"Molecular & Cellular Princ Med CC: Sickle Cell Disease II Richard Sills" GABY

Question 1

What is the primary cause of polymerization of hemoglobin S?

Answer 1

Deoxygenation

Question 2

What are the consequences of Hb S polymerization?

Answer 2

Increased RBC destruction & anemia

Blockage of capillaries causing pain &/or organ dysfunction

Question 3

What can fever, acidosis, and dehydration increase in a patient with hemoglobin S?

Answer 3

The rate and amount of sickling

Question 4

Sickled erythrocytes can cause capillary obstruction leading to localized tissue hypoxia, ___ and possible organ dysfunction

Answer 4

pain

Question 5

Why can SCD be considered the most common life-threatening genetic disorder in the African-American population?

Answer 5

Because its incidence is very high –> 1/400

Question 6

What is one of the biggest challenges when providing appropriate therapy for SCD?

Answer 6

The inability to accurately identify patients destined to have more severe disease

Question 7

Is there great variation in severity in SCD?

Answer 7

YES

Question 8

Why is newborn screening so important for detection of SCD?

Answer 8

It reduces morbidity and mortality by allowing us to recognize & treat complications, especially bacterial septicemia & splenic sequestration crisis, which would often otherwise go unrecognized until it is too late

Question 9

Hemoglobin C and hemoglobin S are distinct mutations of the ___ amino acid on the beta chain of hemoglobin

Answer 9

6th

Question 10

Can patients know they carry AS genes (sickle cell trait) without being tested?

Answer 10

Most likely NO

AS is rarely associated with clinical manifestations

Question 11

Is SC disease usually a milder form of the disease?

Answer 11

YES, but not always

Question 12

What variations exist of the sickle beta thalassemia?

Answer 12

1. sickle beta0 thalassemia
   - very severe
   - no HgA produced
2. sickle beta+ thalassemia
   - much milder
   - some HgA produced

Question 13

Why is urgent administration of appropriate intravenous antibiotics crucial in the management of fever in children with SCD?

Answer 13

Fever is the first sign of sepsis in these children

Question 14

What is the most common complication throughout the life of a SCD patient?

Answer 14

Painful unpredictable vaso-occlusive episodes

Question 15

What is the hand foot syndrome often seen in 1st and 2nd yrs of life of children with SCD?

Answer 15

Painful swelling often both hands and feet

Question 16

Are stroke part of the clinical presentations of SCD patients?

Answer 16

YES

In children these are strokes due to blocking of arterial vessels (thrombotic strokes), while in adults, strokes due to hemorrhage are also seen

Question 17

What does the term acute chest syndrome refer to?

Answer 17

Unique term for acute lung disease in sickle cell disease because difficulty to determine cause

Question 18

Acute Splenic Sequestration Crisis

Answer 18

■ Sudden enlargement of the spleen due to acute vaso-occlusion
■ Occurs in 1st 5 years of life & can rapidly result in hypovolemic shock
■ Acute treatment involves fluid resuscitation & transfusion
■ Teaching parents splenic palpation reduces mortality
■ Just make sure you listen to the family

Question 19

What therapy is available for SCD patients?

Answer 19

1. Mainly supportive
   hydration, pain Rx, oxygenation, RBCs transfusions
2. Specific
   hydroxyurea –> can effectively reduce the incidence of complications, but not enough information how to use it in all patients

Question 20

Why is bone marrow transplant only a potential cure?

Answer 20

It has substantial morbidity & mortality which limits its use to patients with more severe complications

Question 21

A 7 year old boy with homozygous sickle cell anemia was fine until this morning when he could not get out of the bathtub himself. His mother noticed weakness of his left arm and leg and that his face looked funny.
You should:
◆ See the child in clinic the next day
◆ Have the mother observe the child for 2 hours for
improvement
◆ Bring the child in for hydroxyurea
◆ Do a RBC exchange transfusion

Answer 21

The child is likely having a stroke. The correct response is to do a red blood cell exchange which should be done urgently to prevent further damage. This is an emergency. Hydroxyurea can help prevent strokes but is NOT acute management.

Question 22

The mother of a 4 year old with sickle cell disease wants information concerning possible bone marrow transplantation. The child has had no serious complications. There are 2 half siblings. You should:
◆ Do HLA testing on the half sibs & patient HLA test the sibs, parents & patient
◆ Tell her a bone marrow transplant is impossible
◆ Ask whether she is planning to become pregnant again

Answer 22

The answer is to determine if mom is planning to become pregnant since the half-siblings are very unlikely to be appropriate donors. However, a future newborn if born to the same parents has a 25% chance of being the best donor: an HLA identical sibling’s umbilical cord blood (assuming the sibling does not have SCD)

Question 23

■ A 37 year old man with SS disease was well until this morning when he developed fever of 102 and began to have some difficulty breathing
■ T 101.8, RR 65, PR 150, O2 saturation 84%
■ After placing him in 2 L nasal cannula O2,
the saturation increases to 88%
■ What do you do?

Answer 23

With a decreasing arterial oxygen saturation (Normal > 96%), this patient needs supportive care (supplemental oxygen, antibiotics, incentive spirometry) but also needs red cell transfusion support to try to prevent further pulmonary damage.

Question 24

■ A 32 year old woman with hemoglobin SC disease comes to the ER complaining of severe and diffuse pain in both lower extremities
■ She has a history of possibly abusing narcotics in the past
■ You find no abnormalities on exam except that she appears uncomfortable
■ What do you do?

Answer 24

Even with concern about narcotic abuse, you need to initially provide narcotics for severe pain. You cannot chance leaving real pain untreated. It is better to give appropriate pain medication and then observe the patient and more accurately assess how to proceed with additional pain medication.

Question 25

■ A 37 year old woman with sickle cell anemia presents to you in the ER with excruciating chest and abdominal pain. You give 10 mg of morphine IV and she has minimal relief after 15 minutes:
■ What do you do?
◆ Wait 15 min to reach peak morphine effect
◆ Wait because of concern of ↓ respiratory effort due to morphine
◆ Give acetaminophen
◆ Give more morphine
◆ Give ibuprofen

Answer 25

This is a difficult situation the reality is that you do what is basic for a physician – relieve pain. If the first dose was appropriate, carefully but surely provide more while carefully assessing the patient. We more often see inadequate pain relief causing problems as opposed to morphine induced respiratory depression.