Module 11.1 - Sickle Cell Disease

Question 1

What is Sickle Cell Disease?

Answer 1

• It is a group of disorders that affects the hemoglobin characterized by the presence of an atypical form of hemoglobin- Hemoglobin SS- within the erythrocyte
• Most common among individuals with ancestors from Africa and less so from the Mediterranean countries, such as Greece, Turkey and Italy
• Between 1-3 million Americans and more than 100million people worldwide are heterozygous carriers for the sickle cell trait (HbAS)

Question 2

Describe the pathophysiology associated with sickle cell disease

Answer 2

• Cycles of deoxygenation and oxygenation cause the HbSS molecule to polymerize and stiffen
• These polymers can damage the RBC structure, leading to the sickle-shaped RBCs. This change causes a variety of pathologic consequences, including:
  
  • The sickle-shaped RBCs die prematurely leading to hemolytic anemia, microvascular obstruction (vaso-occlusive) and ischemic tissue damage.

Question 3

Who gets sickle cell disease?

Answer 3

• SCD is inherited in an autosomal recessive pattern where each parent carries one copy of the mutated gene.
• Sickle cell anemia (SCA; HbSS) a homozygous form is the MOST SEVERE.
• Sickle cell anemia is uncompensated hemolytic anemia with a shortened RBC survival (10-20 days versus 120 day normal survival); increased erythropoiesis is insufficient to balance the increased rate of destruction.
• Sickle cell trait (HbAS) in which the child inherits HbSS from one parent and normal hemoglobin (HbA) from the other parent, is a heterozygous carrier state and NOT a form of SCD. There must be 2 copies of HbSS for sickle cell disease.
• All forms of SCD are lifelong conditions.

Question 4

What are 2 effective therapies for sickle cell disease?

Answer 4

1. Hydroxyurea: a myelosuppressive agent, is the only effective medication proven to reduce the frequency of painful sickle cell episodes by approx. 50%; raises the level of HbF (fetal hemoglobin) and the hemoglobin level; decreases sickling of RBCs
2. Chronic Transfusion: GOAL of transfusion is a hemoglobin between 8-10g/dL

• Regular PRBC transfusion maintains a hemoglobin SS fraction of < 30% and can prevent stroke recurrence
• The Hb should be maintained between 8- 10g/dL to avoid hyper viscosity associated with higher Hb levels and increased stroke risk.

Question 5

What are the subjective/physical exam findings associated with sickle cell disease?

Answer 5

Symptoms related usually to increased cell viscosity and subsequent vaso-occlusion that results in the following:

• Generalized pain in long bones and joints
• Fever, fatigue and malaise
• Abdominal pain and fullness, nausea, vomiting, and decreased appetite
• Swelling in hands, feet and joints
• Priapism
• Depression (related to chronic pain)
• Chronic hemolytic anemia
• Hypotension
• Tachycardia
• Tachypnea
• Splenomegaly
• Hepatomegaly
• Cardiomegaly
• Jaundice
• Retinopathy
• Delay in secondary sex characteristics with delayed menarche, delayed growth and weight gain in adolescence and decreased physical endurance compared to peers.
• Chronic leg ulcers
• Stroke
• Renal infarction
• Venous thromboembolism
• Anemia – due to splenic sequestration, aplastic crisis or hyper-hemolysis
• Neurologic deficits or seizure disorder

Question 6

What can cause sickle cell crisis?

Answer 6

Sickle cell crisis can be brought on by infection, hypovolemia, hypoxemia, hypothermia

Question 7

What are 4 complications associated with sickle cell disease?

Answer 7

1. Sequestration Syndrome

• Characterized by rapid pooling of blood in the spleen with a resultant drop in blood volume and hematocrit
• Usually rapid in onset and may present with abdominal fullness, LUQ pain, thirst, pallor, tachycardia, and cardiac collapse.
• Diagnosis is made on clinical findings and is often triggered by infection, pain, sepsis, and stroke
• The treatment of sequestration involves splenectomy and blood transfusions.

2. Common neurologic complications occur in 25% of SCA patients, including:

• TIA, Stroke, unexplained coma and epilepsy
• 24% will have overt stroke before age 25 years
• Higher incidence in neurocognitive decline

3. Infection is the leading cause of morbidity and mortality in children, due to:

• Splenic dysfunction
• Bacterial infections: Streptococcus pneumoniae and Haemophilus influenza
• Viral infections: H1N1, parvovirus

4. Pain is the most common phenomena for individuals (approx. 90% of patients)

• Chronic pain
• Acute pain episodes: presentation to emergency rooms when pain no longer manageable at home; too severe
• Causes by ischemic events due to crescent ‘sickle’ RBCs being easily trapped in blood vessels, causing vaso-occlusion (infarction) and pain

Question 8

What laboratory/diagnostic tests are done to diagnose sickle cell disease?

Answer 8

• Hemoglobin electrophoresis confirms the following:
  
  • Hemoglobin genotype for sickle cell disease
  • Hemoglobin F (fetal) and A2 for presence of thalassemia
• Sickle cells (5-50%) found on peripheral blood smear
• DIAGNOSIS IS CONFIRMED BY HEMOGLOBIN ELECTROPHORESIS
  
  • Hemoglobin S usually constitutes approx. 85-95% of Hgb
  • Hemoglobin A will NOT be present in homozygous S disease
  • Hemoglobin F levels variable increased (high Hgb F associated with a more benign disease)
• Serum unconjugated bilirubin, transaminase and alkaline phosphatase: elevated
• Creatinine, serum: lower than normal due to inability of kidneys to concentrate urine

Question 9

What are the 6 steps for the acute management of a patient with sickle cell disease?

Answer 9

1. Pain Control: MAIN priority is pain control. (GOLD STANDARD for the assessment of pain is the patient’s report)

• Opioids (for severe pain):
  
  • Morphine 0.1- 0.15mg/kg
  • Hydromorphone 0.02- 0.05 mg/kg
• Non-opioids (for moderate pain):
  
  • NSAIDs or Acetaminophen for mild to moderate pain
  • Evaluate renal function, adjust accordingly
• Continual reassessment
• Hospitalization if pain does not improve
• Consider PCA pump for severe pain

2. Hydration

• Normal saline boluses to maintain hemodynamic stability and reduce viscosity of blood
• 0.5 – 1 L Normal saline if fluid overload not present
• Maintenance fluids: ¼ or ½ normal saline infusion
• Encourage oral intake

3. Hypoxia:

• Administer oxygen. Use 40% humidified O2

4. Nausea/Vomiting:

• Phenothiazines

5. Acute vaso-occlusive crisis:

• Manage with exchange transfusions

6. Consider blood transfusions for the following:

• Symptomatic anemia- Goal of PRBC transfusion is 10g/dL
• Acute events
• Preoperatively for major surgeries
• Acute sepsis/meningitis
• Prevention of recurrent stroke
• Chronic hypoxia

Question 10

When should you hospitalize a patient with sickle cell disease?

Answer 10

Hospitalization is indicated for:

• Pain not relieved by analgesics for longer than 8 hours
• Sepsis and persistent fever
• Central nervous system disorders:
  
  • Increased lethargy
  • Headaches
• Acute chest syndrome : a high risk acute vaso-occlusive crisis involving the lungs; presents with fever, cough, chest pain and lung infiltrates; LEADING cause of death in adult patients with SCD
  
  • EKG
  • Complete Blood Count
  • Chest x-ray/Chest CT scan
  • Blood and sputum cultures
• Hypoxia
• Surgical emergency
• Pregnancy related complications
• Priapism (may require exchange transfusion or surgical shunting by urologist)

Question 11

How do you chronically manage patients with sickle cell disease?

Answer 11

• Folic acid 1 mg po daily
• Pneumococcal, hepatitis and influenza vaccines
• Foot care and protective shoes to prevent chronic leg ulcers
• Follow-up at least 2-3 times yearly with PCP
• Annual retinal evaluation
• History of priapism should be discussed at each health visit, early treatment provided
• Ongoing chelation therapy for patients with iron overload
• Routine exchange transfusion to increase oxygen carrying capacity while decreasing viscosity and complications related to hemolysis
• Genetic counselling should be offered to include:
  
  • Birth control options
  • Oral contraceptives are NOT contraindicated
• Avoid temperature extremes and physical overexertion that can lead to dehydration
• IN patients with SC Anemia (HgbSS), aliphatic butyrate salts and hydroxyurea increase the level of fetal hemoglobin
  
  • Hydroxyurea 500-750mg daily, used to reduce the occurrence of painful crises, long-term safety is unclear
    
    • A myelosuppressive agent; only effective drug proven to reduce the frequency of painful episodes; decreases sickling of RBCs
  • Erythropoietin is mentioned in literature, but effective dosage schedules are unclear.
• Hematopoietic stem cell transplantation- success cure of HgbSS- mostly in children; higher mortality rate in adults

Question 12

What type of anemia is sickle cell anemia?

Answer 12

It is a hemolytic anemia