Mtb: Hematology 4, G6Pd, Aplastic Anemia, Polycythemia Vera

Front 1

inheritance of G6PD

Back 1

X linked recessive inheritance for an inability to protect RBCs from oxidant stress

Front 2

What leads to this lack of oxidant stress tolerance?

Back 2

the RBCs cannot effectively produce glutathione reducase so they lyse

Front 3

most common trigger for hemolysis in G6PD def

Back 3

infection

Front 4

other causes

Back 4

sulfa, nitrates, dapsone, quinidine, fava beans

Front 5

two ethnicities with high rates of G6Pd def

Back 5

African Americans

Mediterraneans

Front 6

classic smear finding?

Back 6

BITE CELLS

Front 7

And how do you visualize the Heinz bodies?

Back 7

you have to use a special stain with methylene blue

Front 8

Is G6PD level accurate and reliable?

Back 8

only if you have waited 1 to 2 months after an acute hemolytic event before testing for it.

right after hemolysis, the G6PD level is often normal

Front 9

treatment to reverse the hemolysis in G6PD def.

Back 9

nothing- you just have to avoid oxidant stress

Front 10

two diseases caused by deficiency of ADAMTS 13 (a metalloproteinase)

Back 10

TTP and Hus

they are basically different sides of the same disease

Front 11

main association with HUS

Back 11

E coli O157 H7

Front 12

2 diseases known to cause TTP

Back 12

AIDS

SLE

Front 13

3 drugs known to cause TTP

Back 13

ticlodipine

clopidogrel

cyclosporine

Front 14

What is the triad you see in both TTP and HUS?

Back 14

intravascular hemolysis (schistocytes)

thrombocytopenia

renal insufficiency

Front 15

whihc is more common in adults?

Back 15

TTP

HUS is fairly rare in adults

Front 16

another thing that separates TTP clinically from HUS

Back 16

it can show neurologic signs/symptoms as well as fever

Front 17

changes in PT/aPTT

Back 17

none

Front 18

mgmt for TTP/HUS

Back 18

if they are NOT linked t drugs or diarrhea- give steroids

Front 19

so in other words if you TTP associated wtih SLE

Back 19

give steroids

Front 20

but if you have a kid with HUS...

Back 20

do plasma exchange or plasmapharesis

Front 21

does platelet transfusion help TTP/HUS?

Back 21

no it makes the disease worse actually

Front 22

pathogenesis of PNH

Back 22

deficiency of CD55 and 59 (aka decay accelerating factor)

so the surface of their RBCs are prone to complement attack during periods of acidosis

Front 23

what specific gene is defective in PNH?

Back 23

PIG A (phosphatidylinositol class A)- leads to hyperactivity of the complement system

Front 24

so these patients will have relative hypoventilation when sleeping, get acidotic and have all kinds of hemolysis going crazy basically

Back 24

but the hemolysis is not the big problem

Front 25

What is the biggest problem associated with PNH?

Back 25

their biggest most serious complication is clotting

(e.g. Budd Chiari syndrome)

Front 26

so what is the usual presentation of PNH?

Back 26

they just have episodes of dark urine with the first pee of the day from sleeping

Front 27

but what is the most serious underlying defect with this symptom?

Back 27

pancytopenia and iron deficiency anemia

Front 28

most common cause of death in PNH

Back 28

thrombosis

Front 29

most accurate dx test for PNH

Back 29

CD55 and 59 levels

Front 30

another way to say "test for CD55 and 59"

Back 30

flow cytometry

Front 31

best initial therapy for PNH

Back 31

prednisone slows the hemolysis

Front 32

the only curative tx for PNH

Back 32

BMT

Front 33

specific drug used to treat PNH?

Back 33

eculizumab (inactivates C5 in the complement pathway and decreases RBC destruction)

Front 34

so eculizumab is basically

Back 34

a complement inhibitor

Front 35

pancytopenia of unclear etiology is called

Back 35

aplastic anemia

Front 36

two big general causes of aplastic anemia

Back 36

infection and/or cancer invading the bone marrow and decreasing marrow production

Front 37

examples of radiation and toxins that can give aplastic anemia

Back 37

toluene

insecticides

benzene

Front 38

some drugs that can cause aplastic anemia

Back 38

clozaril (agranulocytosis really)

sulfas

phenytoin

carbamazepine

chloramphenicol

alcohol

chemo

Front 39

so some take aways are

Back 39

sulfas

seizure meds

EtOH

chemo

Front 40

some diseases associated with aplastic anemia

Back 40

SLE

HIV

hepatitis

CMV

EBV

PNH

Front 41

also parvo B19 of course in

Back 41

sickle cell

Front 42

What vitamin deficiency can give aplastic anemia?

Back 42

B12 and folate

Front 43

two endocrine medications linked to aplastic anemia

Back 43

PTU and methimazole

Front 44

triad of presentation for aplastic anemia

Back 44

fatigue from anemia

infections from leukopenia

bleeding from low plt

Front 45

aplastic anemia is a dx

Back 45

of exclusion

Front 46

mgmt of aplastic anemia

Back 46

transfusions, antibiotics, and platelets

BMT is the definitive treatment though

Front 47

if the patient is over 50 however, they will not be eligible for a BMT so what do we do?

Back 47

we then give them antithymocyte globulin (ATG) with cyclosporine or tacrolimus

Front 48

Why do we give an immunosuppressnt to treat aplastic anemia?

Back 48

they are IL-2 inhibitors that will effectively stop the actions of the T cells in trying to break down the few cells that the marrow is able to produce

Front 49

a disease characterized by unregulated production of all three blood cell lines

Back 49

PV

Front 50

the mutation responsible for polycythemia vera

Back 50

JAK2 protein kinase defect

Front 51

And what is the classic lab value for workup of PV?

Back 51

you see incredibly high Hct values despite a very low suppressed EPO level

Front 52

symptoms of polycythemia vera

Back 52

they're all related to hyperviscosity:

headache

blurred vision

HTN

fatigue

splenomegaly

bleeding from engorged vessels

thrombosis from hyperviscosity

Front 53

but the main four are:

Back 53

HTN

splenomegaly

bleeding

thrombosis

Front 54

classic presentation of polycythemia

Back 54

itching after hot shower because they have so many basophils pumping out histamine

Front 55

some dx findings in PV

Back 55

Hct over 60%

platelets and WBC are also increased

oxygen levels are normal

EPO is low

Front 56

What should you first exclude before assuming polycythemia vera?

Back 56

secondary polycythemia from chronic hypoxia

Front 57

the most accurate test for diagnosing polycythemia vera

Back 57

JAK2 mutation

Front 58

What other random lab value is elevated in PV?

Back 58

B12 for unclear reasons

Front 59

smal nmber of PV patients will eventually convert into...

Back 59

AML

Front 60

What cancer is assocaited with secondary polycythemia?

Back 60

RCC

Front 61

And how do you tell if a polycythemia is secondary or if it's P vera?

Back 61

secondary shows a HIGH EPO level

Front 62

What change in MCV do you see with PV?

Back 62

low

Front 63

mgmt of poly vera?

Back 63

- phlebotomy

- aspirin to prevent thrombosis

- hydroxyurea

- allopurinol or rasburicase

- antihistamines