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Pediatric hematology-oncology-ward-officer-handbook
- 1. Paediatric Haematology/Oncology
Ward Officer’s
Handbook
Texas Children’s Cancer Center
&
Hematology Service
International Program
Editor: Parth S. Mehta, MD
Assistant Professor of Pediatrics
Baylor International Pediatric AIDS Initiative at Texas Children’s Hospital
Baylor College of Medicine
Texas Children’s Hospital
Houston, Texas USA
© Baylor College of Medicine 2010
- 3. Paediatric Haematology/Oncology Ward Officer’s Handbook
General 4
1. Pain control 4
2. Blood transfusion therapy 4
3. Transfusion reactions 7
4. Intravenous fluids, central lines & useful formulas 8
Oncology 9
1. Neutropenia 9
2. Fever & neutropenia 10
3. Anti-Fungal Therapy 12
4. Antiviral Therapy 14
5. Pneumocystis jerovecii (PCP) Prophylaxis 14
6. Anti-emetic Medications 16
7. Anaphylaxis Precautions 18
9. Oncologic Emergencies 21
10. Immunizations in Oncology Patients 24
11. Constipation 24
Hematology 26
1. Sickle cell disease 26
2. Sickle cell disease with fever 27
3. Sickle cell vaso-occlusive crisis 28
4. Pre-operative preparation of sickle cell patients 29
5. Transfusion therapy in sickle cell disease 30
7. Treatment of bleeding in patients with Hemophilia A 31
8. Treatment of bleeding in patients with Hemophilia B 33
9. Von Willebrand’s Disease 35
10. Immune Thrombocytopenic Purpura (ITP) 36
References 40
© Baylor College of Medicine 2010
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General
1. Pain control
• Intravenous medications
• Morphine sulfate 0.1 - 0.2 mg/kg/dose every 2-4 hrs (Max single dose 15 mg)
• Oral medications
• Ibuprofen 10 mg/kg/dose every 6-8 hours (Max single dose 800 mg, 2400
mg/day)
• Avoid this medication in patients with thrombocytopenia
• GastrointestinaI prophylaxis with ranitidine recommended
• Ranitidine 2-4 mg/kg/dose twice daily
• Oral morphine sulfate
• 0.3 to 0.6 mg/kg/dose every 4-6 hrs
• Intravenous (IV) to oral (PO) dosing conversion is 1:3; 1 mg IV is equivalent
to 3 mg PO
• Different formulations exist including sustained release & immediate re-
lease; refer to prescribing information contained within medication packag-
ing
2. Blood transfusion therapy
• Infection risk of blood transfusion estimates
• National transfusion centers ought to have more accurate incidence figures for
each setting
• Incidence estimates taken from Transfusion 2002; 42:975-79
• HIV 1:2,135,000
• Hepatitis B 1:220,000
• Hepatitis C 1:1,935,000
• Bacterial contamination 1:2,000 platelet units
• General Guidelines for Transfusion Therapy
• Prior to initial transfusion, HIV & Hepatitis B & C screening is recommended
• Premedication
© Baylor College of Medicine 2010
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• Used in patients with a history of prior allergic or febrile transfusion reaction
• One or more of these medications can be used:
• Paracetomol 15 mg/kg PO (Max dose 1000 mg)
• Diphenhydramine 0.5 mg/kg (Max dose 50 mg)
• Hydrocortisone 2 mg/kg (Max dose 100 mg)
• Packed Red Blood Cell (pRBC) transfusion
• Transfuse 10-15 ml/kg pRBC over 2-4 hours
• Response varies depending on concentration of unit, but expect 2-3 g/dL
rise in hemoglobin for each 10-15 ml/kg transfusion given
• Patients with long-standing anemia due to iron deficiency can often be ma-
naged without transfusion therapy
• Pre- & post-transfusion diuretic therapy with furosemide is not routinely
recommended and should be given only if the clinical condition warrants it
(e.g. cardiac dysfunction)
• Whole blood is frequently used where pRBC are not available. To achieve a
similar rise as noted above in hemoglobin, transfuse 20 ml/kg whole blood over
2-4 hours
• Platelet transfusion
• Dosing of transfusion volume
• < 8 kg - give one unit (5 ml/kg)
• > 8 kg - give one random unit/10 kg body weight
• Maximum - 6 random donor units or 1 pheresis unit (where available)
• 1 single pheresis unit is equivalent to 6 random donor units
3
• Expect increase in platelet count by 50,000/mm with above guidelines
• If there is concern for poor response check platelet count from 10-60 mi-
nutes post-transfusion to assess response
• Cautions
• Contraindicated in patients with Thrombotic Thrombocytopenic Purpura
(TTP) and Heparin-Induced Thrombocytopenia (HIT)
• No benefit in patients with Idiopathic thrombocytopenia purpura (ITP)
unless there is life-threatening bleeding
© Baylor College of Medicine 2010
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Platelet count (/mm3) Transfusion Strategy
< 10,000 High risk for bleeding; transfusion likely indi-
cated except in ITP without life-threatening
bleeding (see ITP section)
10,000 - 20,000 Transfusion likely needed if patient has infec-
tion, coagulopathy, splenomegaly, or bleeding
20,000 - 50,000 Transfusion for active bleeding, patients with
brain tumor, or for invasive procedures. Stable
patients rarely ever require transfusion
> 50,000 Transfusion only if there is an underlying plate-
let dysfunction or there is significant bleeding
© Baylor College of Medicine 2010
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• Plasma Transfusion
• Indications for Fresh Frozen Plasma (FFP) use:
• Massive transfusion of pRBC (greater than one blood volume within 24
hours)
• Active bleeding or surgery in patient with prolonged Prothrombin Time
(PT) and/or activated partial thromboplastin time (aPTT) secondary to
factor deficiency for which specific factor replacement is not available
• Dosing of Plasma
• 1 unit contains 200-250 ml
• FFP contains 1 unit/mL of coagulation factors
• 10-15 ml/kg will result in 15-20% rise in factor level
• Factor V & Factor VII may be exceptions as the former is labile & the
latter has a short half-life
3. Transfusion reactions
• Signs & symptoms of transfusion reactions are varied, and can include any or all of
the following:
• Chills & fever
• Hemoglobinuria
• Urticaria
• Chest/spine pain
• Shortness of breath
• Anxiety or restlessness
• Hypotension
• Management of transfusion reaction
• Stop transfusion, change IV tubing, flush line & start normal saline (NS) at 1600
ml/m2/day
• If febrile or urticarial reaction give:
• Diphenhydramine 1 mg/kg PO (Max dose 50 mg)
• Paracetomol 15 mg/kg PO (Max dose 1000 mg)
• Hydrocortisone 2 mg/kg IV (Max dose 100 mg)
• In patients with anaphylaxis adrenaline should be given:
• Adrenaline 1:1000, give 0.01 mL/kg IV
• Adrenaline 1:10,000, give 0.1 mL/kg IV
• Once patient is stable, consider transfusion of additional products unless pa-
tient experienced hemolytic reaction, in such a case, discuss with specialist first
© Baylor College of Medicine 2010
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• Patients with a history of transfusion reactions can be given pre-medication with
diphenhydramine, paracetomol, and hydrocortisone - doses noted above
• If patient experiences only mild urticaria, give diphenhydramine & if symptoms
resolve, continue transfusion slowly
4. Intravenous fluids, central lines & useful formulas
2
• Maintenance IV fluid rate - 1600 ml/m /day
• Body surface area forumla:
• square root (weight [kg] x height [cm] / 3600
• Total Blood Volume (TBV)
• Premature neonate: 100 ml/kg
• Term neonate: 85 ml/kg
• 1 - 4 months age: 75 ml/kg
• > 4 months age: 70 ml/kg
• Plama Volume (PV)
• TBV x (1-Hct)
• Factor VIII Replacement
• 1 unit/kg raises level by 2%
• In anemic patients: dose Factor VIII = (desired level - current level) x PV
• Factor IX Replacement
• 1 unit/kg raises level by 1%
• In anemic patients: dose Factor IX = (desired level - current level) x PV x 2
• Central Lines: while frequently unavailable in the resource-limited setting, these do
come into use at times & sterile technique must be used in handling them
• Hickman/Broviac
• Flush lumens daily
• Heparin 300 units in 5 ml NS
• Dressing change twice per week
• Port-a-Cath
• Flush once per month
• Heparin 500 units in 5 ml NS
• Change dressing twice weekly while in use
© Baylor College of Medicine 2010
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• When central lines are in use, it is imperative to have anti-pseudomonal anti-
biotics such as piperacillin/tazobactam or ceftazidime if these patients are to
receive chemotherapy as pseudomonal line infections are more common & life-
threatening. These antibiotics also provide coverage of S. viridans, and there-
fore ciprofloxacin, while providing Pseudomonas coverage is not a suitable
substitute.
• Central lines should only be used if adequate skill in caring for them is availa-
ble, otherwise they present a greater risk than benefit
Oncology
1. Neutropenia
Neutropenia is defined as a decrease in Absolute Neutrophil Count (ANC):
ANC < 1500 Mild Neutropenia
ANC < 1000 Moderate Neutropenia
ANC < 500 Severe Neutropenia
ANC = total WBC * (% neutrophils + % bands)
Patients with neutropenia are at higher risk for serious infection and therefore:
• No suppositories or enemas with oncologist approval
• No rectal temperature or exam
• No incision & drainage of lesions without oncologist approval
• No NG tube, urine catheter, or LP without oncologist approval
• Prior to blood work or IV, area should be prepped with betadine
© Baylor College of Medicine 2010
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2. Fever & neutropenia
1. Assessment
• Patients should be assessed immediately upon arrival to the clin-
ic/emergency center, and antibiotic therapy instituted immediately after
obtaining blood work.
2. Work Up
• Complete physical exam including visual perianal exam remembering
that physical signs of infection may be subtle in the neutropenic patient.
• Full Blood Count (FBC), Blood Culture
• Obtain according to the presence of symptoms other than fever:
Renal Function Tests (RFT), urinalysis (UA), urine culture, Chest x-
ray (CXR), stool, and throat cultures
3. Therapy
• Monotherapy: Patients meeting the following criteria may be placed on
monotherapy with cefotaxime:
• All patients EXCEPT those with infant Acute lymphocytic leuke-
mia (ALL), acute mylogenous leukemia (AML), aplastic anemia
and bone marrow transplant
• Normal vital signs
• No chills
• No localizing symptoms or findings on physical exam
• Cefotaxime dosing:
1 month – 12 years: 50 mg/kg/dose IV q 8 hours
adults: 1-2 gm IV q 8 hours
(Max. Dose: 2 gm/dose)
© Baylor College of Medicine 2010
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• Multiagent therapy:
Patients not eligible for monotherapy should be started on one of
the following drug combinations:
• If isolated fever and neutropenia without evidence of cardiovascu-
lar compromise or specific PE findings, and patient not allergic to
the drugs:
Gentamicin: infants/children: 2-2.5 mg/kg/dose IV q 8 hrs
(Max Initial Dose: 120 mg/dose)
Cefotaxime: 1 month – 12 years: 75 mg/kg/dose every 8 hrs
adults: 2 gm IV q6 hours
Vancomycin can be added where clinically indicated (e.g. persistent
fever despite 48 hrs antibiotics)
Vancomycin dosing: children: 10-15 mg/kg/dose IV q6 hrs
(Max Dose: 500 mg/dose)
adults: 1 gm IVq 12 hrs or 750 mg IV q 8
hrs (Max Dose: 2 gm/day)
4. Other Considerations:
• When using aminoglycosides and/or vancomycin monitor BUN, Cr at init-
iation then twice weekly as these agents are nephrotoxic. Where availa-
ble, drugs levels can be obtained in therapy will continue for more than 3
days with either agent.
• All toxic appearing patients should be treated with a three-drug combi-
nation such as vancomycin, cefotaxime and gentamicin.
• Patients with specific infectious concerns such as interstitial pneumonitis
or acute abdomen should have antibiotic selections modified as the clini-
cal situation warrants.
• If the patient has a positive blood culture, daily cultures should be or-
dered and continued until negative x 3. Orders should also state to rotate
lumens for antibiotic infusion in patients with central lines.
© Baylor College of Medicine 2010
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• Where indwelling central lines (e.g. Broviac or Port-a-Cath) are available
& used, ready access to anti-pseudomonal antibiotics must be assured.
These agents include piperacillin/tazobactam, ticarcillin/clavulanic acid,
and ceftazidime. Without these medications, surgically placed central
lines should be used only with due regard to the risk incurred.
3. Anti-Fungal Therapy
• Consider in the persistently febrile patient with negative cultures, or the patient
with fever who has been neutropenic for greater than five days.
• Nystatin
• used for thrush
• infants 1 mL applied to each side of the mouth four times per day
• children and adults 5 mL PO four times per day swish and swallow
• Fluconazole
• used for prophylaxis in AML and for the treatment of candidiasis
• monitor liver function tests (AST/ALT q 2-3 weeks)
•
Children (>14 days): Prophylatic and treatment doses: 6 mg/kg/day
Max. Prophylactic Dose=200 mg/day
Max. Treatment Dose=400 mg/day
© Baylor College of Medicine 2010
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Fluconazole Indication Day One Daily Therapy Minimum Duration
Oropharyngeal Candidiasis 6 mg/kg 3 mg/kg 14 days
Esophageal Candidiasis 6 mg/kg 3 - 12 mg/kg 21 days
Systemic Candidiasis 6 - 12 mg/kg 28 days
• Amphotericin B
• follow BUN/Cr daily initially until full dose reached, then 3 x per week
• follow serum K+ daily
• Dosing: 0.25 mg/kg/day for the first dose
• Escalate up to 0.5-1 mg/kg/day as indicated by the clinical situation
• Follow Mg twice/wk ; more frequently if hypokalemia or hypomagnesemia
• May bolus NS 10 mL/kg (Max. 500 ml IV) over 1-2 hours prior ampho B
• Minimizes renal toxicity
• Tubuloglomerular feedback system regulates renal blood flow
• To prevent a drug reaction may use as premedication:
• Paracetomol 15 mg/kg dose (Max. Dose: 4000 mg/day; 1 gm/dose)
• Diphenhydramine (or Chlorpheniramine) 1 mg/kg IV/PO (Max. Dose: 50 mg)
• Hydrocortisone 2 mg/kg IV (Max. Dose: 100 mg)
• To treat rigors with chills:
• Meperidine (Pethidine) 0.5 mg/kg (Max. Dose: 25 mg) may use this dose to
premedicate in the future.
© Baylor College of Medicine 2010
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4. Antiviral Therapy
• Diagnosis made using cultures or polymerase chain reaction (PCR), or antigene-
mia where available, otherwise herpes simplex virus (HSV) and varicella zoster vi-
rus (VZV) can be diagnosed clinically.
• Acyclovir:
• Baseline chemistries prior to therapy, then monitor BUN/Cr 2x week
• Maintain adequate hydration:
• High-dose acyclovir IV, use 2400 mL/m2/day
• Standard-dose, use maintenance IV Fluid rate
• Adjust dose for renal impairment
• In immuno-compromised patients with varicella zoster (shingles) who are afe-
brile and stable, may use oral dosing.
• If febrile institute IV therapy.
• In immuno-compromised patients with chicken pox institute IV therapy
• Patients with herpes simplex may be treated using the oral acyclovir
Intravenous
• HSV (sick/toxic patient): 20 mg/kg/dose q 8 hours
• HSV (well-appearing): 10 mg/kg/dose q8 hours
• Varicella: 20 mg/kg/dose q 8 hours (Max. Dose: None)
Oral
• HSV or shingles: 250-600 mg/m2/dose 4-5 x/day (Max. Dose: 800
mg/dose)
5. Pneumocystis jerovecii (PCP) Prophylaxis
All patients on chemotherapy should receive PCP prophylaxis that continues until 6
months after completion of chemotherapy.
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Trimethoprim/sulfamethoxazole (TMP/SMX) can be given once daily or three times per
week twice daily using the dosing below:
BSA (m2) Regular Strength Tab Liquid (mL)
< 0.3 N/A 2.5
0.3-0.79 0.5 5
0.8-1.39 1 10
1.4-1.89 1.5 15
>1.9 2 20
• Intolerance to TMP/SMX can occur. In such cases use either dapsone or, where
available pentamidine can be used as per the dosing schedule below:
• Dapsone 2 mg/kg PO qAM (Max dose 100 mg)
• Pentamidine given once monthly either aerosolized or IV:
• Aerosolized
• < 5 yrs: 8 mg/kg/dose in 5mL sterile water (Max Dose 300 mg)
• > 5 yrs: 300 mg/dose in 5 mL sterile water
• Administer with salbutomol 2 puffs pre & post pentamidine
• Intravenous
• 4 mg/kg given once monthly
© Baylor College of Medicine 2010
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6. Anti-emetic Medications
• 5HT3 Receptor Inhibitors: These medications are expensive & not readily available
in the resource-limited setting. However, they can be found at times & hence the
dosing is given here.
• Give these medications 30 minutes prior to chemotherapy
• Scheduled dosing is recommended especially for platinum-containing chemothe-
rapy regimens
(1)
• Ondansetron
PO < 4 yrs 0.2 mg/kg/dose
4-12 yrs 4 mg/dose
> 12 yrs 8 mg/dose
IV Wt (kg) m2 Dose
< 10 <0.4 0.15 mg/kg/dose
10-50 0.4-1.2 4 mg/dose
> 50 > 1.2 8 mg/dose
• Granisetron: Pediatric dosing is not well established
PO Adult dose is 2 mg once daily or 1 mg twice daily
Pediatric dosing: 1 mg twice daily
IV Pediatric dosing: 20-40 mcg/kg/day divided once or twice daily
Max dose 3 mg/dose or 9 mg/day
• Dexamethasone
2 2
• 2 mg/m IV or PO with each ondansetron dose or a single 6 mg/m dose
given with the first ondansetron dose
• Promethazine
© Baylor College of Medicine 2010
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• 0.25 - 0.5 mg/kg/dose IV every 6 hours as needed
• This can be given on a scheduled basis especially when 5HT3 Receptor
inhibitor agents are unavailable
• Lorazepam
• 0.03 - 0.05 mg/kg/dose IV or PO every 6 hours
• This drug is particularly beneficial for anticipatory nausea/vomiting
© Baylor College of Medicine 2010
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Emetogenicity of Chemotherapy Agents
Note: sd - standard dose hd - high dose (often difficult to give in resource-poor setting)
None Mild Moderate Severe
6-mercaptopurine 5-fluorouracil Cytarabine (sd) Nitrogen mustards
Vincris- Etopo- Methotrexate (hd) Dacarbazine
tine/Vinblastine side/Teniposide
6-thioguanine Cyclophophamide Carboplatin Cyclophosphamide
(sd) (hd)
L-asparaginase Intrathecal chemo- Daunomy- Cytarabine (hd)
therapy cin/Doxorubicin
Bleomycin Methotrexate (sd) Actinomycin-D Cisplatin
Hydroxyurea Ifosfamide
7. Anaphylaxis Precautions
• Use as a standard protocol when administering the following medications:
• Etoposide or Teniposide
• Carboplatin
• L-Asparaginase
Reaction Grading Scale for Carboplatin, Etoposide, & Teniposide
• Grade I - transient hives
• Grade II - hives, pruritis, lip/tongue swelling, mild wheezing, anxiety
• Grade III - serum sickness, chest tightness, severe bronchospasm, cough, chills,
vomiting, tachycardia, cyanosis
• Grade IV - anaphylaxis with shock & hypotension
© Baylor College of Medicine 2010
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Reaction Grading Scale for L-Asparaginase
• Grade I - Local reaction at injection site with hives < 6 cm occuring < 6 hrs after
administration of medication
• Grade II - Generalized reaction with hives < cm occurring < 6 hrs after administra-
tion of medication
• Grade III - serum sickness, chest tightness, severe bronchospasm, cough, chills,
vomiting, tachycardia, cyanosis
• Grade IV - anaphylaxis with shock & hypotension
Treatment of Reactions:
• Grade I - II
2
• Stop infusion, start NS at 100 ml/m /hr
• Diphenhydramine 1 mg/kg Stat dose (Max dose: 50 mg)
• Hydrocortisone 2 mg/kg IV Stat dose
• Grade III-IV
2
• Stop infusion, start NS at 100 ml/m /hr
• Epinephrine (Adrenaline) 1:10,000 give 0.1 ml/kg IV Push Stat dose
• Epinephrine (Adrenaline) 1:1,000 give 0.01 ml/kg IV Push Stat dose
• After epinephrine given, give diphenhyrdamine & hydrocortisone
Monitor patient closely & repeat medications as needed given clinical condition
For any reaction monitor vital signs every 2-5 minutes until patient is stable including
heart rate, respiratory rate, blood pressure, & pulse oximetry (where available)
Medications that cause a reaction must not be repeated as a repeat dose can be fatal.
A pediatric oncologist ought to be consulted to determine if an alternate medication
would be possible.
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8. Mucositis & Oral Hygiene
Mucositis Grading System
Grade Symptoms
I Painless ulcers, erythema, mild soreness
II Painful erythema, edema, ulcers; patient able to eat
III As per Grade II but patient is unable to eat
IV Requires parenteral or NG tube nutritional support
Medication options for mouthcare
• Mouthwash - 1 L NS + 1 teaspoon table salt + 1 teaspoon NaHCO3 + 5 ml glycerin
• 10 ml swish & spit out four times daily
• Nystatin: can be used as prophylaxis or if there is evidence of thrush
• Infants: 1 ml of 100,000 units/ml solution applied to each side of mouth four
times daily
• Children: 5 ml swish & swallow four times daily
• Magnesium or Aluminum Hydroxide + Chlorpheniramine or diphenhyrdamine
• Mix in a 1:1 ratio (e.g. 50 ml of each), and swish & spit four times daily
• Maximum 5 ml per dose
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Chemotherapy Agents & Mucositis Severity
Minimal or No Mucositis Mild Mucositis Moderate-Severe Mucositis
Asparaginase Bleomycin Cytarabine
Etoposide (VP-16) Cisplatin Daunorubicin
Ifosfamide 6-mercaptopurine 5-fluorouracil
Vincristine Procarbazine Methotrexate
6-thioguanine Doxorubicin
Vinblastine
Cyclophosphamide
9. Oncologic Emergencies
• Tumor Lysis Syndrome (TLS)
• Lysis of tumor cells releases electrolytes & urea cycle products resulting in
hyperuricemia, hyperkalemia, hyperphosphatemia & resultant hypocalcemia
• Severe TLS seen with large tumor burden including (but not limited to):
• Burkitt’s Lymphoma
3
• Acute Lymphoblastic Leukemia with WBC count >100,000/mm
• AML
• Neuroblastoma
• TLS Labs: minimum daily up to every 6hrs as resources allow
• Urea & Electrolytes
• Calcium
• Magnesium
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• Phosphate
• Uric Acid
• Maintain urine output at > 2.5 ml/kg/hr
• Hemodialysis reserved for severe TLS, prevention of severe disease will
obviate requiring this invasive & expensive intervention
• Specific Management
• Hyperuricemia Management
2
• Hydration with 3000 ml/m /day with fluids not containing potassium
1
(e.g. D5 /2 NS)
• Consider adding 40 mEq NaHCO3/L to aid in uric acid excretion
• Need to monitor calcium & phosphate several times daily if adding
NaCO3, where this is not feasible, do not add NaHCO3 to fluids
2
• Allopurinol 100 mg/m /dose PO given three times daily
• Max dose 600 mg/day for age <10 yrs, 800 mg/day for >10 yrs
• Rasburicase: currently not available in the resource-limited setting
• Hyperkalemia
• ECG: T wave elevation (peaked T wave), loss of P wave, widened
QRS complex
• Avoid potassium in fluids to help prevent this complication
• Stop any potassium supplementation if present
• Dextrose 0.5 g/kg with 0.3 units insulin/gm dextrose, infuse over 2
hours
• Kayexalate 1 g/kg/dose PO four times daily
• 1 g/kg lowers potassium by 1 mEq
• Hyperphosphatemia/Hypocalcemia
• Remove NaHCO3 from fluids if Ca x PO4 > 60
• Where calcium & phosphate levels cannot be checked several times
daily, do not add NaHCO3 to fluids
• Hyperphosphatemia - treat with aluminum hydroxide 25 mg/kg/dose
four times daily & avoid foods containing large amounts of phosphate
• Hypocalcemia: 10% calcium gluconate 500 mg/kg IV infusion through
a central line
• Maximum dose 2000 mg/dose
• Monitor calcium level closely including ionized calcium where
available
• Hyperleukocytosis
3
• Defined as WBC > 100,000/mm
• High risk for pulmonary & CNS complications due to viscosity & stasis
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2
• IV fluid rate 3600 ml/m /day
• Monitor WBC counts along with TLS labs
• Monitor pulse oximetry for evidence of pulmonary complications, continuous
monitoring where possible
• Do not transfuse above Hg 8.5 g/dL as pRBC or whole blood may increase
viscosity
3
• May transfuse platelets for active bleeding or platelets <50,000/mm
• Although not available in resource-limited settings, leukopheresis is recom-
mended if possible
• Space occupying lesions
• Mediastinal mass/upper airway lesion
• Avoid sedation
• Elevate head of bed
• Avoid procedures that may compromise airway & consult anesthesia for
procedures
• Obtain diagnostic tissue with the least invasive method - e.g. peripheral
lymph node biopsy preferred over thoracotomy to biopsy chest mass
• May need emergency chemotherapy and/or radiation therapy as a life-
saving measure, even prior to full diagnostic work-up
• Intracranial mass/spinal cord compression
• Intracranial pressure elevation can be treated with dexamethasone;
mannitol can be added for severe cases
• Dexamethasone up to 4 mg IV every 4 hours can be given for cerebral
edema
• Where required, substitution with hydrocortisone or prednisone can
be done, but effects on cerebral edema are much less potent as
compared to dexamethasone
• Any central nervous system involvement by tumor requires immediate
involvement of neurosurgery
• May need emergency chemotherapy and/or radiation therapy as a life-
saving measure, even prior to full diagnostic work-up
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10. Immunizations in Oncology Patients
• Live vaccines, especially oral polio must be avoided for patient & family members
during chemotherapy
• Yellow fever vaccine must be avoided in the patient; however, family members can
receive this vaccine where indicated
• Killed or recombinant vaccines can be administered to the patient & family mem-
bers; response is generally seen despite immunosuppression, however patients
undergoing bone marrow transplant generally require re-immunization 1 year post-
transplant
• Live vaccines can be resumed 6 months after chemotherapy is completed
• Annual injectable influenza vaccine is recommended for immunosuppressed pa-
tients where the vaccine is available
11. Constipation
• Most commonly caused by vincristine, inactivity & opiod medications
• No rectal exam, enemas, or suppositories for patients on chemotherapy unless
discussed with specialist
• Even minor trauma to the rectal mucosa can introduce a life-threatening infec-
tion in patients with neutropenia
• Patients with normal absolute neutrophil count who did not receive chemothe-
rapy in the previous 2 weeks are less likely to have complications
• Management
• A bowel regimen is recommended for all patients on vincristine therapy as pre-
venting constipation is preferred to treating after it has started
• Docusate sodium (stool softener)
• Age < 3 yrs: 10-40 mg/day divided into 1-4 doses
• Age 3 - 6 yrs: 20-60 mg/day divided into 1-4 doses
• Age 6 - 12 yrs: 40-150 mg/day divided into 1-4 doses
• Age > 12 yrs: 50-400 mg/day divided into 1-4 doses
• Bisacodyl (Oral doing only; laxative)
• 3 - 12 yrs: 5 mg PO once daily
• > 12 yrs: 10 mg PO once daily
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• Magnesium hydroxide (laxative)
• < 2 yrs: 0.5 ml/kg/dose
• 2 - 5 yrs: 10-15 ml PO once daily (can be given in divided doses)
• 6 - 12 yrs: 15-30 ml PO once daily (can be given in divided doses)
• > 12 yrs: 30-60 ml PO once daily (can be given in divided doses)
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Hematology
1. Sickle cell disease
• Patients should be receiving prophylaxis penicillin
• Penicillin VK 125 mg PO twice daily for age < 3 years
• Penicillin VK 250 mg PO twice daily for age > 3 years
• Penicillin prophylaxis can be stopped for patients who these criteria:
• No prior documented pneumococcal infection or pneumonia
• Has not had surgical splenectomy
• Has received vaccination with both the 7-valent conjugate pneumococcal vac-
cine and polysaccharide based 23-valent pneumococcal vaccine
• Diagnostics: ideally hemoglobin (Hg) electrophoresis ought to be monitored, how-
ever this is often difficult to obtain routinely in the resource-limited setting
• Where available, Hg S level ought to be followed & checked particularly when
exchange transfusion is available as the goal of exchange is to reduce the Hg S
level usually to < 30%
• Folic Acid supplementation
• Patients with chronic hemolysis, as with sickle cell disease, benefit from folic
acid supplementation in certain cases
• For patients with Hg < 9 g/dL and reticulocyte count > 5%, give:
• 0.5 mg PO daily (age < 2 years age)
• 1 mg PO daily (age > 2 years age)
• In the resource-limited setting, folic acid is often only available as 5 mg tablets,
in this case, give 5 mg for age > 2 years as folate is relatively benign
• 5 mg tablet can be crushed and a suspension made for infants
• 5 mg in 10 ml - 1 ml equals 0.5 mg
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2. Sickle cell disease with fever
• Common pathogens
• S. pneumoniae
• H. influenza type b
• E. coli
• Salmonella
• Mycoplasma pneumoniae and hominis
• Chlamydophila pneumoniae
• Diagnostics
• Full blood count with differential & reticulocyte count
• Blood culture
• CXR - cannot rely on symptoms or physical exam findings
• Where clinically needed - blood chemistries, urinalysis, urine culture
• Management/Treatment
• Admit for intravenous antibiotics if any of the following is found:
• Age < 1 year
o
• T > 40 C
• Toxic or ill-appearing patient
• Any infiltrate on CXR
• Pulse oximeter reading < 92% on room air
• History of bacteremia or pneumonia
• Hg < 6 g/dL or reticulocyte count > 4%
3 3
• WBC < 5,000/mm or > 30,000/mm
3
• Platelet count < 100,000/mm
• Non-toxic patient
• Cefuroxime 50 mg/kg/dose IV every 8 hours
• Toxic patient
• Vancomycin 15 mg/kg/dose IV every 8 hours
• Cefotaxime 200 mg/kg/day divided every 8 hours
• Patient with chest syndrome/pneumonia, add azithromycin
• Patients who do not require admission
• Minimum phone follow-up within 24 hours to check culture results & clinical
condition
• Ceftriaxone 50 mg/kg IV/IM x 1 prior to discharge
• Cefprozil 15 mg/kg/dose every 12 hour for 3 days (or local equivalent) or
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• Erythromycin 50 mg/kg/day divided 4 times daily for 3 days (for patients al-
lergic to cephalosporin)
• If blood culture positive, adjust treatment based on culture & sensitivity
3. Sickle cell vaso-occlusive crisis
• Pain crisis
• Diagnostics: Full blood count with differential & reticulocyte count
• Management
• Pain control with opioid analgesic (see Pain Control section)
2
• Hydration: 2000 - 2400 ml/m /day (if no cardiopulmonary disease)
• Priapism
• Diagnostics: Full blood count with differential & reticulocyte count
• Management
• Pain control with opioid analgesics (see Pain control section)
2
• Hydration: 2000 - 2400 ml/m /day (if no cardiopulmonary disease)
• Consult urology immediately for aspiration & irrigation if 4 hours since onset
• Transfusion only if no detumescence within 12 hours
• There is no indication for oxygen therapy in such cases
• Splenic sequestration
• Diagnostics: Full blood count with differential & reticulocyte count, type & cross
• Management
2
• Hydration: 1600 ml/m /day
• Transfusion with pRBC urgently; transfusion rate dependent on hemody-
namic status
• Aplastic crisis
• Diagnostics: Full blood count with differential & reticulocyte count, type & cross
• Management
• Hydration: maintenance PO fluids, IV fluids if not able to take PO
• Transfusion with pRBC as clinically indicated
• Acute Chest Syndrome/Pneumonia
• Diagnostics: Full blood count with differential & reticulocyte count, type & cross,
chemistries, Blood culture, pulse oximetery, CXR
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• Management
2
• Hydration: IV fluids + PO total at maintenance (1600 ml/m /day)
3
• Consider IV fluids at /4 maintenance to avoid fluid overload even if not
taking PO well
• Pain management - cautious but do not withhold. Balance between pain
control & sedation required as either may lead to respiratory distress
• Respiratory care
• Oxygen therapy with pulse oximetry monitoring
• Salbutomol inhaler/nebulized every 4 hours
• Incentive spirometry 10 puffs every 2 hours while awake
• 10-15 ml/kg pRBC transfusion if significant anemia
• Exchange transfusion often considered ideal; however it is rarely availa-
ble in resource-limited setting
• Antibiotics for pneumonia
• Cefuroxime (dosage as above)
• Azithromycin - M. pneumoniae frequent cause of acute chest syndrome
• Stroke
• Diagnostics: Full blood count with differential & reticulocyte count, type & cross,
emergent CT or MRI (where available)
• Consider omitting contrast as it may exacerbate sickling
• Management
• Exchange transfusion is standard management where available
4. Pre-operative preparation of sickle cell patients
• Diagnostics: Full blood count, type & cross
• Ideally, patients ought to receive exchange transfusion to reduce Hg S < 30%
prior to most surgical procedures
• Where exchange is unavailable, simple transfusions can be utilized to re-
duce Hg S, usually this will require multiple simple transfusion
• Occasional low risk procedures can be done with a simple transfusion and IV
hydration without a Hg S goal level
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5. Transfusion therapy in sickle cell disease
• Sickle cell patients should not be transfused to Hg > 11 g/dL or Hct > 30% as this
results in increased risk for vaso-occlusion and stroke
• Where available, phenotyping should be performed to match blood for Rh and Kell
antigen groups
6. Hemophilia
• Patients with hemophilia can have spontaneous bleeding and/or excessive bleed-
ing with trauma, it is imperative to treat hemophilia patients within 30 minutes
of presentation and then consider diagnostic testing
• Factor VIII deficiency (Hemophilia A)
• 1 unit/kg increases Factor VIII activity by 2%
• Factor IX deficiency (Hemophilia B)
• 1 unit/kg increases Factor IX activity by 1%
Severity Factor Level
Severe <1%
Moderate 1-4%
Mild 5-25%
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7. Treatment of bleeding in patients with Hemophilia A
• It is important to dose Factor VIII to a unit vial dose whenever possible to avoid
waste
• For example, if unit vial is 500 units & patient’s dose is 400 units, order 500
units Factor VIII
• Where available, use recombinant product, otherwise factor concentrate ought to
be given
• Where Factor VIII is unavailable or not immediately available in emergency situa-
tions, FFP at 10-15 ml/kg may be used
• Inhibitor Screen
• Where available, screening for inhibitor should be performed
• If screen positive, defined as > 5 Bethesda Units, recombinant and concentrate
products will not be sufficient even at high doses
• Where available Factor VIIa, Anti-Inhibitor Coagulant Complex, or Porcine
Factor VIII will be required
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• The following table gives general guidelines, however specific cases should be
discussed with the specialist
Event First Factor Dose Subsequent Dos- Comments
(% correction) es
Hemarthrosis 50 U/Kg (100) 25-35 U/Kg (50-70) Ice for 20 mins
q12-24h x 2-5 days
immobilize x 48hr
Soft tissue bleed 30 U/Kg (60) 25 U/kg (50) daily x 2 Ice for 20 mins
days
Hematuria 35 U/Kg (70) 25 U/Kg (50) q12-24h x IV hydration
2-7 days
prednisone 1-2 mg/kg/d
x 1-2 wks
GI Bleed 50 U/Kg (100) 25-35 U/Kg (50-70) Monitor FBC, transfuse
q12h x 2-7 days as required
Mucosal bleeding 35-50 U/Kg (75-100) 25 U/Kg (50) daily x 1- Amicar 100 mg/kg q6h
2 days x 3-5 days where avail-
able
Head Trauma 50 U/Kg (100) 35 U/Kg (70) q8-12h Do not wait for neuro-
logic signs
CT scan after 1st dose
Maintain factor VIII level
> 80%
Major Surgery 50 U/Kg (100) 25-35 U/Kg (50-70) Maintain factor VIII level
q12h x 7-10 days > 50%
Dental Extractions 50 U/Kg (100) 25-35 U/Kg (50-70) Amicar 100 mg/kg q6h
daily x 3 days x 3-5 days where avail-
able
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8. Treatment of bleeding in patients with Hemophilia B
• FFP 10-15 ml/kg where factor concentrate is not available or not immediately
available in emergency situations
• Doses > 50 U/Kg may be associated with thromboembolic complications when less
pure Factor IX concentrates are used
• This requires awareness of risk, this does not mean higher doses should not
be used
• High purity Factor IX can result in anaphylaxis
• Risk should be communicated to family if factor will be given at home
• Anaphylaxis precautions should be followed in the hospital setting
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• The following table gives general guidelines, however specific cases should be
discussed with the specialist
• If using recombinant Factor IX, the dose must be increased by factor of 1.2
• For example, dose of 100 U/Kg will be 120 U/Kg for recombinant factor
Event First Factor Dose Subsequent Dos- Comments
(% correction) es
Hemarthrosis 100 U/Kg (100) 50-70 U/Kg (50-70) Ice for 20 mins
q12-24h x 1-3 days
immobilize x 48hr
Soft tissue bleed 60 U/Kg (60) 50 U/kg (50) daily x 2 Ice for 20 mins
days
Hematuria 70 U/Kg (70) 50 U/Kg (50) q12-24h x IV hydration
2-7 days
prednisone 1-2 mg/kg/d
x 1-2 wks
GI Bleed 100 U/Kg (100) 50-70 U/Kg (50-70) Monitor FBC, transfuse
q12h x 2-7 days as required
Mucosal bleeding 75-100 U/Kg (75-100) 50 U/Kg (50) daily x 1-2 Amicar 100 mg/kg q6h x
days 3-5 days where availa-
ble
Head Trauma 100 U/Kg (100) 70 U/Kg (70) q12-24h Do not wait for neuro-
logic signs
CT scan after 1st dose
Maintain factor IX level
> 80%
Major Surgery 100 U/Kg (100) 50-70 U/Kg (50-70) dai- Maintain factor IX level
ly x 7-10 days >50%
Dental Extractions 100 U/Kg (100) 50-70 U/Kg (50-70) dai- Amicar 100 mg/kg q6h x
ly x 2-7 days 3-5 days if available
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9. Von Willebrand’s Disease
• Most commonly patients have mucocutaneous bleeding
• Heavy menses in adolescent females and older females in the family is common
• It is important to ask specifically about number of days & amount of bleeding
as many women & adolescents will think their heavy menses are “normal”
• Diagnostics: FBC, PTT, Factor VIII, vWF activity & antigen, ristocetin cofactor ac-
tivity, vWF multimers
• Where vWF testing is not available, FBC, PTT, and Factor VIII should be
checked and results & case discussed with specialist
• Treatment
• Desmopressin Acetate can be given for patients who are sensitive (contraindi-
cated in Type 2B vWD)
• Avoid in patients less than 2 years or less than 10 kg
• Potential side effects: headache, flushing, tachyphylaxis, fluid retention, hy-
ponatremia
• Restrict fluid intake following treatment
• Dosing
• 0.3 micrograms/kg infused over 15 mins q12-24 hr (maximum 3 doses)
• Intranasal - 150 micrograms/puff
• < 50 kg: one puff q12-24 hr (maximum 3 doses)
• > 50 kg: 2 puffs q12-24 hr (maximum 3 doses)
• Certain Factor VIII concentrates do contain vWF depending on the preparation
• e.g. Factor VIII from BioProducts Institute in RSA has 500 U vWF per vial
along with 500 U Factor VIII
• Treat with 50 units/kg q12-24 hrs depending on severity of bleeding
• Prophylaxis treatment is not generally indicated
• Cryoprecipitate 1 bag/5 kg body weight can be given in emergency settings
where available and can be repeated every 8, 12, or 24 hrs depending on the
severity of bleeding
• FFP does not contain vWF to any level that will be therapeutic and is not
indicated for vWD
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10. Immune Thrombocytopenic Purpura (ITP)
• History
• History of mucocutaneous bleeding & bruising
• Previous viral infection
• Recent vaccination
• Atypical findings (may suggest disease other than ITP)
• Systemic symptoms
• Current infection
• Evidence of immunodeficiency
• HIV exposure or HIV+ status (although ITP is not uncommon with HIV)
• Family history of low platelets or bleeding disorder
• Medication exposure including antibiotics, anticonvulsants, heparin, antiarr-
hytmia medications, sulfa drugs, aspirin
• Physical exam findings
• Signs of bleeding including active bleeding or old clotted blood (e.g. nares)
• Petechiae
• Bruising
• Atypical findings (may suggest disease other than ITP)
• Evidence of active infection
• Arthralgia
• Bone pain
• Hepatomegaly, splenomegaly, lymphadenopathy
• Dysmorphic features, skeletal abnormalities, growth delay, failure to thrive
• Known specific congenital condition
• Fanconi anemia
• Thrombocytopenia Absent Radii (TAR) syndrome
• Platelet disorder: Bernard-Soulier, May-Hegglin, Gray Platelet syndrome
• vWD Type 2B
• Thrombocytopenic Thrombotic Purpura (TTP)
• Diagnostics
• FBC, reticulocyte count, smear examination
• Results consistent with ITP
• Platelet size normal or large in size
• Occasional giant platelets seen
• normal RBC & WBC morphology
• In the resource-limited setting, microcytic, hypochromic red cells due
to underlying iron deficiency anemia is not uncommon
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• Occasional activated lymphocytes can also be seen
• Results not consistent with ITP
• Predominant giant platelets
• Abnormal RBC morphology
• Leukocytosis or leukopenia
• Immature leukocyte forms
• Small platelets
• Children with atypical features may have ITP but other diagnostics should be
performed as clinically indicated including, but not limited to:
• LDH, uric acid
• Bone marrow examination
• Anti-Nuclear Antibody Titer
• Coombs’ Test
• Coagulation Panel: PT/INR, aPTT
• Chemistries, urinalysis
• Treatment Recommendations
• Various recommendations exist for treatment, the following is based primarily
on recommendations from the American Society of Hematology (ASH) & vari-
ous articles (see references)
3
• Asymptomatic patients with platelets > 30,000/mm
• Observation without treatment
3
• Repeat platelet count weekly for 3 weeks then monthly if < 150,000/mm
• If patient becomes symptomatic at any time refer to appropriate category
below
3
• Asymptomatic, or minor symptoms with platelets 20-30,000/mm
• If asymptomatic observation is appropriate
• Minor symptoms including bruising & petechiae can also be observed, how-
ever outpatient treatment with prednisone is acceptable as well
• Refer to treatment schedules below for details on prednisone therapy
• Monitor platelets at day 7 & day 28 after treatment or weekly as above if no
treatment
3
• Minor symptoms with platelets > 30,000/mm
• Observation without treatment is recommended with platelet count monitor-
ing as noted above for observation group
• Alternatively, where there is clinical concern or follow-up concerns, treat-
ment with prednisone with repeat platelet count day 7 & 28 post-treatment
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3
• Minor symptoms (e.g. bruising) with no bleeding & platelets < 20,000/mm
• Treatment for these patients is advised
• Monitor platelet count at day 7 & 28 after treatment
• Treatment with prednisone, IVIG, or anti-D antibody can be given
3
• Mucous membrane bleeding with platelets < 50,000/mm
• Treatment for these patients is advised
3
• Active bleeding with platelets < 20,000/mm
• Hospitalize, treat with IVIG or high-dose steroids or both
• Discharge when bleeding controlled & platelet count rising (~ 2-3 days)
3
• Bleeding with platelet > 30,000/mm
• Treat with IVIG or high-dose steroids
• Hospitalization based on stability of bleeding, accessibility to care. Sta-
ble patients with fast access to care can be managed as outpatients
• Severe, life-threatening bleeding regardless of platelet count
• Hospitalization & rapid treatment that should begin in Accident & Emergen-
cy
• Treatment with IVIG and high-dose steroids with or without platelet transfu-
sion therapy
• Rule-out TTP prior to platelet therapy as this condition can be worsened
by platelet transfusion
• Emergency splenectomy can be performed in select cases but the patient’s
condition & response to medical therapy must be considered
• Follow-up after 1st month
3
• Asymptomatic patients with platelet > 30,000/mm , monitor platelet count
3
monthly until > 150,000/mm
3
• Patients with platelet count < 20,000/mm must be monitored as clinically
indicated
• Treatment Schedules for Acute ITP
• Chronic ITP is generally reserved for patients with persistent thrombocytopenia
beyond 6 months & management is best done with hematologist consultation
• Prednisone therapy
• Eligible patients
• The importance of excluding ALL prior to prednisone therapy cannot be
stressed enough
• Typical history & physical exam
• No fever, adenopathy, hepatosplenomegaly or arthralgia/bone pain
• FBC with normal WBC differential & RBC morphology
• Peripheral smear shows no immature forms
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• Schedule Options
• Prednisone 4 mg/kg/day divided three times daily for 4 days
• Prednisone 1-2 mg/kg/day divided three times daily for 14 days with 7
days taper
• Methylprednisolone 30 mg/kg once daily for 3 days
• Ranitidine is recommended when treating with corticosteroids
• Intavenous Immunoglobulin (IVIG)
• Eligible patients
• Typical history & physical exam
• No fever, significant adenopathy, hepatosplenomegaly
• Mild to moderate bleeding
3
• Platelet count < 30,000/mm
• Schedule Options
• Patients < 50 kg
• 0.8 - 1 g/kg once or
• 0.5 g/kg daily for 2 days
• Patients > 50 kg
• 0.5 g/kg daily for two days
• Patients with severe, life-threatening bleeding should receive up to 2 g/kg
given over 2-5 days
• Adverse reactions including headache, fever, nausea, & flushing can be
treated by slowing infusion and/or giving:
• Diphenhydramine 0.5-1 mg/kg IV or PO (max dose 50 mg)
• Hydrocortisone 1 mg/kg (max dose 100 mg)
• Paracetomol 15 mg/kg once (max dose 1000 mg)
• Patients with IgA deficiency should not receive standard IVIG preparations
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References
1. Nathan D, Orkin S, Ginsburg D, Look A. Nathan and Oski's Hematology of Infan-
cy and Childhood, Sixth Edition. 2003.
2. Pizzo P, Poplack D. Principles and Practices of Pediatric Oncology. 2006.
3. Suell M, Bomgaars L. Texas Children's Caner Center & Hematology Service
Resident Handbook. 2005.
4. Dodd RY, Notari EPt, Stramer SL. Current prevalence and incidence of infectious
disease markers and estimated window-period risk in the American Red Cross blood
donor population. Transfusion 2002;42(8):975-9.
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