HEMATOLOGY/ONCOLOGY Flashcards
1
Q
What is the pathologic hallmark of Hodgkin disease?
A
Reed-Sternberg cells
2
Q
What is the pathologic hallmark of Acute Myeloid Leukemia?
A
Auer rods
3
Q
What is the prognosis of Hodgkin vs. Non-Hodgkin Lymphoma?
A
Hodgkin: 90% 5 year survival (up to 100% in low risk patients)
Non-Hodgkin: 70-90% 3 year survival
4
Q
Which type of ALL is associated with increased presence of anterior mediastinal mass?
A
Pre-T-cell ALL
5
Q
What causes bitemporal hemianopsia?
A
Suprasellar lesion compressing the optic chiasm
6
Q
What is the definition of “suprasellar”?
A
Situated above the sella turcica
7
Q
Features of craniopharyngioma?
- location
- types of cells
- clinical features (3)
- treatment
A
Location: suprasellar
Type of cells: pituitary gland embryonic tissue (benign, non-cancerous)
Clinical features: increased ICP, bitemporal hemianopsia, endocrinologic abnormalities (DI, growth failure, thyroid dysfunction, etc from pituitary dysfunction)
Treatment: Surgery +/- radiation
8
Q
What is the most common malignant childhood brain tumor?
A
Medulloblastomas (aka primitive neuroectodermal tumors, PNET) - 20% of all pediatric tumors
9
Q
What are 2 features of posterior fossa tumors?
A
Progressive ataxia with headache that may be acute or gradual in onset
Symptoms may result from primary cerebellar invasion or from obstruction of the CSF pathways leading to increased ICP and hydrocephalus
10
Q
What are the most common posterior fossa tumors (4)?
A
- Medulloblastoma (malignant) - 20% of all pediatric tumors
- Cerebellar astrocytoma (benign glial tumor) - 15% of all pediatric tumors
- Ependymoma
- Brainstem glioma
11
Q
What are contents of the posterior fossa? (2)
A
Brainstem and cerebellum
12
Q
Which congenital syndromes give increased risk of Wilm’s Tumor? (4)
A
- Beckwidth-Wiedemann: hemihypertrophy, omphalocele, hypoglycemia, macrosomia, macroglossia
- WAGR: Wilm’s tumor, aniridia (absence of iris), genitourinary abnormalities (hypospadias, horseshoe kidney, cryptochidism, etc.), mental retardation
- Isolated hemihypertrophy
- Denys-Drash syndrome: pseudohermaphroditism, degenerative renal disease
13
Q
What is the most common malignant renal tumor of childhood?
A
Wilm’s tumor
14
Q
In which clinical condition do you see subependymal giant cell astrocytomas?
A
Tuberous sclerosis
15
Q
In patients with Beckwidth-Wiedemann syndrome, what 3 malignancies are they are increased risk for developing?
A
- Wilm’s tumor: need renal ultrasound for screening
- Neuroblastoma: need periodic CXR and urine catecholamines
- Hepatoblastoma: AFP screening in 1st 10 years of life
16
Q
Why do patients with chronic hemolysis have hepatosplenomegaly?
A
Extramedullary hematopoesis in liver and spleen
17
Q
When is the physiological nadir of RBCs in infants?
A
8-10 wks of life: decreased RBC survival (fetal RBCs with alpha-2/gamma-2 Hgb last only 60 d), decreased erythropoesis, nadir goes as low as 95
-for premies: 6-8 wks, nadir goes as low as 70
Then EPO kicks in and start making new RBCs with alpha-2/beta-2 Hgb
By 6 mo of age, should only have trace amounts of fetal Hgb production left but it does stick around until 8 mo
18
Q
What is the differential diagnosis for macrocytic anemia (7)?
A
- Vitamin B12 deficiency (pernicious anemia, ileal resection, strict vegetarian)
- Folate deficiency (malnutrition/malabsoprtion, TMP/sulfa)
- Drugs (alcohol, zidovudine)
- Hypothyroidism
- Bone marrow failure (myelodysplasia, diamond blackfan, fanconi anemia, aplastic anemia)
- Normal newborn
- Down syndrome
**massive reticulocytosis can also cause macrocytosis (ie. after a hemolytic anemia episode)
19
Q
What are 3 key findings in patients with hemolytic anemia?
A
- Splenomegaly
- Jaundice
- Pallor
20
Q
What is a key clinical finding in chronic hemolysis?
A
Gallstone production secondary to hyperbilirubinemia
21
Q
What is one test you should always order in a patient with anemia?
A
Stool sample for occult blood
22
Q
What is the inheritance pattern of:
- G6PD
- Spherocytosis
- Sickle cell disease
A
G6PD: X-linked (see in blacks, greeks, middle eastern)
Spherocytosis: autosomal dominant
Sickle cell: autosomal recessive
23
Q
What are 3 key questions to ask in family hx of anemia?
A
- Ethnicity
- Family members with history of cholecystectomy secondary to gallstones at early age
- Family members with history of splenectomy at early age
24
Q
What deficiency do you see with:
- strict vegetarian
- goat’s milk diet
A
Strict vegetarian: vitamin B12 deficiency
Goat’s milk diet: folate deficiency
25
What are the 2 main classifications for hemolytic anemia?
1. Intrinsic (problems in the RBC)
- Membranopathy (spherocytosis, elliptocytosis)
- Enzymopathy (G6PD, pyruvate kinase deficiency)
- Hemoglobinopathy (Sickle cell, thalassemia)
2. Extrinsic (problems outside the RBC)
- Immune-mediated (isoimmune, autoimmune, drug induced)
- Non immune (DIC, HUS, TTP)
26
What initial studies should be ordered for hemolytic workup (6)
1. CBC + diff
2. Haptoglobin (protein that binds with free Hgb --> will decrease with hemolytic anemia but not a reliable marker if retic count is high since retics have a lot of haptoglobin)
3. Peripheral blood smear
4. Bilirubin
5. Reticulocytes
6. LDH
27
What are examples of 2 drugs that exacerbate hemolysis in G6PD patients?
1. Nitrofurantoin
| 2. Antimalarials
28
Iron deficiency anemia can be seen in which populations (3)?
(Otherwise shouldn't be seen if have a normal diet since iron is stored very efficiently)
1. Infants fed cow's milk prior to 1 yo (causes bowel inflammation and micro-blood loss and decreased Fe absorption)
2. Toddlers taking large volumes of cow's milk (not eating other foods)
3. Menstruating teenage girls (chronic blood loss)
29
Which babies are more likely to have iron deficiency anemia: breast or formula fed babies?
Formula fed babies! Even though breast milk has less iron than formula, the iron in it is more efficiently stored
30
What is the treatment for iron deficiency anemia?
- how long does it take for retics to rise with treatment?
- How long does it take for Hgb to rise with treatment? -How long does it take for repletion of iron stores?
- why is it important to treat iron deficiency anemia?
Therapeutic trial of iron is best diagnostic study for iron deficiency - Elemental iron 4-6 mg/kg/day
- retics take 3-7 days to rise
- Hgb takes up to 30 days to rise
- Repletion of iron stores takes 1-3 months
- important to treat to prevent intellectual and developmental impairment
- repeat CBC + retic count within 1 week of starting iron deficiency
- if Hgb is not increased within 2 weeks, consider non-compliance, wrong diagnosis, ongoing blood loss, etc.
31
When should iron supplementation occur for breast fed babies?
4 mo - iron supplementarion
| 6 mo -introduce iron enriched solid foods
32
Why do you get anemia in chronic inflammatory disease?
HEPCIDIN - a protein in the liver that is responsible for iron hemostasis
-in inflammation, liver makes a lot of hepcidin which interrupts iron release by macrophages and decreases iron absorption in the intestine
33
Which 2 infections can cause autoimmune hemolytic anemia?
1. EBV
| 2. Mycoplasma
34
What is the Mentzer index?
```
Helps differentiate between iron deficiency anemia and Beta
thalassemia trait (aka minor)
-MCV/RBC count < 13 = diagnostic of beta thalassemia
-MCV/RBC count > 13 = iron deficiency
```
35
What are 5 types of early onset (during or within 4 hours of) transfusion reactions?
1. Febrile non hemolytic
2. Hemolytic (febrile or non febrile)
3. Anaphylaxis
4. Urticaria
5. TRALI (transfusion-related acute lung injury)
36
What is the most common transfusion reaction?
Febrile non-hemolytic
37
What is the most common inherited cause of hemolytic anemia?
Hereditary spherocytosis (autosomal dominant)
38
What is transient erythroblastopenia of childhood?
- affects which age groups?
- resolution time?
Isolated acquired red blood cell aplasia, resolves in 1-2 months without intervention and is self-limited
- affects children 6 mo - 6 yo
- 50% have preceding viral illness
- main ddx is diamond-blackfan anemia (look at age, MCV, Hb F, adenosine deaminase levels)
39
What are 2 features seen on CBC that diagnostic for hereditary spherocytosis?
What is the standard diagnostic test for hereditary spherocytosis?
1. CBC (100% specificity):
- increased MCHC (mean corpuscular Hgb concentration)
- increased RDW
2. Blood smear
- spherocytes
Standard diagnostic test: osmotic fragility test
40
What 6 prognostic factors are used to determine high risk in ALL?
1. Initial WBC count at diagnosis > 50,000
2. CNS involvement
3. Age < 1 yo or > 10 yo
4. DNA index < 1.16
5. Cytogenetics t(4;11), t (9;22)
6. Slow response to induction tx
41
What is the induction treatment for low/standard risk ALL (4)?
4 week course of:
1. Vincristine
2. Prednisone
3. Asparaginase
4. IT chemo
42
What is the induction treatment for high/very high risk ALL (5)?
4 week course of:
1. Vincristine
2. Prednisone
3. Asparaginase
4. IT chemo
5. Doxorubicin
43
What are the 3 types of nonhodgkin lymphoma?
1. B cell (aka Burkitt's)
2. T cell (lymphoblastic lymphoma)
3. Large cell
44
In a patient with blasts and a mediastinal mass, how do you decide if it's a leukemia with mediastinal mass or lymphoma?
Bone marrow biopsy - if > 25% blasts, it's leukemia
45
In a patient with lymphoma, what investigations should you order for staging?
1. Bone marrow aspirate
2. Bone scan
3. CT abdomen to rule out abdominal involvement
4. Tissue biopsy (ultimate diagnosis)
46
What is the most common presenting complaint for lymphoma?
Painless firm lymphadenopathy (cervical or supraclavicular)
47
What 4 genetic conditions give increased risk of acute leukemia?
1. Down syndrome
2. Fanconi anemia
3. Wiskott Aldrich
4. NF-1
48
What tests must ALWAYS be performed for diagnostic work up in acute leukemia (4)?
1. Bone marrow aspirate - to confirm diagnosis
2. CXR - to rule out mediastinal mass
3. Lumbar puncture - to rule out CNS involvement
4. Tumor lysis bloodwork
49
What is the overall cure rate for:
- ALL
- AML
ALL - 80%
| AML - 50%
50
What are the 3 most common malignancies in childhood?
1. Leukemia
2. CNS tumors
3. Lymphoma
51
What 2 features should make you consider a hereditary/congenital cause for Wilms tumor?
1. Bilateral renal involvement
| 2. Younger age at onset
52
What are the 4 most common presenting signs and symptoms of Wilms?
1. Abdominal mass
2. Hypertension
3. Hematuria
4. Fever
53
What is the most common site of metastasis in Wilms tumor?
Lungs
54
What is the initial work-up for Wilms tumor (8)?
- BW
- Imaging
1. CBC
2. Urinalysis
3. Liver/renal function tests
4. CXR
5. MRI/CT abdomen
6. MRI/CT chest to rule out mets
7. Urine catecholamines (VMA, HVA) to differentiate between NB
8. Coagulation studies including ristocetin cofactor and VWF
55
What is the treatment for Wilms tumor?
Adjuvant vs. neoadjuvant
- In North America: nephrectomy followed by adjuvant chemotherapy +/- radiation
- In Europe: neoadjuvant chemotherapy followed by nephrectomy
56
What is the differential diagnosis for Wilms tumor (4)?
1. Hydronephrosis
2. Polycystic kidney
3. Neuroblastoma
4. Benign renal tumor (hamartoma, nephroma)
57
Which hematological disorder can develop in patients with Wilms tumor?
Von Willebrand Factor Deficiency - need to screen for this!
58
What is the prognosis of Wilms tumor?
Localized - 85%
| Pulmonary mets - 70-80%
59
What 2 clinical findings should be absent in order to diagnose a patient with ITP?
1. Lymphadenopathy
| 2. Hepatosplenomegaly
60
What is the treatment for ITP?
IVIG or oral steroids (less preferred)
61
In an infant presenting with bilateral periorbital ecchymosis and abdominal mass, what is the most likely diagnosis?
Neuroblastoma (with periorbital metastasis)
| -tumor mets periorbitally causing obstruction of palpebral vessels
62
In neonates with severe thrombocytopenia, what is the mainstay of treatment?
Immediate platelet transfusion to prevent life-threatening hemorrhage (ie. intracranial bleed)
63
What are the classifications of childhood histiocytoses?
- what cells are prominent in each class?
- malignant vs. non malignant?
* **Overall, these conditions are thought to be disorders of immune regulation!!!!
- histiocytes: cells of the monocyte-macrophage series
1. Class I - Langerhans cell histiocytosis
- accumulation of antigen presenting cells (Langerhans cells) = monocyte
- non malignant
2. Class II - Hemophagocytic lymphohistiocytoses (HLH)
- accumulation of antigen processing cells (macrophages) and uncontrolled cytokine release
- macrophages eat up RBCs, platelets and WBCs
- 2 types: familial HLH and infection-associated hemophagocytic syndrome
3. Class III - MALIGNANT
- acute monocytic leukemia -malignant histiocytosis
64
What is the hallmark pathologic sign of LCH on bone marrow biopsy?
Birbeck granule = presence within the monocyte clones in the bone marrow
65
What are the clinical features of Langerhans Cell Histiocytosis? (9 systems)
Can be localized or disseminated
1. Skeletal involvement (80%)
- lytic bone lesions (most commonly in skull)
- if involves vertebral body, can cause collapse and secondary spinal cord compression
- if involves long bones, can cause pathologic fractures
- if involves mandible/maxilla can cause appearance of free floating teeth on xray
2. Derm (50%)
- scaly, papular seborrheic dermatitis of scalp, diaper, axillary or posterior auricular regions
3. Lymphadenopathy (33%)
4. Hepatosplenomegaly (20%) +/- liver dysfunction
5. Ophtho
- bilateral exophthlamos (retroorbital accumulation of langerhans cells)
6. Resp (10%)
- pulmonary infiltrates
7. Endo
- can have pituitary, thyroid or hypothalamic dysfunction leading to poor growth, DI, hypothyroidism
8. Systemic features in multisystem disease:
- fever, weight loss, FTT
9. Heme:
- bone marrow involvement can cause anemia/thrombocytopenia (signifies poor prognosis)
66
What is the diagnostic test for LCH?
| -what additional investigations should be ordered?
Tissue biopsy on skin or bone lesions
| -additional investigations: CBC, liver enzymes, liver function tests, coags, skeletal survey, CXR, urine osmolality
67
What is the prognosis of LCH?
- single system disease
- multi system disease
Single system disease:
- usually bone, lymph node or skin
- generally benign with high chance of spontaneous remission
Multi system disease:
-more difficult to treat but response rate is high and mortality has been reduced by multiagent chemotherapy
68
What is the treatment of LCH?
- single system disease
- multi system disease
Single system disease:
- minimal treatment
- curettage or low-dose local radiation therapy directed at site of involvement
Multi system disease:
-systemic multiagent chemotherapy +/-immunosuppressive therapy (for severe unresponsive disease)
69
What is the diagnostic criteria for hemophagocytic lymphohistiocytosis?
```
Need 1/2 of the following:
1. Molecular diagnosis consistent with HLH (PRF or SAP mutations)
OR
2. Having 5/8 of the following
a. Fever
b. Splenomegaly
c. Cytopenia (affecting 2 or more cell lineages)
d. High triglycerides or low fibrinogen
e. High ferritin
f. Hemophagocytosis in bone marrow, spleen or lymph nodes without evidence of malignancy
g. Low or absent NK cell cytotoxicity
h. elevated soluble CD25
```
70
What is the common initial presentation of HLH?
- history
- age of presentation
- exam findings
Generalized disease process: fever, maculopapular and/or petechial rash, weight loss, irritability
- can present at any age
- exam findings: HSM, lymphadenopathy, respiratory distress, symptoms of CNS involvement
71
What are the laboratory findings seen in HLH? (4)
1. Cytopenia (2 or more cell lines)
2. High triglycerides
3. High ferritin
4. Low fibrinogen
72
What are the two forms of HLH?
- treatment?
- prognosis?
1. Familial HLH
- treatment: chemotherapy (steroids, etoposide, methotrexate)
- prognosis: even with chemotherapy, most cases are fatal
- allogeneic stem cell transplant can cure 60% of patients with FHLH
2. Secondary HLH (due to infection)
- treat underlying infection
- supportive care
- excellent prognosis if infection can be found
- if infection cannot be documented, treat with chemo as in FHLH; worse prognosis
73
For a patient with suspected iron deficiency anemia, what blood tests should be ordered and what are the expected results?
- CBC = microcytic hypochromic anemia
- Iron levels = low
- Total iron binding capacity (TIBC) = high (if there's any iron around, body wants to bind it up fast and efficiently)-
- ferritin: low
- transferrin: low
74
For a patient with iron deficiency anemia who is started on iron, when should you expect to see improvement in:
- retics
- Hgb
- ferritin
Retics: should increase within 2-3 d
- Hgb: should increase within 1-4 wks
- Ferritin: should increase in 3 mo
75
What are the causes of vitamin B12 deficiency? (4)
1. Strict vegan diets
2. Pernicious anemia (autoimmune destruction of gastric parietal cells which usually secrete intrinsic factor needed for vit B12 absorption in the terminal ileum)
3. Parasitic infections
4. Diseases affecting the terminal ileum where vit B12 is absorbed
76
What are the 2 features of Evans syndrome?
1. Autoimmune hemolytic anemia
| 2. ITP
77
What are the clinical features of Diamond-Blackfan anemia? (6)
- cause?
- treatment?
- how to differentiate between Diamond-Blackfan anemia and Transient erythroblastopenia of childhood?
1. Normocytic anemia due to decreased production (absent or markedly reduced erythroid precursors in bone marrow) = need ISOLATED normocytic anemia
2. Short stature (30%)
* **dysmorphisms can occur in up to 45% of cases
3. Facial dysmorphisms
4. Cardiac abnormalities
5. Renal abnormalities
6. Risk of leukemia
- cause: congenital (no clear pattern inheritance)
- treatment: steroids. If not responsive to steroids, then need continuous transfusions. BMT is curative for patients who do not respond to steroids
***Diamond blackfan vs. transient erythroblastopenia of childhood: measure erythrocyte adenosine deaminase (ADA) = will be high in diamond blackfan
78
If a patient with a suspected hemoglobinopathy was transfused prior to Hgb electrophoresis could be done, how long do you have to wait before ordering it to ensure accurate results?
4 months (RBC lifespan of donor blood = 120 d)
79
What are the clinical features of paroxysmal nocturnal hemoglobinuria?
-what do you see on flow cytometry?
1. Hemolytic anemia and hemoglobinuria
- usually hemolysis is worse during sleep and morning hemoglobinuria is typical
2. Hemolysis often precipitated by infection
3. Can see leukopenia/thrombocytopenia
- on flow cytometry: absence of CD59
80
What are the components of hemoglobin?
- components of adult Hgb (Hgb A)
- components of fetal Hgb (Hgb F)
- components of minor adult Hgb (Hgb A2)
- concentrations of each in normal adult blood?
2 alpha and 2 non-alpha polypeptide chains + iron-containing heme group that binds oxygen
- Adult Hgb: alpha-2/Beta-2 (95% of normal Hgb concentration)
- Fetal Hgb: alpha-2/gamma-2 (
81
What is the underlying cause of sickle cell disease?
| -disease severity of Hb SS compared to: Hb SC, Hb S-Beta0 , Hb S-beta+
Single amino acid substitution (glutamic acid --> valine) in at least one B-globin gene affected
- when deoxygenated, Hb S polymerizes to form a sickled erythrocyte with shortened survival and obstruction of small blood vessels
- Hb SS (homozygous, no beta chains at all = A/A/S/S): sickle cell disease
- Sickle cell trait:
- -> Hb SC: less severe than Hb SS
- -> Hb S-beta0: similar to Hb SS in quality and severity
- ->Hb S-beta+ (decreased beta globin production): less severe than Hb SS
82
When does penicillin prophylaxis begin and end for children with sickle cell anemia?
For children with HbSS and S-B0: begins at age of 2 mo and continues until 5 yr of age (controversial whether to stop or not)
-controversial whether to do for sickle cell trait HbSC and HbS-B+
83
What are the immunization recommendations for children with sickle cell anemia? (4)
1. Routine childhood immunizations
2. 23 valent pneumococcal vaccine at ages 2 and 5 yo
3. Meningococcal vaccine after 2 yo
4. Yearly influenza vaccine
84
What are the routine lab/imaging studies that should be performed for health surveillance of children with sickle cell anemia? (5)
-timing?
1. Yearly transcranial doppler ultrasound beginning at age of 2 yo: assess for strokes
2. Yearly Echo beginning at age 15-16 yo: assess for pulmonary hypertension
3. Yearly eye exam beginning at age 10: assess for retinopathy
4. PFTs starting at 6 yo, then q5y: asthma screening (children with SCD and asthma have much poorer prognosis)
5. Yearly renal function tests, urinalysis, urine protein/Cr ratio: screen for sickle nephropathy
85
In which genotypic group of sickle cell anemia is retinopathy most common?
Hb SC disease
86
What is the classic triad for acute chest syndrome?
1. Fever
2. New pulmonary infiltrate on CXR
3. New O2 need (hypoxia)
87
What are acute complications (ie. develop suddenly) of sickle cell disease? (8)
-chronic complications (ie. develop over time)? (5)
Acute complications:
1. Priapism
2. Splenic sequestration
3. Acute chest syndrome
4. Pain crisis
5. Dactylitis
6. Infection
7. Strokes/TIA
8. Aplastic crisis (infection with parvovirus B19)
Chronic complications:
1. Gallstones
2. Pulmonary hypertension (intravascular sickling leads to reduced NO levels)
3. Renal disease (intramedullary sickling leading to papillary necrosis)
4. Retinopathy
5. Avascular necrosis
88
What environmental/clinical conditions exacerbate the sickling phenomenon in sickle cell anemia? (5)
1. Fever
2. Hypothermia
3. Dehydration
4. Hypoxia
5. Acidosis
89
In sickle cell anemia, by what age do children become vulnerable to life-threatening infection? By what age does splenic infarction occur?
- become vulnerable starting at 4 mo of age since sickling of RBCs in the spleen cause dysfunction
- by 2-4 yo, splenic infarction and functional asplenia has occurred
90
Which infections are sickle cell anemia patients susceptible to?
Encapsulated organisms since these are cleared by the spleen
1. H flu
2. Meningococcus
3. Strep pneumo
4. Salmonella
91
A patient with sickle cell disease presents to you with fever > 38.5 degrees celcius and has URTI symptoms. What is your management?
-discharge vs. admit?
All SCD with fever > 38.5 is a medical emergency:
1. Urgent bloodwork: CBC + diff, blood culture +/- urine/CSF culture
2. Rapid administration of 2nd or 3rd generation cephalosporin
3. If child appears well, has reliable parents and does not have signs of SIRS (2 or more of the following with at least 1 being abnormal temp or WBC - fever or hypothermia, high or low WBC, tachycardia, tachypnea), can be managed as an outpatient with close followup after a dose of ceftriaxone
***having a focus of infection does NOT alter the urgency of administering IV abx
92
In aplastic anemia caused by parvovirus infection, how long does the anemia last?
-why are children with sickle cell anemia at higher risk for anemia complications than normal children with parvovirus aplastic anemia?
10-14 d
- in normal children, the arrest of RBC production is not a big deal because their normal RBCs are still around for 120 days so not making any for 10-14 is ok
- in sickle cell disease children, their RBCs' lifespan is only 10-20 days so not being able to make more is a huge problem
93
What is the pathophysiologic mechanism for vasoocclusive crises?
Bone marrow ischemia with resultant infarction
94
Do RBC transfusions aid in the resolution of severe vasoocclusive crises?
NO!
95
What are potential causes of acute chest syndrome? (3)
| -treatment?
Causes:
1. Infection (30% of cases): chlamydia pneumonia, viral infection, mycoplasma
2. Infarction (25% of cases): pulmonary infarctino or pulmonary fat embolism
3. No identifiable cause (45%)
Treatment:
1. Supplemental O2
2. Empiric abx: ceftriaxone + macrolide
3. Bronchodilator prn
4. Analgesia
5. Incentive spirometry
6. Blood transfusion IF decrease in Hgb level from baseline, increasing O2 need
7. IV fluids
96
What is the short- and long-term management of acute stroke in sickle cell disease patients?
1. Immediate PRBC transfusion or partial exchange transfusion = rapid reduction of Hb S percentage leads to reduction in neuro symptoms
2. Long term management: chronic and regular RBC transfusions to prevent second stroke
97
What is the short- and long-term management of splenic sequestration in sickle cell disease patients?
1. Fluids/RBC transfusions asap to treat shock
| 2. Long-term: splenectomy if life-threatening episode or recurrent episodes
98
What is the treatment of priapism in SCD patients?
1. Aggressive analgesia
2. Pseudoephrine and etiliefrine infiltration to decrease vascular engorgement of the corpora cavernosa
3. Urology consult asap for aspiration of the corpora
4. Transfusion or exchange transfusion
99
What is the indication for hydroxyurea in SCD patients?
| -mechanism of action?
Severe or frequent complications of SCD
| -mechanism of action: increases expression of fetal Hgb = inhibits polymerization of HgbS
100
What is the indication for chronic transfusions in sickle cell disease?
Strokes
101
What abnormal facial features may be seen in children with severe thalassemias and why?
Flat nasal bridge, maxillary hyperplasia, frontal bossing due to extramedullary hematopoiesis and expansion of medullary spaces
102
What is Bart's hemoglobin?
What is Hb H?
These are seen in what condition?
Bart's hemoglobin = gamma/gamma/gamma/gamma (4 gamma chains with no alpha or beta) = seen in alpha thalassemia in infancy
Hb H = 4x beta chains = seen in alpha thalassemia
Both have high affinity for O2 and thus does not release O2 to the tissues.
**Seen in alpha thalassemia: relative excess of beta and gamma chains = there are not enough alpha chains around
103
What is Hb H disease?
An alpha thalassemia with 3 gene deletion -,-/-,alpha
| =moderate to severe anemia
104
What is the underlying pathophysiology of alpha thalassemia?
| -clinical features of subtypes?
Defective alpha chain production with relative excess of beta and gamma chains
- alpha chain production is determined by 4 identical alleles (2 on each gene) on chromosome 16
- 1 allele deletion: silent carrier, asymptomatic
- 2 allele deletion: alpha-thalassemia trait, mild anemia
- 3 allele deletion: Hb H disease, moderate to severe anemia
- 4 allele deletion: no normal Hb, hydrops fetalis, fatal
105
What medication is used for iron chelation
Deferoxamine
106
What is the underlying pathophysiology of beta thalassemia?
| -what are the subtypes and clinical features of each?
Defective beta chain production with relative excess of alpha chains
-beta globin production controlled by 2 alleles (1 on each gene) on chromosome 11
Subtypes:
- Beta-thalassemia trait/minor = B0/B or B+/B (mild anemia, usually asymptomatic)
- thalassemia intermedia = B+/B+ (moderate anemia presenting at 2 yo, requires periodic transfusions)
- beta-thalassemia major = B0/B0, B+/B0 (severe anemia within first 6 mo of life, FTT and CHF within first year of life without treatment, transfusion dependent)
```
B = normal beta chain production
B0 = complete absence of beta chain production
B+ = decreased beta chain production
```
107
What is Hg F and Hb A2? Seen in what condition?
Seen in beta thalassemia due to relative excess of alpha chains and a normal amount of delta and gamma chains leading to increased amount of Hgb F (alpha-2/gamma-2) and Hb A2 (alpha2/delta2)
108
What is hemosiderosis?
- gold standard for diagnosis?
- treatment?
Iron overload due to prolonged transfusion therapy
- gold standard: quantitative iron measurement by liver biopsy
- treatment: chelation therapy with deferoxamine
109
How can you differentiate between primary polycythemia and secondary polycythemia?
Primary polycythemia will have low Epo whereas secondary polycythemia will have high Epo (since kidneys were stimulated by something to make Epo)
110
How do you calculate absolute neutrophil count?
ANC = % (polymorphonuclear leukocytes + bands) x total WBC
111
What are the clinical manifestations of cyclic neutropenia?
- inheritance?
- bone marrow findings?
- treatment?
Regular periodic episodes of severe neutropenia occuring every 19-21 days and lasts 3-10 days at a time
- fever, malaise, oral ulcers, stomatitis, pharyngitis, lymphadenopathy, serious bacterial/fungal infections
- autosomal dominant
- bone marrow: granulocytic hypoplastia during episodes of neutropenia
- treatment: G-CSF
112
What is Kostmann syndrome?
- inheritance pattern?
- treatment?
Severe congenital neutropenia: recurrent unusual and/or serious infections
- inheritance: AR
- treatment: G-CSF, BMT
113
What is the most common cause of acquired neutropenia in children?
Infections
114
What is the most common cause of chronic neutropenia in young children?
Autoimmune neutropenia
115
What are the clinical features of Shwachman-Diamond-Oski syndrome?
- complication?
- lab findings?
- treatment?
1. Failure to thrive
2. Pancreatic insufficiency
3. Anemia, thrombocytopenia, neutropenia
4. Eczema
5. Metaphyseal dysostosis
6. Infections
- complication: can transform to leukemia in 25% of patients
- lab findings: neutropenia, elevated stool fecal elastase
- treatment: BMT
116
What are the treatment indications for ITP?
| -treatment options?
In ITP with plt count > 20 and no signs of bleeding, can consider watchful waiting approach
- however, in ITP with plt count < 20, extensive bleeding: 1. IVIG (blocks RES and decreases splenic clearance of platelets, promotes clearance of antiplatelet abs) = 1-5 d course
2. Steroids: several wk course
3. Anti-D immunoglobulin: coats RBCs and antibody coated RBCs compete with abs coated platelets for uptake and clearance by spleen, 1-2 d course of treatment
117
What is the prognosis for ITP?
| -defn of chronic ITP?
50% of children with ITP recover within 1 mo, 80% within 6 mo
-chronic ITP = lasting > 6 mo
118
What are common drugs causing drug-induced thrombocytopenia?
1. Penicillins
2. Benzos
3. Valproic acid
4. Heparin
119
What is the difference between neonatal autoimmune thrombocytopenia vs. neonatal alloimmune thrombocytopenia?
Autoimmune: transplacental transfer of abs from a mom with ITP (abs directed against both mom's and baby's plts)
Alloimmune: mom has been sensitized to paternally inherited antigens present on infant's platelets and thus abs attack baby's platelets (abs directed against baby's plts only)
120
What are 3 causes of microangiopathic thrombocytopenia?
1. HUS
2. TTP
3. Kasabach-Merritt (large hemangioma, can be external or intraabdominal)
121
What are the clinical features of TTP?
- pathophysiology?
- treatment?
Fever, neuro symptoms, microangiopathic hemolytic anemia and thrombocytopenia
- more common in adults
- pathophysiology: platelet aggregation and clumping in vessels
- treatment: immunosuppression and plasma exchange
* **do NOT give platelet transfusions as they worsen clotting and exacerbate CNS/cardiac symptoms
122
Which drug is most frequently associated with aplastic anemia?
Chloramphenicol (antibiotic)
123
What is the differential diagnosis for acquired aplastic anemia?
* **aplastic anemia = 2 or more cell lines down
1. Drugs: chemotherapy, chloramphenicol, radiation
2. Infections: EBV, CMV, HIV, parvovirus, Hep B/C
3. Malignancy: bone marrow infiltration by blood malignancies or metastatic solid tumors
4. Systemic illness: SLE, hypersplenism, storage disorder
5. Primary bone marrow disease: myelodysplastic syndrome
124
What is the differential diagnosis for inherted aplastic anemia?
-most common?
1. Fanconi syndrome (most common)
2. Diamond-blackfan syndrome
3. Shwachman-Diamond syndrome
4. Dyskeratosis congenital
125
What is Fanconi anemia?
- clinical features?
- diagnosis?
- treatment? (3)
Disorder caused by a defect in DNA that renders patient's cells susceptible to damage by environmental toxins and thus bone marrow failure
- get pancytopenia (thrombocytopenia presents first) from bone marrow failure, CAN have short stature, generalized hyperpigmentation, thumb/radii abnormalities, renal abnormalities
- risk of developing malignancy in the future
- diagnosis: see hypocellular bone marrow, diepoxybutane test
- treatment: transfusions, androgenic hormone therapy, BMT
126
You suspect a patient has hemophilia A or B. What is your initial screening test and expected results?
PT and aPTT
- deficiency of factors 8, 9, 11, 12 prolong aPTT (intrinsic pathway) alone whereas deficiency of factor 7 prolongs PT (extrinsic pathway)
- thus, in hemophilia A/B, you get a NORMAL PT and prolonged aPTT
127
What is the management of hemophilia A or B? (3)
| -what are long term complications of hemophilia? (3)
1. Avoid contact sports
2. If bleeding or booked for a procedure, replacement therapy with factor 8 or 9 accordingly
3. Supportive treatment also includes epsilon aminocaproic acid, transexamic acid, FFP, DDAVP
Long term complications:
1. Chronic Arthropathy due to recurrent bleeding into the joint
2. Inhibitor formation to factor 8 or 9 = eventually factor 8 and 9 infusions no longer are effecftive at stopping bleeding
3. Risk of infections from blood products
128
Fill in the blank: Half of patients with hemophilia first present with excessive bleeding after this procedure: ________.
Circumcision!
129
In a patient with suspected coagulopathy, you obtain PT/aPTT and find that PT is prolonged while aPTT is normal. What is your diagnosis?
Factor 7! Extrinsic pathway is affected!
130
What are the 2 functions of von willebrand factor?
1. Carrier protein for factor 8
| 2. mediates platelet adhesion at sites of tissue injury
131
What is the most common type of VWB disease?
- treatment?
- treatment of other types?
Type 1 = 80-85% of cases, mild to moderate bleeding
- treatment: DDAVP given intranasally 20-30 mins prior to minor procedures for prophylaxis and/or for minor bleeding
- treatment of type 2 and 3 VWB disease (severe bleeding): VWB factor concentrates
132
What 2 tests should you order to specifically test for von willebrand factor deficiency?
1. Ristocetin cofactor activity (will be decreased)
| 2. vWF antigen (will be decreased)
133
Which clotting factors need vitamin K?
2, 7, 9, 10, protein C & S
134
Why are newborns susceptible to vitamin K deficiency? (3)
| -what may you see for PT and aPTT?
1. Poor transplacental acquisition of vitamin K
2. Limited ability to store vitamin K in immature liver
3. Lack of gut flora to make vitamin K
- see disproportionate prolongation of PT in comparison with aPTT (since PT reflects factor 7, whereas aPTT reflects factor 8, 9, 11, 12)
135
Which out of the clotting factors has significant extrahepatic synthesis?
Only factor 8!
136
What is the most common inherited cause of hypercoagulability?
Factor 5 Leiden: seen in 30% of children with DVTs
137
What are inherited causes of hypercoagulability? (5)
1. Protein C deficiency
2. Protein S deficiency
3. Factor V Leiden
4. Antithrombin III deficiency
5. Homocystinuria
138
You are seeing a 15 mo girl for short stature. She has history of eczema, recurrent acute otitis media and 6-8 stools per day. On exam, she is frail with bilateral clinodactyly. On labs, she has neutropenia, anemia and thrombocytopenia. What is the most likely diagnosis?
Shwachman-Diamond syndrome: neutropenia in the setting of FTT and short stature should get you thinking about Shwachman-Diamond syndrome!
-clinical features: poor growth, pancreatic insufficiency, metaphyseal dysostosis, eczema, neutropenia, anemia, thrombocytopenia, infections
139
What is heterotaxy syndrome?
| -when should you suspect it?
Paired organs such as lungs or kidneys are mirror images of one another instead of having the unique characteristics of right and left!
- right atrial isomerism with asplenia: dextrocardia with asplenia
- left atrial isomerism with polysplenia
- should raise your suspicion when you see dextrocardia and splenic dysfunction (multiple infections with encapsulated organisms)
140
A 15 yo patient with SLE presents with acute onset low-grade fevers, altered mental status, anemia and thrombocytopenia. Her peripheral smear shows hemolytic anemia with increased schistocytes. She has an elevated creatinine. What is your diagnosis and what is your intervention? Would you give platelets?
TTP = altered mental status, microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure
- treatment: plasmapheresis
- do NOT give platelets as this worsens thrombosis and thus worsens CNS and cardiac symptoms
141
You are treating a patient with DVT using IV heparin; however, despite being on adequate doses, she continues to need higher doses of heparin to achieve therapeutic levels. What should you check on bloodwork to figure out why she is resistant to heparin?
Antithrombin 3 = heparin needs antithrombin III to work, thus, deficiency leads to heparin resistance!
-if found to be deficient, need treatment with recombinant antithrombin III in addition to heparin to fix DVT
142
What is the differential diagnosis for prolongation of PT?
1. Vitamin K deficiency (used for factors 2, 7, 9, 10, C & S)
2. Isolated factor 7 deficiency
3. Liver disease
143
What is the differential diagnosis for isolated prolongation of aPTT?
1. Hemophilia A
| 2. Hemophilia B
144
Name 3 infections you HAVE to think about in a febrile neutropenic oncology patient that you might not have to think about in a non-oncology febrile neutropenic patient?
1. Central line infections:
- ask about chills/diaphoresis/pallor with central line flushes (possible bacteria in the line)
- examine the line site for cellulitis
2. Perirectal cellulitis:
- ask about pain with BMs
- assess perirectal area
3. Typhlitis:
- ask about abdominal pain
145
What is typhlitis?
| -management?
Inflammation of the small bowel wall in neutropenic patients with a predilection for the cecum = a type of necrotizing enterocolitis seen exlcusively in neutropenic patients with leukemia or lymphoma
- Clinical features: can mimic appendicitis - abdo pain, tenderness, vomiting, diarrhea, fever
- confirm with AXR (will see paucity of air in the RLQ, ileus, thickened bowel, air in the bowel wall) ultrasound or CT
- management:
1. NPO
2. Broad spectrum IV abx (amp + gent + flagyl or pip-tazo with gent) = need this for anaerobic coverage!!
3. Serial abdo exams and serial AXRs looking for free air
4. Early surgical consultation if AXR reveals free air
146
What is the management of spinal cord compression due to mass?
- if history and physicam exam suggests cord compression?
- if cord compresion is suspected but there is no neurologic dysfunction?
- if there is evidence of cord compression on history and physical, need to give Dex 2 mg/kg ASAP and get MRI immediately
- if it is suspected but no neurologic dysfunction, give Dex 0.3 mg/kg PO q6h and get MRI within 24 hrs
147
Out of all childhood acute leukemias, what percentage is AML?
- what conditions increase risk of developing AML? (6)
- long term survival?
```
15%
Conditions that increase risk of developing AML:
1. Down syndrome
2. Klinefelter syndrome
3. Fanconi anemia
4. Ataxia telangectasia
5. Neurofibromatosis type 1
6. Shwachman-diamond syndrome
-long term survival: 40-60%
```
148
What is the characteristic genetic translocation seen in CML?
Philadelphia chromosome = t(9;22)(q34;q11)
149
What are the 2 subtypes of hodgkin lymphoma?
| -what are the clinical features of hodgkin lymphoma?
1. NLP = nodular lymphocyte predominant
2. cHL = classic hodgkin lymphoma
- see Reed-sternberg cells
Clinical features:
1. Painless lymphadenopathy
2. 2/3s have a mediastinal mass (may have SVC syndrome)
3. "B" symptoms: fever, weight loss, drenching night sweats
150
What is the usual age of presentation for:
| -Hodgkin lymphoma vs. Non-hodgkin lymphoma?
Hodgkin lymphoma: adolescence
| Non hodgkin lymphoma: < 10 yo
151
Which type of lymphoma is more likely to present as an intraabdominal mass (as opposed to mediastinal)?
-endemic Burkitt's lymphoma: areas of involvement on body?
Burkitt's lymphoma: can cause intussusception and massive TLS due to rapid growth
- also see lymphadenopathy in mesentery and retroperitoneum, spinal cord compression
- endemic Burkitt's: seen in Africa, appears to be caused by EBV, involvement of head and neck (in jaw and orbit especially),
152
In a patient presenting with intussusception out of the usual age range, what malignancy should you be most concerned about?
Burkitt's lymphoma = secondary to masses originating from Peyer's patches in terminal ileum
153
You suspect a child has a brain tumor. What initial imaging should you order?
-once you've confirmed the presence of brain tumor on MRI head, what further imaging should you do?
1. Order CT scan first --> followed by MRI
| 2. If MRI head is positive, NEED to do MRI spine as well due to risk of "drop metastasis" to the spine
154
What is Parinaud syndrome?
Increased ICP at the dorsal midbrain leading to:
1. Downward gaze
2. Pupillary dilation (pressure on the sympathetic fibers on the outside of CN3 responsible for pupillary constriction)
3. Nystagmus
155
What is the classic finding on histology for neuroblastoma?
Homer-Wright pseudorosettes
156
What are clinical features of neuroblastoma (organize based on site of involvement)?
1. Abdominal:
- abdominal pain/mass
- constipation
- resp compromise in infants with massive liver infiltrate
- lower extremity and/or scrotal edema secondary to occlusion of venous and lymphatic drainage
- hypertension due to occlusion of renal vessels
2. Paraspinal:
- radicular pain
- paraplegia
- bowel/bladder dysfunction
3. Thoracic/cervical
- Horner syndrome
- SVC syndrome
4. Orbital:
- ptosis and periorbital ecchymosis (raccoon eyes)
5. Skin:
- blueberry muffin nodules of tumor cells
6. Bone marrow:
- cytopenias
7. Catecholamine overproduction:
- hypertension, flushing, tachycardia, diaphoresis
8. Paraneoplastic:
- opsoclonus-myoclonus
- VIP syndrome: secretory diarrhea due to increased vasoactive intestinal peptide
157
What is the most common primary site of neuroblastoma?
Adrenal glands (medulla) (30%); followed by paraspinal (posterior mediastinal mass)
158
What is the treatment for opsoclonus-myoclonus due to neuroblastoma? (3)
1. Steroids
2. High dose IVIG
3. Gabapentin
159
What is the diagnostic workup for neuroblastoma?
1. CT or MRI of primary tumor
2. MIBG scintiscan (analogue of catecholamine precursors and concentrates in NB cells, localizing the tumor)
- useful for following response to therapy, checking for recurrence
3. Bone scan to look for bone mets
4. Biopsy or resection of primary tumor
5. Bone marrow aspirate
6. Labs: CBC, LDH, ferritin, urine HVA and VMA
160
Which organ can be damaged by MIBG scan?
MIBG scan = looks for neuroblastoma
| -can damage thyroid gland! Need super-saturated potassium iodine given prior to MIBG
161
What is the treatment for neuroblastoma?
Depends on stage of illness: surgery +/- chemotherapy +/- radiation +/- stem cell transplant +/- retinoic acid (accutane)
162
What is the most common pediatric extracranial solid tumor?
Neuroblastoma
163
What is the most common malignant tumor among infants?
Neuroblastoma
164
Where does neuroblastoma tend to metastasize? (4)
1. Liver
2. Bone
3. Bone marrow
4. Skin
165
What is the underlying pathophysiology of opsoclonus myoclonus in neuroblastoma?
Dancing eyes, dancing feet
- thought to arise from a nonspecific antibody reaction to neuroblastoma that cross-reacts with the motor end plate
- symptoms may persist despite neuroblastoma therapy
166
What factors lead to unfavorable prognosis in neuroblastoma? (3)
1. N-Myc amplification in tumor/unfavorable histology
2. Distant mets at diagnosis
3. Age > 1 yo
167
What is stage IV-S neuroblastoma?
Infants < 1 yo with localized tumor with metastatic disease limited to the liver, skin and/or bone marrow
- if they do not have N-myc amplification or unfavorable histology, then the neuroblastomas typically regress spontaneously and do NOT require any treatment!!!!
- only treat with chemo if they have symptoms secondary to mass effect (ie. large abdominal mass or liver disease)
168
What is the prognosis of localized NB if no risk factors for poor prognosis?
- if risk factors for poor prognosis are present?
- stage IV-S disease?
- Localized NB: 95% survival
- if risk factors for poor prognosis (N-Myc amplification, unfavorable histology, distant mets at diagnosis, age > 1 yo): 30-50% survival
- stage IV-S disease: 95% survival
169
What age group is typically affected by Ewing Sarcoma?
- most common presentation?
- what are red flags for malignancy in a patient presenting with localized extremity pain? (5)
Adolescents
- most common presentation: localized pain
- red flags:
1. Constitutional symptoms (occur in 1/3 of patients)
2. Pain continuing at night
3. Palpable mass at site of pain
4. Localized pain > 1 mo duration
5. Pain without adequate trauma to explain the pain
170
Which bones are most commonly affected by Ewing Sarcoma? (3)
Axial skeleton:
1. Pelvis
2. Chest wall
3. Long bones of the legs (most common): tend to occur in the DIAPHYSIS
171
What factors help differentiate between Ewing Sarcoma and Osteosarcoma?
1. Location of lesion:
- Ewing Sarcoma: diaphysis of bone (ED) = letters are closer together
- Osteosarcoma: metaphysis of bone (OM)
2. Appearance of lesion on xray:
- Ewing sarcoma: onion skinning (EW ONIONS!!!)
- Osteosarcoma: sunburst pattern (oS)
172
For patients with Ewing sarcoma, what percentage will present with mets and where is mets most common?
30% will present with mets at presentation
| -most commonly metastasizes to the lungs
173
What is your work-up for a suspected bone tumor?
1. Plain films of site of pain/mass followed by MRI
2. Search for mets: chest CT, bone marrow biopsies, bone scan
3. Bloodwork: elevated LDH has been correlated with poor outcomes in Ewing Sarcoma & osteosarcoma, ALP, lytes, CBC
4. Surgical biopsy of the lesion (definitive diagnosis)
174
What findings will you see on plain xray of a patient with Ewing Sarcoma? (3)
1. Onion skinning (EW ONIONS!!!) = laminated periosteal reaction
2. Diaphysis of bone is most common affected
3. Codman's triangle: raised periosteum
175
What is the treatment of Ewing Sarcoma?
| -prognosis?
Treatment: Chemo, surgical resection +/- radiation
| -prognosis: with no mets: 60% cure, with mets 30% cure
176
What is the most common malignant tumor of the bone in pediatric population?
-peak age of incidence?
Osteosarcoma
| -peaks in adolescence, especially during growth spurt (may be related to rapid bone growth)
177
Which malignancy places you at higher risk of developing osteosarcoma later on in life?
Retinoblastoma (mutation in tumor suppressor Rb gene)
178
What are the most common sites affected by osteosarcoma? (3)
-where does mets go? Percentage of patients presenting with mets at diagnosis?
Most common sites:
1. Distal femur
2. Proximal tibia
3. Proximal humerus
-mets goes to lungs, 15% present with mets at diagnosis
179
What findings will you see on plain xray of a patient with osteosarcoma?
1. Destruction of normal bone with indistinct margins
2. Codman's triangle: raised periosteum due to periosteal reaction
3. Sunburst pattern (soft tissue mass present with osteoid production)
180
What is the treatment for osteosarcoma?
Usually neoadjuvant chemo, followed by surgical resection, followed by more chemo
181
What are 3 common benign bone tumors in pediatric population?
1. Osteoid osteoma
2. Cortical fibroma
3. Bone cysts
182
What are clinical presentations of osteoid osteoma?
- xray finding?
- treatment modalities? (4)
Bone pain, usually worse at night, GREATLY RELIEVED BY NSAIDS
- xray: radiolucent lesion in cortex of the bone associated with sclerosis
- treatment: these lesions do not grow and often regress spontaneously. BUT can still treat with ethanol, laser, thermocoagulation therapy, or CT guided radiofrequency ablation (RFA)
183
What are fibromas and where are they usually found?
- findings on xray?
- treatment?
Fibromas: benign bone tumor made of spindle-shaped fibroblasts
- findings on xray: sharply marginated eccentric lucency in the cortex (multilocular usually)
- treatment: most regress spontaneously but some need curettage and bone grafting to prevent pathologic fractures
184
What are 2 types of bone cysts and what are their characteristic findings on xray?
-treatment of each?
1. Unicameral (ie. ONE chamber) bone cyst: simple bone cysts, fluid filled, usually only diagnosed incidentally or after pathologic fracture.
- on xray: solitary, centrally located lesion
- treatment: steroid injection, curettage or bone grafting
2. Aneurysmal bone cyst: rapidly expanding lesions filled with blood and tissue, usually present with pain and swelling.
- occur in metaphyseal portion of femur, tibia and spine.
- on xray: lytic lesion with sclerotic rim
- treatment: curettage and bone grafting
185
What is macrophage activation syndrome?
Essentially HLH secondary to JRA or SLE! Clinical and lab features are the same as HLH!
186
What is the most common cause of infection-associated HLH?
EBV!
187
Where do germ cell tumors most commonly arise in pediatric population adn what are the peaks in incidence?
>90% arise int he testes or ovaries
| -two peaks: 2 yo and 20 yo
188
What is the associated lab finding with the following:
- Yolk sac tumor
- Choriocarcinoma
- Yolk sac tumor: high AFP
| - choriocarcinoma: high BHCG
189
Where is the most common location of:
- yolk sac tumor
- teratoma
- yolk sac tumor: testes/scrotum
| - teratoma: ovary
190
What are the most common toxicities of the following chemotherapy drugs:
1. Vincristine
2. Anthracyclines (doxorubicin, daunomycin)
3. Alkyating agents (cisplastin, Cyclophosphamide)
4. Etoposide
5. Cytarabine
6. Methotrexate
7. Bleomycin
8. Asparaginase
***Overall: most common side effects of most of these agents (4)
1. Vincristine: peripheral neuropathy, constipation
2. Anthracyclines: cardiomyopathy
3. Alkylating agents:
- cisplastin: permanent hearing loss
- cyclophosphamide: hemorrhagic cystitis
4. Etoposide: secondary acute leukemia
5. Cytarabine: Ara-C syndrome (high fever, malaise, rash, conjunctivitis, myalgias)
6. Methotrexate: hepatotoxicity, nephrotoxicity, neurotoxicity
7. Bleomycin: interstitial pneumonitis --> pulmonary fibrosis
8. Asparaginase: coagulopathy (increased risk of clotting), pancreatitis
* **Most common side effects:
1. Alopecia
2. Myelosuppression
3. Infertility
4. Neurocognitive deficits
191
What are 3 sources of stem cells?
| -what are the advantages and disadvantages of each?
1. Bone marrow:
- advantage: less risk of GVHD compared with peripheral blood, shorter engraftment time (~14 d)
- disadvantage: painful for donor
2. Peripheral blood:
- advantage: shortest time to engraft (10 d)
- disadvantage: higher risk of GVHD, need to give G-CSF to donor to stimulate the stem cells to come out of bone marrow
3. Cord blood:
- advantage: lowest risk of GVHD due to immature immune system of baby
- disadvantage: longest time to engraftment (21 d), may not contain enough cells for adult size recipients
192
What are 3 common complications after hematopoietic stem cell transplant?
- timing
- treatment
1. Infection:
- can occur during prep, after transplant while awaiting engraftment, after engraftement
- hospitalization and broad spectrum abx with any fever up to 12 mo post transplant or as long as they're on immunosuppressive therapy
2. Veno-occlusive disease of the liver:
- from damage to the sinusoidal endothelial cells of hepatic venules leading to obstruction
- timing: 0-28 days after transplant
- weight gain, RUQ pain, increased abdo girth, hepatomegaly, elevated liver enzymes/function tests, reversal of portal blood flow on doppler U/S
- treatment: supportive care
3. Acute GVHD:
- due to immune cells of the donor recognizing recipient tissues as foreign and mounting immune response
- timing: up to 100 d after transplant
- erythematous rash, elevated LFTs/bilirubin, profuse diarrhea, abdominal pain
- treatment: immunosuppression
193
What is the most common complication of hereditary spherocytosis?
Bilirubin gallstones
194
What is the treatment for iron overload in chronic transfusions or ingestion?
-side effects of this medication?
Deferoxamine
Side effects:
1. Hypotension (common) = acute side effect, managed by slowing rate of infusion
2. Pulmonary toxicity (ARDS)
3. Yersinia sepsis
4. Ototoxicity
5. Retinal changes
6. Bone dysplasia with truncal shortening
195
What are lab findings of DIC?
1. RBC fragmentation on peripheral smear
2. Elevated PT
3. Elevated aPTT
4. Decreased platelets
5. Decreased Favot 5, 8, fibrinogen
6. Presence of fibrin split products
196
What is the most common cause of opsoclonus-myoclonus in childhood?
Neuroblastoma
| -if you see this, need to order CT chest, neck, pelvis
197
Which malignancy is associated commonly with DIC?
AML - specifically acute promyelocytic leukemia (APL)
198
What is a drawback in head CT to rule out potential intracranial mass?
Does NOT adequately image the posterior fossa which is the most common site for pediatric brain tumors
-need an MRI head for definitive diagnosis
199
Before using anti-D immunoglobulin in treatment of ITP, what investigation should you do first to ensure anti-D immunoglobulin will actually be effective?
Blood type and screen
- anti-D immunoglobulin (aka WinRHO) will only work for Rh-positive patients with a working spleen!
- anti-D immunoglobulin coats the RBCs and thus the macrophages/spleen preferentially take up the coated RBCs, sparing the platelets
200
What is the treatment of Kasabach-Merritt phenomenon? (3)
1. Steroids
| 2. Alpha-interferon, vincristine
201
What is PHACE(S) syndrome?
1. Posterior fossa malformation
2. large facial Hemangiomas
3. Arterial abnormalities
4. Coarctation of aorta
5. Eye abnormalities
6. Sternal defects
202
In which condition will you see Heinz bodies and bite cells on the peripheral blood smear?
G6PD = -heinz bodies: insoluble precipitates resulting from oxidation
-bite cells: RBCs after the removal of the Heinz bodies by the spleen
203
What is the most serious complication with recurrent transfusions?
Cardiac hemosiderosis (from iron overload)
204
What is koilonychia?
Spooning of the nails in iron deficiency anemia
205
What is the risk of CNS intracranial bleed in ITP?
<1%
206
What is osteopetrosis?
| -clinical features?
Disorder of osteoclastic bone resorption = extremely dense bones and anemia since there is no space for bone marrow to grow
-severe form: deafness/blindness, macrocephaly, hepatosplenomagly, severe anemia
207
A patient presents with an abdominal mass in RUQ. There is also a systolic heart murmur at LSB and RUQ. Low platelets. What is your diagnosis?
Kasabach-Merritt!
208
What is the origin of the following:
- glioma
- ependymoma
- germ cell tumor
- craniopharyngioma
1. Glioma - interstitial tissue of CNS (supportive tissue)
- astrocytes
- oligodendrocytes
- found in optic pathways and cerebellum
2. Ependymoma:
- ependymal cells that line the ventricles
3. Germ cell tumors:
- totipotent germ cells in pineal and supracellar region
4. Craniopharyngioma:
- embryonic precursors of pituitary gland
209
What are the criteria for doing bone marrow in ITP? (3)
1. Abnormal WBC or abnormal differential
2. Unexplained anemia
3. Findings suggestive of bone marrow abnormality on history or physical exam
210
A child is receiving a blood transfusion. She becomes febrile and develops chills. What is your management?
Stop the transfusion and run IV TKVO:
- Fever during blood transfusion = > 1 degree increase in temp and temp > 38 during or up to 4 hrs post infusion
- stop transfusion, keep IV TKVO until you: recheck identification and blood identification to look for transfusion error, get complete vitals, notify the blood bank
- if no clerical error or no serious symptoms (ie. no fever > 39, no chills/dyspnea/chest pain/shock/N/V) AND they look well, give tylenol and continue transfusion cautiously
- if there are serious symptoms, stop transfusion completely and suspect hemolytic transfusion reaction or bacterial contamination
211
What is the number one cause of complications in beta thalassemia major?
Iron overload from chronic transfusions (transfusion dependent)
212
What genetic conditions are associated with childhood leukemia?
- ALL
- AML
ALL:
1. Down syndrome
2. Ataxia telangectasia
3. Wiskott-Aldrich
AML:
1. Neurofibromatosis-1
2. Down syndrome
3. Klinefelter
4. Fanconi
5. Ataxia telangectasia
6. Shwacman-diamond syndrome
213
Which infection are you most at risk of acquiring from a transfusion?
Parvovirus B19 risk is 1:5000
| -CMV is removed by filtering
214
What is the risk of intracranial hemorrhage in neonatal thrombocytopenia due to alloimmune or autoimmune causes?
-treatment?
30%!
| -give IVIG!
215
What is the differential diagnosis for spherocytes on peripheral smear? (4)
1. Hereditary spherocytosis
2. Hyperthermia
3. G6PD deficiency
4. ABO incompatability
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PT reflects function of which clotting factors?
1, 2, 5, 7, 10
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What level of reticulocytes is categorized as reticulocytosis and considered appropriate response to anemia?
>3%
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Name the conditions in which each of the following are seen:
- pencil cell
- spherocytes
- target cell
- fragments
- basket/blister cells
- howell-jolly bodies
- heinz bodies
- basophilic stippling
- Pencil cell = iron deficiency
- Spherocytes = hereditary spherocytosis, autoimmune hemolytic anemia
- target cell: iron deficiency, liver disease, hemoglobinopathies, post-splenectomy
- fragments: DIC, HUS, TTP, burns, microangiopathy
- Basket/blister cells: G6PD (oxidative damage)
- howell-jolly bodies: asplenia or megaloblastic anemia
- heinz bodies: G6PD
- basophilic stippling: lead poisoning
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Where in the body is iron absorbed?
- what vitamin helps iron absorption?
- where is folate absorbed?
- where is vitamin B12 absorbed?
Exclusively in duodenum
- vitamin C helps absorption
- remember that breast milk iron is absorbed up to 50% whereas cow's milk iron is absorbed only up to 10% (so overall, there is less iron in breastmilk but it is better absorbed)
- folate is absorbed in the jejunum
- vitamin B12 is produced by gastric parietal cells and absorbed in the terminal ileum
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Features of iron deficiency anemia on CBC ASIDE from hypochromic, microcytic? (3)
1. Increased RDW
2. Thrombocytosis
3. Mentzer Index > 13
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A blood smear shows basophilic stippling. What are two things on your ddx?
1. Thalassemia
| 2. Lead poisoning
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Indications for splenectomy in hereditary spherocytosis?
1. Transfusion dependence
2. Recurrent hemolytic episodes
3. Massive splenomegaly impacting quality of life (ie. not able to play their favorite sport)
4. Growth failure
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Wilms tumor is associated with all of the following EXCEPT:
a. 11P-
b. NF-1
c. Wiskott-Aldrich
d. Aniridia
e. Beckwidth Wiedemann
Wiskott-Aldrich = no connection to Wilm's tumor
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A patient undergoing chemotherapy has been in contact with chicken pox and immunity is unknown. What is the ideal time frame for administration of VZIG?
Within 96 hours!
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A patient with hemophilia A presents after being struck in the head with a baseball with a 1 minute loss of consciousness. What should you do first: CT head or factor 8 replacement?
Factor 8 replacement!!! Should always receive factor replacement therapy prior to the study in order to avoid unnecessary delays in the treatment of potentially devastating bleeding
-would consider hospitalization for observation in the hemophiliac patient with significant head trauma even with a normal initial head CT
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What is your differential diagnosis for thrombocytosis? (common causes)?
1. Reactive secondary to infection
2. Kawasaki's
3. Iron deficiency anemia
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In a patient with hemophilia A who has developed inhibitors and now presents with a significant bleed, what is your management plan?
1. Factor 7a
2. aPCCs (activated prothrombin complex concentrate)
* **If this is unavailable, may try high doses of factor 8 (100-200 units/kg)
* **In refractory cases, can do plasmapharesis to remove anti-factor antibodies
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A patient with sickle cell disease presents with significantly lower Hgb than baseline. How can you differentiate between splenic sequestration vs. aplastic crisis in patients with sickle cell anemia?
Aplastic anemia from parvovirus:
1. No splenomegaly
2. No reticulocytes (due to bone marrow suppression)
3. Slower onset
Splenic sequestration:
1. Acute drop in Hgb
2. RETICULOCYTOSIS!!!!!
- in any patient with sickle cell disease presenting with a severely low Hgb (especially infants), you need to worry about splenic sequestration! Strokes and acute chest crises don't usually cause a huge huge drop in Hgb like splenic sequestration does
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Which patients with leukemia are at highest risk of SBI?
1. BIGGEST RISK = during induction!!!
2. Older children with AML
3. Infants with ALL
4. Patients who have relapsed
5. Patients undergoing hematopoietic stem cell transplantation
