Grab Bag Of Hematology

Front 1

Incidence of AA

Back 1

3-6 per million per year in US and Europe
3-4 x higher in China, SEA, and Mexico

Front 2

Etiology of AA

Back 2

Idiopathic 70-80%
Medications
Chemicals
Infections
Pregnancy
Other - Thymoma, SLE, GVHD

Front 3

Inherited AA causes

Back 3

Fanconi Anemia, Dyskeratosis Congenita, Shwachman-Diamond Syndrome, Amegakaryocytic thrombocytopenia, familial aplastic anemia, Down syndrome, Reticular dysgenesis

Front 4

DDx of pancytopenia

Back 4

AA, hypoplastic MDS, aleukemic leukemia, HCL, systemic mastocytosis, LGL, myelofibrosis, chemotx/radiotx, PRCA, B12/folate deficiency, anorexia nervosa, mycobacterial infection.

Front 5

When should FA be tested for with AA

Back 5

Patients < 40yo

Front 6

Severe AA definition

Back 6

BM cellularity <25% with 2/3 of following
Neutrophils < 0.5, Plts <20, Retics <20

Front 7

Very severe AA definition

Back 7

As for severe AA but neutrophils <0.2

Front 8

2 year mortality for severe/very severe AA

Back 8

80%

Front 9

Treatment of severe/very severe AA

Back 9

If greater than 40 or no HLA-identical sibling then IST.
If less than 40 and has HLA-identical sibling then related alloSCT.

Front 10

Response rates for IST in AA

Back 10

50% by 3 months and 70-75% by 6 months.

Front 11

EFS for IST in AA

Back 11

35-50% at 5 years

Front 12

Late complications of IST in AA

Back 12

At 11 years:
MDS/AML 8%
PNH 10%
Solid Tumours 11%

Front 13

Dosing of IST in AA

Back 13

ATG 40mg/kg x 4 d
CSA 10-12 mg/kg x 6 months (at least)
Methylprednisolone 1mg/kg x 2 weeks to prevent serum sickness

Front 14

Side effects of ATG

Back 14

Infusion-related: fever, chills/rigors, dyspnea, N/V, diarrhea, hypotension/hypertesnion, malaise, rash, headache.
Serum sickness (1-2 weeks after ATG infusion): fever, chills, malaise, arthralgias, lymphadenopathy, N/V, skin rash.

Front 15

Rates of cGVHD in SCT and AA

Back 15

30-40%

Front 16

Conditioning for sibALLO SCT

Back 16

Cyclophosphamide 50mg/kg x 4 days then ATG 90 mg/kg x 3 days.

Front 17

Outcome for sibALLO SCT

Back 17

aGVHD 65%, cGVHD 56% 9 year OS 88%

Front 18

Clinical manifestations of Gaucher Disease

Back 18

Hepatomegaly, splenomegaly, bone marrow infiltration, bone pain/AVN, Erlenmeyer flask deformity of distal femurs, neurologic disease, cytopenias

Front 19

Sub-Types of Gaucher's and clinical manifestations

Back 19

Type I 90% - no neurologic involvement
Type II 1% - fulminant CNS disease with death <18 months
Type III 7% - subacute/chronic and later onset with neurologic disease (myoclonus, ataxia, progressive dementia)

Front 20

Treatment of Gaucher's

Back 20

IV replacement of glucocerebrosidease with velaglucerase, imiglucerase.
Inhibitor of glucosylceramide synthase with miglustat (CI in pregnancy)

Front 21

Lymphomatoid granulomatosis - most common site of involvement

Back 21

Lung,
can involve brain, kidney, liver, skin, GI tract

Front 22

Lymphomatoid granulomatosis - immunophenotype

Back 22

EBV+, CD20+ CD30+

Front 23

Lymphomatoid granulomatosis - staging

Back 23

Stage I - EBV+ cells <5/HPF. Polymorphous lymphoid infiltrate without cytologic atypia.
Stage II - 5-20 EBV+ cells/HPF. Occasional large lymphoid cell or immunoblasts in polymorphous background
Stage III - Large lymphoid cells numerous though inflammatory background still present

Front 24

Lymphomatoid granulomatosis - treatment

Back 24

Grade I and II - interferon alpha 2b
Grade II - like for DLBCL

Front 25

Padua scoring - when to give thromboprophylaxis

Back 25

Greater than or equal to 4 requires thromboprophylaxis for non-surgical patients (11% vs. 0.3% VTE)

Front 26

Padua scoring

Back 26

3 points for PIMP: 'philia, immobility, malignancy, previous VTE
2 points for trauma or surgery within past month
1 point for CHAAOOS: CHF, hormone, Age >70, AMI, Obesity (BMI >30), Other (acute rheum/infx), Stroke

Front 27

HDN - associated with with antigens

Back 27

Rh - anti-D, anti-c, anti-E
Kell - anti-K1
Duffy - anti-Fya
ABO - anti-A and anti-B IgG only in O mothers

Front 28

HDN - why no disease with most alloimmunization except select ones

Back 28

Low titre antibody, targeted against very low incidence antigens, weak expression on fetal RBC.

Front 29

HDN etiology

Back 29

1. alloimmunization through transfusion
2. maternal-fetal hemorrhage during pregnancy (only need 0.1 ml to induce alloimmunization. 1ml fetal blood will result in anti-D in 1% of women)

Front 30

Neonatal manifestations of HDN

Back 30

Anemia with erythroblastosis fetalis with erythroblasts in the circulation. Increased bilirubin with risk of kernicterus.

Front 31

HDN due to K1 - unique feature

Back 31

Most common HDN type due to use of RhIG
Inhibits growth of fetal erythroid precursors. Degree of anemia out of keeping with degree of hemolysis.

Front 32

Indications for Rhig

Back 32

In Rh -ve female not already sensitized
1. Accidental/emergent transfusion of Rh+ blood
2. Pregnancy with Rh+ fetus
3. Spontaneous or elective abortions
4. Ectopic pregnancy
5. Amniocentesis/CVS/fetal blood sampling
6. Antipartum PV bleeding

Front 33

What is the standard dose of RhIg and how much volume of fetal RBCs does it neutralize

Back 33

300mcg will cover 30ml of Fetal Maternal Hemorrhage

Front 34

When is Rhig given in pregnancy to prevent HDN

Back 34

28 weeks and with 72 hours of delivery of a Rh+ neonate

Front 35

What are 2 tests to determine fetal maternal hemorrhage and their differences

Back 35

Rosette test (qualitative, done first as screen, specific for RhD+ cells), Kleihauer-Betke test (quantitative, specific for fetal RBC)

Front 36

Rosette Test - how is it done?

Back 36

Maternal blood sample incubated with anti-D, D+ fetal cells will be coated with anti-D antibodies.
Addition of D+ indicator RBC added. Rosette forms around fetal cells coated with anti-D

Front 37

Rosette test - sensitivity

Back 37

99-100% sensitive when FMH is greater than or equal to 15ml.

Front 38

How to determine dose of anti-D to give?

Back 38

Rosette test first, if negative give 300mcg. If positive, do Kleihauer-Betke test. Count 2000 cells, determine % of fetal to maternal cells, multiply by 50 to determine amount of RhIg to give.

Front 39

Kleihauer-Betke test - how is it done

Back 39

Blood smear of maternal blood, expose to acid buffer, adult cells sensitive to acid buffer and will appear as ghost cells. Fetal cells resistant.

Front 40

When should maternal group and screen be done

Back 40

At first visit to Ob and at 28 weeks for ABO and Rh antibody screen.

Front 41

What are the the 2 types of RhIg and their differences

Back 41

RhoGAM - viral inactivation by filtration
WinRho - viral inactivation by solvent inactivation

Front 42

If previous HDN, what is surveillance strategy for subsequent pregnancy?

Back 42

Amnio and PCR at 15 weeks to determine Ag status of fetus, if antigen positive, requires fetal monitoring.

Front 43

How frequently should antibody titre and strength be monitored?

Back 43

Bimonthly until 24 weeks then qweekly after.

Front 44

What are examples of critical titres in alloimmunized mothers

Back 44

A difference of greater than 2 dilutions
10 point difference in strength
titres > 16 for anti-D and >8 for anti-Kell

Front 45

In patients without previous HDFN, what is the surveillance strategy once critical titre has been reached?

Back 45

Test father
If homozygous, initiate fetal monitoring
If heterozygous, GA15 weeks amnio with PCR

Front 46

Fetal monitoring for HDFN, when to initiate?

Back 46

If previous HDFN, GA 18 weeks at the earliest.
If no previous HDFN, start when critical titres reached.

Front 47

Fetal monitoring approaches

Back 47

Preferred: 1. Doppler U/S fetal MCA flow which correlates with fetal anemia and is non-invasive q1-2 weeks.
2. Amnio q2weeks until critical OD reached, correlates with anemia using Queenan curve if <27 weeks and Liley curvey if >27 weeks.
3. Cordocentesis

Front 48

Indications for cordocentesis

Back 48

If MCA velocity >1.5 MoM's or deltaOD450 in upper zone 2

Front 49

Indications for intrauterine transfusions

Back 49

Transfusion if deltaOD450 in zone 3 or if fetal Hct is <30% by cordocentesis

Front 50

Management of fetal HDFN

Back 50

If fetus <35 weeks and Hct <30 transfuse type O, D-negative, irradiated, CMV negative blood
If fetus >35 weeks, deliver.

Front 51

Management of neonatal HDFN

Back 51

1. Type and screen, DAT, RBC eluate
2. Phototherapy
3. Treat severe HDN with exchange transfusion

Front 52

Inherited disorders with large platelets and thrombocytopenia

Back 52

Mediterranean Macrothrombocytopenia - normal function
MYH9 - normal function
Bernard-Soulier - abnormal plt function to ristocetin
Grey platelet - abnormal plt function, no granules

Front 53

Test for chronic granulomatous disease

Back 53

NBT - nitroblue tetrazolium
DHR - dihydrorhodamide 123

Front 54

Defect in chronic granulomatous disease

Back 54

NADPH oxidase complex (gp91phox)

Front 55

3 mechanisms in platelet storage pool defects

Back 55

Alpha granule - grey platelet syndrome
Dense granule - Chediak Higashi, Hermansky Pudlak
Urokinase type PA overactivity - Quebec Platelet disorder

Front 56

Preeclampsia - timing of onset

Back 56

Late 2nd to 3rd trimester

Front 57

Gestational thrombocytopenia - timing of onset

Back 57

2nd - 3rd trimester

Front 58

HELLP - timing of onset

Back 58

Late 2nd to 3rd trimester

Front 59

TTP - timing of onset in pregnancy

Back 59

2nd - 3rd trimester

Front 60

AFLP - timing of onset

Back 60

3rd trimester

Front 61

Gestational thrombocytopenia - features.

Back 61

Thrombocytopenia, but not below 70. No risk to offspring. Normalizes post-partum by 6 weeks.

Front 62

ITP - timing of onset in pregnancy

Back 62

Anytime, common in 1st trimester

Front 63

ITP in pregnancy - risk of predisone

Back 63

First trimester - cleft palate

Front 64

ITP in pregnancy - risk to offspring

Back 64

10% will be thrombocytopenic, 5% will have plts < 20.

Front 65

ITP in pregnancy - management

Back 65

Delivery method based on obstetrical indications.
Monitor closely for development of ITP within first 4-7 days after delivery. All thrombocytopenic neonates should undergo cranial u/s (<1% cranial hemorrhage risk). IVIG for severely affected offspring.

Front 66

NAIT - management of neonate

Back 66

Daily CBC
U/S head
if Plts < 20, IVIG and maternal platelet transfusion
if ICH - IVIG/plts/steroids

Front 67

NAIT - management of subsequent pregnancies

Back 67

Fetal platelet count at 20-24 weeks, IVIG if fetal platelets <100, serial platelet transfusions if bleeding or platelets <20.

Front 68

VWD in pregnancy - trend in VWF

Back 68

Increases through 2nd trimester, peaks at term

Front 69

VWD in pregnancy - when to measure levels

Back 69

32 weeks

Front 70

VWD in pregnancy - management

Back 70

Type I - DDAVP 0.3 mcg/kg 1 hour prior to delivery then qdaily post-partum
Type III - humate P 25 u/Kg q12h at deliver then daily for 5-10 days.

Front 71

Gene involved in Gaucher's disease

Back 71

GBA1

Front 72

Most common mutation in Gaucher's disease in Ashkenazic Jews

Back 72

N370S

Front 73

Mutation in Gaucher's resulting in neuronopathic disease

Back 73

L444P

Front 74

Mechanism of neuronopathic disease in Gaucher's

Back 74

Neuronal inability to degrade glucosylceramide and glucosyl sphingosine which are neurotoxic. Neuronal dysfunction results in apoptosis and phagocytic signals for astroglial and microglial cells with primary loss of neurons and neuroinflammatory effects.

Front 75

What are the 8 porphyrias and the involved enzyme

Back 75

1. AIP - HMB synthase
2. HCP - Coproporphyrinogen oxidase
3. VP - Protoporphyrinogen oxidase
4. ADP - ALA dehydratase
5. PCT - Uroporphyrinogen decarboxylase
6. CEP - Uroporphyrinogen synthase
7. EPP - Ferrochelatase
8. XLP - ALAS2

Front 76

3 categories of porphyria

Back 76

Hepatic, hepatic/cutaneous, erythropoietic cutaneous

Front 77

Management of hepatic porphyrias

Back 77

AIP/HCP/VP/ADP
Symptomatic management, carbohydrate loading, hemin IV if glucose load fails

Front 78

HLH 2004 protocol contains which agents

Back 78

Dexamethasone, etoposide, cyclosporin +/- IT MTX.
Pts need prophylaxis with Septra DS, fluconazole, ranitidine

Front 79

PNH - gene mutation

Back 79

PIG-A, which affects GPI anchored membrane proteins

Front 80

Role of CD55

Back 80

Decay accelerating factor, an inhibitor of C3/C5 convertase

Front 81

Role of CD59

Back 81

Membrane Inhibitor of Reactive Lysis, inhibitor of MAC

Front 82

PNH - indications for eculizumab

Back 82

Symptomatic disease, transfusion dependance, thrombosis, end-organ complications

Front 83

Treatment of PCT

Back 83

1. Discontinue EtOH, OCP, iron.
2. Phlebotomize to decrease hepatic iron until ferritin <25 ng/ml.
3. Adjunctive therapy with chloroquine or hydroxychloroquine to mobilize excess porphyrins from liver to promote excretion.

Front 84

How does glucose load work in hepatic porphyrias

Back 84

Acts on PPAR gamma cofactor 1alpha which modulates ALAS1 activity.

Front 85

Chronic Idiopathic Neutropenia - features

Back 85

Mild neutropenia > 3 months, with ANC >1.5 in the absence of clinical, serologic, or ultrasound evidence of underlying disease associated with neutropenia.

Front 86

Drug induced neutropenia causes

Back 86

Anti-thyroid medications, ticlopidine, clozapine, sulfasalazine, trimethoprim-sulfamethoxazole, rituximab

Front 87

Cyclic neutropenia inheritance

Back 87

AD

Front 88

Cyclic neutropenia genetic cause

Back 88

Neutrophil elastase (ELANE)

Front 89

Cyclic neutropenia pattern

Back 89

Periods of severe neutropenia lasting for 4-6 days q21 days.

Front 90

Cyclic neutropenia investigations

Back 90

Serial CBC 3 times per week x minimum of 6 weeks to observe 2 nadirs.

Front 91

Severe congenital neutropenia features

Back 91

ANC <0.2 with recurrent severe infections in first few months of life. Autosomal dominant inheritance.

Front 92

Severe congenital neutropenia genetic cause

Back 92

ELANE

Front 93

Kostmann syndrome genetic cause

Back 93

Autosomal recessive, HAX1 gene

Front 94

Target ferritin in iron replacement

Back 94

50-100

Front 95

Targets for daily elemental iron for replacement

Back 95

150-200mg

Front 96

Options for oral iron replacement and elemental iron content

Back 96

Ferrous Fumarate 100mg per 300mg tab
Ferrous Sulfate 60mg per 300mg tab
Ferrous Gluconate 34mg per 300mg tab

Front 97

Options for IV iron replacement and elemental iron content

Back 97

Iron sucrose 20mg/ml
Iron dextran 50mg/ml

Front 98

Side effects of iron sucrose

Back 98

IV site irritation, fever, myalgias, arthralgias, nausea, diarrhea, H/A

Front 99

Side effects of iron dextran

Back 99

flushing, HA, urticaria, injection site reaction, anaphylaxis (0.7% of infusions), delayed reaction 1-2 days post infusion with fever, chills, backache, arthralgias.

Front 100

Calculation of iron dose to correct anemia

Back 100

1. Determine blood volume 65ml/kg
2. Determine Hb deficit in grams using 140 as normal
3. Determine iron deficit in grams using 3.3mg of elemental iron per g of Hb
4. Calculate volume of IV preparation needed 20mg/L in iron sucrose, 50mg/L in iron dextran.

Front 101

Dosing of iron sucrose

Back 101

Max 200mg per infusion three times per week.