Hematology/Oncology Flashcards Preview

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Flashcards in Hematology/Oncology Deck (223):
1

Lifespan of erythrocyte

120 days

2

Anisocytosis

Varying sizes

3

Poikilocytosis

Varying shapes

4

Erythrocytosis

Polycythemia = ↑ Hematocrit

5

Reticulocyte

Immature erythrocyte marker of erythroid proliferation

6

Platelet
Derived from...
What do they contain
Storage

Derived from Megakaryocytes
Dense granules (ADP, Ca) and α granules (vWF, fibrinogen)
1/3 stored in spleen

7

Results of Thrombocytopenia or Platelet Dysfunction

Petechiae

8

vWF receptor

GpIb

9

Fibrinogen receptor

GpIIb/IIIa

10

Leukocyte
Subtypes
Normal range

Granulocytes (Neutrophils, Eosinophils, Basophils)
Mononuclear cells (Monocytes, Lymphocytes)
4000-10000

11

WBC differential

"Neutrophils Like Making Everything Better"
Neutrophils (60%)
Lymphocytes (30%)
Monocytes (7%)
Eosinophils (2%)
Basophils (

12

Neutrophil
Increased in what state?
Function
Histo
Granules

Bacterial infection
Phagocytic
Multilobed nucleus
Small numerous specific granules (ALP, Collagenase, Lysozyme, Lactoferrin)
Larger less numerous Azurophilic granules are lysosomes (Acid phosphatase, Peroxidase, β-glucuronidase)

13

Hypersegmented polys
Histo
Seen in

5 or more lobes
VitB12/Folate Deficiency

14

Increased Band Cells
What are they?
What do they reflect?

Immature Neutrophils
Increased myeloid proliferation (bacterial infection or CML)

15

Monocyte
Where do they exist?
What does it differentiate into?
Histo

In blood
Macrophages in tissue
Large, kidney shaped nucleus with extensive frosted glass cyto

16

Macrophage
Function
Lifespan
What activates them?
Marker

Phagocytosis, APC via MHCII
Long life in tissues
Activated by γ-Interferon
CD14

17

Eosinophil
Function
Histo
What does it produce?

Defends again helminthic infections. Phagocytic for Ag-Ab complex
Bilobate nucleus. Large eosinophilic granules
Produce Histaminase and Arylsulfatase to limit reaction following mast cell degranulation

18

Causes of eosinophilia

"NAACP"
Neoplastic, Asthma, Allergy, Collagen vascular disease, Parasites

19

Basophil
Function
Histo with function

Mediates allergic reactions
Basophilic granules with heparin (anticoagulant), Histamine (vasodilator), and Leukotrienes (LTD4)

20

Mast Cells
Function
Histo
Physiology
Molecules it releases
What type of reaction is it involved with?
Inhibition?

Allergic reactions in local tissue
Resemble basophils
Can bind Fc portion of IgE to membrane. IgE cross-links upon Ag binding --> degranulation
Releases Histamine, Heparin, Eosinophil chemotactic factors
Type I hypersensitivity reaction
Cromolyn prevents degranulation

21

Dendritic cells
Function
Role Re Immune systems
Expresses...
In skin they are called

Phagocytic APC
Link between innate and adaptive immune systems
MHCII and Fc receptor
Langerhans cells in skin

22

Lymphocyte
Mediates what kind of immunity
Subtypes
Histo

Adaptive immunity
B and T cells
Densely stained nucleus with small amount of cytoplasm

23

B Lymphocyte
What kind of immune response?
Where does it arise from?
Where does it mature?
Where does it migrate to?
What does it differentiate into?
Function
MHC
Markers

Humoral response
Bone marrow
Bone marrow
Migrates to peripheral lymphoid tissues (follicles of lymph nodes, white pulp of spleen, unencapsulated lymphoid tissue)
When encounters Ag, differentiates into Ab producing plasma cell and memory cells
APC via MHCII
CD19 and CD20

24

Plasma Cell
Function
Histo
Pathology

Ab production
Off center nucleus, clock face chromatin, RER, well developed Golgi
Multiple Myeloma

25

T Lymphocyte
What kind of immune response?
Where does it arise from?
Where does it mature?
What does it differentiate into?
Surface marker
Percentage of circulating lymphocytes

Cellular immune response
Bone marrow
Thymus
Tc cells (CD8), Th (CD4), Treg (CD28)
CD3
80%

26

Blood group A

A Ag and B Ab

27

Blood group B

B Ag and A Ab

28

Blood group AB

A and B Ag. No Abs
Universal Recipient of RBCs
Universal Donor of Plasma

29

Blood group O

No Ag. A and B Abs
Universal donor of RBCs
Universal Recipient of Plasma

30

Rh factor

Ag on RBC surface

31

Erythroblastosis Fetalis
PathoPhys
Treatment

Rh- mother exposed to fetal Rh+ blood. Mother makes anti-Rh IgG that crosses placenta and causes hemolytic disease in the next fetus
Rho (D) immune globulin for mother at first delivery to prevent initial sensitization of Rh- mother to Rh Ag

32

Blood groups Re crossing placenta

anti A and anti B IgM does not cross placenta
anti Rh IgG does cross the placenta

33

Intrinsic Coagulation Pathway

Collagen, Basement membrane, Activated platelets, or HMWK --> XII --> XI --> IX
IX + VIII --> X
XII --> Kallikrein

34

Extrinsic Coagulation Pathway

Thromboplastin (tissue factor) --> VII --> X

35

Common Coagulation Pathway

X + V --> II (thrombin) --> Fibrin
XIII (fibrin stabilizing factor) helps stabilize fibrin mesh
Thrombin also activates V, VIII, XIII

36

Kinin Cascade

Kallikrein thurs HMWK into Bradykinin
Bradykinin ↑ Vasodilation, Permeability, and Pain

37

Fibrinolytic System

XII --> Kallikrein --> Plasmin --> Fibrin mesh degradation
Plasmin also activates C3

38

Which reactions of the coagulation cascade require Ca and Phospholipids

XIa --> IX
VII --> VIIa
VIIa and (IXa + VIIIa) activation of X
Xa + Va activation of II

39

Hemophilia A

Deficiency in VIII

40

Hemophilia B

Deficiency of IX

41

VitK Pathway

Oxidized VitK --> [epoxide reductase] --> Reduced VitK
Reduced VitK is a cofactor for the maturation of II, VII, IX, X, C, and S

42

Warfarin
MoA

Inhibits Epoxide Reductase

43

Why are neonates given VitK?

They lack enteric bacteria that produce VitK

44

What does vWF do?

Carries/protects VIII

45

Anticoagulation cascade

Thrombomodulin on endothelial cells --> Protein C
C + S cleaves and inactivates Va and VIIIa

46

What does antithrombin do?

Inhibits activated forms of II, VII, IX, X, XI, XII

47

Function of Heparin

Activates Antithrombin

48

Factor V Leiden mutation
Classical presentation

Factor V resistant to inhibition by protein C
DVT --> PE

49

tPA

Thrombolytic that activates plasmin

50

Platelet Plug Formation Schematic

Injury: vWF binds exposed collagen upon endothelial damage
Adhesion: Platelets bind vWF via Gp1b and release Ca and ADP.
Activation: ADP binding induces GpIIb/ IIIa expression on platelet surface --> aggregation

51

How does ADP affect coagulation

Released by platelets.
Helps platelets adhere to endothelium and induces platelets to express GpIIb/IIIa at platelet surface

52

Platelet Aggregation Pathway

Fibrinogen binds GpIIb/IIIa and links platelets

53

Pro Platelet Aggregation Factors

TXA2 (released by platelets), ↓ blood flow, ↑ platelet aggregation

54

Anti Platelet Aggregation Factors

PGI2 and NO (released by endothelial cells)
↑ blood flow
↓ platelet aggregation

55

Ticlopidine

Inhibits ADP induced expression of GpIIb/IIIa
Causes Neutropenia, Oral Ulcers, Fever

56

Clopidogrel

Inhibits ADP induced expression of GpIIb/IIIa

57

Abciximab

Inhibits GpIIb/IIIa directly

58

ESR
What causes it to increase?
↑ ESR
↓ ESR

Acute phase reactants in plasma (Fibrinogen) cause RBC aggregation and ↑ ESR
↑: Infection, Autoimmune, Malignancy, Pregnancy
↓: "CHaMP"
Polycythemia, Sickle Cell Anemia, CHF, Microcytosis, Hypofibrinogenemia

59

Acanthocyte

Spur cell indicative of Liver disease or Abetalipoproteinemia (cholesterol dysregulation)

60

Basophilic Stippling

"BASte the ox TAiL"
Thalassemias, Anemia of chronic disease, Lead Poisoning

61

Bite Cell

G6PD deficiency

62

Eliptocyte

Hereditary Elliptocytosis

63

Macro-Ovalocyte

Megaloblastic anemia (w/ hypersegmented polys) and Marrow failure

64

Ringed Siderblasts

Sideroblastic anemia
Excess Fe in Mito

65

Schistocyte

Helmet Cell
DIC, TTP/HUS, Traumatic Hemolysis (metal heart valve prosthesis)

66

Sickle Cell

Sickle Cell Anemia

67

Spherocyte

Hereditary spherocytosis, Autoimmune hemolysis

68

Teardrop cell

"RBC sheds a tear because it has been forced out of its home"
Bone marrow infiltration (myelofibrosis)

69

Target Cell

"HALT said the hunter to his target"
HbC disease, Asplenia, Liver disease, Thalassemia

70

Heinz Bodies
Process
Associated pathology

Oxidation of sulfhydryl groups leads to denatured Hb precipitation and damage to RBC membrane --> formation of bite cells
G6PD deficiency and α-thalassemia

71

Howell-Jolly Bodies
What is it?
How are they normally dealt with?
Associated pathology

Basophilic nuclear remnants found in RBCs
Normally removed from RBCs by splenic macrophages
Functional hyposplenia, asplenia, mothball ingestion (naphthalene)

72

Microcytic Anemias

"Find Those Small Plump Cells"
Iron Deficiency, ACD, Thalassemia, Pb poisoning, Sideroblastic anemia

73

Nonhemolytic Normocytic Anemias

ACD, Aplastic, Chronic Kidney Disease

74

Hemolytic Normocytic Anemias

Intrinsic: "SHEEPS"
Spherocytosis, G6PD or PK deficiency, HbC, Sickle Cell Anemia, Paroxysmal Nocturnal Hemoglobinuria
Extrinsic: Autoimmune, Microangiopathic, Macroangiopathic, Infections

75

Megaloblastic Macrocytic Anemias

Folate deficiency, B12 deficiency, Orotic Aciduria

76

NonMegaloblastic Macrocytic Anemias

Liver disease, Alcoholism, Reticulocytosis

77

Iron Deficiency Anemia
What kind of anemia
What causes it?
PathoPhys
Labs
Histo
How may it manifest

Microcytic, Hypochromatic
↓ Fe due to chronic bleeding, malnutrition, or pregnancy
Impaired final step in heme synthesis
↓ Fe and Ferritin, ↑ TIBC
Microcytosis (MCV

78

α Thalassemia
What kind of anemia
PathoPhys
Epidemiology
How # of gene mutations re disease

Microcytic, Hypochromatic
α globin gene mutation
cis deletion in Asians, trans deletions in Africans
4 deletions: No α, excess γ forms γ4 (Hb Barts), Incompatible with life (Hydrops Fetalis)
3 deletions: HbH disease. Very little α, excess β forms β4 (HbH)
1-2 gene deletions: no clinical significance

79

β Thalassemia
What kind of anemia
PathoPhys
Epidemiology

Microcytic, Hypochromatic
Point mutation in splice sites and promoter sequence --> ↓ β
Mediterranean populations

80

β Thalassemia minor
PathoPhys
Symptoms
Diagnosis

Heterozygote: β chain underproduced
Asymptomatic
Increased HbA2 on electrophoresis

81

β Thalassemia major
PathoPhys
Symptoms
Treatment
Complications
Presentation
Hb

Homozygote: β chain absent
Severe anemia
Blood transfusions (--> hemochromatosis)
Marrow expansion (crew cut on skull XR) --> skeletal deformities. Chipmunk facies
HbF (α2γ2)

82

Presentation of HbS/β-Thalassemia Heterozygote

Mild to moderate sickle cell disease depending on amount of β globin production

83

Lead Poisoning
What kind of anemia
PathoPhys
Presentation
Treatment

Microcytic, Hypochromatic
Pb --/ ferrochelatase and ALA dehydratase which leads to ↓ heme synthesis
Pb --/ rRNA degradation causing RBCs to retain rRNA aggregates (Basophilic Stipling)
"LEAD"
Lead lines on Gingivae (Burton's Lines) and on metaphysis of long bones
Encephalopathy and Erythrocyte basophilic stippling
Abdominal colic and sideroblastic Anemia
Drops (wrist and foot)
Treat with Dimercaprol and EDTA
Succimer in children

84

Sideroblastic Anemia
What kind of anemia
PathoPhys
What causes it?
Histo
Labs
Treatment

Microcytic, Hypochromatic
Defect in Heme synthesis
X linked defect in δALA synthase, EtOH, Lead, Isoniazid
Ringed sideroblasts (with iron laden mito)
↑ Fe and ferritin, Normal TIBC
Treat with VitB6

85

Megaloblastic Anemia
Basic Pathology
Consequences

Impaired DNA synthesis --> maturation of nucleus delayed relative to cytoplasm
Ineffective erythropoiesis --> pancytopenia

86

Folate Deficiency
What kind of anemia
Etiologies
Presentation
Histo
Labs

Megaloblastic
Malnutrition (alcoholics), malabsorption, antifolates (methotrexate, trimethoprim, phenytoin), ↑ requirement (hemolytic anemia, pregnancy)
Glossitis
Hypersegmented neutrophils
↓ Folate, ↑ Homocysteine, normal Methylmalonic acid

87

B12 Deficiency
What kind of anemia
Etiologies
Presentation
Histo
Labs

Megaloblastic
Insufficient intake, Malabsorption, Pernicious anemia, Diphyllobothrium latum (fish tapeworm), PPI
Glossitis, B12 invovled with FA and myelin synthesis leading to Peripheral neuropathy w/ sensorimotor dysfunction, Posterior column (vibration/propioception), Lateral CST (spasticity), and Dementia
Hypersegmented neutrophils
↓ B12, ↑ Homocysteine, ↑ Methylmalonic acid

88

Orotic Aciduria
What kind of anemia?
PathoPhys
Presentation
Histo
Labs
Treatment

Megaloblastic
Enzyme deficiency impairs conversion of uridine from orotic acid
Children with glossitis and megaloblastic anemia that cannot be cured by folate or B12
Hypersegmented neutrophils
Orotic acid in urine
Uridine monophopshate to bypass mutated enzyme

89

NonMegaloblastic Macrocytic Anemia
Pathology
What causes it?

Macrocytic anemia in which DNA synthesis is unimpaired
Liver disease, Alcoholism, Retculocytosis, Drugs (5FU, AZT, Hydroxyurea)

90

Intrinsic Hemolytic Normocytic, Normochromic Anemias
Intravascular w/ examples and findings
Extravascular w/ examples and findings

Intra: Paroxysmal nocturnal hemoglobinuria or mechanical destruction
↓ haptoglobin, ↑ LDH, hemoglobin in urine
Extra: Hereditary spherocytosis
Macs in spleen clears RBCs. ↑ LDH + ↑ UCB causes jaundice

91

Anemia of Chronic Disease
What kind of anemia?
PathoPhys
Findings
What can it become?

Normocytic, Normochromic NonHemolytic
Inflammation --> ↑ hepcidin
Hepcidin is released by liver binds ferroportin on intestinal mucosal cells and macs thus inhibiting iron transport
↓ release of iron from macs
↓ Fe, ↓ TIBC, ↑ Ferritin
Can become microcytic, hypochromic

92

Aplastic Anemia
What kind of anemia
What causes it?

Normocytic, Normochromic NonHemolytic
Caused by failure or destruction of myeloid stem cells due to: Radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites), Viral agents (parvovirus B19, EBV, HIV, HCV), Fanconi's Anemia, Idiopathic (immune mediated, stem cell defect, may follow acute hepatitis)

93

Aplastic Anemia
Labs/Histo
Presentation
Treatment

Pancytopenia, severe anemia, Leukopenia, Thrombocytopenia, Normal cell morphology, Hypocellular bone marrow with fatty infiltration (dry bone marrow tap)
Fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infection
Withdrawal of offending agent, Immunosuppressive regimens (antithymocyte globulin, cyclosporine), allogeneic bone marrow transplantation, RBC and platelet transfusion, G-CSF or GM-CSF

94

How does chronic kidney disease lead to anemia?
What kind of anemia?

↓ erythropoietin --> ↓ hematopoiesis --> Normocytic, Normochromic NonHemolytic anemia

95

Hereditary Spherocytosis
What kind of anemia?
PathoPhys
How do RBCs look?
What happens to RBCs
Presentation
Findings
Treatment

Extravascular Intrinsic Hemolytic Normocytic Anemia
Defects in proteins interacting with RBC membrane (Ankryn, Band3, Protein4.2, Spectrin)
Less membrane causes small and round RBCs with no central pallor (↑ MCHC, ↑ red cell distribution width)
Premature removal of RBC by spleen
Splenomegaly, Aplastic crisis (Parvovirus B19 infection)
+ osmotic fragility test, normal or ↓ MCV with abundance of cells; Masks microcytia
Splenectomy

96

G6PD Deficiency
What kind of anemia?
Inheritance
PathoPhys
What happens to RBCs?
Presentation
Histo

Intra/Extra-vascular Intrinsic Hemolytic Normocytic Anemia
X linked
Defective G6PD --> ↓ Glutathione --> ↑ RBC susceptibility to oxidant stress (sulfa drugs, infections, fava beans)
RBCs destroyed extravascularly
Back pain followed a few days later by hemoglobinuria
Heinz bodies and bite cells

97

PK deficiency
What kind of anemia
Inheritance
PathoPhys
Presentation

Extravascular Intrinsic Hemolytic Normocytic Anemia
AR
Defective PK --> ↓ ATP --> rigid RBCs
Hemolytic anemia in a newborn

98

HbC defect
What kind of anemia
PathoPhys
HbSC vs HbSS

Extravascular Intrinsic Hemolytic Normocytic Anemia
Glutamic Acid --> Lysine mutation at reside 6 of β globin
HbSC less severe than HbSS

99

Paroxysmal Nocturnal Hemoglobinuria
What kind of anemia
PathoPhys
Genetics
Presentation
Labs
Treatment

Intravascular Intrinsic Hemolytic Normocytic Anemia
↑ complement mediated RBC lysis (impaired synthesis of GPI anchor or decay-accelerating factor that protects RBC membrane from complement
Acquired mutation in hematopoietic stem cell
Hemolytic anemia, Pancytopenia, Venous Thrombosis
CD55/59 negative RBCs on flow cytometry
Eculizumab

100

Sickle Cell Anemia
What kind of anemia?
Genetics
Pathogenesis
Newborns
Heterozygotes


Extravascular Intrinsic Hemolytic Normocytic Anemia
HbS point mutation in β globin at 6th residue (glutamic acid --> val)
Low O2 or dehydration precipitates sickling (deoxidized HbS polymerizes) --> anemia and vaso-occlusive disease
Newborns are initially asymptomatic b/c of ↑HbF and ↓HbS
Hets resistant to malaria

101

Sickle Cell Anemia
Histo
XR
Treatment

Sickled cells are crescent shaped RBCs
Crew cut on skull XR due to marrow expansion from erythropoiesis (also in thalassemias)
Hydroxyurea (↑ HbF) and bone marrow transplant

102

Sickle Cell Anemia Complications

Aplastic crisis (due to parvovirus B19)
Autosplenectomy (Howell-Jolly Bodies) --> ↑ risk of infections with encapsulated organisms; Functional splenic dysfunction in early childhood
Splenic sequestration crisis
Salmonella Osteomyelitis
Painful crisis (vaso-occlusive): Dactylitis, actue chest syndrome, avascular necrosis
Renal Papillary Necrosis (due to low O2 in papilla)
Microhematuria (medullary infarcts)

103

Autoimmune Hemolytic Anemia
What kind of anemia?
2 kinds?
Labs

Extrinsic Hemolytic Normocytic Anemia
Warm and Cold Agglutinin
Coomb's Positive

104

Coomb's Test

Direct: anti-Ig Ab added to pt's serum --> RBCs agglutinate if coated with Ig
Indirect: Normal RBCs added to pt's serum agglutinate if serum has anti-RBC surface Ig

105

Warm Agglutinin
Ab
Course
What causes it?

"Warm weather is Great"
IgG
Chronic
SLE, CLL, drugs (metyldopa)

106

Cold Agglutinin
Ab
Course
What causes it?

"Cold ice cream is yuMMM"
IgM
Acute anemia triggered by cold
CLL, Mycoplasma pneumonia infections, infectious Mononucleosis

107

Microangiopathic Anemia
What kind of Anemia?
Pathogenesis
Seen in what conditions
Histo

Extrinsic Hemolytic Normocytic Anemia
RBCs damaged when passing through obstructed or narrowed vessel lumina
DIC, TTP/HUS, SLE, Malignant HTN
Schistocytes

108

Macroangiopathic Anemia
What kind of Anemia?
Pathogenesis
Histo

Extrinsic Hemolytic Normocytic Anemia
Prosthetic heart valve and aortic stenosis damage RBCs
Schistocytes

109

Infectious anemia
What kind of anemia
Examples

Extrinsic Hemolytic Normocytic Anemia
Malaria, Babesia

110

Iron Deficiency
Serum Fe
TIBC (transferrin)
Ferritin
Transferrin Saturation (Serum Fe/TIBC)

↓ (primary)


↓↓

111

Chronic Disease
Serum Fe
TIBC (transferrin)
Ferritin
Transferrin Saturation (Serum Fe/TIBC)



↑ (primary)
No change

112

Hemochromatosis
Serum Fe
TIBC (transferrin)
Ferritin
Transferrin Saturation (Serum Fe/TIBC)

↑ (primary)


↑↑

113

Pregnancy or OCP use
Serum Fe
TIBC (transferrin)
Ferritin
Transferrin Saturation (Serum Fe/TIBC)

No change
↑ (primary)
No change

114

Pb Poisoning
What enzymes are affected?
What builds up where?
General Presentation
Adults vs Children re exposure and presentation

Ferrochelatats and ALA Dehydratase
Protoporphyrin and δALA in blood
Microcytic anemia, GI and Kidney disease
Children: lead paint --> mental retardation
Adults: battery, ammunition, radiator factory --> Headache, Memory loss, Demyelination

115

Acute Intermittent Porphyria
Enzyme affected
What accumulates where?
Presentation
Treatment

Porphobilinogen daminase
Porphobilinogen, δALA, uroporphyrin (urine)
Painful abdomen, Port wine colored urine, Polyneuropathy, Psychological disturbances, Precipitated by drugs
Glucose and heme inhibit ALA synthase

116

Porphyria Cutanea Tarda
Enzyme affected
What accumulates where?
Presentation
Frequency

Uroporphyrinogen decarboxylase
Uroporphyrin (tea colored urine)
Blistering cutaneous photosensitivity
Most common porphyria

117

Heme Synthesis Pathway

Mito:
Glycine + Succinyl-CoA --> [δALA synthase + B6] --> δALA
Cyto:
δALA --> [δALA dehydratase] --> Porphobilinogen --> [Porphobilinogen deaminase] --> Hydroxymetylbilane --> Uroporphyrinogen III --> [Uroporphyrinogen decarboxylase] --> Coproporphyrinogen III
Mito:
Coproporphyrinogen III --> Protoporphyrin
Protoporphyrin + Fe --> [Ferrochelatase] --> Heme

118

Rate limiting step of Heme synthesis with regulation

δALA synthase
Inhibited by Glucose and Heme

119

PT

Extrinsic and Common pathways
I, II, V, VII, X

120

PTT

Intrinsic and Common pathways
all factors except VII, XIII

121

Hemophilia A or B
PT
PTT
PathoPhys
Presentation

No change in PT
↑ PTT
Intrinsic coagulation defect
A: VIII
B: IX
Macrohemorrhage: Hemarthrosis, Easy bruising

122

VitK deficiency
PT
PTT
PathoPhys

↑ PT
↑ PTT
↓ synthesis of II, VII, IX, X, C, S

123

Presentation of platelet abnormalities

Microhemorrhage: Mucus membrane bleeding, Epistaxis, Petechiae, Purpura, ↑ bleeding time, possible ↓ platelet count

124

Bernard-Soulier Syndrome
PC
BT
PathoPhys

↓ PC
↑ BT
↓ GpIb --> defect in platelet to vWF adhesion

125

Glanzmann's Thrombasthenia
PC
BT
PathoPhys
Labs

No change in PC
↑ BT
↓ GpIIb/IIIa --> defect platelet-to-platelet aggregation
No platelet clotting on blood smear

126

Idiopathic Thrombocytopenic Purpura (ITP)
PC
BT
PathoPhys
Labs

↓ PC
↑ BT
Anti-GpIIb/IIIa Ab --> splenic macrophage consumption of platelet/Ab complex --> ↓ platelet survival
↑ megakaryocytes

127

Thrombic Thrombocytopenic Purpura (TTP)
PC
BT
PathoPhys
Histo
Labs
Symptoms

↓ PC
↑ BT
Deficiency in ADAMTS13 (vWF metalloprotease) --> ↓ degradation of vWF multimers
↑ vWF multimers --> ↑ platelet aggregation and thrombosis
↓ platelet survival
Schistiocytes, ↑ LDH
Neurologic and renal symptoms, Fever, Thrombocytopenia, and Microangiopathic hemolytic anemia

128

von Willebrands Disease
PC
BT
PT
PTT

No change in PC
↑ BT
No change in PT
No change or ↑ PTT

129

von Willebrands Disease
PathoPhys
Frequency
Severity
Inheritance
Diagnosis
Treatment

Intrinsic pathway defect: ↓ vWF --> normal or ↑ PTT because vWF protects VIII
↓ vWF --> defect in platelet-to-vWF adhesion
Most common inherited bleeding disorder
Mild
AD
Ristocetin cofactor assay
Desmopressin releases vWF from endothelium

130

DIC
PC
BT
PT
PTT

↓ PC
↑ BT
↑ PT
↑ PTT

131

DIC
PathoPhys
What causes it?
Histo
Labs

Widespread activation of clotting leds to deficiency in clotting factors leading to bleeding
"STOP Making New Thrombi"
Sepsis (gram neg), Trauma, Obstetric complication, acute Pancreatitis, Malignancy, Nephrotic syndrome, Transfusion
Schistocytes, ↑ Fibrin split products (D-dimer), ↓ fibrinogen, ↓ factor V and VIII

132

Factor V Leiden
PathoPhys
Epidemiology

Mutant V resistant to degradation by C --> hypercoagulability
Most common cause of inherited hypercoagulability in whites

133

Prothrombin Gene mutation

Mutation in 3' UTR --> ↑ production of prothrombin --> ↑ plasma levels and venous clots --> hypercoagulability

134

AntiThrombin Deficiency
PathoPhys
Treatment

Inherited deficiency of antithrombin --> hypercoagulability
↑ PTT is blunted after heparin administration

135

Protein C or S deficiency
PathoPhys
Treatment

↓ ability to inactivate V and VIII --> hypercoagulability
↑ risk of thrombotic skin necrosis with hemorrhage following administration of warfarin

136

Packed RBCs
Purpose
Use

↑ Hb and O2 carrying capacity
Acute blood loss, severe anemia

137

Transfusion of platelets
Purpose
Use

Increase platelet count
Stop significant bleeding (Thrombocytopenia, Qualitative platelet dysfunction)

138

Transfusion of fresh frozen plasma
Purpose
Use

↑ Coagulation factor levels
DIC, Cirrhosis, Warfarin OD

139

Transfusion of Cryoprecipitate
Contains
Use

Contains Fibrinogen, VIII, XIII, vWF, and Fibronectin
Treats coagulation factor deficiencies involving fibrinogen and VIII

140

Risks of Blood Transfusions

Infection, Transfusion reaction, Iron Overload, HypoCa (citrate is a Ca chelator), HyperK (RBC lysis)

141

Leukemia
What is it?
Where are tumors found?

Lymphoid or Myeloid neoplasm with widespread involvement of bone marrow
Tumor cells are usually found in peripheral blood

142

Lymphoma
What is it?
Presentation?

Discrete tumor masses arising form lymph nodes
Presentations blur definitions

143

Leukemoid Reaction
What is it?
Labs
Contrast with CML

Acute inflammatory response to infection
↑ WBC count with ↑ neutrophils and bands
↑ Leukocyte ALP
In CML, ↓ Leukocyte ALP

144

Hodgkin's Lymphoma
Distribution
Stage re prognosis
Histo
Epidemiology
What is it associated with?
Presentation

Localized, single group of nodes; extra nodal involvement rare. Contiguous spread
Stage is strongest predictor of prognosis
Reed-Sternberg cells
Bimodal distribution: young adulthood and over 55. More common in men except for nodular sclerosing type
EBV
Fever, night sweats, wt loss

145

Non-Hodgkin's Lymphoma
Distribution
Histo
Epidemiology
What is it associated with?
Presentation

Multiple, peripheral nodes. Extra nodal involvement common. Noncontiguous spread
Majority involve B cells (except for lymphoblastic T cell origin)
20-40
HIV and immunosuppression
Few constitutional signs/symptoms

146

Reed-Sternberg Cells
Appearance
What kind of cancer?
Markers
Origin
Re Diagnosis
Re Prognosis

Giant cell. Binucleate, bilobed w/ 2 halves as mirror images (owl eyes)
Hodgkin's Lymphoma
CD30, CD15
B cell origin
Necessary but not sufficient for diagnosis
Best prognosis with strong stromal or lymphocytic reaction against RS cells
RS rich has best prognosis

147

Nodular Sclerosing Hodgkin's Lymphoma
Frequency
Epidemiology

Most common
Affects women and men equally

148

Hodgkin's Lymphoma with worst prognosis

Lymphocyte mixed or depleted forms

149

Burkitt's Lymphoma
What kind of cancer?
Neoplasm of what?
Epidemiology
Genetics
Histo
Associated with what?
Endemic vs sporadic

Non-Hodgkin's Lymphoma
Neoplasm of mature B cells
Adolescents or young adults
t[8 (cmyc), 14 (heavy-chain Ig)]
Starry sky appearance: sheets of lymphocytes with interspersed macs
EBV
Jaw lesion in endemic forms in Africa
Pelvis or abdominal in sporadic form

150

Diffuse Large B cell Lymphoma
What kind of cancer?
Neoplasm of what?
Epidemiology
Frequency
Origin

Non-Hodgkin's Lymphoma
Neoplasm of mature B cells
Older adults but 20% in children
Most common adult NHL
20% mature T cell origin

151

Mantle Cell Lymphoma
What kind of cancer?
Neoplasm of what?
Epidemiology
Genetics
Prognosis
Markers

Non-Hodgkin's Lymphoma
Neoplasm of mature B cells
Older males
t[11 (cyclin D1), 14 (heavy-chain Ig)]
Poor
CD5

152

Follicular Lymphoma
What kind of cancer?
Neoplasm of what?
Epidemiology
Genetics
Course
PathoPhys

Non-Hodgkin's Lymphoma
Neoplasm of mature B cells
Adults
t[14 (heavy-chain Ig), 18 (bcl2)]
Difficult to cure, indolent course
bcl2 inhibits apoptosis

153

Adult T cell Lymphoma
What kind of cancer?
Neoplasm of what?
Epidemiology
Genetics
Presentation
Population affected
Course

Non-Hodgkin's Lymphoma
Neoplasm of mature T cells
Adults
Caused by HTLV1
Cutaneous lesions
Japan, West Africa, Caribbean
Aggressive

154

Mycosis Fungoides
AKA
What kind of cancer?
Neoplasm of what?
Epidemiology
Presentation
Markers
Course

Sezary Syndrome
Non-Hodgkin's Lymphoma
Neoplasm of mature T cells
Adults
Cutaneous patches/nodules
CD4
Indolent course

155

Multiple Myeloma
Histo
Where does it arise from
Frequency
What does it produce?

Monoclonal Plasma Cell cancer (fried egg appearance). Clock face chromatin and intracytoplasmic inclusions w/ immunoglobulins
Arises in the marrow
Most common primary tumor of bone in those over 50
IgG (55%) and IgA (25%)

156

Multiple Myeloma
Associations
XR
Electrophoresis
UA
Blood smear
Presentation

Susceptibility to infection, Amyloidosis
Punched out lytic bone lesions
M spike on protein electrophoresis
Ig Light Chains in urine (Bence Jones Protein)
Rouleaux formation (RBCs staked like poker chips)
"CRAB"
hyperCa, Renal insufficiency, Anemia, Bone lytic lesions/Back pain

157

How to distinguish Waldenstrom's Macroglobinemia from Multiple Myeloma

Both have an M spike but WM doesn't have lytic bone lesions

158

What is the M spike?

Spike in γ on protein electrophoresis
Multiple Myeloma, Waldenstrom's Macroglobulinemia, MGUS

159

MGUS
What does it stand for?
What is it?
Electrophoresis
Symptoms
What is it a precursor to

Monoclonal Gammopathy of Undetermined Significance
Monoclonal expansion of plasma cells
M spike
Asymptomatic
Precursor to multiple myeloma

160

Leukemia
What is it basically?
Pathway of Presentation
Infiltrates?

Unregulated growth of leukocytes in bone marrow
↑ or ↓ # of circulating leukocytes in blood and marrow --> anemia (↓RBCs), infections (↓ mature WBCs), and hemorrhage (↓ platelets)
Leukemic cells infiltrate liver, spleen, and lymph nodes



161

Acute Lymphoblastic Leukemia/Lymphoma
Kind of cancer?
Epidemiology
Presentation
Markers
Response?
Metastasis
Genetics with prognosis

Lymphoid Neoplasm
Under 15
T cell ALL presents with mediastinal mass (leukemic infiltration of the thymus). Peripheral blood and bone marrow have ↑ lymphoblasts
TdT+ (marker for pre-T and pre-B cells), CALLA
Most response to therapy
CNS and testes
t(12;21) --> best prognosis

162

Small Lymphocytic Lymphoma (SLL)/Chronic Lymphocytic Leukemia (CLL)
Kind of cancer?
Epidemiology
Presentation
Difference between them

Lymphoid neoplasm
Over 60
Often asymptomatic. Smudge cells in peripheral blood smear. Autoimmune hemolytic anemia
CLL has ↑ peripheral blood lymphocytosis or bone marrow involvement

163

Hairy Cell Leukemia
What kind of cancer
Epidemiology
In elderly?
Histo
Treatment

Lymphoid neoplasm
Adults
Mature B cell tumor in the elderly
Filamentous hair like projections. Stains TRAP+
Cladribine (adenosine analog resistant to ADA)

164

Acute Myelogenous Leukemia (AML)
What kind of cancer?
Epidemiology
Histo
Smear
Genetics Re Treatment
Common presentation

Myeloid Neoplasm
Median age of onset is 65
Auer Rods
↑↑↑ circulating myeloblasts on peripheral smear
t(15;17) --> M3 AML subtype which responds to all trans Retinoic acid inducing differentiation of myeloblasts
DIC is a common presentation in M3 AML

165

Chronic Myelogenous Leukemia (CML)
What kind of cancer?
Epidemiology
Genetics
Origin
Presentation
Course
Labs
Treatment

Myeloid Neoplasm
30-60
Philadelphia chromosome t(9;22) bcr-abl
Myeloid stem cell proliferation
↑ Neutrophils, Metamyelocytes, Basophils, Splenomegaly
May accelerate and transform into AML or ALL (blast crisis)
Low Leukocyte ALP from immature granulocytes (vs leukemoid reaction - mature cells)
Imatinib

166

Auer Bodies (rods)
What are they?
Where are they commonly seen
What can they cause?

Peroxidase+ Cytoplasmic inclusions in granulocytes and myeloblasts
Acute polymyelocytic Leukemia (M3)
Treatment of M3 AML can release Auer rods and produce DIC

167

Philadelphia Chromosome
Translocation
Associated disorder

t(9;22) bcr-abl hybrid
CML

168

t(8;14)

Burkitt's Lymphoma (c-myc activation)

169

t(11;14)

Mantle Cell Lymphoma (cyclin D1 activation)

170

t(14;18)

Folliclar Lymphoma (bcl2 activation)

171

t(15;17)

M3 AML
Responsive to all trans retinoic acid

172

Langerhans Cell Histocytosis
What is it?
Presentation
Description of cells
Markers
EM

Proliferative disorder of dendiritic cells from monocyte lineage
Child w/ lytic bone lesions and skin rash
Functionally immature and do not efficiently stimulate T lymphocytes via Ag presentation
S100 (neural crest cell origin) and CD1a
Birbeck granules (tennis rackets) on EM

173

Polycythemia Vera
What kind of disorder
RBCs
WBCs
Platelets
Philadelphia Chromosome
JAK2 mutation

Chronic Myeloproliferative Disorder



-
+

174

Essential Thrombocytosis
What kind of disorder
RBCs
WBCs
Platelets
Philadelphia Chromosome
JAK2 mutation

Chronic Myeloproliferative Disorder
No change
No change

-
+ (30-50%)

175

Myelofibrosis
What kind of disorder
RBCs
WBCs
Platelets
Philadelphia Chromosome
JAK2 mutation

Chronic Myeloproliferative Disorder

Variable
Variable
-
+ (30-50%)

176

CML
What kind of disorder
RBCs
WBCs
Platelets
Philadelphia Chromosome
JAK2 mutation

Chronic Myeloproliferative Disorder



+
-

177

Polycythemia Vera
PathoPhys
Presentation

Abnormal clone of hematopoietic stem cell with constitutively active JAK2 receptor that proliferate w/o EPO
Itching after a hot shower

178

Essential Thrombocytosis

Similar to Polycythemia Vera but specific for megakaryocytes

179

Myelofibrosis
What is it?
Histo

Fibrotic obliteration of bone marrow
Teardrop cell
"bone marrow is crying because it is fibrosed"

180

Relative Polycythemia
Plasma Vol
RBC mass
O2 Sat


No change
No change

181

Appropriate Absolute Polycythemia
Plasma Vol
RBC mass
O2 Sat
Associated diseases

No change


Lung disease, Congenital Heart Disease, High Altitude

182

Inappropriate Absolute Polycythemia
Plasma Vol
RBC mass
O2 Sat
Associated diseases
What causes it?

No change

No change
Renal Cell Carcinoma, Wilm's Tumor, Cyst, Hepatocellular Carcinoma, Hydronephrosis,
Ectopic EPO

183

Polycythemia Vera
Plasma Vol
RBC mass
O2 Sat


↑↑
No change

184

Heparin
MoA
Half-life
Use
Can it be used during pregnancy
Monitoring
Tox
Antidote

Activates antithrombin leading to ↓ thrombin and ↓ X
Short half-life
PE, Acute Coronary Syndrome, MI, DVT
Can be used during pregnancy: does not cross placenta
Follow PTT
Bleeding, Thrombocytopenia (HIT), Osteoporosis, Drug-drug interactions
Protamine sulfate

185

Low Molecular Wt Heparin

Acts more on X, better bioavailability, and 2-4 times longer half-life
Can be administered subcutaneously and without laboratory monitoring
Not easily reversible

186

Heparin-Induced Thrombocytopenia (HIT)

Development of IgG Abs against heparin bound to platelet factor 4
Ab-Heparin-PF4 --> platelets --> thrombosis --> thrombocytopenia

187

Lepirudin, Bivalirudin, Argatroban
What kind of molecule
Used by what animals
MoA
Use

Derivative of Hirudin
Leeches
Anticoagulant that inhibits thrombin
Alternative to heparin in pts with HIT

188

Warfarin
AKA
MoA
What molecules are affected?
Metabolism
What happens in lab assay?
Half life

"The EX-PresidenT went to WARfarin"
Coumadin
Interferes with γ-carboxylation of VitK dependent clotting factors II, VII, IX, X, C, and S
CytP450
Affects extrinsic pathway and ↑ PT
Long half life

189

Warfarin
Use
Pregnancy
Monitoring
Tox
Treatment for OD

Chronic anticoagulant (after STEMI, Venous Thromboembolism, Stroke prevention after Afib)
Do not use in pregnant women (crosses placenta)
Follow PT/INR
Bleeding, Teratogenic, Skin/Tissue necrosis, Drug-drug interactions
VitK. For rapid reversal fresh frozen plasma

190

Heparin
Structure
Route of Administration
Site of action
Onset
Duration

Large, anionic acid polymer
Parenteral
Blood
Rapid
Hours

191

Do Heparin or Warfarin inhibit coagulation in vitro?

Only Heparin does

192

Warfarin
Structure
Route of Administration
Site of action
Onset
Duration

Small lipid soluble molecule
Oral
Liver
Slow
Days

193

Thrombolytics
Names
MoA
Labs
Use

Alteplase (tPA), Reteplase (rPA), Tenecteplase (TNK-tPA)
--> Plasmin
↑ PT, ↑ PTT, No change in platelet count
Early MI, Early Stroke, PE

194

Thrombolytics
Tox
Contraindications
OD treatment

Bleeding, Reperfusion arrhythmias
Active bleeding, Intracranial bleeding, Recent surgery, known bleeding diatheses, HTN
Aminocaproic acid

195

ADP receptor inhibitors
Names
MoA
Use
Usually combined w/...
Tox

Clopidogrel, Ticlopidine, Prasugrel, Ticagrelor
Irreversibly blocks ADP receptor. Inhibits fibrinogen binding by preventing glycoprotein IIb/IIIa from bind fibrinogen
Acute Coronary Syndrome; Coronary Stenting; ↓incidence or recurrence of thrombotic stroke
Aspirin
Ticlopidine: Neutropenia, oral ulcers, fever

196

Cilostazol, Dipyridamole
MoA
Use
Tox

Phosphodiesterase III inhibitor. ↑cAMP in platelets thus inhibiting platelet aggregation; Vasodilator
Claudication, Coronary Vasodilation, Prevention of stroke or TIA, Angina Prophylaxis
Nausea, Headache, Facial Flushing, Hypotension, Abdominal Pain

197

GP IIb/IIIa Inhibitors
Names
Structure
MoA
Use
Tox

Abciximab, Eptifibatide, Tirofiban
A is made from monoclonal Ab Fab fragment
Inhibits platelet aggregation by binding GP IIb/IIIa receptor on activated platelets
Acute coronary Syndromes, Percutaneous Transluminal Coronary Angioplasty
Bleeding, Thrombocytopenia

198

Methotrexate
Class of drug
MoA
Use
Tox

Antimetabolite
Folic Acid analog that inhibits DHF Reductase
↓ dTMP --> ↓ DNA and ↓ Protein synthesis
Leukemias, Lymphomas, Choriocarcinoma, Sarcomas, Abortion, Ectopic Pregnancy, RA, Psoriasis
Myelosuppression (reversible w/ leucovorin), Macrovesicular fatty change in liver, Mucositis, Teratogenic

199

5-Fluorouracil
Class of drug
MoA
Use
Tox
OD treatment

Antimetabolite
Pyrimidine analog. Bioactivated to 5F-dUMP, which covalentaly complexes folic acid. The complex inhibits Thymidylate synthase leading to ↓ dTMP --> ↓ DNA and ↓ Protein synthesis
Colon cancer, Basal cell carcinoma (topical)
Myelosuppression (irreversible w/ leucovorin), Photosensitivity
OD treat with Thymidine

200

Cytarabine
Name
Class of drug
MoA
Use
Tox

Arabinofuranosyl Cytidine
Antimetabolite
Pyrimidine analog inhibits DNA pol
Leukemias, Lymphomas
Leukopenia, Thrombocytopenia, Megaloblastic Anemia

201

Azathioprine, 6MP, 6-Thioguanine
Class of drug
MoA
Use
Tox
Metabolism

Antimetabolite
Purine analog --/ de novo purine synthesis
Activated by HGPRT
Leukemias
Bone Marrow, GI, Liver
Metabolized by Xanthine Oxidase

202

Dactinomycin
AKA
Class of drug
MoA
Use
Tox

Actinomycin D
Antitumor antibiotic
Intercalates DNA
Wilms Tumor, Ewing Sarcoma, Rhabdomyosarcoma, (Childhood tumors: "Children ACT out")
Myelosuppression

203

Doxorubicin (Adriamycin), Daunorubicin
Class of drug
MoA
Use
Tox
How to prevent certain toxicity

Antitumor antibiotic
Generates free radicals. Noncovalently intercalate in DNA --> breaks in DNA --> ↓ replication
Solid tumors, Leukemias, Lymphomas
Cardiotoxicity (dilated cardiomyopathy), Myelosuppression, Alopecia
Dexrazoxane (Fe chelator) used to prevent cardiotoxicity

204

Bleomycin
Class of drug
MoA
Use
Tox

Antitumor antibiotic
Induces free radical formation which causes breaks in DNA strand
Testicular cancer, Hodgkin's Lymphoma
Pulmonary Fibrosis, Skin Changes, Minimal Myelosuppression

205

Cyclophosphamide, Ifosfamide
Class of drug
MoA
Bioactivation
Use
Tox
How to prevent toxicity?

Alkylating Agent
Covalently links DNA @ guanine N7
Bioactivation in liver
Solid tumors, Leukemia, Lymphoma, Brain Cancers
Myelosuppression, Hemorrhagic cystitis
Mesna prevents toxicity

206

Nitrosoureas
Names
Class of drug
MoA
Bioactivation?
Use
Tox

Carmustine, Lomustine, Semustine, Streptozocin
Alkylating Agents
Alkylates DNA
Requires bioactivation
Brain tumors
CNS toxicity

207

Vincristine, Vinblastine
Class of drugs
MoA
Use
Tox

Alkaloids that bind to tubulin in M phase and blocks polymerization of MT. Mitotic spindle cannot form
Solid tumors, Leukemias, Lymphomas
Vincristine: Neurotoxicity (Areflexia, Peripheral Neuritis, Paralytic Ileus)
VinBLASTine: Blasts Bone marrow (suppression)

208

Paclitaxel
Class of drug
MoA
Use
Tox

Taxol, MT inhibitor
"It's TAXing to stay polymerized"
Hyperstabilizes polymerized MT in M phase so that anaphase cannot occur
Ovarian and breast carcinoma
Myelosuppression and hypersensitivity

209

Cisplatin, Carboplatin
MoA
Use
Tox
How to prevent toxicity

Cross-links DNA
Testicular, Bladder, Ovary, Lung Carcinoma
Nephrotoxicity, Acoustic nerve damage
Amifostine (free radical scavenger) and Chloride Diuresis

210

Etoposide, Teniposide
MoA
Use
Tox

--/ topoisomerase II --> ↑ DNA degradation
Solid tumors, Leukemias, Lymphomas
Myelosuppression, GI irritation, Alopecia

211

Hydroxyurea
MoA
Use
Tox

--/ Ribonucleotide Reducatse --/ ↓ DNA synthesis
Melanoma, CML, Sicle Cell Disease (↑ HbF)
Bone marrow suppression, GI upset

212

Prednisone as a cancer drug?
Tox

CLL, Non-Hodgkin's Lymphoma
Cushing's, Immunosuppression, Cataracts, Acne, Osteoporosis, Peptic ulcers, Hyperglycemia, Psychosis

213

Tamoxifen, Raloxifene
MoA
Use
Tox

SERM: Receptor antagonist in breast and agonist in bone
Breast cancer. Prevents osteoporosis
T: Partial agonist at endometrium --> ↑ endometrial cancer; Hot flashes

214

Trastuzumab
AKA
MoA
Use
Tox

Herceptin
Monoclonal Ab against HER-2 (c-erbB2), a Tyrosine Kinase
HER2+ breast cancer
Cardiotoxicity

215

Imatinib
AKA
MoA
Use
Tox

Gleevec
Philadelphia chromosome bcr-abl tyrosine kinase inhibitor
CML, GI stroma tumors
Fluid retention

216

Rituximab
MoA
Use

Ab against CD20 (found in most B cell lymphomas)
Non-Hodgkin's Lymphoma, RA (w/ MTX)

217

Vemurafenib
MoA
Use

--/ B-Raf Kinase with V600E mutation
Metastatic melanoma

218

Bevacizumab
MoA
Use

Ab against VEGF inhibits angiogenesis
Solid Tumors

219

Common Chemotoxicities

Cisplatin/Carboplatin: C looks like like ears and kidney
Vincrisine: V like arms and legs
Bleomycin, Busulfan: B like lungs
Doxorubicin: D like heart
Trastuzumab: a T in the heart
CYclophosphamide: CY looks like bladder
5FU, 6MP, Methotrexate: Myelosuppression

220

Busulfan
MoA
Uses
Tox

Alkylates DNA
Alkylates DNA
CML, Ablates bone marrow before transplantation
Pulmonary Fibrosis, Hyperpigmentation

221

Heme degeneration

Heme --> [Heme oxygenase] --> Biliverdin --> Bilirubin

222

Black man on TMP/SMX with anemia and dark urine

G6PD deficiency

223

Dysphagia + Spoon nails

Iron deficiency
Plummer Vinson (esophageal webs)