Sickle Cell Anemia

Question 1

What is SCA?

Answer 1

Sickle cell anemia is an autosomal recessive genetic disorder caused by a mutation in the HBB gene, which provides instructions for making beta-globin, a subunit of hemoglobin. The specific mutation results in the substitution of a single amino acid (valine for glutamic acid) in the beta-globin chain.

Question 2

How does Hb get polymerized in sickle cell?

Answer 2

Under low oxygen conditions, HbS molecules tend to polymerize and form long, rigid structures within the red blood cells. This process is known as hemoglobin polymerization.
The polymerized hemoglobin causes the red blood cells to become stiff and adopt a characteristic sickle shape

Question 3

How does SCA clinically manifest?

Answer 3

The pathophysiology of sickle cell anemia results in a range of clinical manifestations, including recurrent pain crises (vaso-occlusive crises), anemia, susceptibility to infections, and organ damage (especially to the spleen, kidneys, and lungs)

Question 4

What is the MoA of hydroxyurea?

Answer 4

A cancer chemotherapy drug
Shifts haemoglobin production from haemoglobin S to haemoglobin F, which makes the red blood cells more resistant to sickling, and reduces the expression of adhesion molecules on the red blood cells
Inhibits DNA synthesis by inhibiting ribonucleotide reductase. It is relatively selective for rapidly dividing red cells and reduces the production of red cells containing haemoglobin S while favouring production of red cells containing a high concentration of haemoglobin F (rapidly dividing F cells)
Hydroxyurea is a cytotoxic agent that works by increasing the production of fetal hemoglobin (HbF), which interferes with the polymerization of sickle hemoglobin.

Question 5

What is the clinical use of hydroxyurea?

Answer 5

It is one of the most widely used disease-modifying agents in sickle cell anemia, helping to reduce the frequency of vaso-occlusive crises and acute chest syndrome

Question 6

How does SCA lead to vaso-occlusion?

Answer 6

The sickle-shaped red blood cells are less flexible and more prone to sticking together, leading to the formation of clumps in the blood vessels. This process is called vaso-occlusion.
Vaso-occlusion can obstruct small blood vessels, leading to reduced blood flow to various tissues and organs. This results in ischemia, pain, and potential damage to affected organs.

Question 7

Explain the correlation between SCA and hemolysis

Answer 7

Sickle cells are fragile and more prone to breaking apart (hemolysis) than normal red blood cells. This leads to a chronic shortage of red blood cells, causing anemia.
Hemolysis releases hemoglobin into the bloodstream, contributing to the risk of complications such as kidney damage (due to the formation of hemosiderin) and impaired nitric oxide function.

Question 8

How does SCA lead to endothelial dysfunction?

Answer 8

The sickle cells can also damage the endothelial lining of blood vessels, contributing to endothelial dysfunction.
Endothelial dysfunction further exacerbates vaso-occlusion and promotes a pro-inflammatory and pro-thrombotic environment.

Question 9

What is the MoA of L-Glutamine?

Answer 9

L-glutamine is an amino acid that has been shown to reduce oxidative stress and inflammation and improve red blood cell hydration.

Question 10

What is the clinical use of L-Glutamine?

Answer 10

It is approved for use in preventing acute complications of sickle cell disease in both pediatric and adult patients.

Question 11

What is the MoA of blood transfusions?

Answer 11

Transfusions help increase the number of normal red blood cells, improving oxygen delivery and reducing the risk of complications.

Question 12

What is the clinical use of blood transfusions?

Answer 12

Blood transfusions are often used for the treatment of severe anemia, acute chest syndrome, and stroke prevention.

Question 13

How is pain managed in SCA?

Answer 13

Analgesics: Non-opioid and opioid medications are commonly used to manage pain associated with vaso-occlusive crises.
Anti-inflammatory drugs: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used to manage pain and inflammation.

Non-Opioid Analgesics:
Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen may be used for mild to moderate pain.
Acetaminophen can also be considered for pain relief.
Opioid Analgesics:
For moderate to severe pain, opioid medications such as morphine, hydromorphone, or fentanyl may be prescribed.
Patient-controlled analgesia (PCA) devices may be used in some cases to allow patients to self-administer pain medication within prescribed limits.
Adjunctive Medications:
Muscle relaxants and benzodiazepines may be used as adjuncts to manage muscle spasms and anxiety associated with pain.

Question 14

Explain why antibiotics are used in SCA

Answer 14

Prophylactic Antibiotics: Due to the increased risk of infection, particularly with encapsulated bacteria, prophylactic antibiotics such as penicillin are often prescribed in children with sickle cell disease.

Question 15

How can a vaso-occlusive crisis be prevented?

Answer 15

Crizanlizumab is a newer medication approved to reduce the frequency of vaso-occlusive crises in adults and adolescents with sickle cell disease.

Question 16

How does SCA cause an inflammatory response?

Answer 16

The repeated episodes of vaso-occlusion and tissue ischemia trigger an inflammatory response, leading to the release of inflammatory mediators.
Chronic inflammation contributes to the development of complications such as pain, organ damage, and an increased risk of infections

Question 17

List the therapeutic aagents used in the management of SCA

Answer 17

1. Hydroxycarbamide (hydroxyurea)
2. L-Glutamine
3. Blood Transfusions
4. Pain Management using analgesics and NSAIDS
5. Prophylactic Antibiotics
6. IV Hydration

Question 18

What is the rationale for hydration in SCA?

Answer 18

Intravenous (IV) hydration is crucial to prevent dehydration and maintain adequate blood flow. Normal saline is commonly used for fluid replacement

Question 19

What is the rationale for oxygen therapy in SCA?

Answer 19

Supplemental oxygen may be administered to help improve oxygen delivery to tissues and reduce hypoxia.

Question 20

Explain how the medications used in SCA are disease modifying

Answer 20

1. Hydroxyurea is a disease-modifying agent that increases the production of fetal hemoglobin, which inhibits the polymerization of sickle hemoglobin. It is often used to reduce the frequency of crises.
   This medication may take some time to show its full effect, so it is typically used as a long-term preventive measure.
2. L-glutamine oral powder has been approved to reduce the frequency of complications in sickle cell disease, including pain crises.
3. Blood Transfusions:
   In severe cases or complications such as acute chest syndrome, blood transfusions may be considered to increase the number of normal red blood cells and improve oxygen delivery.
4. Antibiotics:
   Prophylactic antibiotics, such as penicillin, are often prescribed to prevent infections, particularly in children with sickle cell disease