6 - American Academy of Pediatrics

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Pediatric Board Review Course
Pediatric Hematology/Oncology
Kusum Viswanathan, MD
Chair, Department of Pediatrics
Director, Divn of Pediatric Hematology/Oncology
Brookdale Univ Hospital and Medical Center
Question
6 week old term infant referred for anemia.
Hb 7.5, Retic 2 %.
Mother O+, Baby A -, Direct Coombs +
Cord blood Hb 14.2 g/dL.
Jaundice of 15mg/dL at 48 hours of life, recd
photo Rx and discharged at 5 days.
No complaints, pale, Bili 3.5, Direct 0.5.
Blood smear shows spherocytes
Most likely explanation for the anemia
1. G 6 PD deficiency
2. Hereditary
He
r
y
m
ol
y
tic
di
se
ib
ilt
pa
t
Rh
he
in
O
AB
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as
e
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m
ca
ne
m
ia
0%
lo
gi
sp
he
r
oc
yt
os
is
0%
Ph
ys
io
ed
it a
ry
6
PD
de
fic
i
en
cy
0%
G
spherocytosis
3. Physiologic
anemia
4. ABO
incompatibilty
5. Rh hemolytic
disease
6
Newborn –anemia- important
Hemoglobin at birth is 17 g/dl, MCV over 100.
Falls to 11-12 by 6 weeks of age- nadir of physiologic
anemia
Anemia at birth could be :
– Hemorrhage, may not have had time to mount a retic response
– Acute hemorrhage- pallor and tachypnea
– Look at MCV- low MCV-suggestive of
chronic feto-maternal hemorrhage
Alpha Thalassemia trait.
– Kleihauer-Betke- Hb F resistance to acid elution
The treatment of choice for alloimune neonatal
thrombocytopenia is
1. random platelet
pl
a
te
le
ts
n
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at
er
na
l
tra
m
ge
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as
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d
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ch
an
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ns
fu
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oi
ds
0%
St
er
IV
IG
n
ns
fu
sio
0%
tra
et
el
5.
0%
pl
at
4.
nd
om
3.
ra
2.
transfusion
IVIG
Steroids
Exchange
transfusion
Washed maternal
platelets
6
Immune thrombocytopenia
Auto-immune: Pregnant women with ITP/Hx of ITP
–
–
–
–
Passive transfer of antibodies (IgG) from mother.
Even when mother has a normal platelet count (Splenectomy)
Nadir-few days; Platelets < 50,00 have 1% risk of ICH.
IVIG to mother, Fetal platelet counts, C sec, US, IVGG to baby
Allo or Iso-Immune: Normal platelet count in mother
–
–
–
–
–
–
–
Similar to Rh disease; PL A1 antigen/ Zw-a negative mother.
97% of population is PL A1 positive
Sensitization early in pregnancy
Plt function defect because Anti-PL-A1 interferes w/aggregation.
Severe bleeding more likely; first born affected
Recovery in 2-3 weeks
Mother’s washed (PLA1 neg) platelets; IVIG; Ultrasound;
Steroids
Kasabach- Merritt, TAR
15 months old girl presented in ER with h/o URI, and scattered
petechiae and ecchymoses over the body and lower extremities.
Physical exam normal, no hepatosplenomegaly.
WBC-14,000, Hb 12.8, Plts-5,000, Diff: Normal - Next
step
nj
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y;
s
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ith
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ist
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.
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ar
No
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bo
n
a
4.
m
3.
0%
rfo
r
2.
perform a bone marrow
aspirate to confirm the
diagnosis
Non-accidental injury;
skeletal survey to rule
out bony fractures
treatment with either
IVIG or anti-D
Administer platelet
transfusion
pe
1.
6
Acute ITP
Usually acute onset; immune mediated; post viral
Peak 2-5 years of age,
PE –no lymphadenopathy (LN), hepatosplenomegaly.
CBC- other cell lines normal, large plts on smear
Treat if plt< 10,000 or wet ITP,
Treat- IVIG best response, 48-72 hours; blocks Fc receptors,SE
– Anti-D (WInRho)- Rh+ ,hemolysis, quick response
– Steroids good response, block phagocytosis, reduces antibodies,
SE, inexpensive, need BM
BM- Increased megakaryocytes, otherwise normal
Chronic- If >6 months, F>M, older, unpredictable
prognosis
Petechiae, HSP
A 2 year old boy presents for evaluation of a chronic pruritic eruption. H/o
recurrent epistaxis, otitis media, and pneumonia
P/E reveals erythematous, slightly scaling patches on the trunk and in the
antecubital and popliteal fossae. Petechiae too- most suggestive of
isk
ot
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sy
nd
r
Al
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ic
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cy
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at
it i
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is t
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de
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rh
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e
La
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At
ax
At
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ro
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sia
0%
sc
el
1. Acrodermatitis
enteropathica
2. Ataxia telangiectasia
3. Atopic dermatitis
4. Langerhans cell
histiocytosis
5. Wiskott-Aldrich
syndrome
6
Large platelets
Normal platelet 7-10 days
Large platelets:
– ITP
– May Hegglin (Dohle
bodies in neutrophils, Plt
function normal).
– Bernard Soulier
syndrome (AR, Plat
function disorder).
Small platelets: Wiskott
Aldrich syndrome ( X-linked,
recurrent infections,
eczematoid rash, platelet
dysfunction)
Platelet function defects
Normal platelet number
Abnormal aggregation
– Glanzmann thrombasthenia--- AR, Bleeding disorder, check h/o
consanguinity
– afibrinogenemia
Abnormal adhesion- Bernard-Soulier, VWD
Ineffective Thrombopoiesis
– MayHegglin Anomaly (Large platelets)
Disorders of Secretion: Storage pool, gray platelet syndrome
Hermansky Pudlak Syndrome:
– AR, Decreased dense granules, In Puerto Ricans
– Oculocutaneous albinism
Thrombocytosis
H- Hemorrhage, Hereditary Asplenia, Down myeloprol.
IPLATELETS-
Infections, Kawasaki, Immune:GVH, Nephrotic syndrome
Polycythemia vera, Myeloproliferative, Essential
Leukemia (CML)
Anemia,- Iron, Vit E deficiency, Sideroblastic
Tumors
Epinephrine, Steroids
Lymphoma, Hodgkins
Exercise
Trauma, Fractures
Splenectomy
Anemia
An 18 month old girl brought in for pallor. Normal diet
and PMH. She is alert, interactive, only pallor, normal
vital signs, No hepatosplenomegaly, lymph nodes or
bruises.
CBC- Normal WBC, Plt, Hb 4.5g/dl, MCV 74,
Anemia
– Reduced production
– Increased destruction
– Loss
What else do you want??
Reticulocyte count
Normal/Low- reduced production
– Iron deficiency anemia- MCV will be low
– ALL (leukemia)- other findings, LN, HSM
– Diamond Blackfan anemia– TEC: Over 1 year of age, Pallor, transient rbc
production failure, recovers, MCV and Hb F high
during recovery, rbc transfusion, rbc ADA normal .
Normal smear
A 2 month old girl with a history of ventricular septal defect
and horseshoe kidney presents for a health maintenance
visit.
Her parents are concerned that she is not feeding well, appearing to
become “tired” soon after beginning to breastfeed. She is tachycardic
and appears pale. Her hemoglobin level is 3.8 g/dL. Peripheral smear
reveals macrocytic red blood cells. The bone marrow aspirate shows
normal cellularity of the marrow with markedly decreased erythroid
precursors.
Which of the following findings is most likely to be identified
during additional physical examination of this patient?
1. Multiple superficial hemangiomas
2. Cutis aplasia
3. Bifid thumbs
4. Speckled white rings in the periphery of the iris
5. Posterior parietal hair whorl
Microcytic anemia is a characteristic laboratory
abnormality of all listed diseases except
ala
Th
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ck
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ce
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ss
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ia
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ra
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it
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as
e
0%
cy
0%
en
4.
de
fic
i
3.
n
2.
Iron deficiency
Lead poisoning
Sickle cell
disease
Thalassemia trait
Iro
1.
6
Microcytic anemia
Question
A blood smear taken from a toddler shows
microcytic hypochromic anemia. Iron
supplementation therapy is started. When will the
reticulocyte response be at maximum?
a. 1-2 days
b. 5-7 days
c. 14-21 days
d. 3-4 weeks
e. about 6 weeks
Iron deficiency questions
Low MCV, low MCHC, low retic, RDW can be normal,
Low Iron, Incr TIBC, Transferrin low, Ferritin low
Causes: Inadequate dietary intake
– Toddlers, too much milk, less solids, Breast fed
need iron supplements
– Blood loss: Menstrual, GI tract, Meckels, Epistaxis
D/D:
Thalassemia trait- MCV much lower in prop to anemia
Anemia of chronic disease- low Fe, low TIBC, normal
/high Ferritin.
Question- Beta Thalassemia
3 year old comes for a routine check and found to be
anemic. P/E Normal. CBC Hb 8.9, MCV 58, Iron levels are
normal. Hemoglobin electrophoresis is done and shows
Beta Thalassemia trait. All are true except:
1. The MCV is always low
2. Fetal hemoglobin is < 2%
3. Hemoglobin A 2 is > 3.5%
4. Does not respond to Iron
5. RDW is usually normal
Beta Thalassemia Minor
Quantitative defect in
globin chains
– Reduced production of
Beta chains
Hb electrophoresis
– Hb A- 2 Alpha, 2 Beta
– Hb F- 2 Alpha, 2 Gamma
– Hb A2- 2 Alpha, 2 Delta
Excess Alpha combines
with Gamma or DeltaIncreased Hb F and A2.
Smear abnormalities
significant even with
MILD anemia.
Anemia
Low MCV, normal RDW,
normal retic
Smear shows aniso and
poikulocytosis, target
cells, microcytes,
misshapen cells,
basophilic stippling
Hb Electrophoresis:
Increased Hb A2 and/or
F.
Normal iron studies, no
response to iron
Beta Thalassemia Major
No production of Beta chains- Chromosome 11
Autosomal recessive
25 % chance with each pregnancy
Pre-natal testing for carriers
Chorionic villous sampling for diagnosis
Transfusion dependent-allows for normal development
Pen Prophylaxis, Anti oxidants
Splenectomy after age 5
Iron overload- inherent and transfusion
Need chelators
Question
4 year old male with no complaints. Routine CBC showed a
Hb9.8, MCV 62, RDW 12.5 , Retic 0.2%, Normal Iron
studies, Hemoglobin electrophoresis was normal with
normal Hb A2 and Hb F. You suspect Alpha Thalassemia.
All of the statements are true except:
1.
2.
3.
4.
5.
It is carried on 4 alleles
The severe form is Hydrops fetalis
Hemoglobin H disease occurs when 3 alleles are affected
Diagnosed by newborn screening when a “fast moving” hemoglobin
is noted.
Fast moving hemoglobin is made up of a hemoglobin with 4 beta
chains
Thalassemia- Alpha
Reduced Alpha chains
4 types- carried on 4 allelles. (xx/xx)
One absent- Silent carrier (x-/xx)
2 absent- Alpha Thal trait (xx/- - or x-/x-)
3 absent- Hb H disease (x-/- -) Has 4 excess
Beta chains)
4 absent- Hydrops fetalis (- -/- -)
NB period: Excess Gamma chains form Hb
Barts- FAST moving Hb on Newborn screening
Case
3 year old patient is brought to the ER with
complaints of feeling very tired over the
past 3 days.
Patient is pale, jaundiced with the spleen
tip palpable.
CBC Hb 5, Retic 5 %, LDH Increased,
What does this sound like??
Question
A previously well
African-American child
visited Africa and was
given malarial
prophylaxis. He
experienced pallor,
fatigue, and dark urine.
His hemoglobin level
decreased from 14.8 to
9 g/dL.
SMEAR
An African-Am child visited Africa & received malaria
prophylaxis. He has
en
cy
0%
de
fic
i
at
it i
s
0%
G6
PD
Si
ck
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ll
oc
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is
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ed
it a
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r
0%
di
se
as
e
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He
p
1. Hereditary
spherocytosis
2. Sickle cell
disease
3. Hepatitis
4. G6PD
deficiency
6
Reticulocyte count- Increased
Hemolysis
– IntrinsicMembrane defects-Hereditary spherocytosis (HS)
Enzyme-G 6 PD deficiency
Hemoglobinopathies
– Extrinsic- AIHA (Auto-immune hemolytic anemia),
DIC, Intravascular hemolysis
Loss
– Blood loss
Children with hereditary spherocytosis have
all of the listed conditions except:
1. positive Direct
gil
i
fra
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rm
al
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se
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in
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4.
5.
sp
l
3.
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2.
Coombs
splenomegaly,
gallbladder stones
abnormalities in
spectrin and /or
ankyrin
increased MCHC
abnormal osmotic
fragility test.
6
Spherocytes
Spherocytes
Nucleated rbc
Coombs-AIHA
Osmotic fragility-HS
HS- with severe anemia
A 6 year old girl who has hereditary spherocytosis
presents with a 1 week history of fever. Physical
examination reveals abdominal pain, vomiting, fatigue
and pallor. Her hemoglobin is typically about 10 g/dL
with a reticulocyte count of 9%, but now, her
hemoglobin is 4 g/dL and the reticulocyte count is 1%.
Her bilirubin is 1 mg/dL. Of the following, the MOST
likely cause for this girl’s present illness is infection
with
–
–
–
–
–
Coxsackie virus
Parvovirus B19
Epstein-Barr virus
Hepatitis A virus
Influenza A virus
HS- with severe anemia
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Ba
1. Coxsackie virus
2. Parvovirus B19
3. Epstein-Barr
virus
4. Hepatitis A
virus
5. Influenza A
virus
6
Newborn Screening Questions
You get a call from a frantic parent because she
received a letter from the State regarding her
baby’s test results on NBS.
FS- SS disease, S-B0 Thal, Sickle cell w/ HPFH.
FSA- Sickle B+ thal, Sickle cell trait
FSC- SC disease
FAS- Sickle cell trait
FAC- Hb C trait
FAE- Hb E trait
FE - Hb EE disease, E-Thal
Sickle cell Questions
Hemolysis- life span 20-50
days. Abnormal cell shape,
abnormal adherence to
endothelium, decreased
oxygenation, Increased
polymerization.
Symptoms start by 2-4 months
of age.
Hb electrophoresis, S >75 %.
Penicillin daily until age 5.
Prevention of pneumococcal
infections-asplenic.
PPV (Pnu-23) age 2, 5
Meningococcal vaccine early
two doses and every 5 years.
Folic acid daily
Sickle cell questions
Vaso-occlusive crisis
New infant born in another country presenting with
swollen hands---Dactylitis
Aplastic crisis:
– low Hb, low retic, Secondary to Parvovirus B 19 infection.
Splenic sequestration crisis:
–
–
–
–
Sudden enlargement of the spleen in SS or older SC patient
Rx- Transfuse
Teach spleen palpation
Splenectomy
The mother of a 10 month old baby with SS disease asks you about
prognostic indicators. All of the following indicate likelihood of more
severe disease except:
1. High WBC
2. Associated alpha
0%
.. .
m
ep
iso
de
he
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w
th
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ss
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la
h
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g
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n
W
BC
0%
As
so
c
thalassemia trait
3. Low hemoglobin
4. Repeated
episodes of
dactylitis
6
Sickle cell
Acute Chest Syndrome
True statements include all except:
1. Presents with a new infiltrate on X-ray
2. Due to infarction, infection, BM fat embolism
3. Treat with antibiotics to cover pneumococcus,
Mycoplasma, Chlamydia
4. Treat with bronchodilator, Incentive spirometry,
transfusion, Steroids (controversial).
5. Intensive hydration is important
TCD- Transcranial Doppler
A routine TCD on a 4
year old patient with
SS disease shows a
Cerebral blood flow
(CBF) of 210
cm/second.
What is the next
step?
STOP studies- STOP
I and II
According to the STOP protocol all children with
abnormal TCD require enrollment in hypertransfusion
protocol till (choose one)
Repeat TCD is
normal
2. Continue
indefinitely
3. the child reaches
18 years
4. MRA/MRI are
reported normal
1.
...
ed
or
t
18
ar
er
ep
es
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RA
/M
RI
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nt
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at
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ly
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al
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6
Sickle cell and Stroke Questions
Affects 10 % of patients
Infarctive stroke (younger patients)
Hemorrhagic stroke (older)
STOP I study established the role of yearly TCD
(transcranial doppler) to measure cerebral blood
flow velocity as a tool for determining stroke risk.
Transfusion therapy as current therapy for
high risk patients (CBF> 200cm/sec)
Reversal of CBF velocity is not sufficient to stop
transfusion therapy. (STOP II)
Sickle cell and Hydroxyurea
FDA approved for adults
Studies in children demonstrated efficacy and
safety
Increases hemoglobin F level
Increases hemoglobin
Decreases WBC – ancillary effect
Reduces number of ACS, VOC
Hydroxyurea is recommended by the
hematologist for patients who have recurrent
vaso-occlusive crises, acute chest syndrome.
A healthy 5 year old boy- 2 day hx of fever, P/E normal
No hepatosplenomegaly, LN, no focus of infection. CBC WBC 3,
Neutrophils 25 %, Hb 12, Platelet 200X109/L, ANC 750. Most appropriate
step is
ist
12
w
ol
og
a
CB
C
in
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at
as
pi
ra
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to
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ks
0%
te
s.
0%
BM
fo
r1
0
da
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ys
da
10
0%
GCS
F
fo
r
in
cil
l
5.
0%
ox
i
2.
3.
4.
Amoxicillin for 10
days
G- CSF for 10 days.
BM aspirate
Refer to a
hematologist
Repeat CBC in 1-2
weeks
Am
1.
6
Case
A 2-year-old boy has had several 10-day-long episodes
of fever, mouth ulcerations, stomatitis, and pharyngitis.
These episodes have occurred at about monthly
intervals. Absolute neutrophil counts have been
50/mm³on day 1 of each illness, 500/mm³ on day 10, and
1,500/mm³ on day 14.
Among the following, the MOST likely cause for the findings in
this patient is
A. chronic benign neutropenia
B. cyclic neutropenia
C. Schwachman-Diamond syndrome
D. severe congenital neutropenia
E.. transient viral bone marrow suppression
Abnormal Bleeding
Epistaxis unrelieved by 15 minutes of
pressure, both nostrils, requiring an ER
visit, documented drop of hemoglobin.
Menstrual periods( amount, pads,
duration)
Bleeding after procedures (circumcision,
dental extractions, T and A-delayed bleed)
Ecchymoses/bruising inconsistent with
the degree of trauma
Bleeding patient
Physical Examination:
Type of bleeding: Superficial or deep
– Bruises, Petechiae
– Epistaxis, Gum bleeding, Excessive menstrual
bleeding
– Site of bleeding
– Bleeding into the joints and soft tissues
– Look for evidence of shock
– Medication history (Aspirin, NSAIDS)
Lab studies
(What do they measure?)
CBC and Peripheral smear
PT, INR and PTT
– PT - Factor VII, common pathway
– PTT- Factor VIII, IX, XI, XII, common pathway
Mixing studies (Inhibitors and deficiency)
Specific coagulation factor assays
Coagulation cascade
Questions on
Circulating anticoagulant
Mixing study
If PT or PTT is prolonged, ask for a mixing
study.
Mix patient plasma with equal amount of normal
plasma, the test will normalize if the abnormal
result is because of a deficiency in factor.
If there is an anticoagulant, it will not normalize
or even if it does, it will become abnormal again
after incubation.
A healthy 2-day-old boy born at term undergoes
circumcision.
Bleeding noted at the site 10 hours after the procedure and increased
steadily over the past 4 hours. Findings on exam are unremarkable
except for bleeding along 2 to 3 mm of the surgical site; no petechiae
or purpura.
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as
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at
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2.
Disseminated
intravascular
coagulation
Factor VIII deficiency
hemophilia
Immune
thrombocytopenic
purpura
Neonatal alloimmune
thrombocytopenia
Von Willebrand disease
Di
ss
1.
6
Hemophilia Questions
Factor VIII deficiency (Hemophilia A)-85%
– X-linked recessive, Carriers asymptomatic
– Severe<1%, Moderate 1-5, Mild 6-30 %
– Treat Recombinant Factor VIII 1unit/kg raises factor
level by 2 %. Half life 12 hrs. Joint bleeds need100%,
muscle bleeds 50 %.
– DDAVP for mild cases.
– 30 % develop inhibitors after infusions with
concentrate (Approx 50 infusions)
Factor IX deficiency (Hemophilia B)
– X-linked recessive, less common
A patient with Hemophilia A has asked you about the
possibility of his children being affected by the disease.
The partner is normal.
th
..
ch
a
00
%
Th
er
e
is
a1
00
%
a1
is
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e
Th
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th
..
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ch
a
ch
a
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a
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4.
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is
3.
er
e
2.
There is a 50 % chance
that his sons will have the
disease.
There is a 50 % chance
that his daughters will be
carriers
There is a 100 % chance
that his sons will have the
disease
There is a 100 % chance
that his daughters will be
carriers
Th
1.
Case
13 year old girl just started her periods and
has been bleeding for the past 16 days.
She has used 14 pads a day and is tired.
Her vital signs are stable, Hb 9.5, PT, PTT
normal.
The mother had heavy periods and her 6
year old brother has nose bleeds for the
past 2 years.
Likely to have:
Questions on Von Willebrand’s Disease
1-2 % of population
Type I - 80 % of cases; Quantitative defect, Autosomal
dominant (AD)
Type 2 - 15-20 %, Qualitative defect
– 2A, 2b (thrombocytopenia), 2M, 2N (AR)
Type 3 - Severe (similar to hemophilia A)
Autosomal recessive (AR)
DDAVP- Releases VWF from endothelial cells and stabilizes
Factor VIII
– SE: Water retention, Tachyphylaxis, hyponatremia.
– For mild Hemophilia, Type I VWD, 2
– Contra-indicated in Type 2B
Rx-Plasma derived VWF containing concentrates
Thrombophilia
A 14 year old male presents with chest pain and difficulty
breathing. He notes that his right calf has been swollen
for the last 3 days and he has difficulty placing his foot
on the ground. P/E Pain on dorsiflexion, Air entry
reduced. CXR and EKG are normal. VQ scan shows a
filling defect and a diagnosis of DVT and pulmonary
embolism is made.
What are the important questions on history?
– History of DVT in family members
– H/o recurrent late miscarriages in mother and her sisters.
– H/o trauma and precipitating factors
The most common cause of familial
predisposition to thrombosis is
io
n
ef
ic i
III
d
m
en
om
bi
n
id
Le
An
t it
hr
V
to
r
0%
en
cy
0%
ut
at
en
cy
cy
C
0%
Sd
ef
ic i
en
Pr
ot
ei
n
tib
an
Pr
ot
ei
n
lia
op
hi
He
m
0%
de
fic
i
od
i
es
0%
Fa
c
1. Hemophilia
antibodies
2. Protein C
deficiency
3. Protein S
deficiency
4. Factor V Leiden
mutation
5. Antithrombin III
deficiency
Tests performed on donated units of blood
...
fro
in
ed
fo
rH
...
on
ly
ar
e
un
it s
0%
un
it s
te
ste
d
fo
r
es
te
d
et
all
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ob
ta
f. .
on
ly
ar
ni
ts
lu
al
0%
HI
..
0%
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es
te
et
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ar
et
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te
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on
ly
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0%
ar
5.
al
4.
ni
ts
3.
lu
2.
all units are tested only for
hepatitis B and C
all units are tested only for
human immuno-deficiency
virus (HIV)
all units are tested for HIV,
hepatitis B, and hepatitis C
all units are tested for HIV,
hepatitis B, hepatitis C, sickle
cell trait, cytomegalovirus,
and Epstein-Barr virus
only units obtained from
donors who have one or
more risk factors are
screened for HIV, all units
are tested only for hepatitis B
and C
al
1.
6
Questions on Transfusion
CMV negative- give leukocyte reduced.
Irradiated products- To prevent GVHD
Washed cellsPhenotype matched
– To prevent allo-immunization
Sickle negative
CANCER IN CHILDREN
Childhood Cancer Distribution
Distribution-All ages
Leukemia
Lymphoma
Brain Tumor
Soft tissue sarcoma
Germ call
Bone
Neuroblastoma
Renal
Retino
Hepato
Carcinoma
Other
A 6-year-old girl has aching in her arms, legs, and back for > 2 weeks.
Results of laboratory tests include hemoglobin, 9.4 g/dL; white blood cell count,
5,600/mm³ with no abnormal cells noted on smear; and platelet count,
106,000/mm³.
Radiographs of long bones reveal osteolytic lesions and radiolucent metaphyseal
growth arrest lines.
m
ye
lit
is
ng
0%
os
te
o
as
e
0%
ad
M
ul
tif
o
ca
l
le
ch
er
d
ise
em
Ga
u
an
0%
po
is o
ni
0%
ia
AL
L
0%
st
ic
ALL
Aplastic anemia
Gaucher disease
lead poisoning
Multifocal
osteomyelitis
Ap
la
1.
2.
3.
4.
5.
6
ALL
(Acute Lymphoblastic leukemia)
75% of all Leukemias
Can present with
generalized bone
pain, fatigue
Bruising, nose bleeds
Unusual fevers,
infection
Lymphadenopathy,
hepatosplenomegaly
ALL- Should know
(Acute Lymphoblastic leukemia)
Abnormal to see blasts in the peripheral smear
Diagnosis: >25 % blasts in the BM.
Normal marrow has < 5 % blasts
Single most common childhood cancer (29% of
all childhood cancers); 2500-3500 cases per
year
Peak age 2-5 years
More likely in Trisomy 21, Ataxia-Telangiectasia, Bloom
syndrome, Kostmann’s, Monosomy 7, DBA, Fanconi
anemia, 20% risk in twin if age <5yrs
ALL Treatment
Induction: 4-6 weeks,
Consolidation /delayed Intensification:
6-12 months; rotating drugs.
Maintenance : Daily oral 6-MP, weekly MTX, Monthly
pulses of Vincristine and Steroid.
Imatinib mesylate-Tyrosine Kinase Inhibitor- Ph
Chromosome positive patients
CNS prophylaxis: Intrathecal chemo
CNS Therapy: RT + Intensive systemic chemo
Testicular disease: RT
SANCTUARY- CNS, Testis
ALL- Prognosis
Prognosis:
WBC, Age, Cytogenetics
– good if hyperdiploidy (>50),trisomy 4,10,17, t(12,21)
– Bad if hypodiploid, Ph. chrom t (9,22),t(4,11), t(8,14)
Immunophenotype: Pre-B good, B and T-worse
Early response, Minimal residual disease (MRD)
Infants: 50 % survival
Early relapse is a poor sign
Down Syndrome and Leukemia
10-20 fold increase
DS: 400 fold Increase in M7 AML
Superior response to Rx of AML
Transient Myeloproliferative disorder in
newborn which resolves within 3 months.
Acute Myeloid Leukemia (AML)
20 % of all leukemias
Increased incidence in < 1 year of age
Higher incidence:
– Downs, Fanconi, Bloom, DBA, Kostmann,
Neurofibromatosis I, Schwachman-Diamond
Chloromas– solid collection in bone/soft tissues
Types: M0-M7, commonest M2
DIC in M3- (Promyelocytic- APML)
M7- Downs syndrome
Question Hodgkins
•
•
•
•
•
16 year old male presents with a painless swelling in the
supraclavicular region. Biopsy shows Hodgkins disease
Stage 2. All are true except:
1. Presence of “B” symptoms is worse for prognosis
2. B symptoms are fever, increasing size of mass
3. Staging depends on whether it is on one or both sides
of the diaphragm
4. Sperm banking should be done
5. Second malignancy can occur in patients who receive
combination chemo and RT
Question
4 year old boy presents with a 6 day history of bilateral, rapidy progressive
1.
2.
3.
4.
5.
facial swelling. There is no history of associated trauma or upper
respiratory symptoms. On P/E, there is significant swelling below both eyes
and of both cheeks. The angle of the jaw is maintained. On examination of
the oral cavity, both the soft and hard palate are swollen as are the gingiva.
The teeth are loose and inverted due to the degree of gingival swelling. A
CT of the sinuses reveals extensive bilateral opacification of both maxillary
sinuses. LDH was 1,850 U/L. Which of the following is the most likely to
cause of this patient’s physical findings?
Human herpesvirus 6
Cytomegalovirus
Cryptosporidium hominis
Parvovirus B19
Epstein-Barr virus
Burkitt’s Lymphoma
Endemic Burkitt’s
– African type, head and
neck, jaw
– 95 % chance of EBV
Sporadic Burkitt’s
– Abdomen
– 15-20 % chance of
EBV
t (8;14)
Immunotherapy: Anti-CD
20 monoclonal antibody;
(Rituximab)
Question
5 yr old boy with
progressive vomiting,
headache, unsteady
gait and diplopia for 4
weeks. MRI shows a
contrast enhancing
tumor in the 4th
ventricle with
obstructive
hydrocephalus.
Brain Tumors- Important to
know
20% of all malignancies in children
Age 3-7 years
Most often infratentorial
Sx: Persistent vomiting, headache, gait
imbalance, diplopia, ataxia, vision loss, school
deterioration, growth deceleration
Associations with Inherited Genetic disorders:
– Neurofibromatosis, Tuberous sclerosis, VonHippel-Lindau disease, Li-Fraumeni (glioma),
Turcot syndrome
Medulloblastoma
- most common CNS tumor
– Trt: Resection, Craniospinal RT, Chemo
– Prognosis: Age, large size, degree of
resection, dissemination, histology.
Wilms Tumor
An 18-month-old girl is
being evaluated because
her mother thinks her
abdomen seems “full.”
Physical examination
reveals an abdominal
mass. Ultrasonography
identifies a solid renal
mass. At surgery, a stage
I Wilms tumor is found.
Stage I Wilms- Chance of 4-year survival is CLOSEST to
0%
0%
95
%
0%
E.
0%
D.
75
%
0%
C.
60
%
5. E.
45
%
4. D.
B.
3. C.
30
%
2. B.
30%
45%
60%
75%
95%
A.
1. A.
6
Wilms Tumor- Important
Presentation: No Sx, HT, Hematuria, Malaise
Histology: favorable(FH) vs unfavorable (UH)
Staging: I-local, II-excised, III-residual, IVmetastases, V -bilateral
Treatment: Nephrectomy, Chemo-all, St I-II-2
drugs-18 weeks, St III-IV- 3 drugs+ RT
Prognosis:
– FH: > 90% at 2 years
– UH: < 60% at 2 years
Congenital anomalies associated with Wilms’ tumor
include all of the following except
1. Polydactyly
2. Aniridia
3. Hemihypertrophy
4. Cryptorchidism
hi
d
Dr
as
h
pt
or
c
sy
nd
ro
m
y
op
h
De
n
ys
-
Cr
y
ih
0%
e
0%
ism
0%
rtr
An
ir i
di
a
0%
He
m
Po
ly
da
c
ty
l
y
0%
yp
e
5. Denys-Drash
syndrome
6
A 9 year old previously healthy girl manifests
progressive painless proptosis and decreased
visual acuity of the left eye during a 2 month
period. The most likely diagnosis is:
a. Pseudotumor of the orbit
b. Trichinosis
c. Retinoblastoma
d. Rhabdomyosarcoma
e. Orbital cellulitis
Rhabdomyosarcoma
Painless non tender mass
60% under age 6
Sites: head & neck, GU, Extremities, mets lungs.
Majority sporadic, associations: B-W, Li Fraumeni, NF 1
Types:
– Embryonal 70%, better prognosis
– Alveolar 30 %, trunk, worse prognosis
Treatment: Surgery, Chemo, local control RT
Mass
The mother of a 22-monthold boy reports that he has
been fussy and tired.
Findings on physical
examination confirm the
presence of a nontender rt
upper quadrant mass.
Bilateral periorbital
ecchymoses also are noted.
Of the following, the MOST
likely cause for these
findings is
A. multicystic kidney
disease
B. neuroblastoma
C. non-Hodgkin lymphoma
D. Hepatoblastoma
E. Wilms tumor
All statements are true about
Neuroblastoma except:
M
gn
os
..
on
l
yd
ia
.. .
os
tc
in
qu
en
t
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e
0%
om
m
ye
ar
ca
on
m
om
0%
s,
97
t..
ri
n
nc
e
ith
rw
be
tte
M
os
tc
sis
0%
<4
an
-cr
tra
ex
0%
N.
..
i..
0%
m
on
5.
Pr
og
no
4.
om
3.
os
tc
2.
Most common extracranial solid tumor
Prognosis better with Nmyc oncogene
amplification and tumor
diploidy (DNA index 1)
Most common cancer in
the first year of life
Frequent in <4 years, 97
% cases by 10 years
Most commonly
diagnosed as Stage III or
IV
M
1.
6
Case
A 16 year old male comes in because he fell in
the supermarket.
P/E shows a small painless mass on the medial
aspect of the knee.
• X ray shows a fracture and a lytic sunburst pattern.
(periosteal elevation)-OS
• Xray shows an onion peel appearance- ES
• Xray- radioluscent, sharp, rounded lesion < 2cm with
reactive sclerosis- Osteoid Osteoma
X ray and MRI
Ewing’s Sarcoma
Osteogenic Sarcoma
MRI, Bone scan, Biopsy, CT Chest for mets.
Peak incidence- 2nd decade
Predisposition: Hereditary retinoblastomas, LiFraumeni, Pagets, RT, Alkylating agents
60 % near the knee (Metaphyses of long bones)
History of fall, pain common symptom, mass,
no systemic symptoms.
Treatment: Sperm banking, Neo-adjuvant
Chemotherapy, limb preserving surgery.
A 16 year old Caucasian
female comes with complaints
of chest pain and difficulty
breathing for the past one
week. She has had fever, wt
loss over the last 2 months.
She has reduced air entry and
CXR shows a moth eaten
appearance of one of the ribs
and a pleural effusion.
Biopsy is done and is
consistent with Ewing’s
Sarcoma
Retinoblastoma- need to know
Presentation: Leukocoria (cats eye reflex), dilated pupil,
esotropia, strabismus
Unilateral 75 % (could be hereditary/non)
– 60 % unilateral and non hereditary
– 15 % unilateral and hereditary (RB1 mutation)
Bilateral 25 %
– 25 % are bilateral and hereditary, have RB1 mutation
– Earlier age, 11mos, Can develop in each eye separately
– Higher incidence of sarcoma, melanoma, brain tumors.
A child with ALL was started on Chemotherapy.
She had a WBC 82,000, Hb 9gm, plt ct 45,000. She
develops tumor lysis syndrome: Which depicts Tumor lysis
..
hi
g
h,
hi
g
P
gh
,
hi
K
0%
LD
H
,
al
,P
al
rm
no
K
0%
LD
.. .
h.
..
no
rm
hi
gh
,P
rm
al
no
K
0%
LD
H
,
LD
H
,
al
no
rm
P
gh
,
hi
0%
h.
..
...
no
r
LD
H
h,
hi
g
K
5.
0%
P
4.
gh
,
3.
hi
2.
K high, P high,
LDH normal, Na high
K high, P normal,
LDH high, Na nl
K normal, P high,
LDH high, Na high
K normal, P normal,
LDH high, Na normal
K high, P high,
LDH high, Na
normal.
K
1.
Tumor lysis syndrome
Rapid destruction of cancer cells.
Release of intracellular ions, also Uric
acid, can cause tubular obstruction and
damage.
Treatment: Allopurinol or Rasburicase
early, hydration, alkalinization, diuretic
therapy.
Spinal cord compression
Presentation: back pain worse with movement, neck flexion,
straight leg raising, valsalva
– Weakness; partial/complete paralysis, Incontinence
Local tumor extension or metastasis
Lymphomas, neuroblastoma, soft tissue sarcomas
Therapy: Urgent treatment to relieve pressure and
prevent permanent neurologic damage.
–
–
–
–
Neurology/Neurosurgery consult
High dose dexamethasone
Emergency radiation therapy
Laminectomy
Questions on-Superior Vena Cava
Syndrome
Mass lesion obstructs flow through the SVC
Symptoms
Dyspnea, edema of face, neck, upper extremities
– Periorbital edema, conjunctival edema (itchy eyes)
– Dysphagia, resp distress, vocal cord paralysis
Tracheal compression: resp distress, wheezing
Due to- NHL, Tcell ALL, Lymphoma,
Secondary cause: occluded central venous catheter
Chemotherapy-Side effects
that you need to know
Anthracyclines: Cardiac toxicity
Vincristine: foot drop, peripheral neuropathy
Cisplatinum: kidney, deafness
Methotrexate, 6MP: Liver toxicity
Bleomycin: Pulmonary fibrosis
Asparaginase: Pancreatitis, Coagulopathy
Etoposide (VP-16): Secondary AML
Cyclophosphamaide: Hemorrhagic cystitis
(MESNA as Uroprotector) and Infertility
Fever, Neutropenia
Single most important risk factor: ANC
Organisms: Gram negative infection,
Staph epi in catheter patients
Medication: Broad spectrum 3rd generation
antibiotics
Anti-fungal after 4 days
Examine patient thoroughly
16-year-old girl, completed therapy at age 8 for Hodgkins
disease with Involved field RT and chemo.
She now develops petechiae, purpura, lymphadenopathy and
hepatosplenomegaly.Lab include: plt 12,000,Hb 8.0 gm/dL;
and WBC 13,000/mm³. She has….
0%
d
nd
uc
e
e.
..
Vi
ra
l- i
an
st
ic
pl
a
ta
on
se
te
-
0%
IT
P
IT
d
el
va
r ic
Dr
ug
La
ed
in
at
in
du
ce
..
ig.
al
m
em
se
co
nd
Di
ss
0%
P
0%
la
0%
sa
5.
La
2.
3.
4.
AML as a second
malignancy
Disseminated varicella
Drug-induced ITP
Late-onset aplastic anemia
due to chemotherapy
Viral-induced ITP
AM
1.
6
You are evaluating a 9 year old child for short stature. She
was treated at 3 yrs of age for ALL, received cranial RT.
Her height is < 5th percentile and she is Tanner stage I. Most
likely to have an abnormal test of
1. Growth hormone
2. Estradiol
3. Follicle stimulating
0%
0%
gh
o.
..
g..
.
at
in
le
ul
re
sti
m
n
op
i
ot
r
yr
oi
d
Th
Go
na
d
st
im
lic
le
as
in
ho
r. .
.
di
in
g
ul
at
wt
h
Fo
l
0%
ol
0%
Es
tra
ho
rm
on
e
0%
Gr
o
hormone
4. Gonadotropin
releasing hormone
5. Thyroid stimulating
hormone
6
Need to know- Late effects of cancer
therapy
RT:

Hypothalamic pituitary axis is impaired;
central hypothyroid and Adrenal insuff.

RT doses higher in brain tumor

GH is dose sensitive to the effects of RT

Age related: < 5 years susceptible

Panhypopituitarism with higher doses

ovarian failure with RT
A 16 year old boy is receiving chemo for
rhabdomyosarcoma
He recd a year of cycles of Vincristine, Actinimycin-D and
Cyclophosphamide.
Most likely endocrinologic late effect of this therapy
1. Growth hormone
deficiency
2. Hypothyroidism
3. Impotence
4. Infertility
5. Osteoporosis
0%
0%
0%
0%
Gr
o
wt
h
ho
rm
on
e
de
fic
i
en
Hy
cy
po
th
yr
oi
di
sm
Im
po
te
nc
e
In
fe
rti
lit
y
Os
te
op
or
os
is
0%
6
Chemotherapy effects
Chemotherapy with alkylating agents
Females:
less effects than males
normal puberty
early menopause
Males:
irreversible gonadal toxicity
sterility with azospermia
Puberty usually not affected (leydig cells)
The most common reason for the failure of
hematopoietic stem cell transplantation is
Ve
no
-
oc
c
0%
0%
0%
ft
v
In
fe
c
tio
s.
n
ho
st
di
se
as
Gr
e
af
tr
ej
ec
tio
n
0%
en
ce
ur
r
ec
er
as
Di
se
lu
siv
e
di
se
as
e
of
.. .
0%
Gr
a
1. Veno-occlusive
disease of the liver
2. Disease recurrence
3. Infection
4. Graft vs. host
disease
5. Graft rejection
6
GVHD ( Graft vs Host disease): All are true
except
0%
0%
0%
0%
ac
tio
n
eG
of
th
VH
e
D
...
Af
st
ar
fe
ts
ct
st
w
ith
he
in
sk
Irr
.. .
in
ad
, li
ia
ve
tio
ra
n
nd
of
Co
bl
..
m
oo
pl
d
et
pr
e
od
HL
...
A
m
at
ch
in
g.
..
0%
re
5.
Ac
ut
4.
he
3.
st
2.
It is the reaction of the
donor lymphocytes
against the host.
Acute GVHD starts within
the first 100 days and
chronic is after 100 days.
Affects the skin, liver and
GI tract
Irradiation of blood
products does not help
Complete HLA matching
prevents GVHD
It
i
1.
6
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