What is the Mentzer Index ?

A quick calculation that helps you identify iron-deficiency anemia vs.

thalassemia minor

How do you calculate the Mentzer Index?

MCV/RBC count

How do you interpret the Mentzer Index?

<13 means thalassemia

>13 means iron deficiency

(iron-deficiency anemia is much more common, so it gets the bigger numbers)

What is the most prevalent sort of hematological disorder in the USA?

Iron-deficiency anemia

What happens to the total iron-binding capacity (TIBC) in iron-deficiency anemia?

It goes up (the body is trying to find more iron)

What happens to serum ferritin in iron-deficiency anemia?

It goes down (because it is a type of iron in the blood)

If iron is provided to a patient with iron-deficiency anemia, when would you expect the reticulocyte count to start going up?

A week (or a little less)

Will the hemoglobin increase before or after the reticulocytes start to go up?

After

(Think of the reticulocytes bringing the hemoglobin out into the circulation – that’s why the hemoglobin can’t go up until their numbers increase)

When your patient reaches a normal hemoglobin, and has normal red blood cell parameters, should you discontinue the iron and switch to dietary strategies?

No –

Continue iron supplementation for 6–8 weeks to replete body stores

Lead poisoning interferes with which two enzymes in the heme-synthesis pathway (mainly)?

Ferrochelatase &

gamma-ALA-D

Both lead poisoning and thalassemia minor can cause basophilic stippling. What differentiates the thalassemia cells?

Thalassemia has “target” cells, too

What should you expect for the RBC count with alpha thalassemia trait?

High or normal

What should you expect for the RBC count with lead toxicity or iron deficiency?

It goes down, of course (That’s why they call it anemia, right?)

Which hemoglobin will be elevated on the electrophoresis of an alpha thalassemia trait patient?

A2

How can you diagnose sideroblastic anemia ?

Bone marrow evaluation only!

How common is sideroblastic anemia in kids?

Rare!

A positive Coombs test means your patient’s anemia is due to what general cause?

Immune system

(autoimmune for SLE)

(isoimmune for Rh or ABO)

Spherocytosis patients have a problem with spectrin and RBC cell membranes. What special complications are they likely to develop?

• Gallstones very young

• Hemolytic & aplastic crises with infections

Which medications are linked to the development of megaloblastic anemia in children?

• Dilantin

• Methotrexate

• Bactrim

(It’s DuMB to get a medication MegaloBlastic anemia – might help you remember the drugs involved)

The classic blood smear for aplastic anemia is . . .?

Normocytic, normochromic,

low retic count

(sudden onset problems with RBCs are generally normochromic, normocytic, because that’s what is normally produced!)

If a patient has short stature and completely normal blood cell lines, except for an aplastic anemia, what diagnosis should you think of?

Diamond-Blackfan

What is the treatment for transient erythroblastopenia of childhood?

Time – most disorders with transient in the name resolve on their own

Which patient group most often develops transient erythroblastopenia of childhood?

1–4-year-olds

(Also seen in the first year, especially after 6 months of age)

What is the usually cited trigger for a bout of transient erythroblastopenia of childhood?

Viral illness

(of course, as with other virus-associated disorders, it is not clear whether viral illnesses actually cause it, or just happen to occur in lots of patients as a coincidence)

If you see a newborn or preemie with hemolysis, what nutritional cause should you consider?

Vitamin E deficiency

What is the underlying pathological process in leukemia ?

Clonal proliferation of an abnormal cell line

Why do leukemia patients develop problems with anemia and bone marrow?

The abnormal clonal cells crowd the normal cells out of space in the marrow

What percentage of leukemia in children is acute lymphoblastic leukemia (ALL) ?

70 %

What is a new name for acute myelogenous leukemia (AML) ?

Acute non-lymphoblastic leukemia (ANLL)

How common is chronic myelogenous leukemia in children?

2–3 % of leukemias

(the rest are ANLL aka AML, or ALL)

What is the importance of having a “CALLA (CD10)-positive” ALL?

Very good prognosis

(Calla lilies are pretty, so it’s a good thing to be Calla+)

Which ALL presents with a mediastinal mass in school-aged children?

T cell ALL –

Easy to treat!

Which ALL is most aggressive & most rare (fortunately)?

Mature B cell ALL

Most ALL falls into what general subtype?

Pre-B ALL

(Easiest ALL to treat!)

In the French-American-British (FAB) classification scheme for AML, which types have Auer rods in the abnormal cells?

M1 & M2

(all of the subtypes start with “M”)

Which FAB type of AML occurs more often in trisomy 21 patients?

M7 (megakaryocytic)

7 × 3 = 21

Classification is 7 trisomy is 3

Particular trisomy involved is 21!

Which type of AML, in the FAB scheme, can be treated with

vitamin A?

(also known as trans-retinoic acid)

M3 (promyelocytic)

What tests should you do when you are initially screening for a suspected leukemia?

CBC and diff

What tests will you need to do to confirm a diagnosis of leukemia, if your initial screen is worrisome?

Bone marrow aspirate & biopsy

When is the likelihood of DIC highest for leukemia patients?

At presentation –

10 % of patients present with DIC

When is tumor lysis syndrome most likely to occur in a patient with leukemia?

When treatment is first started

Trisomy 21 patients are at increased risk for leukemia. How much is their risk of ALL increased?

About 20×

Which very unusual form of AML are trisomy 21 patients much more likely to develop than most children?

M7 or acute megakaryoblastic leukemia (AMKL) –

500× increased risk!

What is unusual about the age of onset for AML in patients with trisomy 21?

It is younger –

Average onset about 2 years & most present before age 5

(general population average age at presentation 7.5 years)

Overall, what percentage of trisomy 21 patients will develop some type of leukemia?

2–3 %

Trisomy 21 patients are very unlikely to develop what general sort of malignancies?

Solid malignancies

Which immunodeficiency disorders put the patient at increased risk for leukemia?

(also at risk for lymphoma)

• Wiskott-Aldrich

• Agammaglobulinemia

• SCID syndrome

(Picture a dog with a runny nose and eyes because he is immunodeficient who WAGs his tail so hard he SCIDs)

Which genetic syndromes increase a patient’s risk of leukemia?

• Trisomy 21 (of course)

• Fanconi’s anemia

• Bloom syndrome

• Ataxia telangiectasia

(To remember the last three, think of a blood smear that looks like it’s “blooming” with FAAT, because it’s all white, due to the leukemic cells)

If you are treating ALL, how long should your initial attempt at induction last?

4 weeks

When you have completed the usual induction course, what do you need to check, to know how to proceed with treatment?

Bone marrow aspirate & CSF

What percentage of patients with ALL will have a successful induction course in just 4 weeks?

90 %

How important is it to check the leukemic cells for chromosomal translocations?

Very important –

Specific translocations change treatment and prognosis

(several worsen the prognosis, but some also improve it)

What is the DNA index for leukemic cells?

A ratio of chromosome number in the leukemic cells to the normal chromosome number, 46

(it is a measure of how much DNA is active in the cell)

Which is better, a lot of active DNA or not very much? Why?

Lots is better – if the cell’s DNA is very active, then it will be very vulnerable to chemo agents

How can you remember which is better for the DNA index – a big number or a smaller number?

Bigger is better, because it means that the DNA takes up more of the cell’s space (therefore it’s more active than small, coiled, DNA)

Which other term is often used & means essentially the same thing as the DNA index?

The “hyperdiploidy” level of the abnormal cells

What is the important cutoff number for the DNA index in ALL?

1.16 – less than 1.16 is high risk

What is the cutoff number for WBC count in ALL that means the patient is at high risk?

>50,000

If you had ALL, what would you want your WBC count to be?

<50,000

(standard risk )

What percentage of ALL patients are in complete remission 5 years after treatment is completed?

Around 85 %

(they are probably cured)

How do the success rates for ALL compare to those for AML?

AML is worse

(overall long-term survival for pediatric patients is about 50 %, though – better for lower risk patients with matched bone marrow transplants)

What is the mainstay of treatment for AML, in general?

Bone marrow transplant after first remission is induced

(induction success rate is 70 %)

Which type of bone marrow transplantation is most often done?

Allogeneic

(HLA compatible, but genetically not identical)

Autologous transplant means that the transplanted cells came from _______ ?

Patient’s own stem cells

How do you determine how vulnerable to infectious agents a neutropenic patient will be?

Calculate the ANC

(absolute neutrophil count )

In case you’ve forgotten, how do you calculate the ANC?

From the differential, add up the neutrophil and band count, then multiply that percentage by the total white count

What is a respectable ANC, meaning that your patient is at little risk of bacterial infection?

>1,000

How fast do you need to get antibiotics into a febrile neutropenic patient?

Emergently!

What is the main determinant of whether a patient will develop acute tumor lysis syndrome ?

Amount of tumor – the more tumor there is, the greater the likelihood

Which two types of white cell cancers are most notorious for generating acute tumor lysis syndrome?

ALL & NHL

(not the National Hockey League – Non-Hodgkin Lymphoma!)

Should you stop chemotherapy if a patient develops acute tumor lysis syndrome?

Yes – until the metabolic status is stabilized (otherwise they may acutely die of their metabolic problems)

What is the standard medication used to control uric acid levels in patients with tumor lysis syndrome?

Allopurinol

What newer medication is nearly always able to avert renal failure (due to uric acid levels) in tumor lysis patients?

Rasburicase

(it makes the uric acid very soluble)

What is the management of last resort for acute tumor lysis patients?

Dialysis

In case you should see it on your boards, what new lab test has largely replaced “bleeding time?”

PFA –

Platelet function activity

Name three ways a female could be affected by hemophilia ?

• Turner syndrome (XO)

• Androgen-insensitivity syndrome (XY)

• Unfavorable lyonization (normal female mosaic pattern, but too many of the good Xs turned off)

A vignette is presented of a male child with a normal CBC, platelets, PT, and bleeding time. The child has a significantly elevated PTT, though. Which familial disorder is this?

Hemophilia

(Factor 8 or 9)

Which children normally have an elevated PTT ?

<6 months old

The family history of a Factor 8- or 9-deficient patient will usually be positive for _________?

History of bleeding problems in maternal uncles

A relatively common cause of a prolonged PTT in children, that is not due to a familial disorder, is ________?

Lupus anticoagulant

(remember that lupus anticoagulant is very unfortunately named – it paradoxically causes increased clotting)

If all CBC and bleeding parameters are normal except the bleeding time, what kind of a disorder is it? (two possibilities)

• Aspirin effect

• Platelet function disorder (hereditary)

An elevated number of megakaryocytes on bone marrow aspirates suggests what disorder?

ITP

How long must idiopathic thrombocytopenic purpura persist to call it “chronic?”

>6 months

What is Evans syndrome ?

More than one autoimmune cytopenia, even if they occur at different times –

Usually it’s:

ITP + immune hemolytic anemia

(may be associated with later lupus in female patients)

What treatment provides the fastest response for ITP?

IVIG

(very expensive, though!)

What is an important complication to be aware of, when using IVIG?

Aseptic meningitis

What age group is most likely to develop ITP in childhood?

2–5-year-olds

When a neonate is thrombocytopenic, what general etiology is most likely?

Maternal causes

(mainly isoimmune or maternal ITP)

Acute ITP is more common in which gender during childhood?

Males

Chronic ITP is more common in which gender during childhood?

Females

How is the response to steroids different in acute vs. chronic ITP?

Good with acute

Variable with chronic

How is the response to IVIG different in acute vs. chronic ITP?

Good with acute

Short-lived for chronic

Is acute ITP more common in young children, or older children?

Young

In general, what controversy exists about treatment for DIC?

Whether to give FFP/cryoprecipitate to promote clotting (which might lead to more damaging micro-clots)

  Or

Heparin to prevent further clotting (which might worsen bleeding but also might prevent using up more clotting factors – it’s an attempt to stop the cascade)

Historically, we have waited for hemophiliacs to have bleeding problems before beginning treatment. What is the current recommendation?

Prophylactic treatment produces much better long-term function

Which is more common, deficiency of Factor 8 or 9?

Factor 8

(1 per 10,000 vs.

1 per 50,000)

If a patient has “severe” Factor 8 or 9 deficiency , what does that say about their factor activity level?

<1 % activity!

If a hemophiliac has a bleeding incident, what is the target factor level?

Depends:

Minor – up to 30 %

Moderate – up to 75 %

Severe – 75 – 100 %

What sort of bleeding is considered “minor” for a hemophiliac?

Soft tissue bleeds and hematuria

What sort of bleeding is considered severe for a hemophiliac?

CNS bleeds, major trauma, surgery, retropharyngeal, or retroperitoneal bleeding

What is the characteristic appearance of hemophiliacs?

Muscle wasting, due to multiple bleeding incidents in soft tissue over time

What is the most common inherited disorder in the US Caucasian population?

von Willebrand’s disease

(1 %)

What over-the-counter medication should von Willebrand’s patients be especially careful to avoid?

Aspirin

What are the lab parameters expected for von Willebrand’s patients?

↑ PTT

↑ Bleeding time

↓ Factor 8

When von Willebrand’s patients bleed, what are the main treatments?

DDAVP

& vWF concentrate

(Factor 8 concentrates are sometimes used, but they are only helpful if they are not very pure, and therefore still contain von Willebrand’s factor)

If you have a child with a hypercoagulable disorder, what is the best therapeutic option in kids?

Low-molecular-weight heparins

Which are more common in kids – carcinomas or sarcomas ?

Sarcomas

90 % of Hodgkin lymphoma patients have what finding at presentation?

Cervical adenopathy – painless, rubbery, & matted

Clinically localized Hodgkin disease usually turns out to be what type?

Nodular sclerotic (NS)

(about 75 % of adolescent cases &

45 % of cases in younger children)

Which type of Hodgkin lymphoma is unusually common in young children (before adolescence)?

Mixed cellularity

(about 33 %)

What does anemia in a Hodgkin patient indicate?

Could be either advanced disease or autoimmune hemolysis

Non-Hodgkin lymphoma patients are at special risk for what cardiac complication?

Pericardial effusion

What percentage of Burkitt lymphoma cases is related to EBV in the USA?

15 % (associated, but not super high)

A male child with lower extremity and scrotal edema could have what sort of tumor?

Something compressing the IVC – often neuroblastoma

A classic presentation of neuroblastoma involving the head and neck is?

Raccoon eyes & proptosis

Which paraneoplastic syndromes are common in neuroblastoma?

Opsomyoclonus (myoclonic jerks & dancing eyes)

& intractable secretory diarrhea (due to VIP secretion)

If a rhabdomyosarcoma is described as “botryoid ,” what does that mean?

It is shaped like a bunch of polyps – often seen when this tumor develops in the GU tract

What sort of cells make a rhabdomyosarcoma ?

Mesenchymal cells that were supposed to become skeletal muscle

(that’s why they can occur anywhere)

Wilms tumors are especially associated with what two physical exam findings?

Hemihypertrophy & aniridia

The name of the Wilms tumor precursor lesion is ________?

“Nephrogenic rests”

(also known as nephroblastomatosis)

The most common bone tumor in kids is _________?

Osteosarcoma

When and where is an osteosarcoma most likely to occur?

• Adolescence

Metaphyses of rapidly growing bones (usually on either side of the knee, or the proximal humerus)

How is osteosarcoma treated?

Excision – but limb-sparing surgery with artificial replacement of bone is now preferred

  +

Chemotherapy

(80 % survival)

Which genetic mutations are associated with osteosarcoma?

RB & p53

Is it common for osteosarcoma patients to have obvious metastases at the time of presentation?

Yes – about 1 in 5 have obvious metastases

Where does osteosarcoma like to go when it metastasizes?

The lungs

(and other bone sites, of course)

Which ethnic group usually develops Ewing’s sarcoma ?

Caucasians

(usually in adolescence)

Are sickle cell patients at increased risk for stroke?

Yes

Should sickle cell patients be routinely screened for stroke risk?

Yes – annual transcranial Doppler

(follow-up with MRA if needed)

At what age is transcranial Doppler examination for stroke risk usually discontinued?

16 years old

What is the role of transfusion therapy for patients with sickle cell, in terms of stroke risk?

Chronic transfusion therapy reduces stroke risk in patients with abnormal findings on transcranial Doppler

(>200 cm/s)

How effective is transfusion therapy in reducing the risk of stroke for patients with abnormal Doppler results?

>90 %!!!

What treatment can cure thalassemia ?

Bone marrow transplant

If a patient has a family history positive for gall stones at an early age, and a few family members had splenectomies, what inherited disorder is the issue?

Spherocytosis

Fever, dark urine, and splenomegaly after travel to Nicaragua =

Malaria

8-year-old female with easy bruising, bleeding from gums, joint pain, and fever for 2 weeks =

ALL (usually)

Fever, exudative tonsillitis, hepatosplenomegaly =

EBV

Fever, bone pain, sudden movements of extremities and

eyes =

Neuroblastoma

(opsomyoclonus)

Cutaneous nodules in a newborn could be what two oncological problems?

Neuroblastoma

Or

Leukemia

Birbeck granules go with what malignancy?

Langerhans cell histiocytosis (LCH)

(Letterer-Siwe or multisystem LCH is the most severe form and develops in kids <2 years old – presents with head, abdomen, and intertriginal rash)

A two-and-a-half-year-old white male with persistent skin rash and history of recurrent pneumonias now has platelets of only 40,000. What is the disorder?

Wiskott-Aldrich

Lytic lesion at the growth plate of the femur + positive bone

scan =

Osteosarcoma

Regression of milestones + anemia/thrombocytopenia with splenomegaly + cherry red

spot =

Niemann-Pick

11-year-old white male with short stature + low white count + fatty pancreatic infiltrates =

Shwachman-Diamond

Most common cause of neutropenia ?

Viral illness

(second most common is normal variation due to inheritance and/or racial variation)

9-year-old white male already diagnosed with both basal and squamous cell skin cancers. Diagnosis?

Xeroderma pigmentosum

Headache + early morning vomiting + blurred vision =

Intracerebral tumor

A 13-year-old white male complains of fever, constipation, and abdominal pain. What oncology problem could be to blame?

Non-Hodgkin lymphoma

A 14-year-old white female has fever, night sweats, and all-over itching. She has a little lump in her supraclavicular area. Diagnosis?

Hodgkin lymphoma

Adolescent with a seizure disorder, mr, and malar spots that look like acne. Diagnosis?

Tuberous sclerosis

In addition to congenital disorders and trauma, why might a patient be anemic?

 (3 general categories)

1. Medication side effect

2. Chronic disease (including rheumatologic ones)

3. Poor nutrition (vitamin/mineral deficiencies)

How do you know whether an anemia is microcytic or macrocytic?

Check the “mean corpuscular volume” (MCV)

(normal is 80–100 for adolescents,

for newborns 100–120,

for children it’s 70s, increasing toward

the adolescent level)

The quantity of reticulocytes in the RBC sample is usually given as an index (%). What should the reticulocyte index be in an anemic patient?

>2 %

(otherwise the marrow is not responding to the anemia, and it may be the problem)

The important causes of macrocytic anemia are ___________?

(4)

1. B12 deficiency

2. Alcoholism/liver dz

3. Reaction to drugs (phenytoin, methotrexate)

4. Folate deficiency

Mnemonic:

Spells BARF!

Jaundice + anemia, especially if both conjugated & unconjugated bili are high = what general diagnosis?

Hemolytic anemia

Schistocytes, “helmet” cells, microspherocytes, and RBC fragments indicate what type of anemia?

Hemolytic anemia

(looks like bites have been taken out of the cells)

Basophilic stippling of RBCs in an anemic patient indicates what diagnosis?

Lead exposure

Spherocytes on the peripheral blood smear of an anemia patient indicates what two possible causes of the anemia?

1. Hereditary spherocytosis

2. Hemolytic anemia (including from incompatibility between maternal & fetal blood types)

Folate & B₁₂ deficiency both produce what change in the neutrophils?

Hypersegmentation of the nucleus

Patients with splenic dysfunction develop what RBC finding?

Howell-Jolly bodies

A patient has his spleen removed after a traumatic injury. He is later noted to have little blue areas in his RBCs. What are these called, and why are they there?

• Howell-Jolly bodies

• Indicates splenic dysfunction or absence

(usually just one per cell)

Hypersegmented neutrophils are seen with which two types of anemia?

B₁₂ & folate deficiency

Which two “mechanical” problems sometimes cause anemia?

1. Mechanical valves

2. Microangiopathic vessel changes that damage & use up RBCs

On physical exam, what do you expect to find with anemic patients?

1. Tachycardia

2. Pallor

3. Systolic ejection murmur

What do anemia patients usually see the doctor for?

1. Tachypnea or palpitations

2. Fatigue

3. Dizzy/light-headed

Why do anemia patients often have systolic ejection murmurs ?

High flow

(same reason healthy pregnant patients often have a murmur)

What causes of microcytic anemia are important to know about?

1. Lead

2. Iron deficiency

3. Thalassemia

4. Anemia of chronic disease

5. Sideroblastic anemia

Mnemonic:

Spells LITAS. Put it together with the macrocytic mnemonic, and you have “LITAS BARF”

What is the most common cause of anemia in the USA?

Iron deficiency

(typically seen in young, menstruating females and toddlers with poor dietary intake and/or excessive milk consumption)

What odd behavior sometimes occurs along with anemia?

Craving for ice, dirt, and other non-nutritive substances

(Called “pica”)

How is iron-deficiency anemia treated?

1. Treat with iron

2. Search for the cause & correct it

If iron-deficiency anemia occurs in a patient who is not menstruating, what is the likely cause?

Occult GI bleeding

What is Plummer-Vinson syndrome ?

1. Esophageal webbing

2. Iron-deficiency anemia

3. Glossitis (tongue inflammation)

In what patient group are you most likely to see Plummer-Vinson syndrome?

Women of northern European & British ancestry

Anemia + a skull X-ray with a “crew-cut” appearance is what disorder?

Thalassemia

(occasionally sickle cell)

If a patient has G6PD deficiency, what would you expect to see on the blood smear?

Heinz bodies

Mnemonic:

Think of them as Heinz 57 varieties – because so many things induce G6PD!

If anemia has a bone marrow cause, what are the three usual reasons to think of?

1. Aplastic anemia (lack of all cell types)

2. Myelofibrotic/myelophthisic changes (marrow replaced by fibrous stuff)

3. Sideroblastic anemia (various problems forming Hgb lead to sideroblastic anemia)

How can you identify the cells of sideroblastic anemia?

1. They are in the marrow (usually)

2. They have iron-inclusion bodies in the RBC

If the peripheral blood smear report says “polychromasia,” what should you conclude?

There are probably immature blood cells circulating

(possible hemolytic anemia)

Echinocytes or “burr cells” mean that what condition is affecting your patient?

Uremia!

Myelofibrosis causes what unusual RBC shape?

Tear-drop-shaped RBCs

(and anemia)

Microangiopathic diseases cause what kind of RBC changes?

Chewed up cells –

Helmets, schistocytes, & fragments

Echinocytes (“prickly-looking” cells), or “burr cells,” go with what metabolic problem?

Uremia

Target cells go with which diseases?

1. Thalassemia

2. Liver disease

If many new RBCs are being made, what will their appearance be on micro exam?

Polychromasia

(part blue, part red – due to immaturity)