Usmle - Heme/onc

Front 1

Erythrocyte: lineage and precursors

Back 1

Myeloid lineage
Pluripotent hematopoietic stem cell
proerythroblast
reticulocyte
erythrocyte

Front 2

Neutrophils, eosinophils, basophils: lineage and precursors

Back 2

Myeloid lineage
Myeloblast
Promyelocyte
Myelocyte
Metamyelocyte
Stab (Band) cell
N, E, B cells

Front 3

Platelets: lineage and precursors

Back 3

Myeloid lineage
Megakaryoblast
Megakaryocyte
Platelet

Front 4

Macrophages: lineage and precursors

Back 4

Myeloid lineage
Monoblast
Monocyte
Macrophage

Front 5

Plasma cell: lineage and precursors

Back 5

Lymphoid stem cell lineage
Lymphoblast
B cell
Plasma cell

Front 6

Active T cell: lineage and precursors

Back 6

Lymphoid lineage
Lymphoid stem cell
Lymphoblast
T cell
Activated T cell

Front 7

Natural killer cell: lineage and precursors

Back 7

Lymphoid lineage
Lymphoid stem cell
Pro-NK
Natural killer cell

Front 8

What is the main source of energy for RBC? Where is it derived from?

Back 8

Glucose

90% from anaerobic respiration to lactate

10% from the HMP shunt

Front 9

What are the components of the dense granules of platelets?

Back 9

ADP and calcium

Front 10

What are the components of the α-granules of platelets?

Back 10

vWF and fibrinogen

Front 11

What is the lifespan of a platelet?

Back 11

8-10 days

Front 12

Where can 1/3 of the platelet pool be found?

Back 12

In the spleen

Front 13

What is the normal count for leukocytes?

Back 13

4,000 to 10,000 / mcL

Front 14

What do the granules of basophils contain?

Back 14

Heparin, histamine, leukotrienes (LTD4), and other vasoactive amines

Front 15

What is released upon mast cell degranulation? Can bind what to its membrane? What prevents degranulation? Involved in what type of HSR?

Back 15

Histamine, heparin, eosinophil chemotactic factors.

Can bind IgE to membrane.

Cromolyn sodium prevents degranulation.

Involved in type I HSR

Front 16

What does eosinophils use to defend against protozoa and helminths? Produces what? Why?

Back 16

Major basic protein

Produces histaminASE and arylsulfatase (mutated in metachromatic leukodystrophy) to help limit the reaction after mast cell degranulation.

NAACP

Neoplasm
Asthma
Allergic processes
Collagen vascular disease
Parasites (invasive)

Front 17

What do the granules of neutrophils contain?

Back 17

hydrolytic enzymes, lysozyme, myeloperoxidase, and lactoferrin.

Front 18

What activates macrophages? Can present what type of MHC? secretes what?

Back 18

IFN-γ

Can present MHC type II

Secretes:
TNF-α
IL-1
IL-6
IL-12 (activates NK-cells and Th1 cells)

Front 19

Dendritic cells: present what on the surface?

Back 19

MHC II and Fc receptor

Main inducers of primary antibody response

Front 20

Dendritic cells express what 2 receptors on their surface?

Back 20

MHC II and Fc receptor

Front 21

Where do B cells mature? Where do B cells migrate to? What CDs are on surface?

Back 21

Mature in the marrow and then migrate to the peripheral lymphoid tissues (follicles of LN, white pulp of the spleen, unencapsulated lymphoid tissue).

Express
CD19
CD20
CD40 (which binds to CD40L on T cells)

Front 22

What CD do all T cells have?

Back 22

CD3

Front 23

Blood type A has what antigen and what antibody?

Back 23

A antigen and B antibody

Front 24

Blood type AB has what antigen and what antibody?

Back 24

A and B antigens and NO antibodies (universal recipient)

Front 25

Hemophilia A: deficiency of what?

Back 25

of factor VIII --> intrinsic pathway defect --> inc PTT

Macrohemorrhage in hemophilia - hemarthroses (bleeding into joints), easy bruising, inc PT and PTT.

Front 26

Hemophilia B: deficienty of what?

Back 26

of factor IX

Macrohemorrhage in hemophilia - hemarthroses (bleeding into joints), easy bruising, inc PT or PTT

Front 27

Vitamin K deficieny: deficiency of what? What drug inhibits these? What values do you have to follow with these?

Back 27

II, VII, IX, X, proteins C and S

Warfarin inhibits these

Follow PT

Front 28

What does antithrombin do? What does heparin do to antithrombin? What lab values should be followed?

Back 28

Antithrombin inhibits II, IXa, Xa, XIa, and XIIa

Antithrombin is activated by heparin

Follow PTT

Front 29

vonWillebrand factor connects what to what?

Back 29

connects subendothelial collagen to platelets via GpIb

Front 30

What is the function of clopidogrel and ticlopidine?

Back 30

They irreversibly block ADP receptors on platelets and prevent the expression of the GpIIb/IIIa receptors on the surface.

Front 31

Bernard-Soulier syndrome: defect? Platelet count? Bleeding time?

Back 31

Deficiency of GpIb, expressed on platelets and connects platelet to the subendothelial collagen via von Willebrand factor.

Platelet count is down, bleeding time is up.

Front 32

Glanzmann's thrombasthenia: defect? platelet count? bleeding time?

Back 32

Deficiency of GpIIb/IIIa, which connects platelets and platelets via fibrinogen.

Labs: blood smear shows no platelet clumping

Platelet count is normal, bleeding time is increased

Front 33

What do aggregated platelets express?

Back 33

Thromboxane A2

Front 34

Thrombomodulin: where can it be found? What does it do?

Back 34

Thrombomodulin is expressed on the surface of (damaged?) vascular endothelial cells.

It activates protein C

Front 35

Platelet aggregation is a balance between pro-coagulant and anti-aggregation factors. What are they?

Back 35

Pro-aggregation: thromboxane A2 (released by platelets)

anti-aggregation: PGI2 (inhibits platelets aggregation and promotes vascular permeability) and NO. Both are released by vascular endothelial cells

Front 36

What is abciximab?

Back 36

A mab that is a receptor antagonist of the GpIIb/IIIa receptor

Mainly used after procedures involving the coronary artery, like angioplasty

Front 37

What effect does calcium have on the platelet plug?

Back 37

It strengthens the plug.

Front 38

What converts vitamin K to activated vitamin K? What inhibits this? What pts lack this?

Back 38

epoxide reductase. Inhibited by warfarin. Neonates lack enteric bacteria which produce vitamin K.

Front 39

von Willebrand factor carries/protects what factor?

Back 39

factor VIII

Front 40

What does activated protein C do?

Back 40

It cleaves and inactivates Va and VIIIa

Front 41

What is the pathophys of factor V Leiden mutation?

Back 41

Factor V Leiden produces a factor V that is resistant to inactivation by protein C --> hypercoagulability

Front 42

tPA converts what to what?

Back 42

Plasminogen to plasmin

Front 43

Acanthocyte (spur cell)

Back 43

Liver disease, abetalipoproteinemia

Front 44

Basophilic stippling

Back 44

Baste the ox TAIL

Thalassemias
Anemia of chronic disease
Iron deficiency
Lead poisoning

Front 45

Bite cell

Back 45

G6PD deficiency

Front 46

Elliptocyte

Back 46

Hereditary elliptocytosis

Front 47

Macro-ovalocyte

Back 47

Megaloblastic anemia (also see hypersegmented PMNs), marrow failure

Front 48

Ringed sideroblasts

Back 48

Sideroblastic anemia

Front 49

Schistocyte, helmet cell

Back 49

DIC, TTP/HUS, traumatic hemolysis

Front 50

Teardrop cell

Back 50

Bone marrow infiltration (e.g. myelofibrosis)

Front 51

Target cell

Back 51

Hbc disease
Asplenia
Liver disease
Thalassemia

HALT said the hunter to his target

Note that lead poisoning presents with basophilic stippling, not target cells

Front 52

Heinz bodies

Back 52

Oxidation of iron from ferrous to ferric leads to denatured Hgb precipitation and damage to RBC membrane. Leads to formation of bite cells.

Assoc w α-thalassemia, G6PD deficiency.

Front 53

Howell-Jolly bodies

Back 53

Basophilic nuclear remnants found in RBCs.

Seen in pts with functional hyposplenia or asplenia

Front 54

Pappenheimer bodies

Back 54

Iron containing granules that are seen because the iron aggregates within mitos and ribosomes. Appear as faint violet or magenta speckles. Assoc w severe anemias and thalassemias

Front 55

Cabot rings

Back 55

Thin, red-staining threadlike strands in the shape of a loop or figure 8 that are found on rare occasions in RBCs.

Assoc w megaloblastic anemia, lead poisoning, disorders of erythropoiesis

Front 56

What are the five main pathologies that lead to a microcytic, hypochromic (MCV <80) anemia?

Back 56

1. Iron deficiency
2. α-thalassemia
3. β-thalassemia
4. Lead poisoning
5. Sideroblastic anemia

Front 57

Iron deficiency anemia: what type of anemia will you see?

Back 57

Microcytic (MCV < 80) hypochromic anemia

Front 58

Plummer-Vinson syndrome

Back 58

Iron deficiency anemia
Esophageal webs
Atrophic glossitis

Front 59

α-thalassemia: Where is it prevalent? What is the defect? How many genes are involved? Consequences of more or less genes being involved?

Back 59

Prevalent in Asia and Africa.

Defect: α-globin gene mutations that lead to dec α-globin synthesis

4 genes involved

Deletion of 4 genes is incompatible with life. This leads to Hb Barts (γ4), wich causes hydrops fetalis.

Deletion of 3 genes leads to HbH disease (β4)

Deletion of 1-2 genes is not assoc w anemia

Front 60

Hb Barts

Back 60

(γ4)

4 deletions in the α locus, not compatible with life --> hydrops fetalis

Note that the γ chains have a high affinity for O2 than normal, so it dec O2 delivery to tissues

Front 61

HbH disease

Back 61

β4

three deletions in the α locus --> HbH disease

HbH disease is comprised of Hb Barts γ4 and one Hb hemoglobin. Both of these have a higher affinity for hemoglobin, thus reducing oxygen delivery to tissues

See microcytic hypochromic anemia with

Target cells, Heinz bodies (precipitated HbH) as well as splenomegaly

Front 62

α-thalassemia trait

Back 62

Means that there are two deletions in the α locus. But two normal alleles are good enough for almost normal erythropoesis, but there is a mild microcytic hypochromic anemia

Can be cis (both deletions on one chr, seen in Asians) or can be trans (deletions are on different chr, seen in blacks)

Front 63

β-thalassemia: prevalent in what pops? What is the defect?

Back 63

Prevalent in Med pops

Defect is in point mutations in splicing sites and promoter sequences.

Front 64

β-thalassemia minor: what is the defect? sx? diagnosis confirmed by?

Back 64

Defect is that the β chain is underproduced.

Usually asymptomatic

Diagnosis is confirmed by increased HbA2 (> 3.5%)

Front 65

See inc HbA2 and inc HbF, what do you think?

Back 65

β-thalassemia minor

Front 66

β-thalassemia major: what is the defect? what are the sx? what is the txt? Other sequelae?

Back 66

β chain is absent --> severe anemia requireing blood transfusion (risk of secondary hemochromatosis)

See marrow expansion ("crew cut" on an X-ray) --> skeletal deformities and chipmunk facies

NOTE: also see the crew cut formation in sickle cell!

Front 67

See inc HbF, what do you think?

Back 67

Either β-thalassemia minor or major

Front 68

"Crew cut" on skull x-ray: what do you think?

Back 68

β-thalassemia major --> marrow expansion

Also see with sickle cell disease

Front 69

HbS/β-thalassemia heterozygote

Back 69

mild to moderate sickle cell disease depedning on the amount of β-globin production

Front 70

What two enzymes does lead poisoning inhibit? What does this result in? Also leads to what and results in what?

Back 70

Ferrochelatase and ALA dehydratase

Results in decreased heme synthesis

Also results in RNA degredation which leads to basophilic stippling

Front 71

Sideroblastic anemia: what is the defect? Txt? Reversible etiologies? Effects on iron panel? Histo?

Back 71

Defect in heme synthesis. Hereditary form is an X-linked defect in the δ-aminovulinic acid synthase gene (the rate-limiting step).

Txt: pyridoxine (B6) therapy

Reversible etiologies: alcohol, lead

See
inc iron
normal TIBC
inc ferritin

Histo: ringed sideroblasts (with iron-laden mitos)

Front 72

What is the composition of HbF and HbA? When does the switch from HbF to HbA occur?

Back 72

HbF (α2γ2)
HbA (α2β2)

The switch occurs around 6 months old. Children with β-thalassemia become anemic around this time.

Front 73

What are the three conditions that cause a macrocytic (MCV > 100) anemia?

Back 73

1. Megaloblastic anemia caused by folate deficiency

2. Megaloblastic anemia caused by B12 deficiency

3. Nonmegaloblastic macrocytic anemias

Front 74

Macrocytic anemia: what is the main problem?

Back 74

Impaired DNA synthesis --> maturation of nucleus of RBC delayed relative to maturation of cytoplasm

Front 75

What two enzymes does lead poisoning inhibit? What does this result in? Also leads to what and results in what?

Back 75

Ferrochelatase and ALA dehydratase

Results in decreased heme synthesis

Also results in RNA degredation which leads to basophilic stippling

Front 76

Sideroblastic anemia: what is the defect? What is the defect assoc w the hereditary form? Txt? Reversible etiologies? Effects on iron panel? Histo?

Back 76

Defect in heme synthesis. Hereditary form is an X-linked defect in the δ-aminovulinic acid synthase gene (the rate-limiting step).

Txt: pyridoxine (B6) therapy

Reversible etiologies: alcohol, lead

See
inc iron
normal TIBC
inc ferritin

Histo: ringed sideroblasts (with iron-laden mitos)

Front 77

What is the composition of HbF and HbA? When does the switch from HbF to HbA occur?

Back 77

HbF (α2γ2)
HbA (α2β2)

The switch occurs around 6 months old. Children with β-thalassemia become anemic around this time.

Front 78

What are the three conditions that cause a macrocytic (MCV > 100) anemia?

Back 78

1. Megaloblastic anemia caused by folate deficiency

2. Megaloblastic anemia caused by B12 deficiency

3. Nonmegaloblastic macrocytic anemias

Front 79

Macrocytic anemia: what is the main problem?

Back 79

Impaired DNA synthesis --> maturation of nucleus of RBC delayed relative to maturation of cytoplasm

Front 80

Megaloblastic anemia caused by folate deficiency: Findings, etiologies

Back 80

Findings:
Hypersegmented neutrophils, glossitis, dec folate, inc homocysteine, but NORMAL methylmalonic acid

Etiologies: malnutrition (alcoholism), malabsorption, impaired matabolism (e.g. methotrexate, trimethoprim), inc requirement (e.g. hemolytic anemia, pregnancy)

Front 81

Megaloblastic anemia caused by B12 deficiency

Back 81

Findings:
Hypersegmented neutrophils, glossitis, dec B12, inc homocysteine, but INC methylmalonic acid

Etiologies: malnutrition (alcoholism), malabsorption (Crohn's), pernicious anemia, Diphyllobothrium latum (fish tapeworm)

Neurologic symptoms: subacute combined degeneration (due to involvement of B12 in fatty acid pathways)

Front 82

What is a way to distinguish folate def from B12 def?

Back 82

Folate: normal methylmalonic acid

B12 def: inc methylmalonic acid

Front 83

Nonmegaloblastic macrocytic anemias

Back 83

1. Liver disease
2. Alcoholism: macrocytosis and bone marrow suppression can occur in the absence of folate/B12 deficiency

3. Reticulocytosis: reticulocytes are bigger than mature RBCs, leading to an increased MCV

4. Metabolic disorder (e.g. orotic aciduria): congenital deficiencies of purine or pyrimidine synthesis

5. Drugs: 5-FU, AZT, hydroxyurea.

Front 84

Anemia of chronic disease, aplastic anemia, kidney disease: what type of anemia do these cause?

Back 84

Nonhemolytic, normocytic, normochromic anemia

Front 85

Hereditary spherocytosis, G6PD def, pyruvate kinase def, sickle cell, HbC defect, paroxysmal nocturnal hemoglobinuria: what type of anemia do these cause?

Back 85

Intrinsic hemolytic, normocytic, normochromic anemia

Front 86

autoimmune, microangiopathic (DIC, TTP/HUS), infectious agents: what type of anemia do these cause?

Back 86

Extrinsic hemolytic, normocytic, normochromic anemia.

Front 87

PNH, autoimmune (cold agglutinins), mechanical destruction (e.g. aortic stenosis, mechanical valve), microangiopathies (DIC, TTP/HUS): what type of anemia do these cause?

Back 87

Intravascular hemolysis, normocytic, normochromic anemia

Front 88

Herediatry spherocytosis, G6PD deficiency, pyruvate kinase def, sickle cells anemia, HbC defect, autoimmune (warm agglutinins): what type of anemia do these cause?

Back 88

Extravascular hemolysis, normocytic, normochromic anemia.

Front 89

Anemia of chronic disease: Iron panel, what is up and what is down? What can happen in long standing disease?

Back 89

Inflammation --> inc hepcidin (sequesters iron) --> less release of iron from macrophages --> dec iron --> dec TIBC --> inc ferritin

Can become microcytic, hypochromic in long-standing disease

Front 90

Aplastic anemia: pathologic features? causes (4)? Sx? Treatment?

Back 90

Pathologic features: pancytopenia charcterized by severe anemia, neutropenia, and thrombocytopenia. Normal cell morphology, but hypocellular bone marrow with fatty infiltration.

Causes:
1. Radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites)
2. Viral agents (parvovirus B19, EBV, HIV)
3. Fanconi's anemia (inherited defect in DNA repair)
4. Idiopathic (immune mediated, primary stem cell defect) - may follow acute hepatitis

Sx: fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infection.

Treatment: withdrawal of offending agent, immunosuppressive regimens (antithymocyte globulin, cyclosporin), allogenic BM transplant, RBC and platelet transfusion, G-CSF, or GM-CSF

Note that antithymocyte globulin is an infusion of horse or rabbit derived abs agains human T cells.

Front 91

Hereditary spherocytosis: what type of anemia? defect? pathogenesis? findings? labs?

Back 91

Intrinsic hemolytic normocytic anemia

Defect: defect in proteins interacting with RBC membrane skeleton and plasma membrane (e.g. ankyrin, band 3.1, or spectrin)

Path: less mem causes small and round RBCs with no central pallor (Inc MCHC, inc RDW (red cell distribution width)) --> premature removal by spleen

Findings: splenomegaly, aplastic crisis (B19 infection). Howell-Jolly bodies present after splenectomy. Can also see bilirubin gallstones secondary to hemolysis.

Labs: positive osmotic fragility test.

Front 92

Pyruvate kinase deficiency: what type of anemia? Path? Presenation?

Back 92

Intrinsic hemolytic normocytic anemia

Path: defect in pyruvate kinase --> dec ATP --> rigid RBCs

Presentation: hemolytic anemia in the newborn

Front 93

Sickle cell disease: what % of AAs carry the trait? What % have the disease? Why are newborns usually asymptomatic? What is the mutation in SC? What promotes sickling?

Back 93

Trait = 8%, disease = 0.2%

Newborns are usually asymptomatic due to inc HbF and dec HbS

The mutation is a singel aa replacement in the β chain (glutamic acid --> valine)

Low O2 or dehydration precipitates sickling.

Front 94

What are some complications that sickle cell homozygotes face?

Back 94

1. Aplastic crisis (due to parvovirus B19 infection)

2. Autosplenectomy --> inc risk of infection with encapsulated organisms

3. Salmonella osteomyelitis

4. Painful crisis (vaso-occlusive)

5. Renal papillary necrosis (due to low O2 in papilla, esp vasa recta)

6. Splenic sequestration crisis (spleen lacks collateral blood supply)

Front 95

What is the treatment for Sickle cell anemia?

Back 95

Hydroxyurea (inc HbF) and BM transplantation

Front 96

HbC defect: path? presentation? histo?

Back 96

This mutated form reduces the normal plasticity of host erythrocytes causing a hemoglobinopathy

In homozygotes, nearly all Hb is in the HbC form, resulting in mild hemolytic anemia

See target cells,

Front 97

Paroxysmal nocturnal hemoglobinuria

Back 97

Path: intravascular hemolysis due to inc complement-mediated RBC lysis (impaired sysnthesis of GPI anchor/decay-accelerating factor [CD55, CD59] in RBC membrane).

Especially susceptible to lysis by complement in an ACIDIC environment. Stress exacerbates lysis (infection, menstruation, surgical procedures, exposure to cold, vaccines, etc.).

Especially prone to VENOUS THROMBOSIS --> abdominal pain --> death (via Budd-Chiari)

Also see pigment gallstones and granulocytopenia leading to frequent infections.

Also aplastic anemia/leukemias

Labs: see increased URINE HEMOSIDERIN. Can also do the "sugar-water" test or the Ham test

Front 98

Warm agglutinin: seen with what disease states?

Back 98

Seen in CHRONIC anemia with SLE, in CLL, or with certain drugs (e.g. α-methyldopa)

Warm weather is GGGreat

Front 99

Cold agglutinin: triggered by what? assoc w what diseases?

Back 99

ACUTE anemia triggered by cold

Seen with Mycoplasma pneumoniae infections or infectious mononucleosis

Cold ice cream - MMM

Front 100

Autoimmune hemolytic anemias are usually positive for what test?

Back 100

For the Coombs test

Front 101

Explain the direct Coombs test

Back 101

Anti-Ig antibody added to pt's RBCs, agglutinate if RBcs are coated with Ig.

Front 102

Explain the indirect Coombs test

Back 102

Normal RBCs are added to pt's serum, agglutinate if serum has anti-RBC surface Ig.

Front 103

In iron deficiency anemia, what is the:

Serum iron?
Transferrin and TIBC?
Ferritin?
% transferrin saturation (serum Fe/TIBC)?

Back 103

Serum iron = low

Transferrin and TIBC = HIGH (the liver produces more tranferrin, presumably to maximize use of the little iron that is available)

Ferritin = Low

% transferrin saturation (serum Fe/TIBC) = Low

Front 104

Anemia of chronic disease:

Serum iron?
Transferrin and TIBC?
Ferritin?
% transferrin saturation (serum Fe/TIBC)?

Back 104

Serum iron = low (b/c the body "holds" iron intracellularly as ferritin)

Transferrin and TIBC = LOW (The body produces less transferrin to keep the Fe away from pathogens)

Ferritin = HIGH

% transferrin saturation (serum Fe/TIBC) = unchanged

Front 105

Hemochromatosis:

Serum iron?
Transferrin and TIBC?
Ferritin?
% transferrin saturation (serum Fe/TIBC)?

Back 105

Serum iron = INC

Transferrin and TIBC = low

Ferritin = high

% transferrin saturation (serum Fe/TIBC) = very high

Front 106

Pregnancy/OCP use:
Serum iron?
Transferrin and TIBC?
Ferritin?
% transferrin saturation (serum Fe/TIBC)?

Back 106

Serum iron = unchanged

Transferrin and TIBC = HIGH (just because the liver is working overtime???)

Ferritin = unchanged

% transferrin saturation (serum Fe/TIBC) = low

Front 107

Lead poisoning: What are the two affected enzymes? What is the accumulated substrate? What are the sx in general? In children? In adults?

Back 107

Ferrochetalase and ALA dehydratase

Protoporphyrin (blood)

General sx: Microcytic anemia, GI, and kidney disease. Lead lines on gingivae (Burton's lines) and on the epiphyses of long bones on x-ray. See encephalopathy and Erythrocyte basophilic stippling. Abdominal colic and sideroblastic anemia. DROPS - wrist and foot drop.

sx/txt in children: exposure to lead paint --> MR. Succimer for kids (It "sucks" to be a kid who eats lead)

sx/txt in adults: environmental exposure (battery/ammunition factory) --> HA, memory loss, demyelination. Dimercaprol and EDTA are first line.

Front 108

Acute intermittent porphyria: affected enzyme? Accumulated substrate? Sx? Txt?

Back 108

Affected enzyme: Porphobilinogen deaminase (aka uroporphyrinogen-I-synthase)

Accumulated substrate: porphobilinogen, δ-ALA, uroporphyrin (in urine)

Sx: 5 P's

Painful abdomen
Pink urine
Polyneuropathy
Psychological disturbances
Precipitated by drugs (esp inducers of CYP 450 like barbs/alcohol)

Note that pts are normal except when affected by env, drugs.

Seen more commonly in women
Txt: glucose and heme, which inhibit ALA synthase (and thus the accumulation of toxic precursors)

Front 109

Porphyria cutanea tarda: affected enzyme? Accumulated substrate? sx?

Back 109

Affected enzyme: Uroporphyrinogen decarboxylase

Accumulated substrate: Uroporphyrin (tea-colored urine)

Presentation: blistering cutaneous photosensitivity. Most common porphyria

Front 110

Idiopathic thrombocytopenic purpura (ITP): defect? Platelet count? Bleeding time? Nature of this illness? Histo? See inc what type of cell?

Back 110

Anti GpIIb/IIIa antibodies --> peripheral platelet destruction

Systemic illness is not present in ITP!

No schistocytes!

Platelet count down, bleeding time up.

Labs: increased megakaryocytes

Front 111

Thrombotic thrombocytopenic purpura (TTP): defect? causing what? Labs? PC/BT? sx?

Back 111

Deficiency of ADAMTS13 (vWF metalloprotease) --> dec degredation of vWF multimers.

Pathogenesis: inc amounts of large vWF multimers --> inc platelet aggregation and thrombosis

Labs: schistocytes, inc LDH

PC down
BT up

Sx: pentad of:
neurologic
renal symptoms
fever
thrombocytopenia
microangiopathic hemolytic anemia

NOTE that TTP is similar to HUS, but HUS has no neuro sx.

Front 112

von Willebrans's disease: path?


PC:
BT:
PT:
PTT:

Back 112

vWF carries/protects FVIII, so dece vWF leads to an intrinsic pathway defect and normal or inc PTT

dec vWF --> defect in platelet to collagen adhesion

Mild but most common bleeding disorder

PC: normal
BT: inc
PT: normal
PTT: normal or inc

Front 113

DIC: path? labs? PC/BT?PT/PTT?

Back 113

Widespread activation of clotting leads to a deficiency in clotting factors, which creates a bleeding state.

Labs:
Schistocytes
Inc fibrin split products (D-dimers)
DEC fibrinogen
Dec factors V and VIII


PC: dec
BT: inc
PT: inc
PTT: inc

Front 114

Prothrombin gene mutation: associated with what?

Back 114

mutation in the 3' untranslated region, assoc w venous clots.

Front 115

ATIII deficiency: see what after administration of heparin?

Back 115

Inherited deficiency of antithrombin III; reduced inc in PTT upon administration of heparin (because heparin works through antithrombin)

Front 116

Protein C or S deficiency: has what consequences? associated with danger upon giving what drug?

Back 116

Dec ability to inactivate factors V and VIII.

Inc risk of hemorrhagic skin necrosis following administration of warfarin.

WISN is a potentially catastrophic complication of warfarin therapy that arises as a consequence of the different half-lives of the vitamin K-dependent proteins. One day after initiation of usual doses of warfarin, protein C activity is reduced by approximately 50%. Owing to their longer half-lives, the levels of the vitamin K-dependent clotting factors II, IX, and X decline more slowly (factor VII activity declines at approximately the same rate as protein C). The reduced level of protein C activity relative to these other procoagulant molecules creates a transient hypercoagulable state. This effect is more pronounced when large loading doses of warfarin are administered. Indeed, WISN typically occurs during the first few days of warfarin therapy, often when daily doses in excess of 10 mg are administered

Front 117

Hodgkin's lymphoma:
Distinctive cell type?
Typical sx?
See what type of lymphadenopathy?
50% of cases assoc w what?
Demographics?
Good prognosis = what?

Back 117

Hodgkin's lymphoma:
Distinctive cell type: Reed-Sternberg cell

Typical sx: Constitutional "B" signs/sx: low-grade fever, night sweats, weight loss

See what type of lymphadenopathy: nontender mediastinal lymphadenopathy

50% of cases assoc w what: EBV

Demographics: bimodal: young and old; more common in men except for nodular sclerosing type.

Good prognosis = high lymphocytes, low RS cells

Front 118

Non-hodgkin's lymphoma:
Assoc w what diseases?
Spread?
Sx?
Demographics?

Back 118

Assoc w what diseases: HIV and immunosuppression

Spread: multiple, peripheral nodes; extranodal involvement common; noncontiguous spread

Sx: fewer constitutional signs/sx

Demographics: peak incidence for certain subtypes at 20-40 years of age

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Reed-sternberg cells: description? CDs? RS cells are undergoing what?

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binucleate or bilobed with the 2 halves as mirror images ("owl's eyes")

Necessary but not sufficient for dx

CD30+ and CD15+

Cells in RS are undergoing "hypersomatic hypermutation"

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Name the four types of Hodgkin's lymphoma in order of decending incidence

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Nodular sclerosing (65-75%)
Mixed cellularity (25%)
Lymphocyte predominant (6%)
Lymphocyte depleted (rare)

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Nodular sclerosing type of Hodgkin's disease:

RS
Lymphocytes
Prognosis
Comments: path? demo?

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RS: low
Lymphocytes: high
Prognosis: excellent
Comments: Most common; see collagen banding, lacunar cells; women > men; primarily young adults

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Mixed cellularity type Hodgkin's disease:


RS
Lymphocytes
Prognosis
Comments

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RS: ++++
Lymphocytes: +++
Prognosis: intermediate
Comments: numerous RS cells

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Lymphocyte predominant Hodgkin's lymphoma:


RS
Lymphocytes
Prognosis
Comments

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RS: +
Lymphocytes: ++++
Prognosis: excellent
Comments: < 35 year old males

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Lymphocyte depleted type Hodgkin's lymphoma:


RS
Lymphocytes
Prognosis
Comments

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RS: high relative to lymphocytes

Comments: older males with disseminated disease

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Burkitt's lymphoma:

Ages?
Translocation? what genes are involved?
Variations?
Histopath?
Associated with what? What other malignancies can this cause?
2 common presentations

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Adolescents and young adults

t(8;14) c-myc gene moves next to the heavy-chain Ig gene (14)

t(8;22) myc/lambda
t(2;8) kappa/myc

"Starry sky" appearance

Assoc w EBV (which is assoc with nasopharyngeal cancer)

Endemic form in Africa: jaw lesion
Sporadic form in abdomen or pelvis

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Diffuse large cell lymphoma:

Occurs in
Comments:

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Non-Hodgkin's lymphoma

Occurs in usually older adults, but 20% in children.

Most common adult NHL
May be mature T cell in origin

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Mantle cell lymphoma

demo?
translocation?
prognosis?
CD?

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NHL

Older adults

t(11;14)

Poor prognosis

CD5+

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Follicular lymphoma:

Occurs in?
Translocation?
Expression of what?
Course?

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NHL

Occurs in adults

t(14;18) --> bcl-2 expression

Difficult to cure, indolent course; bcl-2 inhibits apoptosis

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Adult T-cell lymphoma:

Caused by?
Presentation?
See in what pops?
Course?

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Caused by HTLV-1

Adults present with cutaneous lesions; esp affects pops in Japan, West Africa, Caribbean

Aggressive

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Mycosis fungoides/Sezary syndrome: presentation? Course?

Back 130

Cutaneous T cell lymphoma

Adults present with cutaneous patches/nodules

Indolent

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Malignant histiocytosis: description

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A common subtype of NHL. Large cells w/ vesicular nucleus and prominent nucleolus. Nontender LNs or extranodal involvement

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Multiple myeloma:

Produces large amounts of what?
Hyper what?
General sx?
Assoc w what amyloidosis?
lesions on x-ray?
Characterized by what on serum protein electrophoresis?
See what other distintive finding in urine?
RBC effects?

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Produces large amounts of IgG (55%) or IgA (25%)

Hypercalcemia

Renal insufficiency, inc susceptibility to infection, anemia

AL

Punched out lesions on x-ray

Characterized by monoclonal immunoglobin spike (M protein) on serum protein electrophoresis.

See Ig light chains in urine (Bence Jones protein [most are VkCk])

Blood smear shows RBCs stacked like poker chips (Rouleaux formation).

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Waldenstrom's macrogobulinemia: excess of what? leading to what sx? Lack of what lesions?

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Excess IgM --> hyperviscosity symptoms

Lack of lytic bone lesions

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Plasmacytoma

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Solitary myeloma

Involves soft tissues (lungs, nasopharynx, nasal sinuses). Has plasma cell proliferation with M-spike of IgG, resembling m.myeloma but without metastatic potential. Some develop into mm in 10-20 years

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Heavy chain disease

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Excessive amounts of heavy chain gamma (IgG), alpha (IgA), or mu (IgM) are made

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MGUS: basic description

Back 136

asymptomatic monoclonal gammopathy

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Acute lymphoblastic leukemia/lymphoma (ALL):

CP in children? adolescent males?
Bone marrow replaced by what?
Postive for what?
Responsive to therapy?
May spread to what two places?
What translocation indicates a better prognosis?

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May present with BM involvement in childhood or mediastinal mass in adolescent males.

Bone replacement replaced by INC lymphoblasts

TdT+ (marker of pre-T and pre-B cells), CALLA+

Most responsive to therapy

May spread to CNS and testes

t(12;21) --> better prognosis

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Small lymphocytic lymphoma (SLL)/Chronic lymphocytic leukemia (CLL):

Affects who?
sx?
see what on peripheral smear?
abs?
What is the difference bet SLL and CLL?

Back 138

Affects older adults > 60

Often asymptomatic

Smudge cells on peripheral smear

Warm antibody autoimmune hemolytic anemia

SLL is the same as CLL, except CLL has inc peripheral blood lymphocytosis

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Hairy cell leukemia

Affects who?
Tumor of what type of cell?
sx?
typical marker?

Back 139

Affects the elderly

Mature B-cell tumor, cells have filamentous, hairlike projections

Often assoc w massive splenomegaly

Stains with TRAP (tartrate-resistant acid phosphatase)

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AML

Characteristic histo?
See inc what on peripheral smear?
responds to what?

Back 140

Auer rods

Inc circulating myeloblast on peripheral smear

M3 responds to all-trans retinoic acid (vitamin A), inducing differentiation of myeloblasts.

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Chronic myelogenous leukemia?

translocation? products?
proliferation of?
May accelerate or transformation into what?
characteristic lab level?
responds to what?

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Defined by the Phildelphia chromosome (t[9;22]) makes bcr-abl

Myeloid stem cell proliferation, presents with inc neutrophils, metamyelocytes, basophils

See splenomegaly

May accelerate and transform to AML or ALL ("blast crisis")

Very low LEUKOCYTE ALKALINE PHOSPHATASE (vs. leukemoid reaction)

Responds to imatinib

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M0

Back 142

undifferentiated (MPO negative)

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M1/M2

Back 143

Myeloblastic leukemia without maturation (has MPO)

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M4

Back 144

Myelomonocytic leukemia, has both myeloblasts and monoblasts (nonspecific esterase)

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M5

Back 145

Monocytic leukemia (nonspecific esterase)

High incidence of infiltration, esp of gums

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M6

Back 146

Erythroleukemia, see abnormal erythroid precursors

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M7

Back 147

Acute megakaryocytic leukemia; assoc w myelofibrosis due to PDGF

platelets

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Approximate ages:
ALL
AML
CML
CLL

Back 148

ALL: < 15
AML: median onset ~ 60
CML: 30-60
CLL: > 60

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See what inc lab value with the "leukemoid reaction?"

Back 149

inc leukocyte alkaline phosphatase

Front 150

Langerhans cell histiocytoses (histiocytosis X):

lineage?
markers?
characteristic histo?
older terms?

Back 150

Proliferative disorders of dendritic (Langerhans) cells from the monocyte lineage. Defective cells expres S-100 and CD1a. Birbeck granules ("tennis rackets" on EM) are characteristic.

Older terms include:
Letterer-Siwe disease
Hand-Schuller-Christian disease
Eosinophilic granulomas

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Polycythemia vera:

RBCs
WBCs
Platelets
Philadelphia chr
JAK2 mutations

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Abnormal clone of hematopoietic stem cells are increasingly sensitive to growth factors. Assoc w low levels of EPO

RBCs: high
WBCs: high
Platelets: high
Philadelphia chr: -
JAK2 mutations: +

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Essential thrombocytosis

RBCs
WBCs
Platelets
Philadelphia chr
JAK2 mutations

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Similar to p. vera, but specific for megakaryocytes

RBCs: normal
WBCs: normal
Platelets: high
Philadelphia chr: -
JAK2 mutations: + (30-50%)

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(myeloid metaplasia) with myelofibrosis

RBCs
WBCs
Platelets
Philadelphia chr
JAK2 mutations

Back 153

Fibrotic obliteration of bone marrow

RBCs: low
WBCs: variable
Platelets: variable
Philadelphia chr: -
JAK2 mutations: + (30-50%)

Front 154

CML:

RBCs
WBCs
Platelets
Philadelphia chr
JAK2 mutations

Back 154

bcl-abl transformation leads to inc cell division and inhibition of apoptosis

RBCs: low
WBCs: high
Platelets: high
Philadelphia chr: +
JAK2 mutations: -

Front 155

Myelodysplastic syndrome (MDS)

Back 155

refers to myeloid disorders featuring maturation defects and ineffective hematopoesis. MDS produces cytopenia and ACUTE leukemias, whereas myeloproliferative disorders produce polycythemia and CHRONIC leukemia.

Front 156

Heparin:

What does it do?
Half life?
Onset of action/indications?
Can use during pregnancy because?
Use what for reversal?

Back 156

Cofactor for the activation of antithrombin, decreases thrombin and Xa

short half life

Immediate anticoagulation for PE, stroke, acute coronary syndrome, MI, DVT.

Doesn't cross placenta, so can be used in pregnancy

For rapid reversal, use protamine sulfate (positively charged molecule that can act by binding negatively charged heparin

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Pros and cons of low-molecular weight heparins

Back 157

Pros:
act more on Xa
have better bioavailability
2-4x longer half life
can be admin subQ and w/o monitoring labs

Cons: not easily reversible

Front 158

Heparin-induced thrombocytopenia

Back 158

Heparin binds to platelets causing autoantibody production that destroys platelets and overactivates the remainging ones, resulting in a thrombocytopenic, hypercoagulable state

Front 159

What drugs are used as alternatives to heparin in pts with HIT?

Back 159

Lepirudin, bivalrudin

Front 160

What do you give in the case of a warfarin overdose?

Back 160

IV vitamin K and FFP

Front 161

Thrombolytics: name four. MOA? Effect on labs? Treat toxicity with what?

Back 161

Streptokinase, urokinase, tPA (alteplase), APSAC (antistreplase)

Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots.

PT up, PTT up, no effect on PC

Treat tox with: aminocapric acid (an inhibitor of fibrinolysis)

Front 162

Aspirin toxicity

Back 162

Aspirin is a weak acid --> OD caused hyperventilation --> pCO2 down --> resp alkalosis --> anaerobic glycolysis --> lactic acid buildup --> elevated anion gap --> metabolic acidosis

Front 163

Toxicity of ticlopidine

Back 163

Neutropenia

Front 164

Vinca alkaloids vs. paclitaxel: MOA

Back 164

Vinca: inhibit microtubule formaion

Paclitaxel: inhibit microtubule disassembly

Front 165

MTX causes myelosuppression which is reversible with what drug? What other SE are assoc w MTX?

Back 165

Reversible with leucovorin (folinic acid)

Macrovascular fatty change in liver; mucositis; teratogenic

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5-fluoruracil (5-FU): notable about SE.

Back 166

Myelosuppresion is not reversible with leucovorin

Rescue with thymidine

Front 167

6-MP: what does it do? inc tox with what? why?

Back 167

dec de novo purine synthesis.

Metabolized by XO, thus inc tox with allopurinol

Front 168

6-thioguanine: has what advantage over 6-MP?

Back 168

can be given with allopurinol

Front 169

Cytarabine: what is it? Tox?

Back 169

Pyrimidine antagonist --> inhibition of DNA polymerase

Leukopenia, thrombocytopenia, megaloblastic anemia

Front 170

Dactinomycin: used for what? tox?

Back 170

Used for childhood tumors (children ACT out)

Wilm's tumor, Ewing's sarcoma, rhabdomyosarcoma.

Tox: myelosuppression

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Doxorubicin (Adriamycin), daunorubicin: MOA? Part of what drug regimen? Main toxs?

Back 171

Generate free radicals, noncovalently intercalate in DNA --> breaks in DNA --> dec replication

Part of the ABVD drug regimen for Hodgkin's lymphoma

Cardiotoxicity
Myelosuppression
Marked alopecia
Toxic to tissues with extravasation

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Bleomycin: specific to what stage? MOA? Part of what regimen? Tox?

Back 172

Specific to G2

Induces formation of free radicals, whcih cause breaks in DNA strands

Part of the ABVD regimen for Hodgkin's

Pulmonary fibrosis
Skin changes
minimal myelosuppression

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Etoposide (VP-16), teniposide: specific for what stage? MOA? Toxs?

Back 173

Late S to G2 phase specific.

Inhibits topoisomerase II --> inc DNA degredation

Myelosuppression
GI irritation
alopecia

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Cyclophosphamide, ifosfamide: MOA? tox?

Back 174

Covalently cross link DNA at guanine N-7

Requires bioactivation by the liver

Myelosuppression
Hemorrhagic cystitis - can be partially prevented with mesna

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Nitrosureas (carmustine, lomustine, semustine, streptozocin): requires what? goes where? used for what? tox?

Back 175

Require bioactivation. Cross the BBB.

Used to txt brain tumors, including glioblastoma multiforme

CNS tox (dizziness, ataxia)

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Busulfan: MOA? Used for? tox?

Back 176

Alkylates DNA

Used for CML, also for ablating BM in hematopoietic stem cell transplants

Pulmonary fibrosis, hyperpigmentation

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Vincristine, vinblastine: specific for what phase? Part of what drug regimen? tox of vincristine? tox of vinblastine?

Back 177

Alkaloids that bind to tubulin in the M phase and block polymerization of microtubules so that the mitotis spindle cannot form.

Part of the MOPP (vincristine = Oncovin) regimen for Hodgkin's lymphoma, Wilm's tumor, choriocarcinoma

Vincristine:
Neurotox (areflexia, peripheral neuritis), paralytic ileus

VinBLASTine: BLASTs bone marrow (supression)

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Paclitaxel, other taxols: MOA? used for? tox?

Back 178

Hyperstabilize polymerized microtubules in M phase so that mitotic spindle cannot break down (anaphase acannot occur)

Ovarian and breast carcinomas

Myleosuppression and hypersensitivity

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Hydroxyurea: MOA? specific for what phase? used for? tox?

Back 179

Inhibits Ribonucleotide reductase --> dec DNA synthesis (S-phase specific)

Melanoma, CML, sickle cell disease (inc HbF)

BM suppression, GI upset

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Tox assoc w tamoxifen? How is this different from raloxifene?

Back 180

Tamoxifen may inc the risk of endometrial cancer via partial agonist effects. May also cause hot flashes.

Raloxifene does not cause endometrial carcinoma because it is an endometrial antagonist

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Trastuzumab (Herceptin): MOA? Tox?

Back 181

Monoclonal ab against Her-2 (erb-2). Helps kill cancer cells that overexpress Her-2

Cardioxicity

Front 182

Imatinib: MOA? use? tox?

Back 182

Philadelphia chromosome bcr-abl tyrosine kinase inhibitor

CML, GI stromal tumors

Fluid retention