Sickle Cell Disease Flashcards
- Sickle cell disease is characterized by disorders of (…) structure
- They are also characterized by presence of an abnormal hemoglobin (…)
- Mutation causes (…) to be replaced by (…)
- hemoglobin structure
- HbS
- valine; glutamic acid
- Sickle cell disease is what type of disease (inheritance)?
- The cells go through deoxygenation and dehydration so the RBCs solidify and stretch into an elongated (…)
- autosomal recessive
- sickle shape
Sickle cell disease consists of a group of chronic hemolytic anemias, all characterized by what?
- vaso-occlusive events
- hemolytic anemia
- vasculopathy
- widespread acute/chronic organ damage
- premature mortality
What is this describing:
- child inherits Hb S from one parent and normal hemoglobin (Hb A) from the other; the heterozgous carrier rarely has symptoms
sickle cell trait
Sickle cell disease extent, severity, and clinical manifestations depend on what?
percentage of hemoglobin that is Hb S
In sickle cell disease, sickling is an occasional, intermittent phenomenon characterized by what 3 things?
- decreased oxygen tension (PO2) of the blood (hypoxemia)
- increased hydrogen ion concentration in the blood (decreased pH)
- increased plama osmolality, decreased plasma volume, and low temperature
Describe the polymerization of sickle cell disease and the sickled cells?
sickled erythrocyte stiffens, changing from a flexible, beneficial cell to an inflexible one that starves and damages tissues
What are the different types of hemoglobin (involved in sickle cell disease) and what are they composed of?
- hemoglobin A: two alpha and two beta chains
- hemoglobin A2: two alpha and two delta chains
- hemoglobin F: two alpha and two gamma chains
- Different genes code for the structure of each from of (…)
- Over (…) hemoglobin variants have been identified but most variants cause no disease
- Other common forms include hemoglobin (…) which result from variations in the (…) hemoglobin chain
- hemoglobin
- 1000
- S, C, E, D; beta
- Sickle cell disease results from a mutation in the (…) gene
- Which hemoglobin has a higher oxygen affinity?
- beta-globin gene
- hemoglobin F
What do providers strive to increase in patients with sickle cell disease to keep them away from a sickle cell crisis?
hemoglobin F
On a hemoglobin electrophoresis, what are the normal levels of this values in adults:
- Hb A
- Hb A2
- Hb F
- 95% to 98%
- 2% to 3.5%
- < 2%
On a hemoglobin electrophoresis, what are the normal levels of this values in children:
- Hb A (newborn)
- Hb A2 (6 months)
- Hb F (> 6 months)
- 50% to 80%
- 8%
- < 2%
- What is a hereditary condition involving an abnormality in the structure of hemoglobin?
- What are the main two disorders of this?
- hemoglobinopathy
- sickle cell and thalasemia
People can develop acquired hemoglobinopathies, what are some examples of these conditions?
- methemoglobin
- carboxyhemoglobin
What is this describing:
- family of autosomal recessive hemoglobinopathies
- AT substitution in codon 6 of the beta-globin gene on chromosome 11 (GAG to GTG)
- mutated globin is now known as Hb S
sickle cell disease
- In sickle cell disease, (…) is replaced with (…), leading to the formation of sickle hemoglobin
- When deoxygenated, HbS causes (…) and subsequently, (…) and (…)
- glutamic acid; valine
- cellular damage, hemolytic anemia, vaso-occlusion
Presentation of sickle cell disease is significantly affected by O2, HbF, and HbS. What happens to these factors that cause sickling?
- decrease in O2, decreases solubility
- decrease in HbF, decreases solubility
- decrease in HbS, decreases solubility
In sickle cell, an increase in viscosity causes what?
- painful episodes
- acute chest syndrome
- osteonecrosis
What are the different types of sickle cell?
- normal: HbAA
- sickle cell anemia: HbSS most severe
- HbSC disease: HbS and HbC
- HbSE disease: HbS and HbE
- HbS-HPFH: HbS and HPFH
- sickle cell trait: HbAS usually asymptomatic
- What is the life expectancy of an individual with sickle cell anemia?
- Diagnosis is mainly based on (…) to find which chromosomes are changed
- Presentation varies based on concentrations of (…) and (…)
- Problems begin around (…), when protective HbF levels fall to adult levels
- 40-50 years old
- genetic testing
- HbS and HbF
- 6 months of age
- Carriers of Sickle Cell are protected against (…) because the red cells contain a predominance of HbA compared with HbS (usually (…)% HbS) and the HbA inhibites hemoglobin polymerization except under extreme conditions
- What are these extreme conditions?
- The carrier state is not generally regarded as harmful, and carriers have a (…) life expectency
- intracellular sickling; 35-40%
- prolonged hypoxia, acidosis, or dehydration
- normal
Those with sickle cell trait have an increased risk for extreme exercise and physicial exertion-related injury broadly including (…), (…), and (…)
- exertional rhabdomyolysis
- heat-associated collape
- unexplained sudden death
- (…) abnormalities are among the most common manifestions of SCT
- This includes (…) and (…) which can lead to (…) and (…)
- Individuals with SCT, like those with SCD, are at an increased risk for (…), specifically (…)
- renal abnormalities
- hematuria and impaired urinary concentrating ability; albuminuria and CKD
- venous thromboembolism, specifically pulmonary embolism
What are the HbS, HbA2, and HbF percentages in an individual with SCD?
- HbS: > 85%
- HbA2: 2-3%
- HbF: 2-15%
What is this picture showing a peripheral smear of?
sickle cell disease
All of the disorders under the classficiation of sickle cell disease have 5 common characteristics, what are they?
- vaso-occlusive events
- hemolytic anemia
- vasculopathy (blood vessel disease)
- widespread organ damage
- early mortality
- When abnormal Hb S is present in erythrocytes of can occur?
- (…) causes further reduction in PO2 in the microcirculation and erythrocytes sickle
- This can be (…) so sickled erythrocytes regain normal shape and function
- However, sickled cells can (…), slowing blood flow, promoting hypoxemia, and increase sickling
- This can decrease (…), (…) and (…), increasing sickling
- hypoxemia, decreased pH, low temperature and/or decreased plasma
- persistent hypoxemia
- reversible
- clog vessels
- blood pH, hemoglobins affinity for oxygen, and PO2 drops
What are some clinical manifestations of sickle cell disease (long list)?
- painful episodes:
- acute chest syndrome
- stroke
- osteonecrosis
- priapism
- proliferative retinopathy
- splenic infarction and sequestration more common in HbSC disease
- leg ulcers
- gallstones
- aplastic crisis due to B19 parvovirus
- chronic kidney damage
- osteopenia (bone marrow hyperplasia)
- nutritional deficiencies: folic acid, sinc, calories
- pneumococcal disease and sepsis (infection most common cause of death)
What clinical manifestations of SCD are associated with higher hemoglobin and are beneficially affected by high HbF?
- painful episodes
- acute chest syndrome
- osteonecrosis
What clinical manifestations of SCD are associated with lower hemoglobin and are less affected by HbF?
- stroke
- priapism
- What clinical manifestations of SCD are associated with higher hemoglobin and HbSC disease?
- Which are associated with lower hemoglobin and are beneficially affected by high HbF?
- proliferative retinopathy
- leg ulcers
What is associated with chronic kidney damage from SCD and is described as the inability of the tubules of the kidneys to concentrate urine, bed wetting, and proteinuria?
glomerular disease: hyposthenuria
What are the 5 classic crises that will lead to a person with sickle cell to be hospitalized?
- vasoocclusive crisis (thrombotic crisis)
- aplastic crisis (B19 parvovirus)
- sequestration crisis
- hyperhemolytic crisis
- acute chest syndrome
Which classic SCD crisis is this describing:
- sickling is in microcirculation, extremely painful, and symmetric
- hands and feet exhibit painful swelling (hand-foot syndrome)
vasoocclusive (thrombotic) crisis
Which classic SCD crisis is this describing:
- transient cessation in red blood cell production occurs as result of a viral infection
aplastic crisis
Which SCD crisis is this describing:
- large amounts of blood pool in the liver and the spleen (starts storing RBCs instead of keeping them active)
sequestration crisis
Which SCD crisis is this describing:
- rate of RBC destruction is accelerated
hyperhemolytic crisis
Which SCD crisis is this describing:
- sickled RBCs attach to the endothelium of the injured, underventilated, and inflamed lung and fail to be reoxygenated
acute chest syndrome
An aplastic crisis of SCD is usually due to what virus?
B19 parvovirus
- Prior to age 20 , you will see patients who have SCD with (…), (…), and (…)
- Between age 20-40, those with SCD may have complications precipitated by what?
- Patients should avoid what?
- dactylitis, delayed growth and sexual maturation, moderate anemia
- red cell dehydration, acidosis, hypoxemia, stress, menses, and temp changes
- avoid high altitudes > 7000 ft and deep sea diving
People with SCD between age 20-40 are at risk for what complications?
- the painful episode
- acute chest syndrome
- acute anemia
- infections
- cerebrovascular disease
- digestive diseases
- cholelithiasis
- osteonecrosis
- osteomyelitis
- leg ulcers
- priapism
What is this describing:
- complication for patients with SCD between age 20-40
- acute and intense pain initiated by sickle vaso-occlusion; episodes vary in severity, number, length, and frequency
- unexplained death can occur during these (cardiac damage, pulmonary HTN)
- can be worse than post-op/traumatic pain
the painful episode
What is this describing:
- complication for patients with SCD between age 20-40
- second most common reason for hospitalization, frequent cause of death in adults
- infarction or infection
acute chest syndrome
What are some symptoms of acute chest syndrome?
- fever
- chest pain
- wheezing
- cough
- hypoxia
- new lung infiltrates
(…) has trophism for erythroid progenitor cells and impairs cell division for days during infection causing aplastic anemia
Parvovirus B19
What is this describing:
- complication for patients with SCD between age 20-40
- sequestration of blood in spleen/liver, aplastic crisis, severe vaso-occlusive events
- Hct of pts typically between 25-30%, acute episodes < 20% when severe
acute anemia
What does this describe:
- commonly caused by parvovirus B19
- selective destruction of the RBCs
- pancytopenia does not typically occur
aplastic crisis
What is this describing:
- complication for patients with SCD between age 20-40
- common trigger to a sickle cell crisis
- increases susceptibility - asplenia/hyposplenia (common to get staph infections)
infections
What is this describing:
- complication for patients with SCD between age 20-40
- silent cerebral infarction and stroke caused by occlusion of large vessels
cerebrovascular disease
What is this describing:
- complication for patients with SCD between age 20-40
- most common type is liver disease
digestive diseases
What is this describing:
- complication for patients with SCD between age 20-40
- a consequence of the accelerate bile pigment turnover
- affects > 50% of adult SC patients
- resultant obstructive jaundice
cholelitiasis
What is this describing:
- complication for patients with SCD between age 20-40
- hip and shoulder joints affected in 50% of patients
- check CTs to make sure this is not happening
osteonecrosis
What is this describing:
- complication for patients with SCD between age 20-40
- common in staphylococcal or salmonella infections
osteomyelitis
What is this describing:
- complication for patients with SCD between age 20-40
- can be small and superficial
- heals spontaneously with rest and good hygeine
- caused by increased vasoconstriction
leg ulcers
What is this describing:
- complication for patients with SCD between age 20-40
- affects 40% of male patients and may vary in severity, potentially resulting in impotency
- caused by decreased venous outflow
priapism (painful erection)
Patients with priapism from SCD have higher incidence of what?
- stroke
- pulmonary HTN
- renal failure
- leg ulcers
- premature death
People with SCD above the age of 40 are at risk for what complications?
- pulmonary hypertension
- nephropathy
- eye disease
- cardiovascular complications
What is this describing:
- complication for patients with SCD over age 40
- 30-43% have tricuspid regurgitation (secondary)
- associated with six to ten fold increased risk in mortality
- irreversible right heart failure
pulmonary HTN
What is this describing:
- complication for patients with SCD over age 40
- hyposthenuria (failure to concentrate urine) is present in almost all patients (proteinuria, renal insufficiency)
- 4% pts develop renal failure
nephropathy
What is the survival time after diagnosis in patients who develop renal failure from SCD?
4 years, even with dialysis
What is this describing:
- complication for patients with SCD over age 40
- present in < 20% of patients with SCD and 40% of those with HBSC disease (because they live longer)
eye disease (retinopathy)
Patients over 40 with SCD can have what type of cardiovascular complications?
- right/left ventricular systolic and diastolic dysfunction, elevated CO, cardiomegaly, myocardial ischemia (rare)
- in PE: enlarged heart, hyperacive precordium, audible systolic ejection murmur, BP in normal range
- SCD is usually suspected based on (…)
- RBCs may appear (…) or (…) depending on reticulocyte count
- (…) is suspected in cases earlier in life, tends to be (…) later in life
- Patients may present with (…), (…), and (…)
- How will WBCs and platelets be affected?
- How will indirect bilirubin be affected?
- family history
- normocytic or macrocytic
- microcytic; normocytic
- hemolytic anemia, reticulocytosis, increased LDH
- elevated WBC, thrombocytosis
- elevated indirect bilirubin
- Working up a patient with SCD, the electrophoresis demonstrates (…) in red cells (> 50%) which is diagnostic
- Peripheral smear reveals (…) (5-50%) and (…), (…), and (…)
- You can perform (…) to look for genotype
- Anyone above (…)% is suspected homozygous for SC, but above (…) is diagnostic
- Hb S
- sickled cells, target cells, nucleated RBCs, and Howell-jolly bodies
- genetic testing
- 50%; 85%
What is this peripheral smear showing?
Howell-Jolly bodies
What is the treatment overview for patients with SCD?
- prevention of crisis: avoid fever, infection, acidosis, dehydration, constricting clothes, exposure to cold
- immediate correction of acidosis and dehydration with IV fluids
- routine childhood immunizations, annual flu vaccine, pneumococcal and meningococcal vaccines
- infections: aggresive antibiotic therapy
- oxygen (only needed when individual is hypoxic)
- management of pain
- genetic counseling and psychological support
- In young children with SCD, (…) is vital
- Low dose daily (…) from birth to age 6 should be given unless they’ve had a splenectomy
- Vaccinations are important since they are more susceptible to infections and illnesses; what vaccines should adults get?
- preventing infection
- penicillin
- pneumococcal, influenza
Patients with SCD who are having acute pain can be given (…); however, in renal insufficency, they should be switched to (…)
- NSAIDs
- acetaminophen
Patients with SCD who have chronic pain should be treated with (…) and (…); BUT avoid (…) due to CNS side effects
- hydration
- opioid analgesics (morphine, hydromorphone)
- meperidine
- What is the most common treatment for SCD as it causes an increase in HbF?
- This is used in nearly all children and adults with (…) and (…); lifelong with SS
- This drug can drease rate of painful episodes by (…)%
- Administer with caution with patients with (…)
- What category is this drug in pregnancy?
- hydroxyurea
- SCD and HbS-beta thalassemia
- 50%
- bone marrow depression - can cause leukopenia
- D
What are some side effects of hydroxyurea?
- infertility
- rashes
- GI complications
What are the RBC effects of hydroxyurea?
- increases HbF
- decreases HbS polymerization
- decreases RBC membrane damage
- decreases hemolysis
- increases Hb
- improves tissue oxygenation and decreases inflammation
What are the vascular effects of hydroxyurea?
- decreases WBCs and platelets
- decreases endothelial activation and adhesion
- decreases thrombosis and microparticles
- decreases vasoconstriction
- improves tissue oxygenation and decreases inflammation
What is this smear showing:
effects of hydroxyurea: decrease in sickled cells, increase in RBCs
What is the main hemoglobin F inducing therapy for SCD?
hydroxyurea
How is acute chest syndrome treated in patients with SCD?
- bronchodilators (albuterol)
- RBC transfusions if severe
- PFTs (pulmonary function tests) for restrictive disease screening
How is bone disease treated in patients with SCD?
Vitamin D and calcium supplements (strengthening bones, especially in young pts)
How is pulmonary HTN treated with patients with SCD?
- hydroxyurea
- anticoagulation therapies
- bosentan
- epoprostenal
(blood thinners and vasodilators)
How is renal disease treated in patients with SCD?
- avoid NSAIDs
- dialysis and renal transplant may be needed in end stage SCD
How is priapism treated in patients with SCD?
- oral adrenergic agonists (etilefrine) and PDE5 inhibitors (sildenafil) for prophylactic treatment
- aspiration and irrigation if erection lasts longer than 4 hours
- if longer than 24 hours, operation to create shunts is needed
What is done for stroke prevention in patients with SCD?
transcranial doppler screening (20-40 y/o)
- What can be used to prevent a recurrent stroke in SCD pts and are used prior to surgery?
- These may result from (…) which can be treated with (…) therapy if becoming (…) dependent
- chronic RBC transfusions
- iron overload
- iron chelation therapy (deferasirox, desferrioxamine, deferiprone)
- RBC transfusion dependent
What only cures in about 10% of cases of SCD and is not particularly recommended due to 10% mortality?
stem cell transplant
Patients with SCD should be admitted for management of (…), (…), or (…) that do not respond to outpatient interventions
- acute chest syndrome
- aplastic crisis
- painful episodes
Patients with sickle cell anemia should have their care coordinated with a (…) and should be referred to a (…), if only is available
- hematologist
- Comprehensive Sickle Cell Center
Hemoglobin structural alterations observed with sickle cell disease:
1. are irreversible
2. increase the flexibility of erythrocytes
3. are stimulated by deoxygenation
4. are stimulated by alkalosis
3. are stimulated by deoxygation
- Sickling or change in the structure of the erythrocyte is stimulated by (…), (…), (…), and (…)
- The structural changes seen with sickling are (…); once sickling begins, it tends to continue until (…) returns to normal; then it ceases spontaneously
- Erythrocytes become (…) due to polymerization
- (…) can produce sickling
- hypoxia, acidosis, dehydration, and cold
- reversible; PO2
- stiffened
- acidosis
