Sickle Cell Disease Case

1
Sickle Cell Disease Case

• Elizabeth M. Bailey, MD

2
Patient Presentation

• 9 yo AA boy with Hb S-Beta-thal disease
• Prior care at another institution
• 5 day h/o R buttock pain c/w prior VOC pain
• Tylenol/Codeine Motrin no longer adequately
  controlling pain
• Also intermittent diffuse chest pain
• No fever, cough, SOB, N/V/D, sick contacts

3
TIME OUT! Whats Sickle-Beta Thalassemia disease?

• Sickle trait defect in beta globin gene,
  glutamate for valine substitution, charged a.a.
  affects protein folding of Hgb molecule in
  deoxygenated state?can lead to distortion of RBC
  shape
• 8 AA heterozygous, 1500 AA homozygous
  representing SS disease, most common form of
  sickle cell disease
• Hb A 2 normal alpha, 2 normal Beta chains
• Hb S 2 normal alpha, 2 BetaS chains

4
Hemoglobinopathy Alphabet Soup

• Hb F 2 normal alpha, 2 normal gamma chains
• Other abnormal Hb forms exist (C, E, O), w/
  various defects in Beta chain, these can
  sometimes participate in Hb S polymerization,
  affecting expression of Hgb S trait
• Hgb A2 tetramer of alpha chains
• Hgb A2 and F are increased if there arent enough
  beta chains around, as in Beta thal. The various
  causative genetic defects of B thal each lead to
  a decrease or absence of gene product, the beta
  chain.

5
Sickle-Beta Thalassemias

• If one beta gene is defective (BetaS) and the
  other is malfunctioning (Beta0 or Beta), sickle
  disease will likely be expressed (this combo
  occurs in 0.06 AA)
• Hb S-Beta thal is usually milder (even than SC)
• Hb S-Beta0 thal is usually more severe (like SS)
• Amount of Hgb A present may be prognostic
• Hb F presence may alter expression

6
Past Medical History

• Diagnosed at 2 months old on newborn screen
• Mom w known S trait, dad unaware, no other FHx
• 20-25 prior admissions for pain crises, q3-4mo
• Last admission 4 months ago for pain crisis
• Baseline Hgb 8, gets 2 transfusions/yr
• ACS x 2 w/ exchange transfusion (last8 mo ago)
• Priapism x 1 (hospitalized at age 6)
• Admission for L arm swelling/fevers at age 3

7
Further History

• BH FT, emergent c/s at 7 mos gestation, BW 4lbs
  10oz, 3 week NICU stay for feeding issues
• PMH/PSH only as above
• Meds Folate, MVI, Tylenol w codeine, Motrin
• NKDA
• Imm UTD, Influenza PCV 23 given this year
• DH Walked 10-12 mo, talked 9 mo, 4th grade
  taking 3rd grade courses due to school absences

8
What do you want to know?Physical Exam

• General WDWN boy in moderate discomfort
• VS T 37.3, HR 100, RR 24, BP 109/66, spO2 98 RA
• HEENT normal except mild scleral icterus
• CHEST CTAB, good aeration, no w/r/r, no
  increased WOB, CV RRR, 2/6 SEM along LSB
• ABDOMEN soft, nt, nd, no HSM
• GU normal Tanner 1 male
• MS TTP at back/buttocks RL, hip ROM limited by
  pain, no erythema/warmth/swelling

9
What labs do you want to send?

• WBC 12.4 diff 45N 33.2L 10.9M 10.3E 0.6B
• Hgb 7.1 Hct 22.1 Reticulocyte ct 2.63 Plt 372
• SMA, LFT wnl, except TB 1.4
• UA SG 1007, negative
• CXR promiment cardiac silhouette, clear lungs
• Hgb electrophoresis 0 A, 4.9 A2, 10.9 F,
  84.2 S
• Hip XR wnl, no aseptic necrosis
• Bcx and Ucx sent Admitted on morphine PCA

10
Later that day

• Approximately 24 hrs after presentation, he
  developed sudden onset of fever to 39.8, spO2
  decreased to 86 RA, RR increased to 40s, HR
  150s, BP 90s/50s, R sided crackles.
• Luckily for the senior, there was a good intern
  on
• CXR showed consolidation RUL and RLL
• WBC 22.6 70.7N Hgb 5.6 Plt 314 Rtc 1.92
• Repeat Bcx/Ucx sent, started ceftriaxone,
  azithromycin, 2L NC, tylenol, MSO4 bolus, PRBC
• VS improved in next hour, weaned off O2 in 2d

11
Further hospital course

• Pain control maximized in next days with Fentanyl
  PCA
• Received total of 2 PRBC transfusions
• Albuterol given for wheezing which developed
  transiently
• Plan to discuss chronic transfusion protocol /-
  hydroxyurea therapy given recurrent ACS episodes

12
ACUTE CHEST SYNDROME

• Definition a new pulmonary infiltrate some
  combo of fever, cough, CP, tachypnea, wheezing,
  SOB, hypoxemia, leukocytosis. (But recall that XR
  lags behind)
• Main criteria in kids Fever and infiltrate (esp
  in upper lobe) SOB, chills and cough w
  middle/lower lobe infiltrate in adults
• Important to note that diagnosis in kids may NOT
  be suspected before the CXR (fever and cough
  alone may not alert you). Thus, all febrile kids
  w sickle cell disease should have a CXR.
• Epidemiology Affects 30 SCD pts, 2nd most
  common SCD complication, peak age group 2-4 yo,
  higher prevalence in winter
• Mortality rate 1.8 kids, 4.3 adults, leading
  cause of death in SCD

13
Etiology of ACS

• Vasocclusion in lungs (chronic leads to pulm HTN
  and decreased lung compliance)
• Infection (especially in children)
• Pulmonary fat embolus (seen in 44-60 ACS cases
  who had bronch/BAL) There may be a preceding pain
  crisis. More common in older pts.
• Noncardiogenic pulmonary edema
• some combination of above
• may happen after anesthesia/surgery, esp. abd
  surg
• 50 initially admitted for other reasons

14
ACS and Infection

• Most common identified organism in ACS in all age
  ranges is Chlamydia pneumoniae.
• In 1 study, 25 0-9 yo ACS pts had an organism
  identified
• In order of decreasing frequency C. pneumoniae,
  Mycoplasma, RSV, S. aureus, S. pneumo.
• Another study 26 SCD patients with positive cx
  for S. pneumo also had ACS
• Ceftriaxone (clinda if allergic) macrolide 1st
  line, add Vancomycin if more severe

15
Other ACS Predisposing Factors

• There is also significant chronic pulmonary
  morbidity in SCD.
• Nocturnal hypoxemia is a RF for VOC
• Watch out for comorbid asthma, but also, in
  non-asthmatic SCD patients, 2 small studies
  showed airway hyperreactivity responsive to
  albuterol/lower airway obstruction

16
Halftime Show MY NIECE CAITIE!
17
Treatment of ACS

• In children, infection likely, so empiric abx are
  the rule. Must cover S. pneumo, H flu, atypicals.
• Incentive spirometer use q2h
• Careful pain control w toradol/narcotic if
  necessary (allow max inspiratory effort dont
  overmedicate and sedate, dont undermedicate and
  cause splinting)
• Supplemental O2 to keep sats 92
• Control fever with acetaminophen
• careful hydration, follow wt, i/o, avoid pulm
  edema

18
Treatment of ACS, continued

• Consider PRBC for mild-mod ACS, especially if Hgb
  1 g/dL below baseline and needs O2? Dont get
  Hgb10 can increase vasocclusion.
• Consider albuterol even if no current wheezing,
  especially if prior h/o RAD/asthma/wheezing
• What about exchange transfusion? Consider for
  more severe ACS, progressive hypoxemia,
  multilobar lung disease, prior h/o severe ACS

19
Treatment of ACS, continued

• Major danger is hypoxemia ? worsening sickling
  and VOC ? MOSF. If tachypneic, check ABG to
  distinguish anxiety, pain, hypoxemia, metab
  acidosis. After that, may follow pulse ox.
• If pAO2 transfusion.
• Some would do an exchange transfusion earlier in
  course of ACS, in kids.
• With exchange transfusion, O2 usually starts to
  improve despite CXR appearance
• Goal Get Hgb S to

20
Treatment of ACS, continued

• If severe, rapid or unresponsive to treatment,
  may need mechanical ventilation or even ECMO
• Small studies show benefit of inhaled NO in kids
  with severe ACS
• Controversial some support use of IV steroids
  for mild-mod ACS. BUT potential relapse when
  d/ced AND prolonged use of corticosteroids can
  increase risk of fat embolism

21
What tests to send off?

• CBC and retic daily until clinically improving
• TC (ideal neg for sickle cell Hgb, matched for
  minor red cell antigens, and leukoreduced)
• Bcx (/- urine, stool, sputum cx) if febrile
• ABG if severe disease, pulse ox tends to
  overestimate hypoxia
• Follow LFT and SMA for signs of liver or renal
  failure (given risk for MOSF)
• Repeat CXR if worsening

22
Prevention of ACS

• Pulmonary toilet when admitted for VOC, etc. and
  post-op especially, possible pre-surgical
  transfusion
• Incentive Spirometer USE!!!!
• Appropriate pain control and hydration
• Prevent/treat infections and any resp illness (eg
  RAD)
• KEEP VIGILANT TO DETECT IT EARLY WHEN PATIENTS
  ARE ADMITTED FOR OTHER SCD COMPLICATIONS

23
Follow-up/Prevention of Recurrence

• ACS is less common during chronic transfusion
  programs (which were initiated to prevent strokes
  in pts w abnormal TCD) could do this only during
  high-risk time (e.g. winter months)
• Hydroxyurea decreases freq of ACS must follow
  CBC
• Periodic PFT (multiple ACS events can lead to
  pulmonary HTN)
• Sibling-matched BMT (multiple ACS events is an
  indication)

24
Brief Overview of Health Maintenance in Sickle
Cell Disease

• Genetic counseling (parents and patient)
• Education re s/s, pain control/hydration, when to
  seek care, how to palpate spleen, knowing
  baseline labs history
• Start PCN 125 mg po bid by 2-3 months, increase
  to 250 mg po bid at 5 years old, when to stop? At
  5 yo? Continue if h/o SBI/spleen out. (PCN at
  least for SS SB0 thal, ?SC SBthal)
• Routine vaccines, Hib, PCV-7 then PCV-23 at 2
  yo, booster at 5 yo, yearly influenza vaccines,
  Meningovax
• Folate at 1 year
• Follow growth and development closely
• Yearly retinal exam by ophtho after 10 yo, TCD p
  2 yo

25
Sources

• AAP. Health supervision for children with sickle
  cell disease. Pediatrics. 2002 109(3).
• AAP Red Book. 2003 Report of the Committee on
  Infectious Diseases. 26th ed.
• Atz AM, DL Wessel. Inhaled nitric oxide in sickle
  cell disease with acute chest syndrome.
  Anesthesiology 1997 87(4) 988.
• Behrman Nelson Textbook of Pediatrics. 16th ed.
  2002.
• Emre U, ST Miller, M Gutierez, P Steiner, SP Rao,
  M Rao. Effect of transfusion in acute chest
  syndrome of sickle cell disease. J Pediatr 1995
  127(6)901.
• Fixler J, L Styles. Sickle cell disease. Pediatr
  Clin N Amer 2002 49(6).
• Hoffman Hematology Basic Principles and
  Practice, 3rd ed. 2000.
• Johns Hopkins. The Harriet Lane Handbook a
  manual for pediatric house officers, 16th ed.
  2002.
• Koumbourlis AC, HJ Zar, A Hurlet-Jensen, MR
  Goldberg. Prevalence and reversibility of lower
  airway obstruction in children with sickle cell
  disease. J Pediatr 2001 138(2).
• Lynch A, JD Tobias. Life-threatening infection in
  two children with hemoglobin S-beta-thalassemia.
  J Pediatr 1995 126(4) 581.
• Mahoney DH. The acute chest syndrome in children
  and adolescents with sickle cell disease.
  www.uptodate.com
• Morris C, E Vichinsky, L Styles. Clinical
  assessment for acute chest syndrome in febrile
  patients with sickle cell disease is it accurate
  enough? Ann Emerg Med 1999 34(1).

26
Sources, continued

• Miller ST, E Wright, M Abboud, B Berman, B Files,
  CD Scher, L Styles, RJ Adams. Impact of chronic
  transfusion on incidence of pain and acute chest
  syndrome during the stroke prevention trial
  (STOP) in sickle-cell anemia. J Pediatr 2001 139
  (6).
• Needleman JP, LJ Benjamin, JA Sykes, TK Aldrich.
  Breathing patterns during vaso-occlusive crises
  of sickle cell disease. Chest 2002 122(1).
• Perseu L. The effect of the beta thalessemia
  mutation on the clinical severity of the sickle
  beta thalassemia syndrome. Haematologica 1989
  74(4) 341.
• Quinn CT, GR Buchanan. The acute chest syndrome
  of sickle cell disease. J Pediatr 1999135(4).
• Rogers ZR, GR Buchanan. Bacteremia in children
  with sickle hemoglobin C disease and sickle beta
  thalassemia is prophylactic penicillin
  necessary? J Pediatr 1995 127(3) 348.
• Rucknagel DL. Progress and prospects for the
  acute chest syndrome of sickle cell anemia. J
  Pediatr 2001 138(2).
• Sullivan KJ, SR Goodwin, J Evangelist, RD Moore,
  P Mehta. Nitric oxide successfully used to treat
  acute chest syndrome of sickle cell disease in a
  young adolescent. Critical Care Medicine 1999
  27(11) 2563.
• Wethers DL. Sickle cell disease in childhood
  part I. Laboratory diagnosis, pathophysiology and
  healthy maintenance. American Family Physician
  2000 62(5).
• Wethers DL. Sickle cell disease in childhood
  part II. Diagnosis and treatment of major
  complications and recent advances in treatment.
  American Family Physician 2000 62(6).