sickle cell anemia

Question 1

sickle cell disease

1. inheritance
2. caused
3. aa substitution

Answer 1

1. A- co-dominant
2. caused by a single base pair substitution in the Beta-globin gene
3. glutamic acid to valine substitution

Question 2

variant hemoglobin, meaning the
mutation imparts a biochemical change in
the hemoglobin molecule.

Answer 2

HbS

Question 3

heterozygous inheritance or sickle trait

Answer 3

Hb AS

Question 4

homozygous inheritance; severe disease

Answer 4

Hb SS

Question 5

most benign of the sickle diseases

Answer 5

sickle cell trait

Question 6

sickle cell trait:

1. HbA:HbS ratio is
2. trait is for
3. risks
4. primary clinical impact
5. common in

Answer 6

1. 60:40
2. protects cells from assuming the sickle shape
3. no anemia but risk of splenic infarction at high altitude and death with extreme dehydration/hyperthermia
4. primary clinical impact is around child-bearing
5. common in African-americand and less in hispanic americans

Question 7

sickle cell disease includes

Answer 7

1. Hb SS
2. Hb Sc
3. sickle thalassemia

Question 8

disease modifiers for sickle cell disease

Answer 8

1. tissue oxygenation status
2. pH
3. HbF levels
4. co-inheritance of other hb gene abnormalities

Question 9

Heterozygous inheritance of hemoglobin S offers some protection against

Answer 9

malaria

Question 10

what leads to polymerization of HbS

Answer 10

RBC deoxygenation

Question 11

HbS polymers have increased or decreased solubility

Answer 11

decreased

Question 12

what can increase HbS

Answer 12

cellular dehydration

Question 13

what happens when RBC become sickle

Answer 13

sickle RBC adhere to the vascular endothelium leading to an activation of coagulation and cytokines cascades leading to increased blood viscosity, entraptment of RBC and leading to vaso-occlusion and pain

Question 14

Hemoglobin S polymers are unstable leading to _________ (both intra- and extra-vascular).

Answer 14

red cell hemolysis

Question 15

due to the sickle survival shortened life to 10-16 days what happens to the bone marrow?

Answer 15

marrow erythropoiesis cannot fully compensate in severe hemolysis leading to anemia.

Question 16

sickle disease the Hb is -_______ and the WBC/platelets are _____

Answer 16

sickle disease the Hb is decreased and the WBC/platelets are normal/elevated

Question 17

MCV in HbSS

Answer 17

normal to low-normal

Question 18

MCV in sickle thalassemia

Answer 18

low

Question 19

MCV in HbSC

Answer 19

low

Question 20

_____ HbS is insoluble in presence of a concentrated phosphate buffer solution and forms a turbid suspension

Answer 20

Deoxygenated

Question 21

Sickle solubility test is positive in all sickle conditions but is unable to distinguish between the various genotypes (thus used as a screening test)

Answer 21

yep

Question 22

Hb electrophoresis on cellulose acetate

1. HbS
2. HbC

Answer 22

1. HbS migrates more slowly than nl hb and fetal hb but migrates in smae position as Hb variants, HbD and HbG
2. HbC migrates more slowly and in the same position as HbA2 and HbE

Question 23

citrates Agar (pH)

1. S separated from
2. C separated from

Answer 23

1. D and G

2. A2 and E

Question 24

HbS by HPLC

Answer 24

has a distinct retention time

Question 25

sickle cell complications

Answer 25

multi organ disease ** pregnancy- perilous high morbidity and mortality

Question 26

erythroid aplasia, often due to parvovirus B19 infection

Answer 26

aplastic crisis

Question 27

pooling of erythrocytes in the | spleen with acute splenomegaly and shock-like state

Answer 27

sequestration crisis

Question 28

marked red cell hemolysis

Answer 28

hemolytic crisis

Question 29

acute pain exacerbations | obstruction of microcirculation with painful tissue hypoxia and microinfarction primarily of bones

Answer 29

Acute pain (vasoocclusive) crisis:

Question 30

chronic sickle cell complications (6)

Answer 30

1. chronic hemolytic anemia 2. pain syndrome 3. skin- leg ulcers 4. endocrinopathies- Growth retard 5. Bone disease- acute dactylitis 6. ocular

Question 31

often the first symptom of SCD in babies

Answer 31

acute dactylitis Presents between 6-18 months as HbF levels decrease Uncommon once hematopoiesis shifts to axial skeleton (≈ age 6)

Question 32

Most common lung complication in sickle disease and Most frequent cause of death in adults

Answer 32

acute chest syndrome

Question 33

Acute chest syndrome 1. onset 2. defined by 3. repeat episodes lead to

Answer 33

1. Onset insidious or rapid and fulminant evolving out of a pain crisis 2. defined by new: - pulmonary infiltrate - pleuritic chest pain - - fever >38.5 - dyspnea, tachypnea, wheezing, cough 3. repeat episodes lead to pulmonary HTN and right sided heart failure (cor pulmonale)

Question 34

obliterative vasculopathy, with severe intimal hyperplasia, | fibrosis, and thrombosis

Answer 34

pulmonary HTN

Question 35

Joint space narrowing, erosion of acetabular plate --> | chronic pain, can require joint replacement

Answer 35

avascular necrosis

Question 36

Chronic hemolysis predisposes to leg ulcerations. | Very challenging to treat: hyperbaric oxygen, skin grafting

Answer 36

yep

Question 37

Free Hb is a potent inhibitor of all_____ → EC dysfunction & NO resistance

Answer 37

NO bioactivity

Question 38

Proliferative retinopathy similar to diabetic eye disease | Vitreous hemorrhage can lead to retinal detachment and blindness

Answer 38

sickle retinopathy

Question 39

Narrowing or occlusion of medium and large | cerebral arteries

Answer 39

CNS Vasculopathy & Stroke in SCD

Question 40

A leading cause of death in | children and adults with SCD

Answer 40

stroke

Question 41

which sickle type has the highest risk in developing stroke

Answer 41

HbSS

Question 42

Pathogenesis of stroke (2)

Answer 42

1. ischemic infarcts | 2. hemorrhagic stroke

Question 43

progressive vasculopathy arising from neo-vascularization to establish collateral flow because of large vessel occlusion (high incidence in Asians; “puff of smoke”)

Answer 43

moyamoya

Question 44

in adults over age 29; related | to the formation of moyamoya* vessels in the brain

Answer 44

hemorrhagic stroke SCD

Question 45

in children aged 2 - 9 years with | second peak in adults over 29 years

Answer 45

ischemic infarct SCD

Question 46

disease modifying therapy for sickle disease

Answer 46

hydroxyurea

Question 47

hydroxyurea mechanism

Answer 47

increases HbF production

Question 48

future managment of sickle disease

Answer 48

1. bone marrow transplantation | 2. L-glutamine to reduce intracellular oxidant stress and thus reducing pain crises

Question 49

treatment for sickle cell

Answer 49

treat some of the complications such as pain crisis, acute chest syndrome, ischemic stroke risk, intracranial hemorrhage

Question 50

red cell transfusion in SCD leads to

Answer 50

iron overload

Question 51

preventive car and health maintenance (3)

Answer 51

1. folic acid- chronic anemia 2. penicillin 3. health maintenance