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Heme & Onco > HemePath > Flashcards

HemePath Flashcards

1
Q

Hemophilia

CF:
Tx:

A

Hemophilia

Type: def factor
A: VIII
B: IX
C: XI

  • hemarthroses, easy bruising, inc bleeding after trauma/ surgery
  • Tx: Desmopressin c resp factor concentrate
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2
Q

Acanthocytes/ spur cells

A

Liver disease

A betalipoprotenemia

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3
Q

Echinocytes/ burr cells

A

ESRD
Pyruvate kinase def
Liver disease

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4
Q

Dacrocytes/ tear drop cells

A

Bone marry infiltration, Myelofibrosis

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5
Q

Schistocytes/ helmet cells

A

Dx for traumatic mech

Microangiopathic:
DIC
TTP/HUS
HELLP

Microangiopathic anemia
mechanical hemolysis: prosthetic heart valves & Aortic stenosis

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6
Q

Degmacytes/ bite cells

A

G6PD def

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7
Q

Spectrum mutation

A

RBC memb protein gene

Hereditary elliptocytosis

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8
Q

Macro-ovalocytes

A

Megaoblastic anemia

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9
Q

Target cells

A

HALT

HbC
Asplenia
Liver diseases
Thalassemia

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10
Q

Ringed sideroblasts

A

Sideroblastic anemia:
Lead poisoning
Myelodysplastic syndrome
Alcoholism

MAL

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11
Q

Howell-Jolly bodies

A

Hyposplenia (SCA)
Asplenia

Basophillic nuclear remnants: no iron

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12
Q

Basophillic stippling

A

Sideroblastic anemia
Thalassemia

Basophillic ribosomal ppt: no iron

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13
Q

Pappenheimer bodies

A

Sideroblastic anemia

Basophillic granules: IRON

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14
Q

Heinz bodies

Stain?

A

G6PD def

+iron

Crystal violet stain

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15
Q

Anaemia classification

A

Normocytic : MCV 80-100 fL — Hemolytic & non-hemolytic

Microcytic: MCV <80 fL — TAIL

Macrocytic: MCV >100 fL — Megaloblastic & Non-megaloblastic

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16
Q

Corrected Reticulocyte count / Reticulocyte Index

A

RI = reticulocyte% x actual/ normal Hct

N Hct ~ 45%

  • measure of BM response to anemia
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17
Q

Microcytic anaemia

A

TAIL

Thalassemia
ACD
Iron def anemia
Lead poisoning

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18
Q

Iron def anaemia labs

A 
Iron: dec
TIBC: inc 
Ferretin: dec
RDW: inc
RI: dec
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19
Q

Normocytic non-hemolytic anaemia

A

Dec RI

Early iron def anemia
Anemia of chronic disease
Aplastic anemia
Chronic kidney disease

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20
Q

Normocytic hemolytic anemia : intrinsic

A
  • Membrane defects: Hereditary spherocytosis Paroxysmal nocturnal hemoglobinuria
  • Enzyme deficiencies
    G6PD deficiency
    Pyruvate kinase deficiency
  • Hemoglobinopathies
    Sickle cell anemia
    HbC disease
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21
Q

Normocytic hemolytic anemia: extrinsic

A

Autoimmune
Microangiopathic
Macroangiopathic
Infections

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22
Q

Macrocytic megaloblastic anaemia

A
  • Defective DNA synthesis
    Folate deficiency
    Vitamin B12 deficiency
    Orotic aciduria
  • Defective DNA repair
    Fanconi anemia
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23
Q

Macrocytic non-megaloblastic anaemia

A

Diamond-Blackfan anemia
Liver disease
Alcoholism

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24
Q

Lead poisoning

  • Path
  • Sx
  • Tx
A
  • ferochelatase & ALA synth inhib
  • LEAD
    Lead/ Burton lines on gingivae & long bones
    Encephalopathy & Erupythrocytic basophillic stippling
    Abd colic & Sideroblastic Anaemia
    Drop— wrist & foot drop
  • I line: Dimercaprol & EDTA
    Chelation in kids: Succimer
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25
Q

Sideroblastic anaemia

  • Etiology
  • Inheritsnce
  • RF
  • Labs
  • Tx
A
  • ALA synth gene defect
  • XL
  • Alcohol. Lead poisoning. B6 def. Cu def. Drugs ISONIAZID, LINEZOLID
  • iron : inc.
    TIBC: dec
    Ferretin: inc
    Ringed Sideroblasts
  • Pyridoxine, B6
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26
Q

Alpha-Thal

Genetics

A

Alpha globin gene deletion on chrom 16

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27
Q

Alpha-Thal variants

A

aa/a- : a-Thal minima
a-/a- : a-Thal minor, cis. (mild anaemia)
aa/- - : a-Thal minor, trans
- -/-a : HbH (beta4)
- -/ - - : Hb Barts (gamma4). (Hydrops Fetalis)

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28
Q

Beta-Thalassemia genetics

A

Point mutations on splice sites & promoter seq

Chrom 11

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29
Q

Beta-Thalassemia variants

A
  1. B-minor: dec beta chain production.
    - inc HbA2
  2. B-major: beta chain absent
    - inc HbF, HbA2
    - crew-cut app & chipmunk facies
    - inc risk of Aplastic anemia (ParvoB19)
  3. B-Thal heterozygous/ HbS
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30
Q

Anemia of chronic diseases

Labs

A

Hepcidin: inc

Iron: dec
TIBC: dec
Ferretin: inc

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31
Q

PNH

Genetics:
CF:
Dx:
Tx:

A

Genetics: PIGA gene mutation > dec CD55/DAF—CD59 meadiated complement inhib > inc RBC lysis

CF: Pancytopenia, hematuria in the morning

Dx: Coombs -

Tx: Eculizumab (against C5)

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32
Q

G6PD def

Genetics:
Etiology:
CF:
Labs:

A

Genetics: XLR

Etiology: DSixP - Dapsone, Sulfa drugs, Primaquine, Fava beans

CF: back pain, hemoglobinuria

Labs: Heinz bodies & Bite cells

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33
Q

Macrocytic anemia causes

SE drugs

A 
PMSH
Phenytoin 
Methotrexate
Sulfa drugs
Hydroxyurea
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34
Q

Triphalangeal thumbs w Rapid-onset Ana is within 1st year of life

A

Diamond-Blackfan anemia

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35
Q

RBC memb protein defects

A

Hereditary Spherocytosis

-ankyrin, band, spectrin,

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36
Q

Hereditary Spherocytosis

Genetics:
Etiology:
CF:
Labs:

A

Genetics: AD

Etiology: RBC memb defect (spectrin, ankyrin, band)

CF: spleenomeg, aplastic crisis, extravasc hemolysis

Labs: inc osmotic fragility test. Inc MCHC. N/dec MCV

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37
Q

Hemolytic anemia in newborn

A

Pyruvate kinase def

AR

In 2,3 BPG

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38
Q

Point mutation in beta-globin gene

A

SCA

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39
Q

Salmonella osteomyelitis complication of

A

Sickle cell crisis

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40
Q

SCA labs

A

Dec HbA
Inc HbS
Inc HbF

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41
Q

Glutamic acid got lysine mutation in beta-globin chain

A

HbC

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42
Q

Direct Coombs test

A

Anti-IgG (Coombs reagent) + pt RBC

+ve if RBC coated w Ig agglutinate

-ve if no agglutination

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43
Q

Indirect Coombs test

A

Pt serum + normal RBC

+ve if serum has anti-RBC surface Ig & agglutinates

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44
Q

AIHA

Types:
CF:
Dx:
Tx:

A

Coombs+

Warm: IgG mediated aRBC agglutination & alpha-Methyldopa

Cold: IgM mediated RBC agglutination. Blue fingers & toes.
Seen in CML, M.pneumonia, Mononucleosis

Tx: Rituximab

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45
Q

Malaria, Babesia

A

Extrinsic hemolytic anemia

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46
Q

HSR against plasma proteins in transfused blood

A

MC IgA deficient pts w anti IgA ab

Type I

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47
Q

Fever, chills, dec BP, chest/back pain & hemoglobinuria following a blood transfusion

A

HSR type II
Acute hemolytic transfusion reaction

  • complement mediated cell lysis
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48
Q

Vascular deposits of immune complex

A

HSR type III

SLE, RA

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49
Q

Pre-existing ab that bind antigens & activate complement, see in?

A

Type II HSR

ABO incompatibility
Acute hemolytic transfusion reaction

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50
Q

Head & neck cancer spread to?

A

Ant cervical/ Jugular LN

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51
Q

JAK2 mutation

A

Polycythemia Vera

  • clinal prolif of erythrocytes : inc Hct
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52
Q

Glycoprotein produced by peritibular fibroblasts in renal cells

A

EPO

  • only in response to hypoxia
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53
Q

High-volume blood transfusion (>9 units/hr) complications

A

Hypocalcemia (d/t Ca2+ chelation by citrate anticoagulant in stored blood. Also occurrs in low transfusion in liver diseases since citrate metabolized by liver)

Dec coagulation factors

Vol overload

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54
Q

Blood transfusion reactions & electrolyte abn

Hypercalcemia:
Hyperkalemia:

A

Hypercalcemia: rapid blood transfusion (d/t Ca2+ chelation by citrate anticoagulant)

Hyperkalemia: ABO incompatibility ( release of intracellular K)

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55
Q

SE of synthetic EPO

Epoetin, Darbepoetin

A

Iron def anaemia d/t inc RBC production & rapid iron depletion

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56
Q

Hb switched to fetal form in?

A

Hydroxyurea Tx in SCA since HbF unaffected by sickling

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57
Q

What improves nuclear maturation

A

B9 & B12

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58
Q

Tumor lysis syndrome electrolytes

A

Inc K,
Inc PO4
Inc uric acid
Inc Lactate dehydrogenase

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59
Q

MC & fatal presentation of neonatal Vit K def

A

Inc intracranial P d/t intracranial hemorrhage

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60
Q

Polypeptide regulator of iron hemostasis

Synth by?

A

Hepcidin, liver

61
Q

Hepcidin

Release:
Inhibition:

A

Inc synth d/t: inc iron levels & inflamm

Dec synth d/t: hypoxia, inc erythropoesis

62
Q

Neutropenia

A

Absolute neutrophil count <1500cells / mm3

63
Q

Corticosteroid

Inflamm response pathogenesis

A

Neutrophilia (d/t dec activation of neutrophil adhesion molecules, dec migration out of blood to sites on inflamm: dec inflamm response)

Eosinopena & lymphopenia (inc sequestration of eosinophils in LN & apoptosis of lymphocytes)

64
Q

Leukoerythroblastic shift

A

Left shit

Inc immature cells

Seen in anemia (physiologic), fibrosis & BM tumors

65
Q

Heme synth disorders

A

Enzyme: disease

ALA synth : Sideroblastic anemia

ALA dehydratase : lead poisoning

Porphobilinogen deaminase: AIP

Uroporphyrinogen decarboxylase : PCT

66
Q

MC porphyria

RF:
Etiology:
CF:
Tx:

A

PCT

  • exacerbated by alcohol
  • Hep C
  • TEA-COLOURED URINE. blistering, photosensitivity, hyperpigmentation
  • avoid sun, phlebotomy, Hydroxychloroquine
67
Q

vWF def

  • labs
  • CF
  • Tx
A

Platelet count : N
Ristocetin cofactor assay : abn
Factor VIII def
PTT inc

Menorrhagia, gingival bleeding

OCP, Desmopressin

68
Q

VWF def vs Bernard-Soulier syndrome

Labs

A

N plasma + pt plasma + ristocetin

= agglutination in vWF def

= no agglutination in BSS since GpIb R deficient

69
Q

Def of GpIb receptors

CF:
Tx:

A

Bernard-Soulier Syndrome

Thrombocytopenia, enlarged platelets, mucocut bleeding

70
Q

Def of GpIIb/IIIa receptors

CF:
Tx:

A

Glanzmann thrombasthenia

Mucocut bleeding

71
Q

Hageman (XII) factor def

A

Inc PTT

thromboemboli

72
Q

Meds causing Sideroblastic anemia

A

LIC
LINEZOLID
Isoniazid (inhib pyridoxine phosphokinase: B6 to Pyridoxal 5’po4, cofactor for d-ALA synth)
Chloramphenicol

73
Q

Heme metab

A

Heme -heme oxygenase- Biliverdin -biliverdin reductase- Unconj bilirubin -bilirubin glucoronyl transf- Conj bilirubin -Bact dehydrogenase- Urobilinogen — stercobilinogen

74
Q

SCA pathogenesis

A

glu → val substitution : formation of a hydrophobic pocket on the beta globin surface that interacts with a complementary nonpolar residue on another hemoglobin molecule : causes polymerization of HbS molecules and subsequent erythrocyte sickling : membrane damage and permanent distortion of red blood cells.

Red cell sickling is promoted by low oxygen levels, increased acidity, and dehydration.

75
Q

HbC pathogenesis

A

glu → lys

basic polar (positively charged) lysine (lys) residue. Because lys is charged (although it has opposite polarity to glu), there is no hydrophobic interaction between hemoglobin molecules and no polymerization/sickling.

76
Q

Anti GpIIb/IIIa Ab

Etiology:
Labs:
Tx:

A

Immune thrombocytopenia

Seen in SLE, HIV, HCV, CLL

Inc megakaryocytes

  • steroids, Rituximab, Eltrombopag, Romiplostim, IVIG
77
Q

Inhib/ def of ADAMTS13

Pathogen:
CF:
Labs:
Tx:

A
  • mostly females.
    vWF metalloprorease
    Inc platelet aggregation n thrombi formation
  • Triad: thrombocytopenia, Microangiopathic HA, acute kidney injury + fever + neurological Sx
  • N PT & PTT.
    Platelets dec
    Hb dec, LDH inc, Schistiocytes
    Creatinine inc
  • Rituximab. Plasmapheresis. Steroids.
78
Q

HUS

Epi:
Pathogen: 
CF:
Labs:
Tx:
A

Children

  • shiga ~ toxin, EHEC O157:H7
  • thrombocytopenia, microangiopathic HA, acute kidney injury + bloody diarrhea
  • N PT & PTT.
    Platelets dec
    Hb dec, LDH inc, Schistiocytes
    Creatinine inc
  • supportive care
79
Q

Multiple myeloma

Pathogen:
CF:
Labs:

A

Pathogen:
plasma cells into BM - dec hematopoesis. Dec B cell n plasma cells

CF:
inc bact infections. Bone pain. Renal insufficiency

Labs: 
Normocytic anemia (ineffective erythropoesis). Hypercalcemia.
80
Q

Hb -bound- 2,3 DPG

A

N

Dec O2 affinity for Hb : more O2 release in peripheral tissues

81
Q

Beta-globing mutation causing dec 2,3BPG binding

A

Familial erythrocytosis

82
Q

Hemophilia inheritance

A

XLR

Given phenotypically normal parents, the probability that a female sibling of a male affected by an X-linked recessive disease will give birth to an affected child is 1/8.

83
Q

Sickling promoted by.

A

Dec O2
Dec blood vol
Inc blood pH

Organs w inc metabolic demand promote sickling by extracting more O2 from the blood (O2 unloading)

84
Q

Methemoglobin induced as a Tx for

A

Cyanide poisoning

Amyloid nitrite induces MethHb since it binds CN & prevents CN from binding to cytochrome c in ETC

85
Q

Cyanide poisoning antidotes

A

Amyl nitrite
Hydrocobalamin
NaThisulphate

86
Q

UROD def

Uroporphyrinogen decarboxylase

A

Porphyria cutanea tarda

87
Q

RF Porphyria CT

A 
Alcohol
Smoking
Halogen HC
HCV
HIV
88
Q

+ve Coombs test

A

Autoimmune hemolytic anemia

HDF/N

89
Q

t(8:14)

A

Burkitt

Cmyc (8) oncogene

8: 2 (kappa light chain)
8: 14
8: 22 (lambda light chain)

90
Q

t(9:22)

A

CML

BCR-ABL

91
Q

t(11:14)

A

Mantle cell

Cyclin D

92
Q

13q deletion

A

CLL

93
Q

t(14:18)

A

Follicular lymphoma

Bcl2 (B-cell lymphoma2) 18 to 14, Ig heavy chain

Bcl2: anti-apoptotic
- over expression causes immortality

94
Q

t(15:17)

A

APML

RAR-a,17 / PML, chrom 15

95
Q

Hematogenous ca spread

A

Sarcoma
RCC
HCC

96
Q

Perineural ca spread

A

Pancreatic ductal adenoca

Prostate

97
Q

Transcoelomic ca spread

A

Ovarian

98
Q

Diffuse large B cell lymphoma

A 
#MC NHL
rapidly enlarging mediastinal/ neck/ abd mass
#mc involves oropharyngeal lymphoid or GIT
  • B : fever, wt loss, night sweats
99
Q 
#MC NHL
2#MC NHL
A

Diffuse large B cell

Follicular

100
Q

MC leukemia in children

A

ALL

101
Q

Spleenomeg + pancytopenia in older men

A

Hairy-cell leukemia

102
Q

Hypophosphorylated Rb

(f)

Mutation

A

Active. Tumor suppressor gene.

13q14

regulates the G1→S checkpoint n stops it : does no let damaged DNA to proceed

- mutations:
Retinoblastoma
Osteosarcoma 
Breast Adenoca 
Small cell lung ca
Bladder ca
103
Q

Molecular policeman

A

P53

Induced of apoptosis

104
Q

BRCA1 n BRCA2 mutation

A

Breast n ovarian ca

106
Q

MCC anemia in elderly on antacids

A

Megaloblastic d/t B12 def

107
Q

Replacement of BM w fat cells

A

Aplastic anemia

RF: toxic chemicals- industrial solvents/ chemicals, insecticides

108
Q

Replacement of BM w fibrosis

A

Myelofibrosis

Dacrocytes / tear drop cells

109
Q

Inc nuclear-cytoplasmic ratio

A

Slow nuclear division
Inc cytoplasmic maturation

Cells w inc replication rate

110
Q

AIHA etiology

A

M.pneumoniae
EBV

Abx against RBC

111
Q

Inc PTT

A 
Hemophilia A (factor VIII def)
Heparin
112
Q

Inc Bleeding time

A

Uremia/ ESRD

113
Q

Inc aPTT n BT

A 
VWF def 
Platelet dys(f): inc BT
dec factor VIII: inc PTT
114
Q

Inc PT, PTT , BT

A

DIC

115
Q

Inc PT, PTT

A

Warfarin

PT&raquo_space; PTT

116
Q

Over expr/amplification of genes causing mutation

A

Proto-oncogenes

KRAS: colorectal ca
ABL
BRAF
HER1
Erb B2/ HER2/ neu
MYC
RAS
SIS
TFGA
117
Q

Large irreg lymphocyte w abundant cytoplasm

A

EBV

118
Q

Dry tap + spleenomeg in mid-aged men

Dx?

A

Hairy cell leukemia
Infiltrates BM n RES

TRAP+ve (older test)

Dx: flow cytometry

119
Q

Loss of (f) mutation genes

A

Tumor-suppressor/ anti-oncogenes

APC/ b-catenin 
BRCA1, 2 (DNA repair)
RB (G1–S checkpoint)
TP53
DCC
NF1
VHL
WT1
120
Q

Hemolytic anemia, hypercoag, pancytopenia

Dx?

A

PNH

121
Q

Neck swelling w epistaxis n headaches

A

Nasopharyngeal ca

Pre-malignant lesion transformed to malignant d/t oncogenic viral proteins expressed by EBV

122
Q

MCC HNSCC in young non smokers

A

HPV

123
Q

Keratin pearls

A

Irreg foci of keratinization

HNSCC

124
Q

Hemolytic anemia periph blood smear

A
  1. Inc Reticulocytes : large, immature RBC d/t ribosomes
  2. Spherocytes: reduced cell memb w dec surface area : partially phagocytized
  3. Nucleated erythrocytes: immature
125
Q

Construction worker w microcytic anemia, comstipation, neurological changes,

A

Lead poisoning

Basophillic stippling

126
Q

Ringed Sideroblasts vs basophillic stippling

A

RS:
Bone marrow
Ppt of iron granules in dev RBC

BS:
periph blood
Ribosomal aggregation

127
Q

Neutrophils in different stages of maturation seen in?

A

CML

BCR-ABL
Philadelphia chromosome

128
Q

Pure red cell aplasia

A

Dec RBC production d/t inhib of precursor by IgG autoab or cytotoxic T lymphocytes

Seen in thymoma, lymphocytic leukemia, Parvovirus

129
Q

Missense mutation in beta-globin

A

SCA

130
Q

Direct polymerizarion inhib in SCA by?

A

Voxelotor

131
Q

What metabolizes pro-carcinogens?

A

CyP450 monooxygenase

132
Q

Child, mucocut bleeding

+ no platelet clumping

A

Adhesion defect d/t defective GpIIb/IIIa R on platelet surface

Glanzmann trombasthenia

Tx: Abciximab

133
Q

New onset neurological Sx + anemia w Schistiocytes + thrombocytopenia + acute kidney injury
Dx?

A

TTP

134
Q

Elderly w osteolytic lesions, inc Ca2+ , anemia, acute kidney injury

CDx?

A

Multiple myeloma

Dx: light chain in urine electrophoresis

135
Q

JAK2 mutation

A

Cytoplasm is tyrosine kinase : clonal prolif of myeloid cells

Polycythemia Vera

136
Q

MC malignancy of childhood

A

T-ALL

Mediastinal mass

137
Q

Stacked-coin agglutination in periph blood

A

Rouleaux formation

D/t inc circulating proteins which disrupt the electrostatic charge on RBC n cause aggregation

  • seen in infection, RA, Multiple myeloma. Waldenstrom macroglobulinemia (inc paraproteins/ immunoglobulins)
138
Q

Age-related changes in hematopoietic stem cells

A
  1. Inc fat n dec mass of bone marrow
  2. Dec response to stimulators cytokines : limited gen of new cells in resp to stress
  3. Dec cytokine signaling n cellular BM composition : dec gen of new cells in response to blood loss or hypoxia
  4. Inc medullary size d/t loss of endosteal cortica bone : inc # risk
139
Q

Erythrocytosis

Polycythemia DDx

A
  1. RBC mass
    - Inc in Absolute erythrocytosis
    - N mass in Relative
  2. EPO
    - Dec in 1° erythrocytosis: Polycythemia Vera
    - inc in 2° d/t chronic hypoxia, smoking, COPD, abn secretion
  3. SaO2 + PaO2
    <92% + <65% in 2°
140
Q

Polycythemia classification

A
  1. Absolute (true inc in RBC mass)
    i. Polycythemia Vera
    ii. 1° erythrocytosis (low EPO)
    iii. 2° erythrocytosis : inc EPO d/t hypoxia (SaO2<92% or PAO2 <65 mmHg) or abn secretion by neoplastic / other tissues
  2. Relative (N RBC mass)
    - dehydration, excessive diuresis
141
Q

HbA 93%
HbF 2%
HbA2 5%

Dx?

A

Beta-thal minor

142
Q

MC NHL in adults

A

Follicular lymphoma

143
Q

Intra erythrocytic rings seen in

A

Malaria

144
Q

Lymphocytes w cytoplasmic projections

A

Hairy cell leukemia

145
Q

Abn retinoic acid receptor seen in?

A

AMPL/ AML M3

PML/RAR-a fusion
t(17:15)

Auer rods

146
Q

Paraneoplastic inc in EPO seen w?

A

» Paraneoplastic Rise to High Hct Levels «

  1. Pheochromocytoma
  2. RCC
  3. HCC
  4. Hemangioblastoma
  5. Lymphoma
147
Q

Paraneoplastic Marantic endocarditis seen w?

A

Marantic/ Nonbacterial endocarditis d/t Pancreatic adenoca

148
Q

Paraneoplastic inc in EPO seen w?

A

» Paraneoplastic Rise to High Hct Levels «

  1. Pheochromocytoma
  2. RCC
  3. HCC
  4. Hemangioblastoma
  5. Lymphoma
149
Q

Paraneoplastic Marantic endocarditis seen w?

A

Marantic/ Nonbacterial endocarditis d/t Pancreatic adenoca

Heme & Onco (5 decks)

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