HemeOnc Flashcards
When is a physiological drop in H&H expected by?
2-3 month of life (8-10 weeks) in term infants
How low of a Hgb can be normal for a term infant who is 8-10 weeks?
9
What is done for asymptomatic physiologic anemia of infancy?
No further laboratory evaluation
In a premature infant, when can the physiologic nadir of H&H happen?
1-2 months (7-8 weeks)
What is the etiology of physiological anemia in newborns?
Low erythropoietin production
What is the equation for normal MCV?
Roughly 70 + 2(age in years)
What is the first thing you should do with a question concerning anemias?
Figure out whether it is micro-, macro-, or normocytic
What is normal MCV for children?
70-90 (adults is 80-100)
What is the MCV in a microcytic anemia?
Under 70
What are the 3 main considerations for a microcytic anemia?
- Thalassemia
- Too little iron
- Too much lead
What are the 3 usual hemoglobins?
- F (2 alpha/2 gamma)
- A (2 alpha/2 beta)
- A2 (2 alpha/2 delta)
What are thalassemias caused by?
Defects in genes that code for hemoglobin chains- proper quantities aren’t produced
What are hemoglobinopathies caused by?
Errors in sequencing of hemoglobin chains (quality)
Which patients will eventually get iron overload?
Anyone undergoing regular transfusion therapy (thalassemia, sickle cell, aplastic anemia)
What is done to remove excess iron in the body?
Chelation therapy
What happens if iron builds up in the body?
Toxic buildup in liver (hemosiderosis) and hearts
What is a significant cause of morbidity and mortality in chronically transfused patients?
Toxic buildup of iron in the liver and heart
Where are the 2 alpha globin genes located?
Chromosome 16
4 alleles (aa/aa)
What causes alpha thalassemia?
Mutations in one to all 4 of the alpha globin alleles
What happens if only one or two alpha alleles (alpha globin gene) are defective?
Children are typically asymptomatic and it is picked up on routine screening
What do labs show for kids with 1 or 2 defective alpha alleles (alpha globin gene)?
Microcytic hypochromic anemia with normal iron and lead studies
What is it called when one alpha allele is defective?
“Silent trait”
What is it called when two alpha alleles are defective?
“Alpha thalassemia trait”
How is alpha thalassemia diagnosed?
Hemoglobin electrophoresis
If hemoglobin electrophoresis is done in the neonatal period, what does the electrophoresis show?
Hemoglobin Bart (gamma chains banding togther)
For alpha thalassemia with silent trait or alpha thalassemia trait, what is the treatment?
No treatment
What happens when there are 3 defective alpha globin genes?
Hemoglobin H disease
What does Hemoglobin H disease lead to?
Hemolysis and hepatomegaly
What can Hemoglobin H disease be treated with?
- Transfusions
2. Usually a splenectomy
What does 4 defective alpha globin genes cause?
Hydrops fetalis
What does hydrops fetalis result in?
Still birth or death soon after birth
If a hydrops fetalis survives, what do they require?
Transfusions for life
How are thalassemias diagnosed?
Hemoglobin electrophoresis
What is elevated in thalassemias?
Hemoglobin F
What is caused by a defect in one of the beta globin gene alleles?
Thalassemia minor or thalassemia trait
True or False: Patients with thalassemia minor or thalassemia trait are asymptomatic?
True
How is thalassemia minor or thalassemia trait diagnosed?
When a mild microcytic anemia is noted on incidental testing
What results from severe deficiency of beta globin due to a mutation in both beta globin gene alleles?
Thalassemia Major/Cooley’s anemia
-Can’t make hemoglobin A1, so body makes A2 (delta) or F (gamma)
Small for age Greek child with anemia and an enlarged liver/spleen?
Thalassemia major
How do patients with thalassemia major present?
- 1st year of life
- Profound microcytic, hypochromic anemia
What physical exam findings is seen in Thalassemia major?
Hepatosplenomegaly
What is seen on XR in Thalassemia major?
- Thickened bone
2. Skull has “hair-on-end” appearance
What causes the “hair-on-end” appearance in skull XR for thalassemia major?
Extramedullary hematopoiesis
What is the treatment for Thalassemia major?
Chronic transfusion therapy
What are the 2 long term complications with beta thalassemia major?
- Cholelithiasis
2. Hemosiderosis (iron deposition in heart, liver, pancreas)
What are the findings for sickle cell anemia on hemoglobin electrophoresis?
Hemoglobin F
Hemoglobin S
What are the findings for beta thalassemia on hemoglobin electrophoresis?
Low/No Hemoglobin A1
Elevated hemoglobin A2
Hemoglobin F
10 week old infant of Mediterranean descent with hemoglobin of 9.0 and MCV of 89… diagnosis?
Physiologic anemia of infancy… this is a normocytic anemia, don’t be fooled by ethnicity of Mediterranean
When does the risk for iron deficiency anemia in infants begin?
After 4 months
Who is the risk for iron deficiency anemia higher in, breast fed or formula fed infants?
Breast fed
When does the risk for iron deficiency anemia happen in preterm infants?
Earlier than 4 months (as in term infants) especially with no iron supplementation
Why are infants who are given cow’s milk (versus formula or breast milk) before 12 months of age at increased risk for iron deficiency anemia?
Because of low amount of iron absorbed
True or False: Iron deficiency anemia is typically completely asymptomatic?
True
18 month old with pallor and tachycardia?
Iron deficiency anemia
Low hemoglobin (<6) and low MCV (<60)?
Iron deficiency anemia
Child with a history of drinking lots and lots and lots of cows milk (probably still on the bottle)?
Iron deficiency anemia
What else does low iron cause besides anemia?
Mild delays in cognitive development (even without frank anemia)
You find a microcytic anemia in a kid drinking too much milk, what do you do?
Trial of iron
If anemia improves after a one month trial of iron, what do you do?
Continue the iron treatment (it was probably iron deficiency anemia)
If anemia doesn’t improve after a one month trial of iron, what do you do?
Investigate for other causes of microcytic anemia (lead toxicity or thalassemia) or of chronic iron deficiency (celiac)
How is iron deficiency anemia treated?
Ferrous sulfate (until 2 months after Hgb levels normalized- replenishes iron stores), improve diet (limit milk), get them off the bottle
When is parenteral iron administration given?
Rarely- only if cannot take PO iron or in extreme social circumstances
What is the most common environmental illness in kids?
Lead poisoning
What does lead poisoning affect?
Production of heme (interferes with a variety of enzyme systems)
Microcytic anemia with a high RDW?
- Iron deficiency anemia
2. Lead toxicity
Microcytic anemia with a normal RDW?
Thalassemia
Microcytic anemia with a low RDW?
Nothing
Choice of 2 microcytic anemias, one with lower RDW likely due to?
Thalassemia (vs. Iron deficiency)
When is FEP (free erythrocyte protoporphyrin) elevated?
- Lead poisoning
2. Iron deficiency anemia
When is FEP (free erythrocyte protoporphyrin) normal?
Thalassemia
What typically coexists with lead poisoning and enhances lead absorption?
Iron deficiency
What is the gold standard test for lead poisoning?
Whole blood lead level (not fingerstick)
What is an immature RBC with iron-bloated mitochondria surrounding the nucleus?
Ringed sideroblast
What is a ringed sideroblast evidence of?
- Lead poisoning
2. Sideoblastic anemia
What is the MCV in macrocytic anemia?
> 100 (often around 110)
What is B12 frequently due to?
Poor absorption of B12 (often from GI disorder like Crohn’s disease)
Name 4 things B12 deficiency can be due to?
- Intrinsic factor deficiency (pernicious anemia)
- Bacterial overgrowth
- Following a bowel resection
- Vegetarian diet
Compromised gut + Heme question?
B12 deficiency
3 B’s of B12 deficiency?
B12 Deficiency:
- Bacterial overgrowth
- Bowel resection
- HLS-B27 (Crohn’s)
Goat’s milk?
Macrocytic anemia from folic acid deficiency
What 2 deficiencies often coexist?
B12 and folate
What happens if you treat someone with a folate deficiency, but don’t correct the B12?
CBC will look better, but this can lead to irreversible neurologic damage
What 3 things should you think of with a normocytic anemia?
- Patient is bleeding
- Patient has chronic disease
- Hemolytic process
What are 3 reasons that a red cell might be destroyed?
- Enzyme problems (G6PD)
- Structural problem (HS)
- Weird shape (Sickle Cell)
When a red cell breaks open, where do you find the remnants and in what form?
Urine, hemosiderin/bilirubin
Is serum haptoglobin low or high in hemolytic anemia?
Low- Used up in transporting released hemoglobin from RBCs
What results in an elecated retic count?
Hemolytic anemia
What is a normal retic count?
1%
What is the one exception of a hemolytic anemia not causing an elevated retic count?
Parvovirus (if it causes aplastic crisis in someone with a chronic hemolytic anemia- Sickle cell or Hereditary spherocytosis)
What is a sign that a hemolytic process in immune-mediated?
Positive Coombs test
What does the direct Coombs test identify?
Antibodies on the surface of the red cell
What protects a red cell from oxidative stress (which can lead to hemolysis)?
G6PD
What are small, purple granules in the red cell that form as a result of damage to the hemoglobin molecule?
Heinz bodies
What condition do you see Heinz bodies in?
G6PD
African American or Mediterranean boy with dark urine who is jaundiced and anemic
G6PD
Sudden onset of pallor and anemia in an otherwise healthy child?
G6PD
What are 5 things that can cause oxidative stress leading to issues in someone with G6PD?
- Sulfa-containing antibiotic (Bactrim)
- Nitrofurantoin
- Moth Balls
- Antimalarial meds
- Fava beans
True or False: Hepatomegaly is seen in G6PD
False: There is NO hepatomegaly or splenomegaly in G6PD
How is G6PD inherited?
X-linked
When should testing for G6PD deficiency be done?
Several weeks after an episode
-Testing right after or during an episode isn’t reliable because reticulocytes have a large amount of G6PD and can lead to false negative test
If you have a negative test for G6PD, does it rule this out?
Not necessarily. If the negative test was right after an episode, it could be a false negative test.
What is treatment for G6PD?
- Hemodynamic support (Fluid +/- RBCs)
2. Remove the oxidant stressor
What might newborns with G6PD require?
Phototherapy and/or exchange transfusion (to help resolve the indirect hyperbilirubinemia)
What is the most common inherited cause of hemolytic anemia?
Hereditary Spherocytosis
What is caused by defects in the surface of red cells resulting in loss of erythrocyte surface area?
Hereditary Spherocytosis
How is hereditary spherocytosis inherited?
Autosomal dominant (most common… an autosomal recessive form can also occur)
What is the main feature of hereditary spherocytosis?
Chronic hemolysis
How does hereditary spherocytosis present?
- Mild/Mod anemia
- Splenomegaly
- Intermittent jaundice
- Gallstones
Is the mean corpuscular hemoglobin concentration (MCHC) decreased or increased in Hereditary Spherocytosis?
Increased- More hemoglobin per volume (smaller cell with same amount of Hgb)
How is hereditary spherocytosis diagnosed?
Osmotic fragility test- Cells break open more easily
What results from a spectrin deficiency or spectrin mutation?
Hereditary Spherocytosis
Ankyrin deficiency can also case HS, but spectrin is better choice
In hereditary spherocytosis when can you monitor until recovery?
If hemolysis isn’t severe (Hgb >5-6)
What can be curative for Hereditary Spherocytosis?
Splenectomy
What is the most common cause of aplastic crisis in children with hereditary spherocytosis?
Parvovirus B19
What is the most common reason for children with hereditary spherocytosis to require a blood transfusion?
Aplastic crisis due to Parvovirus B19
Are defects of structure typically dominant or recessive?
Dominant
Are enzyme defects typically dominant or recessive?
Recessive
What is the mutation in Sickle Cell?
Substitution at amino acid 6 of the beta globin chain (valine is substituted for a glutamic acid)
Which type of anemia is a result of an amino acid substitution?
Sickle Cell
When does sickle cell anemia typically present clinically?
Not until after 6 months of age
When are children typically diagnosed with sickle cell disease?
When their newborn screens come back abnormal
How does vasoocclusive crisis present?
Acute pain secondary to ischemia and infarction
How is a vasoocculsive crisis treated?
Rehydration and pain control
What is dactylitis?
Pain and swelling of the hands and feet, typically seen in infants with sickle cell
How is dactylitis treated?
Aggressive pain control
How does sequestration crisis present?
Shock
What causes a sequestration crisis?
Pooling of blood in the liver and spleen- usually in response to an infection
True or False: Sequestration is considered a medical emergency?
True- Requires hospitalization and transfusion
When do you typically do a splenectomy in a sickle cell patient?
After the 2nd or 3rd sequestration episode
What typically causes aplastic crisis in sickle cell patients?
Parvovirus infection (people with sickle cell or HS need high retic counts to keep up with increased red cell destruction…if this isn’t working, Hgb decreases)
How are aplastic crises treated?
Blood transfusions as needed
What should make you think of a hyperhemolytic crisis?
History of sickle cell with a recent infection
What often precedes an aplastic crisis or sequestration crisis?
Hyperhemolytic crisis
When do you see priapism?
Sickle cell
True or False: Antibiotic prophylaxis with penicillin is recommended for all children with sickle cell disease through age 5?
True
What extra vaccination should children with sickle cell disease receive?
Pneumococcal
Why do older children with sickle cell get antibiotics and a septic workup for fevers?
Because they are considered to be asplenic
What does the spleen remove from red cells?
Howell-Jolly bodies (you will see these nuclear particles once asplenic)
Howell-Jolly Bodies?
Sickle Cell
Heinz Bodies?
G6PD
True or False: Most states screen newborns for sickle cell disease?
True
Consider if child newly emigrated from developing country
By what age do children with sickle cell have functional asplenia?
5
What is typical of the abdominal exam for a child with sickle cell after age 5?
Small, hard, non-palpable spleen
If you have an older child with a palpable spleen, what should you think?
Either hemoglobin SC or sickle trait and thalassemia together (Hemoglobin-S, Beta-thal)
Children with sickle cell and thalassemia are resistant to what?
Malaria (thought how these two genes remained in gene pool)
What are the 3 features of acute chest?
- Chest pain
- Infiltrate on CXR
- Hypoxia
Sickle cell patient with chest pain, infiltrate on CXR, and hypoxia, what do you do next?
Get an ABG to confirm the hypoxia (O2 sats usually not good enough for diagnosis)
What can resolve chronic hemolysis in patients with hemolytic anemias?
Partial or total splenectomy
What must you do a few weeks before a splenectomy in a kid with a hemolytic anemia?
Vaccinate against H. Flu, S. Pneumo, and N. Meningitidis
What 3 bacteria are post-splenectomy patients at risk for after surgery?
- H. Flu
- S. Pneumo
- N. Meningitidis
True or False: Children with splenectomies should have antibiotic prophylaxis until adolescence?
True- this should be a consideration
If you have a post-splenectomy patient with fever, what do you do?
CBC, blood cultures, IV ceftriaxone
What is the treatment for ACS?
Transfusion
When transfusing someone for ACS, what do you have to consider?
Starting Hct… if it is low, simple transfusion is fine. If it is high, they may require an exchange transfusion
Which two problems is chest pain in a child with sickle cell difficult to distinguish between?
Pneumonia v. Pulmonary infarct
If you have a child with sickle cell disease who presents with fever, cough, and chest pain, what do you treat for?
Both pneumonia and pulmonary infarct (hard to tell difference between two)
African American child with stroke symptoms, what do you do?
Transfusion then MRI (treat before diagnose)
Child with symptoms of stroke, new to US, how do you diagnose the underlying disorder?
Hemoglobin electrophoresis (sickle cell is underlying disorder)
How to diagnose the problem would be MRI
What type of hematologic disease is cholelithiasis associated with?
Sickle cell disease
Child with sickle cell disease presents with right upper quadrant tenderness- what do you do?
Abdominal US (cholelithiasis)
What are anemias due to suppression of the red cell line in the bone marrow?
Hypoplastic and aplastic anemias
What can aplastic anemia present similarly to?
Acute leukemia
What are some features of acute leukemia that help to differentiate it from aplastic anemia?
- Hepatosplenomegaly
- Lymphadenopathy
- Depression of WBC or Plt counts
- High LDH
- High uric acid
- Fevers
- Bone pain
- Blasts
How is diagnosis for either aplastic anemia or acute leukemia confirmed?
Bone marrow biopsy
What drug is responsible for an aplastic crisis?
Chloramphenicol
What type of anemia is Fanconi’s anemia?
Aplastic anemia
When does Fanconi’s anemia present?
Later in childhood (usually after age 3)
Does Fanconi’s anemia present with macrocytic or microcytic anemia?
Macrocytic
What type of hemoglobin is elevated in Fanconi’s anemia?
Fetal hemoglobin
Name 4 physical characteristics associated with Fanconi’s anemia?
- Abnormal skin pigmentation
- Growth retardation (short stature)
- Renal abnormalities (urinary retention)
- Absent or hypoplastic thumb
What type of anemias are Fanconi and Diamond-Blackfan?
Macrocytic
How is Fanconi’s anemia inherited?
Recessive
Which type of anemia puts children at risk for transformation to AML or myelodyslpastic syndrome?
Fanconi’s
What will patients with Fanconi’s anemia require?
Transfusion of RBCs and platelets
What is the cure for Fanconi’s anemia?
Bone marrow transplant
What can lead to a prolonged remission in Fanconi’s anemia?
- Immunosuppressants
2. Androgens (less common)
Which two conditions are profound isolated red cell anemias that present in infancy/toddlerhood?
Diamond-Blackfan Anemia
Transient Erythroblastopenia of Childhood
What anemia is due to an arrest in the maturation of red cells?
Diamond-Blackfan Anemia
What anemia is a consequence of a suppression of erythroid production?
Transient Eryhtroblastopenia of Childhood
What are shared features of DBA and TEC?
- Low Hgb and retic count
- Gradual onsent
- Relatively asymptomatic
Which often presents with anemia at birth, DBA or TEC?
DBA
Which 2 anemias affect the red cell line exclusively?
- TEC
2. DBA
If you see a 2 or 3 year old with an anemia exclusively affecting the red cell line, what is it?
Probably TEC (will not be DBA because this affects infants)
What is the difference in time-course between DBA and TEC?
DBA is chronic
TEC is transient
Kid with severe anemia who has thumb abnormalities, urogenital defects, or craniofacial problems?
DBA
Mnemonic for DBA
DBA:
Dysmorphic facies
Babies
Anemia
What is the median age of onset for TEC?
18-26 months (T for Toddler)
What is median age of onset for DBA?
2-3 months (BA for baby)
Which type of anemia, TEC or DBA, almost always has a spontaneous recovery?
TEC (DBA rarely has a spontaneous recovery)
Which type of anemia, TEC or DBA, is more likely to have dysmorphology?
DBA (uncommon in TEC)
What type of anemia, TEC or DBA is less likely to require transfusions?
TEC (Transfusions are common in DBA)
Which type of anemia, DBA or TEC, are steroids helpful?
DBA (Steroids aren’t indicated for TEC)
Which has a higher incidence, DBA or TEC?
TEC is common (DBA is extremely rare)
Child with severe anemia (Hgb 3-5) who has a reticulocytosis (retic count 5-10%), recent viral illness… what is the cause?
Probably TEC (now in recovery phase)
What is the typical course for TEC?
Usually resolves spontaneously within several months…transfusion is rarely needed.
True or False: Steroids are used in TEC
False: Steroids are used with DBA
What 3 things are blood donations typically tested for?
- Hep B
- Hep C
- HIV
What is the MCV in DBA versus TEC?
- DBA is macrocytic
- TEC usually normal (unless patient is recovering with a reticulocytosis and MCV may be slightly elevated)
If you get a question with dark urine or a positive Coombs test (DAT), what type of anemia should you think?
Hemolytic anemia (look for signs of hemolysis)
What type of transfusion reaction presents as fever and chills?
Febrile Non-hemolytic reactions
How is the risk of febrile nonhemolytic reactions reduced?
By using leukocyte-filtered blood
True or False: Pre-medicating with anytipyretics prevents Febrile Non-hemolytic reactions?
False
What type of reaction occurs with transfused blood isn’t properly cross-matched?
Hemolytic reactions
How do allergic reactions to blood products typically present?
Urticaria
What should you do if a kid has an allergic reaction to a blood transfusion?
Stop the transfusion and give an anti-histamine
True or False: When a patient has an allergic reaction to a blood transfusion, you can resume it if the urticaria goes away quickly after pausing and giving anti-histamine?
True
What is the definition of neutropenia?
Absolute neutrophil count (AND) of less than 1000 during first year of life and less than 1500 after 1st year of life
What is mild neutropenia?
ANC between 1000 and 1500
What is moderate neutropenia?
ANC between 500-1000
What is severe neutropenia?
ANC under 500
What are some classic presentations of neutropenia?
- Recurrent mucosal ulceration (mouth to perirectal)
- Gingivitis
- Cellulitis
- Abscess Formation
- Pneumonia
- Septicemia
What are some endogenous organisms that kids with neutropenia are most commonly infected with?
- S. Aureus
- S. Epi
- Gram-negatives
- Enterococci
What should recurrent mucosal ulcerations make you think of?
Neutropenia
Cyclic neutropenia, severe congenital neutropenia (Kostmann syndrome), chronic benign neutropenia, Shwachman-Diamond are all types of what?
Congenital neutropenias
What is the most common cause of acquired neutropenia?
Infection
What specific group of drugs are known to cause neutropenia?
Macrolides (but lots of drugs can do it)
What should you think of for a kid that is neutropenic after a cold?
Transient neutropenia (viral suppression)
How long does transient neutropenia typically last?
Couple of days
What treatment is needed for transient neutropenia?
None- No treatment or monitoring is needed
How is ANC calculated?
Multiplying the WBC by the % of segs plus bands
What needs to be done for a patient known to have neutropenia (from any cause) if they get a fever?
Blood culture and antibiotics
What should you do for a kid with an ANC <500 and a fever?
Admit to hospital and start IV antibiotics
Previously well child with febrile illness, no heptaosplenomegaly, no lymphadenopathy, WBC is 3.5, what is next step in management?
Repeat WBC in a few weeks- Transient neutropenia due to viral illness
How is cyclic neutropenia inherited?
Autosomal dominant
What is the timing for cyclic neutropenia?
Low WBC lasts around a week and reappears every month or so
What other findings are seen with cyclic neutropenia?
- Oral lesions (common)
2. Enlarged lymph nodes
What age does cyclic neutropenia typically present in?
Younger than 10
How is diagnosis of cyclic neutropenia made?
Frequent CBCs (2x per week for 2 months)- Have to document the cycle
What 2 bacteria are responsible for most deaths in untreated patients with cyclic neutropenia?
- Clostridia perfringens
2. Gram-negative organisms
What is the treatment for cyclic neutropenia?
- Manage infections
2. Daily rhG-CSF (recombinant human granulocyte colony stimulating factor)
What does rhG-CSF do?
Reduces the number of neutropenic days
How is chronic benign neutropenia usually picked up?
Incidental finding
True or False: Children with chronic benign neutropenia rarely have oral ulcers or other signs of infection?
True
When kids with chronic benign neutropenia have oral ulcers or other signs of infection, what can be helpful?
G-CSF
How is chronic benign neutropenia differentiated from cyclic neutropenia?
Frequent CBCs
When to children with chronic benign neutropenia usually outgrow this?
By age 2
What is another name for severe congenital neutropenia?
Kostmann syndrome (Kostmann agranulocytosis)
How is Kostmann agranulocytosis inherited?
Autosomal recessive
What causes Kostmann agranulocytosis?
Arrest in the development of neutrophils
True or False: Kostmann agranulocytosis can cause a severe neutropenia and result in life-threatening infections?
True
How do you distinguish between Kostmann syndrome and cyclic neutropenia?
- Cyclic neutropenia: ANC will be normal as cycle ends
2. Kostmann syndrome: ANC remains low
True or false: In Kostmann agranulocytosis the ANC will increase in response to G-CSF, but won’t if it is cyclic neutropenia?
False: In both disorders ANC will rise in response to G-CSF
What is given to manage Kostman agranulocytosis?
rhG-CSF (this is life-saving)
What is helpful for patients with Kostmann agranulocytosis who don’t respond to rhG-CSF?
Stem cell transplantation
What are the two main components of Shwachman-Diamond Syndrome?
- Pancreatic exocrine insufficiency (leads to steatorrhea)
2. Pancytopenia
How do patients with Shwachman-Diamond Syndrome present?
Short stature, diarrhea/steatorrhea, recurrent infections, skeletal abnormalities
What types of infections do kids with Shwachman-Diamond Syndrome typically get?
- Upper respiratory
2. Skin
What skeletal abnormalities do kids with Shwachman-Diamond syndrome get?
- Clinodactyly
2. Syndactyly
What is the mnemonic for Swachman-Diamond Syndrome?
SDS:
- Substandard neutrophils
- Dumb pancreas
- Steatorrhea/Skeletal abnormalities
What other chronic illness can Shwachman-Diamond Syndrome get confused with?
Cystic Fibrosis- Both present with pancreatic insufficiency
How can you distinguish between Shwachman-Diamond Syndrome and CF?
-Scwachman-Diamond Syndrome has decreased cell lines (neutropenia/anemia/thrombocytopenia), normal electrolytes, no history of chronic pulmonary problems, normal sweat test
What is the treatment of Shwachman-Diamond Syndrome?
- Control/prevent infections
- Give pancreatic enzyme supplementation
- Prevent orthopedic abnormalities
- Monitor for leukemic transformation
What is the definition of thrombocytopenia?
Platelet count lower than 150,000
What 2 things cause thrombocytopenia?
- Decreased production of platelets
2. Increased destruction of platelets
How do kids with thrombocytopenia present?
History of easy bruising and bleeding (especially mucosal bleeding)
What part of the medical history is important for thrombocytopenia?
Recent meds
What medications can cause thrombocytopenia?
- Sulfas
- Seizure meds
- Vanco
How long does it take platelet counts to return to normal after discontinuing a drug that is causing it?
About one week
True or False: ASA and ibuprofen cause thrombocytopenia?
False- ASA and ibuprofen result in abnormal platelet function, but platelet count will be normal
What problems with platelets can cause bruising, petechiae, epistaxis, or GI bleeding?
Both thrombocytopenia and functional platelet disorders
What is deep muscle or joint bleeding likely due to?
Coagulopathy (not a platelet problem)
What is the most common hematologic abnormality in neonates admitted to the ICU?
Thrombocytopenia
True or False: Thrombocytopenia may be present with neonatal sepsis?
True
What is the most common cause of true neonatal primary isolated thrombocytopenia?
Related to maternal factors: Allo- or Auto- antibodies
What is the most common reason for a low platelet count?
Clumping from improper collection
What is an isolated, transient, but severe thrombocytopenia in a neonate due to platelet destruction by maternal antibodies?
Neonatal alloimmune thrombocytopenia
How does neonatal alloimmune thrombocytopenia work?q
Occurs when fetal platelets display the antigen inherited by the father- triggers maternal antibodies to attack them (similar to Rh disease)
What symptoms does the mother have with neonatal alloimmune thrombocytopenia?
Mother is asymptomatic, her platelets are normal
What happens in infants with autoimmune thrombocytopenia?
Mom has antibodies to her own platelets and infant’s plaetmets
True or False: In autoimmune thrombocytopenia, both Mom and child have low platelets?
True
Healthy 3 year old with recent viral illness, low platelet count, ecchymoses, and petechiae?
ITP
What % of cases of ITP resolve in 3 months?
50%
What % of cases of ITP resolve in 6 months?
75%
What should you think when you have a patient with ITP who has persistent or severe headaches?
Intracranial hemorrhage
Which ITP patients should be referred to hematology?
Those with persistent ITP, mucosal bleeding, atypical features (other cell line deficits)
When is prognosis for ITP worse?
If it presents in an older kid (over age 10)
What happens in kids who present with ITP that are over 10?
It is likely to become a chronic problem
When is ITP more likely to be a single occurrence?
Younger patients
What is treatment for mild ITP?
Nothing
What can be given for ITP with extremely low platelet levels?
IVIG
In chronic ITP, what is a treatment consideration?
Splenectomy (should be avoided in kids under 5)
What can be a cause of purpura?
Vasculitic disorders
Bruising or purpura in a child with normal or increased platelet count?
HSP or other form of vasculitis (may consider abuse)
True or False: Shin bruising is normal in a 2 year old?
True
What is another name for anaphylactoid purpura?
HSP
What is a good treatment for ITP?
Steroids
Why are steroids not a first line treatment for ITP?
Because if it is actually leukemia rather than ITP, you can kill the child
What causes thrombocytopenia in Kasabach-Merritt Syndrome?
Localized consumptive coagulopathy
What is it called when you have a hemangioma that serves as a “sand trap” for paltelets?
Kasaback-Merritt Syndrome
True or false: The bone marrow is normal is Kasabach-Merritt Syndrome?
True
What are patients with Kasabach-Merritt Syndrome at risk for?
DIC
What is the treatment for Kasabach-Merritt Syndrome?
Control the hemangioma, give transfusions as needed
What should you think when you have an XR without a radius?
TAR- Thrombocytopenia Absent Radius
Is the WBC elevated or decreased in TAR?
High
50% of patients with TAR are symptomatic by what age?
1st week of life
What % of patients with TAR have symptoms by 4 months?
90%
What 3 blood disorders are associated with upper limb abnormalities?
DBA, Fanconi, TAR
What two blood disorders have problems with abnormal thumbs?
DBA and TAR
What skeletal abnormality is present in TAR?
Absent radius
What are the platelet counts in DBA, Fanconi, and TAR?
Normal in DBA, Low in Fanconi and TAR
What is the Hgb in DBA, Fanconi, and TAR?
Low in DBA and Fanconi, normal in TAR
When does DBA present?
At 2-3 months
When does Fanconi present?
After age 3
When does TAR present?
First month
What are the vitamin K dependent factors?
2, 7, 9, 10
What should you consider in early onset Vitamin K dependent bleeding?
Maternal factors (medications Mom is on)
What are some medications that can interfere with a Mom’s Vitamin K stores?
- Anticonvulsants
- Warfarin
- Some antibiotics
What are common sources of bleeding in an infant with a coagulopathy (like Vitamin K deficiency)?
- Venipuncture sites
- Penis after circumcision
- Mucous membranes
- GI tract
Infant born at home who is exclusively breast fed presents in the first week of life with bleeding?
Vitamin K deficiency
What lab is abnormal in hemorrhagic disease of the newborn (deficiency in the Vitamin K factors)?
Elevated PT (extrinsic pathway)
Who is more likely to get vitamin K deficiency, breast fed or bottle fed infants?
Breast fed (vitamin K is in fortified formulas)
What are the 2 main types of hemophilia?
- Hemophilia A (Factor 8 deficiency)
2. Hemophilia B (Factor 9 deficiency- Christmas disease)
How are Hemophilia A/B inherited?
X-linked recessive
If you have a patient with hemophilia who is bleeding in the antecubital area after a blood draw, is this concerning?
Yes- Can lead to nerve compression (this is a medical emergency)
True or False: Blood should not be drawn from the jugular or femoral veins of individuals with hemophilia who haven’t received replacement therapy?
True- This can be fatal
What is another name for Hemopbilia B?
Christmas disease (X-mas disease = X-linked recessive)
What family history is likely for hemophilia?
Affected uncles and boy cousin’s on Mom’s side
What presents in the neonatal period with bruising, bleeding from their circumcision, or bleeding at the site of venipuncture?
Hemophilia
What lab is abnormal in hemophilia?
PTT- it is prolonged
How is hemophilia diagnosed?
By measuring factor levels
What are old kids with hemophilia subject to?
Deep joint bleeds
What can cause mortality in kids with hemophilia?
Intracranial bleeding
What is the treatment for hemophilia?
Factor supplementation
What should be done for a patient with hemophilia who suffers head trauma without any clinical signs?
Replacement therapy (even without clinical signs)
Can a female with bleeding symptoms have hemophilia (for boards)?
No- Not hemophilia, think von Willebrands
Child who develops a hemotoma from the vitamin K shot… what do you think?
Hemophilia
Child with excessive bleeding after a circumcision… workup?
Look for a congenital factor deficiency
Prolonged PT?
Vitamin K deficiency (Factors 2, 7, 9, 10)
Prolonged PTT?
Hemophilia (Factors 8, 9)
True or False: Hemophilia can present in absence of a family history?
True
What should you think if they mention that Mom has a family history of a bleeding disorder?
They are hinting at an X-linked recessive disease
What is the % chance of being born with an X-linked recessive disease if a male is born to a Mom who is a carrier?
50%
What causes Von Willebrand’s Disease?
Abnormal von Willebrand factor
What is Von Willebrand Factor required for?
Normal Factor VII function as well as normal platelet aggregation
Kid with either excessive bleeding after a dental procedure or tonsillectomy, epistaxis, or girl with menorrhagia?
Von Willebrand
If a preoperative screening shows an abnormal PTT, what should you think of?
Von Willebrand
What happens to PT and PTT in Von Willebrands?
PT is normal
PTT is usually normal, but can be slightly prolonged for some people
What happens to levels of Von Willebrand factor in Von Willebrands disease?
They are low
If you have a girl with bleeding and levels of Von Willebrand factor are low, what is your diagnosis?
Von Willebrands
If you have a boy with bleeding and levels of Von Willebrand factor are low, what is your diagnosis?
Not clear- Need to measure Factor VII and IX levels to establish a diagnosis
What happens to bleeding time in Von Willebrand’s?
It is prolonged
What is the treatment for Von Willebrands?
Usually nothing
What can be given for minor bleeds in Von Willebrands?
Intranasal or IV DDAVP (desmopressin)
How does desmopressin help in Von Willebrands?
It causes an increase in plasma vWF and factor VIII
What should be given for Von Willebrands in the setting of major surgery or life-threatening bleeds?
Replacement with a factor VIII concentrate
For Von Willebrands with major bleeds, is Factor VIII concentrate or cryoprecipitate better?
Concentrate
What can help with mucosal bleeding in Von Willebrands by inhibiting fibrinolysis?
Amicar (aminocaprioic acid)
What is typically in the history for DIC?
Sepsis, malignancy, sever burns (major illness)
What happens to platelets, fibrinogen, D-dimer, PT, PTT, and thrombin time?
Platelets low Fibrinogen low D-Dimer elevated PT/PTT unpredictable Thombin time prolonged
What is the most important factor in management fo DIC?
Treating the underlying condition
What is needed in DIC if clotting factors are low, if fibrinogen is low, or if Hgb is low?
Clotting factors: Platelets or FFP
Fibrinogen: Cryoprecipitate
Hgb: PRBCs
Patient with unilateral pain in long bone, adolescent going through a growth spurt…?
Don’t be tricked into picking growing pains. Growing pains typically bilateral and usually only at night. This may be a bone tumor.
Weeks of unilateral limb pain, what should you do?
XR to look for malignancy
What are 3 clues that limb pain in a child is “real”?
- No longer participating in sport
- Limping
- Waking at night crying in pain
What i treatment for osteogenic sarcoma (osteosarcoma)?
Amputation or limb salvage + chemo to prevent spread
Where do mets from osteosarcoma go?
Lungs
What are 3 elevated labs you might see in osteosarcoma?
- LDH
- Alk Phos
- Sed rate
What is the most common primary malignant bone tumor in children and adolescents?
Osteosrcoma
When is the peak incidence of osteosarcoma?
In the teens (coincides with the growth spurt)
If there is trauma, should this steer you from a diagnosis of osteosarcoma?
No… there may be trauma, but with any other signs of potential tumor, like preceding recurrent persistent pain consider osteogenic sarcoma
Which type of bone tumor has a soft tissue component/
Ewing Sarcoma
True or False: Ewing Sarcoma isn’t usually seen in African Americans?
True
Which type of bone tumor is more common in African Americans?
Osteogenic Sarcoma
Which type of bone tumor typically presents in a teenager going through a growth spurt who has pain?
Osteogenic sarcoma
What are common sites for osteogenic sarcoma?
Proximal and distal long bones (femur and humerus)
True or false: Both osteogenic sarcoma and ewing sarcoma can occur in long bones?
True
What is the treatment for bone tumors?
Chemo, radiation, surgery
Where do bone tumors commonly metastasize?
Lungs
What is the main location for osteogenic sarcoma mets?
Lungs
Tibia or femur pain that is worse at night, but relived by ibuprofen?
Osteoid osteoma
Which bone lesion has a central radiolucent area surrounded by thick sclerotic bone?
Osteoid osteoma
What is the most common childhood malignancy?
Leukemia
What are 4 types of childhood leukemia?
- ALL
- ANLL
- CML
- CLL
What is the most common childhood leukemia?
ALL (80%)
When is the highest incidence of ALL?
2-5 years of age
True or False: Both genetic and environmental factors are believed to contribute to development of ALL?
True
Child with bone pain or joint pain/swelling with fevers. Labs have pancytopenia?
Think ALL
True or False: The WBC count may be normal or elevated at presentation with ALL?
True
Name 2 exam findings that could help to differentiate ALL from aplastic anemia.
- Enlarged liver
2. Enlarged spleen
What is needed to formally diagnose leukemia?
Bone marrow examination
What is the treatment goal in kids with ALL?
Induce remission with one course of chemo
What is the 5 year survival rate for children with newly diagnosed ALL?
80%
What is the probability of achieving complete remission in 4 weeks with current chemo regimens?
Over 95%
True or False: Even with treatment, kids with ALL are at risk of relapse?
True
What are 2 “sanctuary sites” of ALL that are more resistant to therapy?
- CNS
2. Testes
What are 2 common sites of relapse in ALL?
CNS and testes
True or False: Each ALL relapse has same prognosis as initial presentation?
False- each relapse has a worse prognosis
What is the most common congenital condition associated with leukemia?
Downs
Name 6 conditions which have an increased risk of leukemia.
- Down
- Ataxia telangectasia (+ other immunodeficiency syndromes)
- Fanconi anemia
- Bloom Syndrome
- Klinefleter syndrome
- Neurofibromatosis
In the context of a clinical picture of ALL, what are atypical lymphocytes?
Lymphoblasts (they can get reported incorrectly as atypical lymphocytes- don’t get confused with mono if clinical picture is leukemia)
What 2 things are survivors of ALL at increased risk of?
- Neuropsychological abnormalities
2. Cognitive defects
What is a major cause of death in kids with leukemia?
Infection
What 2 things increase the risk for infection in kids with leukemia?
- Indwelling catheters
- Neutropenia
*These kids get broad-spectrum IV antibiotics
What are the 2 main types of lymphoma?
- Hodgkin’s
2. Non-Hodgkin’s (everything else)
Patient with unexplained lymphadenopathy with other symptoms like cough, new-onset wheezing, trouble swallowing, face/neck swelling, chest pain, dyspnea?
Get a CXR (could be lymphoma)
What does unexplained pruritus make you think of?
Lymphoma
What presents in teens as non-tender enlarged cervical or supraclavicular lymph nodes?
Hodgkin’s lymphoma
What are 3 symptoms commonly seen with Hodgkin’s lymphoma?
- Weight loss
- Fevers
- Night sweats
True or False: Hodgkin’s lymphoma is a slow-growing malignancy
True
What is seen on CBC in Hodgkin’s lymphoma?
Elevated WBC with relatively low lymphocyte count
Lymph node biopsy with Reed Sternberg cells?
Hodgkin’s
What should you think of with enlarged lymph nodes in younger children versus adolescents?
Younger children: More likely to be an infection
Adolescents: More likely to be lymphoma
What can present with an enlarged cervical lymph node?
Atypical mycobacteria (will have other signs like a positive PPD)
If you have an enlarged supraclavicular lymph node, is this likely to be atypical mycobacteria?
No… see this with cervical nodes, not supraclavicular ones
True or False: Supraclavicular adenopathy means lymphoma until proven otherwise?
True
What is the next step after findings supraclavicular adenopathy?
CXR
Which type of lymphoma is more likely in a small child versus a teen?
Non-hodgkin
How does Non-Hodgkin lymphoma present?
Rapidly, typically with airway compression versus painless cervical adenopathy.
What should a non-tender mass in the abdomen make you consider?
- Wilms
- Neuroblastoma
- Non-Hodgkin lymphoma
What are 4 things a patient with Langerhans Cell Histiocytosis might present with?
- Persistent scalp or diaper seborrheic rash
- Chronic ear drainage or chronic mastoiditis
- Lytic lesions in the skull or vertebral collapse
- Excessive urination
What is responsible for excessive urination in Langerhans Cell Histiocytosis?
DI and pituitary involvement
How is Langerhans Cell Histiocytosis diagnosed?
Skin biopsy and electron microscopy
What is another name for Histiocytosis X?
Langerhans Cell Histiocytosis
What is the most common solid tumor of infancy?
Neuroblastoma
What is the second most common solid tumor of childhood?
Neuroblastoma
What is the most common solid tumor of childhood?
Brain tumors
Where does neuroblastoma initially present in 50% of cases?
Adrenal glands
What is the survival rate if neuroblastoma occurs before 12 months of age?
95%
What is the only known tumor to spontaneously regress?
Neuroblastoma
What are 8 examples of typical presentation of neuroblastoma?
- Persistent bone or joint pain
- Non-tender abdominal mass
- Weight loss, anorexia, night sweats, fever
- UTI (obstructing abdominal mass)
- Raccoon eyes and proptosis (from mets)
- Horner syndrome
- Irritability, HTN, diarrhea (catecholamine production)
- Opsoclonus-myoclonus (dancing eyes)
What causes Horner syndrom seen in neuroblastoma?
Mediastinal tumor compressing recurrent laryngeal nerve (this also affects speech)
If you have a kid with a neuroblastoma who has HTN, what is causing the HTN?
Renal artery compression (pick this over excess catecholamine production)
True or False: Labs can be relatively normal in neuroblastoma?
True
What are some lab abnormalities you can see in neuroblastoma?
- Pancytopenia (from bone marrow involvement)
- Elevated ferritin
- Elevated LDH
- Elevated Alk Phos
What are the 2 ways you can diagnose neuroblastoma?
- Biopsy tumor
2. Elevated urine VMA/HMA with neuroblasts found in bone marrow (with this, biopsy not needed)
When do you order urine catecholamines when suspecting neuroblastoma?
Never… this measures epinephrine and norepinephrine… specifically order urinary VMA/HMA
What is the most important prognostic feature for neuroblastoma?
Age
When is the prognosis for neuroblastoma better?
Under 1, excellent prognosis
Over 1, poor prognosis
What are 2 things you should think of with raccoon eyes?
- Child abuse (basal skull fracture or basilar head bleeds)
2. Neuroblastoma
What is the MIBG scan used for?
Neuroendocrine tumors (pheochromocytomas or neuroblastomas)
True or False: Surgical staging for neuroblastoma is important in treatment?
False… don’t do surgical staging
What testing is needed to locate a neuroblastoma?
CT with contrast
What testing is needed to locate mets from a neuroblastoma?
Bone scan
What test is necessary in neuroblastoma to determine the extent of disease?
Bilateral bone marrow evaluation
What 3 tests are important to determine staging for neuroblastoma?
- CT with contrast
- Bone scan
- Bilateral bone marrow biopsy
What tumor presents with leukocoria or strabismus?
Retinoblastoma
What age group does retinoblastoma usually occur in?
Children under 5
What is leukocoria?
White pupil
What % of retinoblastoma presents with leukocoria?
60%
What % of retinoblastoma presents with strabismus?
20%
What is the typical presentation for a retinoblastoma?
Mom brings in picture with normal red reflex in only one eye
What % of retinoblastoma have a family history?
5%
What are the 3 mainstays of treatment for retinoblastoma?
- Surgical excision
- Chemotherapy
- Radiation
How does sporadic retinoblastoma usually present?
Unilateral
How does genetic retinoblastoma usually present?
Bilateral
What is the inheritance for retinoblastoma?
Autosomal dominant with incomplete penetrance
Where is the gene for retinoblastoma located?
Long arm of chromosome 13
True or False: Lab investigation is often recommended for prognosis and genetic planning with genetic retinoblastoma?
True
What is the % of a child getting retinoblastoma if a parent had it in 2 eyes?
50%
What is the % of a child getting retionblastoma if a parent had it in 1 eye?
5% (1/20)
What is the % of a child getting retinoblastoma if a sibiling had unilateral disease?
5% (1/20)
True or False: Kids with retinoblastoma in one eye need to be monitored for disease in the other eye
True
True or False: Retinoblastoma doesn’t increase risk of development of other malignancies?
False: Risk for other malignancies (sarcoma or malignant melanoma) increases
What is the most common soft tissue sarcoma in children?
Rhabdomyosarcoma
Kid with constipation who has a visible or palpated mass on rectal exam?
Rhabdomyosarcoma
Where do younger kids (2-6) tend to get rhabdomyosarcoma?
Head and neck
Where do older kids (teenagers) tend to get rhabdomyosarcoma?
Truncal or extremity
How is diagnosis of rhabdomyosarcoma made?
Biopsy
How is rhabdomyosarcoma treated?
- Chemo
- Surgery
- Radiation
Kid with trauma to an extremity and the pain is getting worse after a couple of weeks…?
Rhabdomyosarcoma (don’t be fooled by history of trauma… atypical pain after trauma)
Grape-like mass protruding from the vagina?
Rhabdomyosarcoma
What are two considtions that can get worse after a trauma injury?
- Rhabdomyosarcoma
2. Osteogenic sarcoma
What is the most common pediatric abdominal malignancy?
Wilms tumor (nephroblastoma)
What is the median age for diagnosis of Wilms tumor?
3.5 years
What is the most common presentation of a Wilms tumor?
Asymptomatic abdominal mass
What are 5 exam findings with Wilms tumor?
- Asymptomatic abdominal mass
- Hypertension
- Gross hematuria
- Aniridia
- Hemihypertrophy
How is diagnosis of Wilms tumor made?
Histology
How is Wilms tumor recognized on an XR?
It doesn’t calcify
If you see calcification on an abdominal mass XR is it neuroblastoma or nephroblastoma?
Neuroblastoma
What are 2 things assocaited with hemihypertrophy?
- Wilms tumor
2. Beckwith Wiedemann Syndrome
What types of tumors are children with Beckwith Wiedemann syndrom at risk for developing?
- Wilms
- Hepatoblastoma
- Other cancers
Half the body being larger than the other?
Hemihypertrophy
How is Wilms tumor managed?
- Nephrectomy
2. Chemo/radiation according to stage
What % of kids with Wilms tumor stage 1 and 2 may be cured?
90%
What occurs with the rapid breakdown of a large number of tumor cells?
Tumor Lysis Syndrome
When is tumor lysis syndrome most common?
At the initiation of chemo for large tumors, lymphomas, or leukemia
What 3 things help prevent/treat Tumor Lysis Syndrome?
- Hydration
- Alkalinization
- Allopurinol
What happens to phosphate, potassium, uric acid, calcium, and sodium in tumor lysis?
- Phosphate elevated
- Potassium elevated
- Uric acid elevated
- Calcium decreased
- Sodium not affected
What should you be on the lookout for with any tumor in or around the spine?
Cord compression- this presents with neurological symptoms or bowel/bladder dysfunction
How is cord compression from a spinal tumor managed?
Steroids and/or radiation
What is the primary symptom of an anterior mediastinal mass?
Respiratory distress (especially when supine)
When do you intubate for an anterior mediastinal mass?
You don’t- Airway compression will be below the vocal cords and if patient is anesthetized there will be no way to maintain oxygenation/ventilation
What are the 4 things that can result in symptoms from anterior mediastinal massess?
- Thymoma
- Teratoma
- Thyroid carcinoma
- Lymphoma
Which tumor resulting in an anterior mediastinal mass most commonly results in airway compromise?
- Lymphoma
What is given for any chemo patient who is exposed to varicella?
VZ-IG
Why do you never give systemic steroids unless you know malignancy has been ruled out?
Tumor lysis syndrome
*Especially with things like ITP, JIA, new-onset wheezing, and mono where symptoms overlap
What is the treatment for an anterior mediastinal mass?
Treat underlying condition
-Can use steroids/radiation in an emergency with airway compromise
What is the side effect of alkylating agents for chemo?
Gonadal dysfunction
What is the side effect of cyclophosphamide?
Hemorrhagic cystitis
How do you monitor kids getting cyclophosphamide?
Serial urinalysis (watch for cystitis and bleeding)
How do you manage hemorrhagic cystitis?
Hydration to increase urine output
What is the side effect of cisplatin?
Hearing loss and peripheral neuropathy
What is the side effect of bleomycin?
Pulmonary fibrosis
What results from extrinsic compression of the SVC by an anterior mediastinal tumor?
SVC syndrome
What type of anterior mediastinal tumor most commonly causes SVC syndrome?
Lymphoma
How does SVC syndrome present?
- Red face (plethora)
- Facial swelling
- Upper extremity edema
- Distended neck veins
- Neurologic symptoms
What is the side effect of anthracycline (doxorubicin and daunomycin)?
Cardiac toxicity
What are the side effects of vincristine and vinblastine?
- Neurotoxicity
2. SIADH
What is the side effect of methotrexate?
- Oral/GI uclers
2. Bone loss
