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Flashcards in Heme Onc Deck (64):
1

Alpha Thal

Defect in alpha chain that leads to decreased production
-4 in total, 4 mutated leads to Hb Bartz and fetal hydrops
-3 mutated leads to B4 tetramers of HbH
-Cis mutations on same chromosome are more common in asians and transmutations are more common in blacks

2

Beta Thal

-Splicing or promotor error leads to altered expression level
-Minor usually presents with a slight increase in HbA2 (D) and major usually presents with profound anemia and increased fetal hemoglobin
-Can get secondary hemochromatosis and treat with difuimox

3

Lead Poisoning

-Leads to a sideroblatic anemia with increased Fe deposits in mitochondria
-Inhibits Ferrocheltase
-Basophilic stippling occurs because of dysfunction of An enzyme that degrades ribososmes, basophilic stipplic is ribosomal RNA
-Dementia, belly pain, decreased IQ
-Wrist drop and neurologic signs
-Treat with succimer, EDTA, dimercaperol

4

Sideroblastic anemia

-X linked is defect in ALA dehydratase which leads to decreased heme synthesis in mitochondria leading to Fe accumulation and sideroblastic anemia
-Can also be seen with B6 deficency as B6 is a necessary cofactor for HLA-D
-Decreased B6 from INH, Alcohol, dietary
-Treatment is B6
-There will be elevated Fe and Ferretin with normal TIBC

5

Folate Deficency

Caused by diet, MTX, phenytoin
-Megaloblastic with pancytopenia, no neurologic complaints
-Increased homocysteine with normal methylmalonic acid
-Glossitis

6

B12

Pernicous anemia, D lattum from fish, Crohns, PPI?
-Leads to megaloblastic anemia with neurologic dysfunction
-Elevated homocysteine and methylmalonic acid
-Involves posterior columns, spinocerebellar, and corticospinal
-May also cause dementia

7

Orotic Aciduri

-Impaired UDP synthase, backs up into urea cycle (Carbamoyl P)
-Doesn't correct with Folate and B12
-Give uridine to bypass enzyme

8

Macrocytosis without megaloblastosis

Think of liver or alcoholic
-Can also be due to drugs which cause reticulocytosis: 5-FU, AZT, hydroxyurea

9

Intravascular

Intrinsic red cell defect and lysis in vasculature, decreased haptoglobin and increased LDH
-PNH and mechanical valve

10

Extravascular

-Most commonly in spleen, stuctural or functional defect
-UCB emia, increased LDH, Jaundice

11

Anemia of chronic disease

Mediated by cytokines IL-6 that increases hepcidin from liver which is master regulator
-Also reduces EPO
-Increased ferretin with decreaed Fe and TIBC, sequester in tissues

12

Aplastic

Viral
-Drugs, Chemo, Radiation
-Fanconi's syndrome (DNA repair)

13

Spherocytosis

-Defect in anhyrin or spectrin leads to osmotic fragility (band 3)
-increased MCHC
-Overactive spleen that consumes RBC leadin to elevated UCB
-Aplastic crisis

14

G6PD

a

15

Pyruvate Kinase

Defect in glycolysis (PEP synthesis) leads to decreased ATP and fragility of red cells
-Hemolytic disease in newborns is common presentation

16

HbC

Milder than SS
-Add lysine instead of valine

17

PNH

-GPI to DAF leads to hemolysis comlpement mediated
-Increased risk of venous thromboembolus
-PE or Budd Chiari
-Diagnose with flow
-Is a mutation post zygotic, in HSPC

18

Sickle Cell

Gluatmine to valine
-Sickling at low Oxygen tensions
-Splenic sequestration crisis: Massive autoinfarcion of spleen leading to rapid decrease in RBC number
-EMH
Renal papillaryu necrosis

19

Warm Hemolytic Anemia

-IgG
-CLL, Lupus, Methyldopa
-Haptens like penicilin

20

Cold Hemolytic anemia

-CLL, M Pneumonia, Hepatitis, mono

21

Microangiopathic

HUS, TTP, DIC, SLE, Malignant HTN

22

OCP changes to Fe profile

-Increase binding globulins leading to decreased increased ferretin

23

AIP

-Defect in porphobilinogen deaminase, or uroporphyrin synthase
-Leads to increase in uroporphyrin and porphobilinogen
-Psychosis and red urine
-Brought on by drugs (phenobarbitol)
-AD in cytosol

24

PCT

-Skin hypersensitivity
-Uroporphyrin deaminase leads to tea colored urine and skin sens

25

Hemophilia A/B

defect in intrinsic cascade, factors 8 and 9
-Hemarthroses and increased PTT
-Significant bleeding
-XR

26

Vitamin K deficency

-Longterm antibiotics or pancreatic/malabsorption

27

Platelt defects

-Lead to purpura and mucosal bleeding (epistaxis)

28

Bernard Soulier

GP 1b impaired adhesion, increased BT
-Decreased platelt count

29

Glanzmans

GP2b3a impaired aggregation, increased BT. Normal platelt count

30

ITP

Antibody to Gp2b3a leading to consumption of platelts by spleen
-Leads to thrombocytopenia and increased megaK
-Bleeding time
-Commonly young viral

31

TTP

Defect is ADAMSTS13, which is MMP that cleaves vWF multimers
-Leads to increased vWF multimers that elads to abberant clotting and platelet consumpton
-microangiopathic hemolytic anemia and decreased palteltes
-Neurologic and renal symptoms

32

vWF defect

AD decrease in vWF number or function
-Leads to increased bleeding time
Dx with risotcetin assay
-Treat with DDVAP to increase release from WP bodies
-vWF also protects factor 8, so depending on severity, can decrease factor 8 levels and increase PTT
-Most common inherited bleeding disorder AD

33

Factor V lieden

Site on factor 5 can't be cleaved by protein C
-Activated by thrombomodulin and factor S
-Hypercoagulable

34

PT

-Noncoding region increases expression leading to hypercoag

35

ATIII

-Decreased levels will lead to hypercoag
-Blunted PT response to heparin

36

C/S def

Leads to hypercoag, can have skin necrosis with warfarin administration

37

Transfusions

-Can induce hyperkalemia due to lysed RBC or hypocalcemia due to citrate

38

Leukemoid Vs Leukemia

-Leukemoid will have classic left shift and will have luekocyte acid phosphatase
-Leukemia will not have LAP

39

Hodgkins

-Reed Sternberg cells CD15 and 30
-Involves a single group of nodes
-Constiutional B symptoms
-Greater than 50% arise in the context of EBV

40

Nonhodgkins

-Multiple nodes throughout body, don't involve Reed Sternberg cells,
-Commonly effect immunosuppressed
-majoirty are B cells and are monocellular

41

Reed Sternberg

-Larg bilobed/binucleate cells, positive for CD 15 and 30
-Secrete cytokines and attract a pleimorphic cell mixture

42

Hodgkins

-Younger and older
-Multiple cell type
-Nodular sclerosing is the most common and has large bands of fibrosus throughout nodes
-Lymphocyte mixed or depleted is a worse prognosis

43

Follicular Lymphoma

14:18 translocation
-14 is Ig and 18 is BCL-2
-LEads to lack of death, large germinal celnter appearing B cells that lack macrophages, can turn into DLBCL
-Most common

44

DLBCL

-Loss of normal cellular architecture and germinal center morphology
-USually the end of the road for other cancers
-Aggressive and worse prognosis

45

Burkitts

-t8:14, puts C-Myc onto IgHC gene region
-LEads to massive growth (Jaw/ABdomen) characterized by lots of macrophages and cellular death in starry sky backgound
-Is associated with EBV (Like hodgkins)

46

Mantle

t11:14
-Move cyclin D onto promotoer leads to overexpressiona dn increased rate of entry into S phase

47

Marginal Zone

-Occurs in the context of chronic inflammation
-H Pylori, Sjogrens, Hashimotos

48

Adult T Cell

Usually has cutaneous involvemtn
-Associated with HTLV-1 and seen most commonly in asians and carribeans

49

Szesary/Mycosis Fungoides

T cell lymphoma that has extensive skin involvment
-Normally can be treated
-Sezeary when enters blood and mycoces when confined to skin

50

Multiple Myeloma

-Leukemia of plasma cells that have a characteritic clock faced nuclei with nucleoli (Produce large ammounts of Ig) and have cytoplasmic inclusions of Ig
-Characterized by M spike of monoclonal Ig on SPEP
-Light chains are excreted into the blood in excess and cause AL amyloid throughout body and especially in kidney. Nephrotic syndrome that may progress to renal failure
-Lytic bone lesions lead to hypercalcemia
-Anemia and pancytopenia due to overdrowding of marrow space
-Increase susceptibility to infection, and is most common cause of death
-Elevated Ig secretion also puts a lot of positive charge and protein into the blodd that breaks the zeta potential between RBC and leads to roleaux formation
-Hyperviscosity also common

51

Waldenstroms

-M spike of IgM, lack of lytic lesions and other signs
-Increaed hyperviscosity syndrome

52

MGUS

-ELevated M spike that is IgG or IgA that does not have other findings consistent with MM

53

Leukemia

-INcrease in wWBC in the blood
-Major problem is a loss of normal marrow function leading to anemia and immunodeficency
-THere will also be hyperviscosity and decrease platelets that can lead to hemorrhage
-Acute is greater than 20 percent blasts
-THere will be no increase in LAP which is how you distingush from leukemoud reactin
-Also look for a monoclonal appearance of Differential

54

ALL

-Leukemia of immature B and T cells, B cells is most common
-Can be identigied with tdt positivity and CALLA
-Commonly seen in downs syndrome
-T ALL may present as a mediastinal mass in teenagers due to involvment of thymus
-If cells enter CNS and testes treatment becomes more difficult becase drugs can't cross BBB

55

SLL/CLL

-Mature naive lymphocytes that are enter blood or nodes
-SLL has more nodal involvment while CLL has more blood involvment
-SLL may progress to DLBCL
-CLL is noticed by the appearance of smudge cells on a smear
-Increase risk of warm and cold agglutanins due to naive mature cells
-hypogammaglobulinemia and increased risk of infection
-Seen very comonly in older patients, and is indolent unless transformes to other kinds.

56

Hairy Cell

-TRAP positive mature B lymphocytes
-HAve characteristic cytoplasmic extensions
-Treat with clarbarapine, which is an adenosine analog that leads to toxic accumulation and cell death
-Can get a dry tap on marrow aspirate and will see increased EMH and HSM

57

AML

-Acute leukemia with an increased number of blasts, greater than 20 percent
-Many subtypes and distinguished with presence of auer rods which are crystalized MPO, if these cells are ruptured can activate compliment cascade and leads to DIC
-M3 or APL is famous, has 15,17 translocation involving the ATRA receptor. Immautre cells that if treated with ATRA will mature and can be cured
-Can be a consequence of myelodysplastic syndromes
-Monocytes commonly infiltrate gums

58

CML

-Characterized by 9:22 translocation of BCR to ABL
-Treated with imatinib inhibitor of ABL
-Type of myelodysplasia, distinguish from a leukemoid reaction using LAP and also with the presence of basophils and other types of cells
-Immunodeficecny is the biggest risk
-Also can transform to AML

59

Langerhans Cell histiocytosis

-Langerhans cell tumor,
-involves skin and characteristic bierbeck granules
-S-100 positive (neural crest marker) also CD1a positive
-also can have lytic bone lesions

60

Myelodysplasia

-Characterized by JAK-2 mutations
-Increase in all cells and the disease is named for the most prominent one

61

Polycythemia Vera

-Myelodysplasia of RBC leads to increase in hematocrit
-OFten presents as pruritis folling shower, increased mast cell activation
-Hyperviscosity syndromes with blurry visiona dn headache, can also get budd chiari
-JAK 2 mutation is characteristic, needs phlebtemy

62

THrombocytosis

-Seen commonly in downs patients
-Is myelodysplasia of thrombocytes (MEgaK)
-Generaly has JAK-2 mutation
-Rarely transforms to malognancy becaue thrombocytes are anucleate

63

Myelofibrosis

-Burnout of marrow, fibrosis leads to teardrop cells
-See increased levels of EMH and HSM

64

PV causes

-Loss of volume leads to concentration of RBC
-PHysiologic adaptations to low oxygen (heart failure, lung diease, shunts)
-EPO producing tumors: RCC, HCC, VHL, Hydronephrosis and renal disease, wilms