of SCD

Question 12

HPFH

Answer 12

Hereditary persistence of fetal hemoglobin

Question 13

Transcranial Doppler

Answer 13

Used to screen for stroke/loss of brain function due to decrease in blood supply - also used to diagnose SCD

Question 14

Why might a patient with SCA be jaundiced?

Answer 14

Heme degradation product bilirubin accumulates during impaired liver funcion is associated with scleral yellowing– occlusion in the liver can cause a build up of bilirubin which can cause a yellowing of the skin

Question 15

Symptoms of Sickle Cell Anemia:

Answer 15

Hand-foot syndrome, stroke, osteonecrosis, retinopathy, acute chest syndrome, splenic/liver damage

Question 16

What does the spleen do?

Answer 16

Removes red blood cells and encapsulated organisms

Question 17

Genetics

Answer 17

Sickle cell disease is an autosomal recessive disorder

-sickle cell disease has at least one HbS + one other HbS or beta-thalassemia, or HbC variants of HBB gene

Question 18

Sickle beta thalessemia disease genotype

Answer 18

HbAbeta+

Question 19

Sickle cell anemia genotype

Answer 19

HbSS

Question 20

What sickle cell-related treatment has shown superior outcome in the acute management of stroke?

Answer 20

Blood transfusion (children with history of silent strokes identified by MRI and then given a blood transfusion every month to reduce stroke development – long term transfusion therapy can lead to oxidative damage and organ damage due to iron overload and the body’s inability to excrete it – transfusions can cause diabetes in long term due to organ damage

Question 21

Treatments

Answer 21

Penicillin to fight infections and sepsis & meningitis - Ibuprofen to decrease inflammation during crisis and swelling (also increasing hydration - inc blood volume) and increase oxygen to fight hypoxia

Question 22

What is used to treat acute chest syndrome?

Answer 22

Hydroxyurea - inhibits DNA synthesis, increases level of fetal hemoglobin, possibly through changes in microRNA expression - but its also carcinogenic and can cause a low white blood cell count

Question 23

Increasing beta sheets. . .

Answer 23

leads to self-association and the formation of amyloid fibers (prion disease and alzheimers)