Case 30

Question 1

What are key findings from history in a 2 yr old with sickle cell disease and acute chest syndrome?

Answer 1

Chest pain

Question 2

What are key findings from physical exam in a 2 yr old with sickle cell disease and acute chest syndrome?

Answer 2

• Tachypnea with rhonchi
• Decreased breath sounds
• Hypoxia
• Fever
• Increased splenomegaly

Question 3

What is on the differential diagnosis for acute chest syndrome?

Answer 3

Sepsis, Rib infarction, congestive heart failure, pericarditis

Question 4

What are key findings from testing in a child with acute chest syndrome?

Answer 4

New infiltrates on chest Xray, Cardiomegaly, Leukocytosis.

Question 5

Pathophysiology of Sickle Cell Disease (SCD):

Answer 5

• Substitution of valine for glutamic acid at the sixth amino acid position of the hemoglobin molecule
• This abnormal hemoglobin polymerizes when deoxygenated
• Polymers then deform the RBC into characteristic sickle cells
• Sickle cells have increased adherence and block blood flow in the microvasculature
• Result: Local tissue hypoxia, pain, and tissue damage
• The abnormal hemoglobin also induces hemolysis of the RBCs leading to chronic anemia and elevation of the reticulocyte count

Question 6

What is the inheritance of sickle cell disease?

Answer 6

-Gene mutation frequency 7-10 percent among african americans living in the US
-Sickle cell trait is also seen in the Hispanic population but with a lower gene frequency.
-Autosomal recessive:
–Normal gene (A)
–Sickle hemoglobin gene (S)
–If both parents have one copy of the sickle cell gene (S), then:
25percent of offspring could have sickle cell disease (SS)
25percent are expected to have normal AA globin
50percent are expected to have sickle cell trait (AS)

Question 7

Evaluating pain in patient with sickle cell disease:

Answer 7

• A scale that shows faces (in stages from happy to crying) is validated for children ages 4 and up.
• Children with SCD who have frequent pain crises sometimes understand the faces scale earlier than age 4 (even as young as 2)
• Sometimes, even children over 4 years are too ill to comply with the request. In this case, parental judgement is best tool for assessing child’s pain.

Question 8

Physical Exam for child with SCD - General:

Answer 8

Growth impairment common in children with SCD due to chronic anemia, poor nutrition, painful crises, endocrine dysfunction, and/or poor pulmonary dysfunction.

Question 9

Physical Exam for child with SCD - HEENT:

Answer 9

Observe sclera for signs of icterus (clue to the degree of RBC hemolysis)

Question 10

Physical Exam for child with SCD - CV:

Answer 10

Flow murmur common in SCD.

Question 11

Physical Exam for child with SCD - Abdomen:

Answer 11

• Enlargement of spleen is common during first few years of life in children with SCD
• Massive enlargement or rapid change in spleen size can indicate sepsis or splenic sequestration crisis (life-threatening complication that occurs when blood pools in the spleen, leading to severe anemia and shock)
• Routine assessment of the spleen size by the parents can lead to earlier detection and treatment
• Spleen becomes progressively fibrotic and by the time the child is four to six years old, is no longer palpable.
• Children with hemoglobin SC or S beta thalassemia can have splenic enlargement into adolescence

Question 12

Physical Exam for child with SCD - Neurologic:

Answer 12

Evaluate for potential stroke.

Question 13

What is on the differential diagnosis for acute chest syndrome?

Answer 13

Sepsis, Rib infarction, Congestive heart failure, pericarditis.

Question 14

Acute Chest Syndrome:

Answer 14

• One of the most common causes of death in patients with SCD
• Clinical features: Fever, cough, chest pain, shortness of breath, and decreased oxygenation
• CXR findings: Multilobar infiltrates (more commonly lower and middle lobes), effusions, and atelectasis.
• Difficult to discern if lung infiltrate due to infection, pneumonia, or atelectasis

Question 15

Sepsis

Answer 15

• Decreased splenic function in SCD leads to decreased resistance to infection with encapsulated organisms (Strep pneumo., Haemophilus influenzae type b, Neisseria meningitidis).
• Usually non-focal
• New infiltrates would not be a usual finding unless the sepsis leads to acquired/adult respiratory distress syndrome (ARDS)

Question 16

Rib infarction:

Answer 16

Always consider when child with SCD presents with chest pain (could be vaso-occlusive crisis)

Question 17

Congestive heart failure:

Answer 17

• Can occur in patients with SCD and chronic anemia
• Tachypnea is common sign of CHF in children
• Usually does not cause chest pain on its own

Question 18

Pericarditis:

Answer 18

• Uncommon cause of chest pain
• -Presents with tachypnea and fever
• -Can present with effusion and infiltrate

Question 19

Newborn screening for SCD:

Answer 19

• Knowing a newborn’s screening results is important, because beginning penicillin prophylaxis as soon as possible (definitely by two months of age) is vital in preventing pneumococcal sepsis.
• Universal screening for inherited blood cell disorders now occurs in virtually all of the states and in the District of Columbia

Question 20

Nomenclature seen on the newborn screen:

Answer 20

• At birth, the predominant hemoglobin is hemoglobin F (fetal)
• Normal adult hemoglobin is hemoglobin A
• Hemoglobin F is always listed first, followed by other hemoglobins listed in order of concentration:
• -FS would be the most common hemoglobin pattern when looking for sickle cell disease
• -When one of the globin genes has a mutation for S and the other has a mutation for thalassemia (i.e., produces little or no normal hemoglobin) you may see patterns such as FSA (S-beta thalassemia +) or FS (S-beta thalassemia 0), both of which are sickling disorders.
• -When one gene has the S mutation and one gene has the mutation for hemoglobin C, then the pattern is FSC.

Question 21

FS

Answer 21

Most common hemoglobin pattern for sickle cell disease

Question 22

FSA or FS

Answer 22

One globin gene has a mutation for S, and the other has a mutation for thalassemia, producing sickling disorders of a milder phenotype

Question 23

FSC

Answer 23

One gene has the S mutation and the other has the mutation for hemoglobin C

Question 24

Prenatal diagnosis of SCD:

Answer 24

• Sample fetal blood obtained in utero

- DNA extraction from chorionic villi

Question 25

CBC:

Answer 25

- Hgb, hematocrit, and reticulocyte count can be interpreted only in relation to prior values and whether or not the child has had recent transfusion therapy. - Baseline Hgb for children with sickle cell is often between 6 and 9 mg/dL. - Although there is accommodation to the chronic anemia, the lower the baseline hemoglobin, the more difficult it is for the patient to withstand any acute change - Patients with SCD frequently demonstrate an exaggerated leukocytosis and thrombocytosis in response to stress; CBC findings do not usually definitely help to identify pneumonia or which of the ACS causes is present.

Question 26

Transcranial Doppler:

Answer 26

Study of intracranial blood-vessel flow to assess risk of stroke

Question 27

Chronic issues in SCD:

Answer 27

Anemia can cause chronic fatigue; will be more severe due to myelosuppression from infections such as Parvovirus or from hypersplenism (when spleen enlarges and traps blood cells)

Question 28

What are signs of medical emergencies in SCD:

Answer 28

- Fever - Slurred speech - Tachypnea, chest pain, cough - Increased jaundice - Increased pallor - Priapism

Question 29

Fever in SCD:

Answer 29

May be the only sign of serious infection

Question 30

Slurred speech in SCD:

Answer 30

- Stroke - -10 percent of children with SCD will have a stroke by age 15 - -An exchange transfusion may be indicated to lower the hemoglobin-S level and prevent progression or recurrence

Question 31

Tachypnea, chest pain, cough in SCD:

Answer 31

Lungs are a site of sickling problems. - Acute chest syndrome (ACS) - -May be result of infectious process, intrapulmonary sickling or pulmonary fat embolism (all appear similar on CXR) - -Requires supplemental oxygen and transfusion therapy

Question 32

Increased jaundice in SCD:

Answer 32

- Baseline jaundice typical in SCD and not an emergency - Marked increase in the level of jaundice, however, may indicate an increase in the degree of hemolysis and a need for transfusion (may be associated with a viral illness)

Question 33

Increased pallor in SCD:

Answer 33

- Baseline pallor is a typical finding from the anemia of SCD and does not constitute an emergency - Increased pallor, however, can be due to splenic sequestration, increased hemolysis, or a temporary inhibition of erythroid production (aplastic crisis)

Question 34

Priapism in SCD:

Answer 34

Sickling in the penile arteries can cause permanent damage.

Question 35

Prevention of complications in SCD:

Answer 35

1. Antibiotic prophylaxis | 2. Immunization

Question 36

Antibiotic Prophylaxis for SCD:

Answer 36

- Due to decreased splenic function and consequent decreased resistance to infection with encapsulated organisms (Strep pneumo., H. influenzae type b, Neisseria meningitides), infants and young children with SCD are at increased risk for sepsis - When given to infants with sickling disorders, penicillin significantly decreases the risk of mortality from overwhelming sepsis. - Prophylaxis is usually continued until the child is five or six years of age (after this, little data to support its use except in patients who have had documented sepsis and bacteremia, or who have had their spleens removed).

Question 37

Immunization for SCD:

Answer 37

- Hemophilus influenza type B conjugate vaccine and 13-valent pneumococcal conjugate vaccine (Preener 13) given at two, four and six months - To expand antibody coverage beyond the 13 initial serotypes, children with sickling disorders also receive the 23-valent pneumococcal polysaccharide vaccine at two years of age, with a repeat dose three to five years later. - The meningococcal conjugate vaccine is also given at age two years to children with functional asplenia (most children with SCD), with a booster dose three to five years later - Annual influenza vaccine

Question 38

Complications of SCD:

Answer 38

1. Acute Chest Syndrome (ACS) 2. Sepsis 3. Waldeyer's ring lymphoidal-tissue hypertrophy 4. Bilirubin gallstones

Question 39

Management of Pain in Acute Chest Syndrome:

Answer 39

- Can decrease the ability to fully expand the lungs - Narcotic analgesia relieves the pain and improves ability to take a deep breath - Narcotics are respiratory depressants, however, and therapeutic balance must be carefully maintained

Question 40

Management of Hydration in Acute Chest Syndrome:

Answer 40

- IV infusion because respiratory distress and tachypnea both increase fluid demands and make it difficult for the child to tolerate oral liquids - Correct dehydration, provide replacement for insensible losses (increased with fever and tachypnea), and give maintenance fluids - 1.5 times normal maintenance because dehydration may contribute to intracellular hemoglobin polymerization and RBC sickling - With ACS, avoid hydrating too vigorously and causing pulmonary edema from volume overload

Question 41

Management of Incentive Spirometry in Acute chest syndrome:

Answer 41

-Encourage deep breathing to avoid atelectasis

Question 42

Management of Antibiotics in acute chest syndrome:

Answer 42

- Practice guidelines and clinical data support the use of antibiotics in ACS - Infectious agents causing ACS include: Viruses, chlamydia, mycoplasma, and bacteria. - Effective antibiotic choices depend on local patterns of antimicrobial resistance

Question 43

Transfusion of packed RBCs in acute chest syndrome if:

Answer 43

- Hemoglobin below baseline - Increasing respiratory rate or chest symptoms - Declining oxygen saturation - Progressive infiltrates

Question 44

Exchange transfusion or erythrocytapheresis in Acute Chest Syndrome:

Answer 44

Reserve for especially severe disease and/or hypoxemia not corrected by oxygen therapy.

Question 45

Sepsis in SCD:

Answer 45

- Fever may be the only sign of sepsis in children with sickle cell disease and must be dealt with as a medical emergency, with rapid evaluation, blood cultures and institution of broad spectrum parenteral antibiotics while waiting for culture results to guide therapy. - Children with sickle cell disease also get "normal" colds and other viral illnesses. - Lack of normal spleen function as well as other more subtle immunologic deficiencies call for a rapid and aggressive approach.

Question 46

Waldeyer's Ring Lymphoidal-tissue hypertrophy in SCD:

Answer 46

- Common in children with SCD, evidenced by: - -Excessive snoring - -Obstructive sleep apnea - Treatment: Tonsillectomy with adenoidectomy

Question 47

Bilirubin Gallstones in SCD:

Answer 47

- Result of increased release of hemoglobin during the breakdown of the abnormal RBCs - Rare in the first five years of life; found increasingly in adolescents - Treatment: Cholecystectomy (if symptomatic cholelithiasis)