A 20-year-old male presented with a history of delayed puberty, decreased growth, severe joint pain, weakness, and cough. His past history included episodes of jaundice, body aches, pains, and gallstones. Examination found decreased growth, delayed puberty, anemia, jaundice, leg ulcers, and enlarged spleen. Laboratory tests showed anemia and abnormalities consistent with sickle cell disease. The patient's family history also included similar problems in a cousin who died at a young age after receiving blood transfusions. The presentation and family history are consistent with sickle cell disease.

1. Dr. Afzal Haq Asif
Associate Professor
COCP, KFU
Dec 02, 2013
Dr Afzal Haq Asif
1

2. Case
A 20 years old male reported with history of delayed
puberty, decreased growth, severe joint pain, severe
weakness and cough. He also have defective vision
Past history reveals episodes of jaundice, severe body
aches and pains, and gall stones
In his childhood he used to have frequently fever
swelling of the hands and feet and pain in the chest,
abdomen, limbs, and joints and nosebleeds and
frequent upper respiratory infections
Dec 02, 2013
Dr Afzal Haq Asif
2

3. Case
O/E; Decreased growth, delayed signs of puberty
severely anemic, mildly jaundiced, ulcers on right leg,
inflamed gums
Enlarged spleen.
Temp 39.1°C, diaphoretic, and uncomfortable.
HR of 90, BP 116/84 mm Hg, RR 26
O2 Sat 89% and improved to 94% with 6 L/min
via face mask.
Family history: similar problem in one of his cousin
who died at the age of 30, who used to receive blood
transfusions
Dec 02, 2013
Dr Afzal Haq Asif
3

4. Case
WBC of 17 500/μL
62% neutrophils
25% lymphocytes
9% monocytes
2% eosinophils
1% basophils
1% atypical lymphocytes.
Hb was 8 g/dL
reticulocyte 25%
platelet 206 000/μL.
Dec 02, 2013
Dr Afzal Haq Asif
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5. Case
Which lab test you will advise?
What is most probable cause of patients problem?
What complications the patient may have?
Design therapeutic objectives for this patient?
Dec 02, 2013
Dr Afzal Haq Asif
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6. Dec 02, 2013
Dr Afzal Haq Asif
6

7. Hemoglobin: Introduction
Normal: alpha gene at Chr 16, beta at Chr.11
HbA:
2 Alfa + 2 beta
97-98%
Hb A2: 2 Alfa + 2 delta
2-3%
Hb F;
2 alfa + 2 gamma
>1%
Hb S:
Glutamic acid at 6 in beta chain replaced with
Valine
HbC:
……………………………………………………………………….Lysine
Thalassemia:
Thalassemia describes a group of inherited disorders
characterized by reduced or absent amounts of hemoglobin
Alfa: less alfa chain Chr.16
Beta: Chr.11: less beta, beta thalassemia minor
 or no beta, all alfa chain beta thalassemia major :
Dec 02, 2013
Dr Afzal Haq Asif
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8. SICKLE CELL DISEASE
An autosomal recessive genetic disease of Hb synthesis
Result of a single–amino acid substitution in the β-globin
chain of the Hb molecule, valine for glutamate at position
6
Sickle cell trait: Pt. with hetrozygous genotype
Epidemiology in KSA:
 “The prevalence of SCD in Saudi Arabia varies
significantly in different parts of the country, with the
highest prevalence is in the Eastern province, followed by
the southwestern provinces. The reported prevalence for
sickle-cell trait ranges from 2% to 27%, and up to 2.6%
will have SCD in some areas”
 Ann Saudi Med. 2011 May-Jun; 31(3): 289–293.
Dec 02, 2013
Dr Afzal Haq Asif
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9. Comparison with USA
African Americans:
SCD: 0.3%
Saudia:
Saudia:
SCT: 8.0%
Dec 02, 2013
Dr Afzal Haq Asif
2.6%
2-27%
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10. Dec 02, 2013
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11. Dec 02, 2013
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12. Dec 02, 2013
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13. Dec 02, 2013
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14. Pathophysiology
 Normal Hemoglobin A: two alpha and two beta chains, 96-97%
 Glutamic acid is on the 6th position of the Beta chain
 Hemoglobin S: Chr.11
 Due to a one point mutation, glutamic acid is replaced by valine at
position 6 in beta chain
 HbS: during deoxygenation


Polymerize
Crystellize


in RBC’s…………………….leading to………………….. Sickling of Cells:
RBC cell membrane changes:
activate coagulation pathways
 Rate of polymerization and sickling augmented by:
 Hypoxia, deoxygenation
 Infections,
 Acidosis,
 Physical exercise,
 Vasoocclusion due to cold as well as hypertonic dehydration
Dec 02, 2013
Dr Afzal Haq Asif
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15. Clinical Presentation
Sickle cell trait (SCT) Carrier, recessive
Rare painless hematuria; normal Hgb level; heavy
exercise under extreme conditions may provoke gross
hematuria and complications
Sickle cell anemia (SCA)
Anemia
Chronic hemolytic anemia: jaundice, gall stone,
splenomegaly
Acute Pain crises,
Microvascular disruption of organs (spleen, liver, bone
marrow, kidney, brain, and lung), gallstone, priapism,
leg ulcers, anemia (Hgb 7-10 g/dL)
Dec 02, 2013
Dr Afzal Haq Asif
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16. Clinical Presentation
Sickle cell hemoglobin C:
Painless hematuria
Aseptic necrosis of bone: less common
Vaso-occlusive crises less common, occur late in life
Pregnancy-related problems; mild anemia (Hb 10–12
g/dL)
Sickle cell β-thalassemia
Rare crises; milder severity than sickle cell disease
because of production of HbA;
Hb 10–14 g/dL with micro-cytosis
Sickle cell Alfa-thalassemia or β0 Thalassemia
No HbA production; severity similar to sickle cell anemia;
Hb 7–10 g/dL with microcytosis
Dec 02, 2013
Dr Afzal Haq Asif
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17. Diagnosis
Laboratory findings
RBC’s: 5-50 % sickled
Low hemoglobin; 7-10%; HbA; 0%; HbS 85-98%
Increased reticulocytes: 10-25%, platelet, and leukocyte
counts; and sickle forms on the peripheral smear
Routine neonatal screening programs: DNA from
fetal cell for mutation
Dec 02, 2013
Dr Afzal Haq Asif
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18. Goals of Therapy
To reduce
Hospitalizations,
Complications,
Mortality
Dec 02, 2013
Dr Afzal Haq Asif
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19. Treatment
GENERAL PRINCIPLES
 No Treatment for the primary disease
 Lifelong multidisciplinary care
 general measures,
 preventive strategies,
 treatment of complications and acute crises.
Routine immunizations plus influenza, meningococcal,
and pneumococcal vaccinations.
Prophylactic penicillin for children with sickle cell disease
until they are 5 years old.
 Penicillin V potassium, 125 mg orallytwice daily until 3 years of age and
then 250 mg twice daily,
 Benzathine penicillin, 600,000 units intramuscularly every 4 weeks.
Folic acid, 1 mg daily, is recommended in adult patients,
pregnant women, and patients of all ages with chronic
Dec 02, 2013
hemolysis. Dr Afzal Haq Asif
19

20. Fetal hemoglobin stimulators and other
strategies
 Hydroxyurea, a chemotherapeutic agent
 Stimulate HbF by stimulating erythropoiesis
 In patients with frequent painful episodes, severe symptomatic anemia, acute chest
syndrome, or other severe vasoocclusive complications.
 Butyrate and 5-aza-2-deoxycytidine.
 Chronic transfusion every 3 to 4 weeks The optimal duration is
unknown
 to prevent stroke and stroke recurrence in children.
 Maintain HbS of less than 30% of total hemoglobin..
 Risks include, hyperviscosity, viral transmission (requiring hepatitis A and B
vaccination), volume and iron overload, and transfusion reactions.
 Allogeneic hematopoietic stem cell transplantation
 The only therapy that is curative.
 Best candidates are




Dec 02, 2013
younger than 16 years of age,
With severe complications,
Have HLA-matched donors.
Risks: mortality, graft rejection, and secondary malignancies
Dr Afzal Haq Asif
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21. Stem Cells in the Treatment of SCD
Skin stem cells cure mice of sickle cell anemia
Success is proof that technique has potential to
cure disease
http://www.msnbc.msn.com/id/22136029/
Dec 02, 2013
Dr Afzal Haq Asif
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22. Complications
Acute Chest Syndrome
Septicemia
Stroke or CVA
Acute splenic sequestration crisis (ASSC)
Aplastic Crisis
VasoOcclusive pain: Sickle cell crisis
Severe pain is an emergency called acute sickle
cell crisis
Osteomyelitis
Dec 02, 2013
Dr Afzal Haq Asif
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23. Sickle Cell Crisis
Rapid diagnosis and treatment are necessary to minimize
morbidity and mortality.
Dec 02, 2013
Dr Afzal Haq Asif
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24. Case 1
A 16-year-old boy with a history of SCD presented
to the ED with a 3-day history of fever, cough, and
SOB.
Five days prior, he had been evaluated and
treated for severe pain in his legs and arms.
He complained of persistent and worsening pain
in both his lower extremities and pain in his chest,
in spite of oral narcotic therapy.
Dec 02, 2013
Dr Afzal Haq Asif
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25. Case 1
His medical history included multiple, vasoocclusive,
painful crises, including an episode of priapism, and
he had received multiple blood transfusions over his
lifetime.
Dec 02, 2013
Dr Afzal Haq Asif
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26. Case -1
On examination
Temp 39.1°C, diaphoretic, and uncomfortable.
HR of 80, BP 116/84 mm Hg, RR 26
O2 Sat 89% and improved to 94% with 6 L/min
via face mask.
Conjunctivae were icteric
Mucous membranes were moist
Dec 02, 2013
Dr Afzal Haq Asif
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27. Case 1
Cardiovascular II/VI systolic ejection murmur.
labored respiration with suprasternal and
intercostal retractions.
decreased breath sounds in the right midzone
and lower zone, and scattered crepitations on the
right side.
no lower extremity edema
Abdominal examination Normal
CNS Normal
Dec 02, 2013
Dr Afzal Haq Asif
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28. Case 1 500/μL
WBC of 17
62% neutrophils
25% lymphocytes
9% monocytes
2% eosinophils
1% basophils
1% atypical lymphocytes.
Hb was 8 g/dL
reticulocyte 25%
platelet 206 000/μL.
ABG on room air
•PO2 59 mm Hg
•PCO2 29 mm Hg
•pH 7.32
•HCO3 13 mmol
A chest x-ray right lower-lobe consolidation
with a moderate right pleural effusion.
Dec 02, 2013
Dr Afzal Haq Asif
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29. Case-1
In the ED, he received
 antipyretics
 supplemental oxygen
 cefotaxime 2 g IV
 packed red blood cell transfusion was initiated after 20 mL/kg of
normal saline was infused
Over the next hour, while waiting for a bed to become
available in the intensive care unit, the nurse noticed that
the patient's oxygen saturation continued to worsen, and he
was hypoxic even on supplemental oxygen of 12 L/min via
nonrebreather mask.
He underwent emergency intubation
A diagnostic pleural tap was performed which
demonstrated an exudative fluid.
The resulting Gram stain and culture were negative.
Dec 02, 2013
Dr Afzal Haq Asif
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30. Case 1
What is it
Dec 02, 2013
Dr Afzal Haq Asif
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31. Acute Chest Syndrome.1
1 of the most serious and life-threatening
complications of SCD
Leading cause of mortality and morbidity
in affected patients, since the impact of
more effective antimicrobials and the
pneumococcal vaccine
Caused by a vasoocclusive crisis involving
the pulmonary vasculature.
Not distinguishable from pneumonia
Dec 02, 2013
Dr Afzal Haq Asif
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32. Acute Chest Syndrome.1
Dx
New infiltrate on chest radiograph in combination
with at least 1 clinical sign or symptom
Chest pain
Cough
Wheezing
Tachypnea
•Fever and cough are the most common in children
•chest pain, sob, and chills are common in adults.
Fever
Dec 02, 2013
Dr Afzal Haq Asif
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33. Acute Chest Syndrome.1
Common causes
Pulmonary infection:
Mycoplasma pneumoniae more
commonly associated with acute chest
syndrome
Thromboemboli
Fat emboli
Rib infarction
Possible causes
Iatrogenic: excessive
hydration or
narcotic use
Infection and fat emboli were the most common
identifiable causes.
Vichinsky EP, Neumayr LD, Earles AN, et al. Causesand outcomes of the acute chest syndrome in sickle cell disease.
National Acute Chest Syndrome Study Group [published erratum appears in N Engl J Med 2000; 343:824]. N Engl J Med
.2000;342:1855–65
Dec 02, 2013
Dr Afzal Haq Asif
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34. 1.Acute Chest Syndrome
Therapeutic Modalities
Supportive measures
 Oxygen for hypoxia
 Appropriate hydration
 Appropriate pain control
Antibiotics: third-generation cephalosporin + macrolides
Transfusion therapy:
 Reports of dramatic improvement in clinical condition after
initiation of transfusion


Simple transfusion
Exchange transfusion
Experimental therapy
 Nitric oxide
 Corticosteroids
Bodo I, Khoury H, Blinder M. Rapid resolution of the acute chest syndrome of sickle cell disease after automated red cell exchange.
Blood 1997;90 Suppl 1:23b
Dec 02, 2013
Dr Afzal Haq Asif
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35. 2.Septicemia
SCD pts have impaired immunologic function that is
caused by splenic dysfunction.
Impairment of splenic function can occur in infants as
young as 3 months.
High risk for encapsulated organisms such as S
pneumoniae and H influenzae.
Recommended antibiotic
 Third-generation cephalosporin; ceftriaxone, or cefotaxime
 Vancomycin should be added to protect against penicillinresistant strains of S pneumoniae if suspected until culture
results become available
 All SCD patients with fever must be managed with extreme caution
because of the risk of overwhelming bacteremia which can rapidly
lead to septic shock
Dec
 02, 2013
Dr Afzal Haq Asif
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36. 3.Stroke or CVA
Major complication of SCD
Is a leading cause of death in both and disability children
and adults
The most common is blockage of the intracranial internal
carotid and middle cerebral arteries.
 Patients with stroke usually present with obvious signs
such as acute hemiparesis, aphasia or dysphasia, seizures,
severe headaches, cranial nerve palsy, altered mental
status, or coma.
The most common tends to be hemiparesis.
Can be very subtle, such as a slight limp
Dec 02, 2013
Dr Afzal Haq Asif
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37. Treatment: Stroke or CVA
Initial therapy is
exchange transfusion in an ICU setting to reduce Hb
S to less than 30% of total Hb.
After acute clearance of symptoms should be started
on a long-term transfusion therapy.
If not on a long-term transfusion program have an
80% chance of recurrent stroke within 3 years of the
initial event
Long-term transfusion involves regularly scheduled
blood transfusions aimed at reducing the percentage
of Hb S and not at normalizing the Hb level.

Dec 02, 2013
Dr Afzal Haq Asif
37

38. A 44-year-old diabetic presented to the ED
complaining of nonexertional dyspnea and severe
back pain for 12 hours before presentation.
The patient reported malaise, fatigue, weakness
that started 3 days before, chronic blurred vision,
insomnia, and anxiety.
The remainder of the review of systems was
unremarkable.
Dec 02, 2013
Dr Afzal Haq Asif
38

39. Case 2
O/E
HR
RR
Temp
BP
37C
o2 sat
101 bpm
31/min
148/62 mm Hg
99%.
The patient was awake, alert, and oriented
He was motionless to avoid back pain.
Dec 02, 2013
Dr Afzal Haq Asif
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40. Case 2
O/E
Normal S1 and S2
Chest Normal
Strength was 4/5 in all 4 extremities.
Deep tendon reflexes were normoactive.
Normal flexor plantar response was obtained, and no
meningismus
Dec 02, 2013
Dr Afzal Haq Asif
40

41. Case 2
WBC
11.2 × 109/L (with no abnormalities in
differential count)
Hg of
9.4 g/dL
HCT of
26.3%
MCVof
76.7 Femtoliters (fL)
MCH
27.3 pg
Platelets of
144 × 109/L.
Dec 02, 2013
Dr Afzal Haq Asif
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42. Case 2
• Blood glucose
• AST
• ALT
• ALK Ph
Total bilirubin level of
79 U/L
30 of U/L
475 U/L
2.3 mg/dl
Direct bilirubin level of
0.8 mg/dL
267 mg/dL
ESR 54 mm/h
C-reactive protein level of 2.3 mg/dL.
ECG Normal
MRI of the lumbar spine was Normal
Dec 02, 2013
Dr Afzal Haq Asif
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43. Case 2
Despite aggressive narcotic treatment of back
pain, the pain continued to increase
CT abdomen: an enlarged spleen
1 hour later hypotension of 90/50 mm Hg.
The new CT scan of the abdomen revealed an
increasing splenomegaly compared with the
previous one
Dec 02, 2013
Dr Afzal Haq Asif
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44. Case 2
Despite transfusion therapy, the patient's Hb
progressively dropped to a level of less than 4 mg/dL
over the course of 3 hours, with thrombocytopenia
(<50 × 109/L).
immediately transferred to an ICU.
altered mental status.
Airway protection with intubation and mechanical
ventilation were initiated.
As the patient was rapidly deteriorating, an emergent
splenectomy was performed
The patient recovered every organ function and, 6 months
later, has resumed his normal activities
Dec 02, 2013
Dr Afzal Haq Asif
44

45. 4.Acute splenic sequestration crisis (ASSC)
 Clinical Presentation:
 Sudden impounding of red blood cells by the spleen
 Characterized by the rapid fall in hemoglobin concentration, rise in
reticulocyte count, and splenomegaly
 Requires prompt recognition and treatment.
 In the adult patient, ASSC is extremely rare.
 Hypotension caused by large volumes of blood (mainly sickled
cells)
entrapped in the spleen.
 Hb levels may fall acutely more than 2 g/dL less than the patient's normal
value, causing circulatory compromise
Treatment:
 Prompt diagnosis and therapy with RBC transfusions
 Surgical splenectomy may be indicated in certain patients to prevent recurrences
Dec 02, 2013
Dr Afzal Haq Asif
45

46. Aplastic Crisis.5
Temporary cessation of red cell production with a
corresponding decrease in the reticulocyte count.
Approximately 80%, are thought to be caused by human
parvovirus B19 infection
Diagnosis is made by comparing baseline blood and
reticulocyte counts to those obtained during the acute
illness.
Sign Symptoms: , tachypnea, tachycardia, or hypoxia
Treatment:
 Simple blood transfusion to raise serum Hb back to the patient's
baseline and to prevent heart failure secondary to severe anemia.
 Parvovirus B19 is contagious, affected persons should be isolated
from pregnant women, who are at risk for miscarriage with
infection, and from immuno-compromised patients and those
with chronic illness
Dec 02, 2013
Dr Afzal Haq Asif
46

47. Osteomyelitis.6
Most commonly caused by Salmonella species or
Staphylococcus aureus
Bone pain or joint pain with localized swelling
and decreased range of motion, along with fever,
should alert the physician to the possibility of
osteomyelitis.
Increased white blood cell count and elevated
ESR
Broad-spectrum antibiotic:
Ceftriaxone:
Dec 02, 2013
Dr Afzal Haq Asif
47

48. Priapism.7
Painful prolonged erection of the penis
Caused by sickling of the red blood cells producing venous
stasis in the erectile tissue of the penis.
The resulting stasis causes ischemia, hypoxia, and pain.
Treatment:
 Initial treatment involves intravenous hydration and analgesia.
 Antianxiety agents
 Vasoconstrictors to force blood out of corpus cavernosum:
 Phenyl ephedrine
 Epinephrine
 Vasodilators: to relax smooth muscles:


Terbutaline
Hydrallazine
 Episodes refractory to this initial management include direct
irrigation of the corporeal bodies of the penis
Dec 02, 2013
Dr Afzal Haq Asif
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49. Dec 02, 2013
Dr Afzal Haq Asif
49

50. 8.Vaso-occlusive pain Crises: Summary
 Most common symptoms of SCD
 Severe pain
 Caused by sickle-shaped red blood cells trapped in small blood vessels
causing localized ischemia.
Triggered by
 Dehydration, fever, cold exposure, and emotional stress
 Therapy
 Intravenous/Oral hydration
 Pain management
 It is useful to assess pain in a standard manner using pain
measurement scales ……………..See next
Causal Treatment: (treatment of the cause)
 Poloxamer 188 (Flocor) a surfactant returns RBCs to a non
adhesive state and blocks RBC aggregation to enhance blood flow
in ischemic areas
Dec 02, 2013
Dr Afzal Haq Asif
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51. Pain scale
0
– Pain free.
 Mild Pain – Nagging, annoying, but doesn't really interfere with daily living
activities.
 1 – Pain is very mild, barely noticeable. Most of the time you don't think
about it.
 2 – Minor pain. Annoying and may have occasional stronger twinges.
 3 – Pain is noticeable and distracting, however, you can get used to it and
adapt.
 Moderate– Interferes significantly with daily living activities.
 4 – Moderate pain. If you are deeply involved in an activity, it can be
ignored for a period of time, but is still distracting.
 – Moderately strong pain. It can't be ignored for more than a few
minutes, but with effort you still can manage to work or participate in
some social activities.
 6 – Moderately strong pain that interferes with normal daily activities.
Difficulty concentrating.
Dec 02, 2013
Dr Afzal Haq Asif
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52. Pain Scale
 Severe Pain – Disabling; unable to perform daily living activities.
 7 – Severe pain that dominates your senses and significantly limits your
ability to perform normal daily activities or maintain social relationships.
Interferes with sleep.
 8 – Intense pain. Physical activity is severely limited. Conversing
requires great effort.
 9-Excruciating pain. Unable to converse. Crying out and/or moaning
uncontrollably.
 10 – Unspeakable pain. Bedridden and possibly delirious. Very few
people will ever experience this level of pain
Dec 02, 2013
Dr Afzal Haq Asif
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53. Pain Management
Mild to moderate pain
 NSAID’s or acetaminophen.
Moderate pain
 Weak opioid, such as codeine or hydrocodone.
Severe pain
 IV opioid morphine, hydro-morphone, fentanyl, and methadone.
 Titrate to pain relief and then administer on a scheduled basis with as-
needed dosing for breakthrough pain.
 Patient-controlled analgesia can be used
 Avoid
 Meperidine should be avoided because accumulation of the normeperidine
metabolite can cause neurotoxicity, especially in patients with impaired renal
function
 Minimize dependence /addiction by :
 Aggressive pain control,
 Frequent monitoring,
 Tapering medication according to response
Dec 02, 2013
Dr Afzal Haq Asif
53

54. Principles of pain management (WHO guidelines)
 Morphine is the preferred agent in treatment of sickle cell pain.
 Start by the mouth
 By the Clock:
 Regular analgesia (4-6 hourly) with breakthrough doses when needed
 By the ladder:
 Patients move up the ladder or may also move down the ladder if pain decreases.
 Individualized Therapy:
 Start with higher step for Patients presenting with moderate to severe pain.
 Some don’t tolerate oral medication, plan for alternative route.
 Consider non drug therapies. as well
 No standard dose of opioid - morphine from 5mg to 1000mg every four hours.
 With attention to detail:
 Total analgesia usage should be monitored every 24 hours,
 Breakthrough doses should be adjusted in line with changes to regular medication.
 New pain should be assessed promptly
 Patients should be informed of possible adverse drug effects.
Dec 02, 2013
Dr Afzal Haq Asif
54

55. Dec 02, 2013
Dr Afzal Haq Asif
55

56. When and how IV
REASSESS before starting IV opioids and ADJUST dose
frequently, but not before 8 hours
Scheduled IV Narcotic Dosing for 24 hours, round the
clock
Morphine sulfate: 0.1 mg/kg,
every 3-4 hours.
5 - 10mg, IV scheduled
Hydromorphone: 0.015 mg/kg, 0.75 - 2mg, IV scheduled
every 3-4 hours.
Monitor vital signs and pain level, using the pain scale,
before and after every dose
Dec 02, 2013
Dr Afzal Haq Asif
56

57. IV dosing: cares
Doses should be based on level of tolerance to
opioids. Most SCD patients have some opioid
tolerance.
Maximum analgesic effect within 10-15 minutes and
will usually last 2-3 hours.
 Consider around-the –clock (ATC) (patient may
refuse) to ensure the patient is offered the medication
consistently at the preferred interval.
Dec 02, 2013
Dr Afzal Haq Asif
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58. Scheduled IV Narcotic Dosing -- Opiate Tolerant patients
Convert the patients usual oral dose to IV:
Morphine IV/PO ratio: 1:3
Hydromorphone IV/PO ratio: 1:5
 Example: Patient is taking morphine SR 60mg PO
q12h and is now in pain crisis, requiring an additional
10mg PO q4 hours. 10mg X 6 = 60 mg + (60 mg x 2) =
180 mg PO morphine/day.
 Convert PO to IV: 180mg PO / 3 = 60mg IV over 24h =
10mg IV q4h
 Start with 50-75% of the calculated equianalgesic dose
if changing / converting to a different opioid to allow
for incomplete cross-tolerance between opioids.
Dose adjustment for taper
Decrease dose by 25% per day once the patient’s pain is
under control for 24 hours
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59. Monitoring the patient
Chest X-ray: Order for any patient with cardiopulmonary
complaints, hypoxia, know chronic lung disease, fever,
tachycardia, or tachypnea.
Complete blood count q24 hours
Comprehensive metabolic panel, magnesium,
phosphorous q48 hours
Keep magnesium level > 2 mg/dL:
 Magnesium < 1.8 mg/dL, replace with IV magnesium
 May need to follow with daily oral supplementation
 Magnesium > 1.8 mg/dL, replace with oral product
Lactic dehydrogenase (LDH) q72 hours
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60. PCA

Patient-controlled analgesia (PCA) is a method of
pain control that gives patients the power to control
their pain. In PCA, a computerized pump called the
patient-controlled analgesia pump, which contains a
syringe of pain medication as prescribed by a doctor,
is connected directly to a patient's intravenous (IV)
line.
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61. Patient Controlled Analgesia (PCA)
 For setting where scheduled IV dosing is not controlling the patient’s pain.
 There is no “PCA protocol.”
 Continuous opioid infusion
 should not be used in opioid naive patients until assessed the needs over a
given period of time (i.e. after 12 hrs of demand/bolus doses)
 Only use a in patients with a known opioid requirement.
 Those patients taking daily opioids: calculate an equianalgesic dose of
currently used opioids over past 24 hrs and then convert to an
equianalgesic basal rate
 Example: Patient taking 120 mg extended release morphine Q 12 hrs now
in crisis taking an additional 15 mg immediate release morphine q 4 hrs. 15
mg X 6 = 90 mg + (120 mg X 2)= 330 mg PO morphine/day. Convert to IV
equivalent 330/3= 110 mg IV morphine/24 hrs = 4-5 mg/hr.
 If changing/converting to a different opioid, start with 50-75% of the
calculated equianalgesic dose to allow for incomplete cross-tolerance
between opioids. Afzal Haq Asif
Dec 02, 2013
Dr
61

62. Titration of Dose
Basal infusions will take at least 8 hours to reach steady state.
Do not titrate the basal rate more frequently than every 8
hours.
Never increase basal rate by more than 100% at any one time.
Demand Doses: Adjust demand dose size every 30-60 minutes
to quickly reach adequate analgesia.
 For mild-moderate pain increase dose by 25-50%.
 For moderate-severe pain increase dose by 50-100%.
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63. Converting IV to Oral Pain Management
Once the IV dose has been tapered to 50% of the
initial dose, start oral morphine or hydromorphone:
Morphine & Hydromorphone: Add total daily dose of
IV morphine received; multiply by 2-3 to determine
total daily dose.
Immediate release formulations should be
administered on a scheduled basis, every 4 hours.
Sustained release formulations should be
administered every 12 hours.
Morphine to oral Oxycodone:
Convert morphine 10mg IV q4h to oxycodone 30 mg PO
q6h.
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64. Adjunct therapies
Bowel regimen: All patients on opioids must also be
on a bowel regimen of stool softener and a cathartic.
May administer Hydroxyzine 25-50 mg PO with each
narcotic dose.
Itching:
Diphenhydramine 50mg IV/PO can be given with the
initial dose of morphine and PRN
Diphenhydramine may be given in conjunction with
opiates for additive effect.
 Nausea: administer prochlorperazine 10mg PO PRN
nausea.
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65. Evaluation of Therapeutic outcomes
All patients should be evaluated regularly to establish
change in baseline, parameters
Laboratory evaluations
 complete blood cell and reticulocyte
counts
HbF level.
Kidney
and Liver function tests and pulmonary
function
Patients should be screened for retinopathy.
The efficacy of hydroxyurea can be assessed by monitoring
the number, severity, and duration of sickle cell crises.
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66. References and further reading
Pharmacotherapy: pathophysiologic approach
http://www.nejm.org/doi/full/10.1056/NEJM19940603
302303
http://www.ncbi.nlm.nih.gov/pubmed/11694150
Vaso-occlusive disorders
Future prospects: Stem cell therapy:
http://newsroom.ucla.edu/portal/ucla/ucla-stem-cell-
gene-therapy-for-246937.aspx
For some references please visit:
https://www.facebook.com/COCP.Therapeutics?
ref=hl
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67. Thank You Very Much
Dec 02, 2013
Dr Afzal Haq Asif
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68. Thank
you
very
much
Dec 02, 2013
Dr Afzal Haq Asif
68