Transcript Sickle Cell Disease Part I & II MR 8/7/09 J. Chen

Sickle Cell Disease
Part I & II
MR 8/7/09
J. Chen
Introduction
• Sickle Cell Disease is a chronic hemolytic anemiaincludes hemoglobin varients:
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SS
SC
S-beta thalassemia
SO Arab
SD
• Characterized by hemolysis, vascular occlusion, organ
ischemia, end organ damage
• Genetic Defect-Substitution of valine for glutamate at
codon 6 on chromosome 11
• Autosomal Resessive
Epidemiology
• 1:375 Black newborns
• 1:12 Black has sickle cell trait
• SCD-SS (60%), SCD-SC (25-30%)
• Geographic distribution corresponds to distribution of
malaria
Diagnosis
• NB screen in 44 states
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93.1%-100% sensitivity
99.9%
• Other states HbEp should be done <3mo for high risk
• Hemaglobin electrophoresis is definitive test along with DNA analysis
• Other techniques:
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Isoelectric focusing
High-performance liquid chromatography
• Prenatal Diagnosis CV sampling (1st trimester), amniocentesis (2nd trimester)
• Sickledex not recommended in newborns 2nd high false negative
Clinical
• Clinical manifestations appear within first year as fetal
Hb concentration declines
• Young children are at risk for bacterial infections,
splenic sequestration, stroke
• Adolescents and adult begin to experience end organ
damage: Pulm HTN, renal disease, strokes, avascular
necrosis, leg ulcers, chronic pain syndrome
Infection
• Functional Asplenia seen as early as 2 months
• By 1 year of age ~30% have functional asplenia, by 6
years ~90%
• Organisms that pose the greatest danger include
encapsulated respiratory bacteria, particularly
Streptococcus pneumoniae (400x higher)
Infection
• Consider osteomyelitis when dealing with a
combination of persistent pain and fever.
• Bone that is involved with infarct-related vaso-occlusive
pain is prone to infection.
• Staphylococcus and Salmonella are the 2 most likely
organism
• Meningitis is 200 times more common in children with
HbSS.
Management of
Infection
• Prevention
• Heptavalent pneumococcal vaccine 2,4,6 mo age
• 23-valent pneumococcal vaccine at 2yr and 5ys
• Penicillin prophylaxis no later than 3month-5years
(125mgBID until 3y then 250mgBID)
Management of
infection
• Treatment
• early recognition; aggressive diagnostic evaluation including
CBC count, urinalysis, chest radiographs, and blood cultures;
• prompt administration of intravenous antibiotics active against
S pneumoniae; and close observation.
• <12 months with a temperature > 39C who appear toxic, with
an infiltrate on chest radiograph and an elevated WBC count,
should be admitted to the hospital.
• Consider only outpatient treatment if no high-risk features
appear on history, physical examination, or laboratory
evaluation; if the child is older than 12 months; and if
outpatient follow-up care can be ensured.
Acute Chest
Syndrome
• Definition-radiologic appearance
of a new pulmonary infiltrate and
fever
• +/- Hypoxia
• ~50% experience 1 episode
• ~35% of admissions
Acute ChestManagement
• Broad-spectrum antibiotics including a cephalosporin
and macrolide
• O2, hydration, incentive spirometry
• Transfusion therapy for associated hypoxia or Hct<18
Acute Chest
• Multiple ACS episodes may lead to chronic restrictive
pulmonary disease and possible pulmonary HTN.
• Children with recurrent ACS should be evaluated by
PFT’s
• Exchange transfusion reserved for severe ACS
• Recurrent ACS may consider Hematopoietic stem cell
transplant
VOC pain crisis
• Pain, resulting from vascular occlusion and ischemia
• the most common feature of sickle cell disease and can
affect any body part.
• Can be debilitating and affect school, job, social
• Bone pain is often due to bone marrow infarction.
• During the first 18 months of life, the metatarsals and
metacarpals can be involved, presenting as dactylitis or
hand-foot syndrome.
Dactylitis, HandFoot Syndrome
• Strong predictor of overall severity (ie, death, risk of
stroke, high pain rate, recurrent acute chest syndrome).
• Episode before age 1 year are at high risk of a severe
clinical course.
VOC crisis cont…
• Episodes may be triggered by:
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Infection
Temp extremes
Dehydration
Stress
No identifiable cause
• Average length of stay-4days
VOC-Management
• Aggressive hydration: 1 ½ Maintanence
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D51/2 or 1/4NS
• Aggressive pain management
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Moderate pain: Acetominophen +/- codein, NSAIDS
Severe pain: Opioids (morphine, hydromorphone)
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PCA
• >10days opioids may become tolerant and need to be weaned
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Methadone
• Physical therapy, relaxation therapy
• Hydroxyurea-decrease frequency of VOC and need for blood
transfusion by 50%
To be Continued
• Part II:
• Acute Splenic Sequestration
• Cerebrovascular Disease
• Chronic Organ Damage
• Osteonecrosis
• Retinopathy
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Priapism
Cholecystitis
Pulm HTN
Future Therapy
Acute Splenic
Sequestration
• sudden enlargement of the spleen along with a greater
than 2-g/dL (20-g/L) decrease in Hb from baseline
with reticulocytosis.
• sudden circulatory collapse and was a common cause
of death prior to early diagnosis and education through
newborn screening programs.
• <3y with SS or other varients
• Recurrence is common
Cerebrovascular
Disease
• 11% of patients who have Hb-SS by age 20 years, and
silent infarction is detected on neuroimaging studies in
another 22%.
• The peak incidence of overt stroke occurs in children
between 2 and 10 years of age
• TCD-Flow Velocity >200cm/sec
• Screening recommended annually for all children with
Hb-SS or S-beta Thal ages 2-16y
Cerebrovascular
Disease
• Current guidelines recommend indefinite transfusion
therapy for patient with abnormal TCD
Priapism
• sustained, painful, and unwanted erection
• According to one study, the mean age at which priapism
occurs is 12 years
• By age 20 years, as many as 89% of males with sickle cell
disease have experienced one or more episodes of priapism.
• Recurrent episodes of priapism can result in fibrosis and
impotence, even when adequate treatment is attempted.
• Prolonged priapism is an emergency that requires urologic
consultation.
Therapies
• Hydroxyurea
• Elevates concentration of fetal Hb
• Decrease frequency of VOC, ACS, hospital admissions,
blood transfusion by 50%
• >5yr age with severe complications
Transfusion
• Simple PRBC transfusion
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Aplastic Crises
Splenic Sequestration
ACS
Preoperatively
• Exchange transfusion reserved for stroke, severe ACS,
unremitting priapism, preop cardiac/neuro/retinal
surgery
Hematopoietic Stem
Cell Transplant
• Only Cure
• Requires human leukocyte antigen-matched sibling donor
• Indications
• Stroke
• Positive TCD result
• Multiple ACS or VOC episodes
• Event free survival 95%
• Only 14% have HLA matched sibling donor
Future Therapy
• HSCT with umbilical cord blood transplant,
haptoidentical transplants
• Finding new fetal Hb-modulating agents
• Modulating red blood cell dehydration
• Nitric oxide therapy and corticosteroid for ACS
• A 14-month-old boy who has sickle cell disease (SCD)
developed a fever to 104°F (40°C) 3 hours ago. He has had
nasal congestion for 2 days but no fever. He had been
drinking normal amounts of fluids until he became febrile
and since has taken only very small amounts. His physical
examination reveals normal blood pressure. Oxygen
saturation is 96% in room air. The only abnormalities are
possible crackles over the right upper lobe and a spleen
palpable 1 to 1.5 cm below the left costal margin. Complete
blood count reveals a hemoglobin of 6.9 g/dL (69 g/L),
white blood cell count of 18x103/mcL (18x109/L), and
platelet count of 675x103/mcL (675x109/L). Blood culture
is obtained. Of the following, the most appropriate initial
step is to:
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Administer a bolus of normal saline over 1 hour.
B.
Administer intravenous ceftriaxone.
C.
Ensure that prophylactic penicillin
has been administered and is continued.
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D.
Obtain a chest radiograph.
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E.
Transfuse packed red blood cells.
• Answer: B.
• The mother of a 2-year-old boy who has SCD noted
decreased activity and increasing pallor in the boy over the
past 8 hours. She has been taught splenic palpation, and she
reports that his spleen usually is not palpable, but was 3
inches below the rib cage before leaving home. Physical
examination reveals a pale, lethargic child. His temperature
is 100.4°F (38°C), heart rate is 195 beats/min, respiratory
rate is 40 breaths/min, and blood pressure is 60/32 mm Hg.
He is crying, and the edge of his spleen appears to be 6 cm
below the left costal margin. A blood count, blood culture,
and cross-match are obtained. Of the following the most
appropriate next step is:
• A.
A bolus of intravenous normal saline.
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B.
vancomycin.
Intravenous ceftriaxone followed by
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Transfusion of antigen-matched
packed red blood cells.
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D.
Transfusion of uncrossed-matched,
O-negative packed red blood cells.
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E.
Urgent ultrasonography to confirm
splenic enlargement.
• Answer: A
• Parents of a newborn in whom SCD was diagnosed by
newborn screening come to you for counseling and
education. Although they understand that the first
painful event is not likely to occur for at least several
months, they are concerned about their child's future if
painful events should begin early. Which of the
following types of pain is a clinical predictor of severe
disease if it occurs before 1 year of age?
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Abdominal tenderness.
B.
respiratory rate.
Chest tenderness and increased
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C.
Hip pain.
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D.
Painful swelling of the hands and
E.
Priapism.
feet.
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• Answer-D.