SCD 1 Flashcards
(37 cards)
1
Q
What is Sickle Cell Disease? (3)
A
- A person with sickle cell disease has one different substance in the way it makes hemoglogin.
- The position where there should be glutamic acid has one amino acid valine in its place.
- This one change causes the chemical to form long strings when it lets loose of its oxygen. Thus the red cell becomes “sickled.”
2
Q
Definition and Types of SCD (5)
A
- A group of genetic disorders characterized by the inheritance of sickle hemoglobin (Hb S) from both parents or Hb S from one parent and an abnormal hemoglobin or thalassemia from another parent
Sickle cell Disease
- Sickle cell anemia(SS)
- Sickle C disease(SC)
- Sickle beta thalassemia
- (SboThal and Sb+Thal)
3
Q
History of advances in SCD (6)
A
- National newborn screening program
- Infection prevention with penicillin prophylaxis
- Vaccines against encapsulated organisms
a. Prone to infections of encapsulated organs (ex: strep pneumo) - Hydroxyurea to decrease painful crises and possibly ameliorate end-organ injury associated with SCD
- Chronic red blood cell transfusions to reduce stroke risk
- Cure with hematopoietic stem cell transplant (HSCT)
4
Q
Four different shapes of RBC
A
- Normal cell
- Spherical cell
i. Spherocytosis
ii. Must do reticulocyte count - Oval cell
i. Ovalcytosis
ii. Must do reticulocyte count - Sickle cell
5
Q
Normal Hemoglobin (4)
A
a. Disc-shaped
b. Soft
c. Easily flow through small blood vessels
d. Lives for 120 days
6
Q
Sickled Hemoglobin (5)
A
- Sickle-shaped
- Hard
- Often get stuck in small blood vessels
- Lives for 20 days or less
i. Will have high reticulocyte count (if bone marrow is working normally) - Diseases such as parvovirus which causes aplasia of bone marrow will significantly increase the patient’s anemia and HR will increase; could lead to heart failure
* Tx: blood transfusion
7
Q
SCD Pathophysiology (6)
A
- Normal adult hemoglobin (HbA) is a tetramer of four proteins, two alpha- and two ß-globin chains.
- In SCD, the abnormal ß-globin chains called hemoglobin sickle are produced as a result of the substitution of valine for glutamic acid on position 6 of the beta globin gene on chromosome 11.
- The interactions between mutated ß-chains leads to abnormal protein folding and polymerization, causing red blood cell (RBC) sickling.
- The severity of sickling depends on the inheritance pattern of the HbS gene
- HbS polymerization is exacerbated by changes to temperature, pH, and hydration.
- Interactions between rigid erythrocyte polymers and the vascular endothelium drives platelet activation and inflammation, causing vascular dysfunction
* Platelet activation can lead to stroke in these patients
8
Q
Hemoglobinopathies (2)
A
Beta Chain substitutions
- Hgb S: Valine for glutamic acid (6th position, beta chain)
- Hgb C: Lysine for glutamic acid (6th position, beta chain)
9
Q
Hgb Changes (2)
A
- HgB F which has a greater affinity for oxygen to facilitate transport across the placenta is produced in utero
- Within 6 months this is replaced by HgB A
10
Q
Alpha chains (6)
A
- There are four alpha chains that make up hemoglobin
- Alpha globulin chain production is controlled by two pairs of genes are chromosome 16
- If you have a deletion in one of four genes, you are asymptomatic
- If you have a deletion in two of the four genes, you have alpha thal trait—mild anemia, asymptomatic
- If three of the four genes are absent, you have hemolytic anemia with moderately severe anemia, symptomatic
- If you are missing all four genes, you will be stillborn at birth and have hydrops fetalis
11
Q
Beta globulins (4)
A
- Controlled by two genes are chromosome 11
- Beta globulin production can be almost absent to almost fully normal
- Leads to excessive alpha globulin production dependent on the amount of beta globulin production
- Beta thal can be trait (one gene is defective in production), intermedia (2 defective genes with moderate decrease in beta production), severe (2 defective genes with severe defects in beta production)
12
Q
Sickle Cell Anemia - HbS (9)
A
- More severe; Will be sick, will get pneumonias and other encapsulated organism infections
* Salmonella osteomyelitis - Structural variant of β-globin
- Due to single nucleotide change
- Changes the codon of the 6th amino acid from glutamate to valine (GAG->GTG: Glu6Val)
- Red blood cells sickle under low oxygen tension
- Due to aggregation of Hb S under low oxygen tension
- Distort shape of red blood cells, making them less deformable in capillaries, and cause occlusive disease
- Heterozygous carriers unaffected
- Carrier frequency: 8% in African Americans, 25% in West Central Africa
13
Q
Prevention Measures (5)
A
- Immunization; at age 2 and 5 get PV23 because it is a polysaccharide vaccine so it needs Bcells which aren’t mature until age 2
- All routine childhood vaccines
- Needs Pneumococcal 23 vaccine at age 2 and 5 years later
- Flu vaccine
- Meningococcal vaccines
14
Q
Genotype and baseline hemoglobin and severity (4)
A
- HbAS (trait): Normal
- HbSS: severe; stroke risk
- HbSC: Moderate-severe; stroke much less common
- HbSB+ and HbSBo: moderately severe, Hb severe
15
Q
CBC and SCD (7)
A
- Anemia is expected
- Variations based on genotype and clinical condition—know your patient’s baseline
- Thrombocytosis is common in patients with SCD because of underlying inflammation
- Leukocytosis and thrombocytosis are common during inflammatory crises
- VOC, ACS, osteomyelitis; thrombocytopenia may indicate hepatic or splenic sequestration.
a. Spleen cannot protect against encapsulated organisms - Hydroxyurea may cause pancytopenia
a. Due to increased hemoglobin F - High white cell count, high reticulocytes → always know patient’s normal
16
Q
Liver function tests expected findings (4)
A
- elevation of the indirect hyperbilirubinemia
- If elevated above baseline, consider hemolytic crisis or cholelithiasis especially if there is an elevated direct hyperbilirubinemia
- AST is usually modestly elevated due to hemolysis
- Hydroxyurea toxicity may cause elevations in AST and ALT
17
Q
Reticulocyte count expected findings (3)
A
- Given short half life of sickle cell erythrocytes, patients are dependent on reticulocyte production to maintain their hemoglobin
- A low reticulocyte count may be found as a harbinger of aplastic crisis or during such crises
- Hydroxyurea also suppresses the reticulocyte
18
Q
Exchange transfusions expected findings
A
The goal of emergent exchange transfusion is to decrease the HbS to at least 30% (equal to the HbS fraction in patients with HbAS)
19
Q
Chest X-ray expected findings (2)
A
- Indicated for any patient with chest pain, fever or cough.
- Findings of a new infiltrate makes the diagnosis of acute chest syndrome
20
Q
Complications from SCD (8)
A
- Constant Hemolysis
- Splenic Sequestration: Sickle cells become trapped and destroyed in the spleen
- Shortage of red blood cells or anemia
- Pain episodes
- Stroke or Brain Damage
- Kidney failure
- Pneumonia or Chest Syndrome
- Increased Infections
21
Q
Hemolysis and SCD (3)
A
- Lactate dehydrogenase, aspartate aminotransferase (AST), unconjugated bilirubin, and reticulocyte count are serological markers of hemolysis
a. May be elevated at baseline in patients with SCD.
b. LDH will always be elevated with hemolysis
c. Total bili will be elevated; indirect (unconjugated) not direct
i. Elevated because red cells are being lysed and bilirubin is byproduct of hemolysis - In intravascular hemolysis, free hemoglobin will be released into circulation and hence haptoglobin will bind the hemoglobin.
a. Causes a decline in haptoglobin levels - Labs you must look at: LDH, Retic count, AST, haptoglobin, CBC and bili *
22
Q
Spleen function (3)
A
- Acts as a filter against foreign organisms that infect the bloodstream.
- Filters out old red bloods cells from the bloodstream and recycles them
- Fall in hemoglobin at least 20% from baseline.
23
Q
Splenic Sequestration (5)
A
- Sudden trapping of blood within the spleen
- Usually occurs in infants under 2 years of age
- May be associated with fever, pain, and respiratory symptoms.
- Circulatory collapse and death can occur.
- Thrombocytopenia is uncommon and should alert the PNP to the possibility of hepatic or splenic sequestration
24
Q
Splenic Sequestration: Treatment (4)
A
- Intravenous fluids
- Blood transfusion as necessary
- Spleen removal or splenectomy after 2 yrs. of age
- Parents are taught spleen palpation maneuvers because early identification and prompt treatment helps prevent severe presentations and death
25
Vaso-Occlusive Crises (6)
1. Pain episodes
2. Rapid assessment
3. Patients present with severe pain as early as 6 months of age.
4. Most sickle cell-related pain in children is managed at home with supportive care and oral pain medications.
5. Hydroxyurea is the only medicine that decreases the pain crisis frequency.
6. In older children and adolescents, VOC pain is often symmetric and regional, usually in the back or extremities, although it can affect any part of the body.
26
Vaso-Occlusive Crises Tx (5)
1. Hydration
* Isotonic fluids should be administered only if patients appear dehydrated as they may exacerbate hemolysis;
* Otherwise, half normal saline at maintenance rate is the mainstay
2. Endari
3. NSAIDS
4. Opioids
5. Complementary Care
27
ENDARI (L-Glutamine Oral Powder) (2 and 4 side effects)
1. FDA approval under orphan drug status for patients with SCD who are 5 years and over
2. Reduced episodes of painful crisis
3. Side effects:
a. Constipation
b. Nausea, abdominal pain
c. Cough
d. Back and chest pain
28
Hand Foot Syndrome – Dactylitis (3)
1. Sickle dactylitis is one of the first complications in sickle cell syndromes with the highest incidence between ages six months and two years.
2. The sickle red cells cause painful swelling of the hands and feet. This is treated with fluids and pain medication. It usually will go away in a few days without any problems.
3. Edema in younger children **
i. Older child will complain of pain but you won’t be able to see anything
29
Physical Exam of VOC (2)
1. On physical exam, VOC pain is not usually accompanied by edema or erythema, although patients may be tender at the site of pain.
2. Evaluating and treating sickle cell VOC is vexing to clinicians because of the dependence on subject pain reports.
30
Lab evaluation with VOC (6)
1. CBC
2. reticulocyte count
3. liver function tests
4. bilirubin levels.
5. No laboratory values can confirm a painful crisis.
6. CRP and LDH are often elevated, signifying the non-specific presence of inflammation and hemolysis, respectively
31
Pain (2)
1. How pain is discussed and managed during childhood affects an individual’s reaction to and ability to cope with the pain as an adolescent and as an adult.
2. Older children and adults are faced not only with their present pain, but also with the memory of past episodes of pain and the seemingly inevitability of future pain.
32
Fever in SCD Patients (9)
1. Children with SCD are functionally asplenic and at increased risk of serious bacterial infections.
2. At particular risk for infection with encapsulated organisms (Streptococcus pneumoniae, Haemophilus influenza, and Neisseria meningitidis) and enteric Gram-negative organisms such as Salmonella.
3. Penicillin prophylaxis and 23-valent pneumococcal vaccination have decreased the rate of bacteremia among children
4. Any child with SCD and fever should be screened for bacterial infection with at least an aerobic blood culture.
5. A Complete history of a febrile child with SCD
a. Penicillin adherence for children younger than 5 years old
b. Attention to pneumococcus, H. influenza, and meningococcal vaccination status.
c. Penicillin-resistant organisms or non- vaccine pneumococcal serotypes may cause infection
6. Fever as a temperature > 38.5° C or 101.3° F.
7. Immediate evaluation with a complete medical history and physical
8. CBC with reticulocyte count, blood culture and to consider a urine culture prompt administration of a parenteral antibiotic that covers S. pneumonia and Gram-negative organisms such as a third-generation cephalosporin.
9. Admission of any ill-appearing children and those with risk factors for bacteremia, including infants younger than 6 months of age, CBC different from baseline, missed penicillin doses, pulmonary disease, or concern for ability to return for a second dose of antibiotics.
33
Kidney complications (4)
The medullary region of the kidney is composed of renal tubules and medullary blood vessels where sickling can occur.
1. Hyposthenuria
2. Enuresis; Due to failure to concentrate urine
3. Nocturia
4. Dehydration
34
Anemia - Jaundice (4)
1. The average red cell life is reduced from a normal of 120 days down to an average of 10 to 20 days in sickle cell anemia.
2. This produces anemia, a high reticulocyte count, and a bone marrow factory that is producing 3 to 4 times more red cells than normal.
3. Anemia can lead to shortness of breath and is one reason for modified gym classes.
4. Findings: pallor, tachycardia, systolic murmur, hepatomegaly, CHF
35
Risk factors for acute chest syndrome (3)
1. Respiratory infections
2. Treatment with opiates
3. Splinting due to chest or abdominal pain
36
Acute chest syndrome (4)
1. Pneumonias or infections in the lung and acute chest syndrome, caused by sickling red cells blocking blood vessels in the lung, are the most common complications.
2. Infections are treated with antibiotics and acute chest is treated with exchange tx.
3. The # of ACS episodes increases risk of mortality.
4. ACS can result in death.
37
ACS Treatment (5)
1. Empiric antimicrobial coverage with a third-generation cephalosporin and a macrolide to cover community-acquired, atypical pneumonia and encapsulated organisms.
2. Treat the pain and dehydration, risk and benefits of possible respiratory depression
3. Hydration with fluids at a rate between two-thirds and maintenance is sufficient.
4. In the absence of an additional indication for transfusion, such as severe anemia or worsening clinical status, transfusions are not emergently indicated.
5. Empiric use of short-acting bronchodilators for SCD patients in patients with comorbid asthma
