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*First Aid in Brainscape* > Basem Goueli's Heme Onc > Flashcards

Basem Goueli's Heme Onc Flashcards

1
Q

Erythrocytes

A

Live for 120 days; 100% of energy is from glucose (10% used for HMP shunt, 90% energy); membrane contains chloride/Bicarbonate antiporter;

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2
Q

Platelets/Thrombocyte

A

Involved in primary hemostasis, derived from megakaryoctye, lives for 8 to 10 days, Contains dense granules (ADP and calcium) and alpha granules (vWF, fibrinogen). about 1/3 of platelet pool is stored in spleen

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3
Q

what is the vWF receptor

A

GpIb

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4
Q

what is the fibrinogen receptor

A

GpIIb/IIIa

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5
Q

What are the granulocytes

A

neutrophils, eosinophils, basophils;

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6
Q

What are the mononuclear cells

A

monocytes and lymphocytes

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7
Q

What is the normal WBC differential %

A

Neutrophils (54 to 62), Lymphocytes (25-33), Monocytes (3-7), Eosinophils (1-3), Basophils (0-.75)

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8
Q

Neutrophil

A

acute inflammatory response cell. Small Granules contain ALP, collagenase, lysozymes, lactoferrin; Larger granules (lysosomes) contain proteinases, acid phosphatase, myeloperoxidase, beta-glucuronidase

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9
Q

Hypersegmented neutrophils (5 or more lobes) seen in

A

Vit b12/folate deficiency

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10
Q

Increased neutrophil “band cells” seen in

A

immature neutrophils seen in states of increased myeloid proliferation (bacterial infections, CML)

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11
Q

Monocyte

A

differentiates into macrophages in tissues; Large, kidney shaped nucleus, “frosted glass” cytoplasm

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12
Q

macrophage: activated by? Functions?

A

activated by gamma interferon; can be a MHC class II antigen presenting cell; phagocytoses stuff; important in granuloma formation

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13
Q

Eosinophils

A

defend against hemonthic infections (using major basic protein), Bilobate nucleus, highly phagocytic for antigen antibody complexes. Produces histamine and arylsulfastase (helps limit reaction following mast cell degranulation)

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14
Q

Causes for eosinophilia

A

Always pronounce Eosinophilia like a stereotypically black person: NAACP! N=neoplasia, A=Asthma, A=Allergic processes, C=Connective tissue, P=Parasites

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15
Q

Basophils

A

Mediates allergic responses, Densely basophilic granules, contain heparin, histamine, and leukotrienes

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16
Q

Isolated Basophilia: what is going on

A

Super rare; can be sign of myeloproliferative state such as CML

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17
Q

Mast cell

A

mediates allergic reaction in local tissues, Can bind the Fc portion of IgE to membrane. IgE cross links upon antigen binding, causing degranulation, which releases histamine, heparin, and eosinophil chemotactic factors; involved in Type I hypersensitivity reactions. Cromolyn sodium prevents mast cell degranulation.

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18
Q

Dendritic cell

A

Highly phagocytic APC. Is a link between innate and adaptive immune system. Called langerhans cell in the skin, expresses MHC class II and Fc receptor on surface

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19
Q

Lymphocytes

A

Divided into B cells, T cells, and NK cells. B cells and T cells mediate adaptive immunity. NK cells are part of the innate immune response. Round densely staining nucleus with small amounts of pale cytoplasm.

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20
Q

B lymphocytes

A

part of humoral (antibody mediated) immune response; arises from stem cells in bone marrow; matures in marrow; migrates to peripheral lymphoid tissue (follicles of lymph nodes, white pulp of spleen, unencapsualted lymphoid tissue). When antigen is encountered, B cells differentiate into plasma cells that produce antibodies, and memory cells. Can function as an APC via MHC II

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21
Q

T lymphocytes

A

Mediates cellular immune response, originates from stem cells in the bone marrow, but matures in thymus. T cells differentiate into Cytotoxic T cells (CD8, recognize MHC I), helper T cells (CD4 recognize MHC II), and regulatory T cells, CD28 (costimulatory signal) necessary for T cell activation. The majority of circulating lymphocytes are T cells (80%).

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22
Q

Plasma cells

A

Produces large amounts of antibody specific to a particular antigen. Eccentric nucleus. Clock faced chromatin distribution, abundant RER, well developed Golgi.

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23
Q

Multiple Myeloma is a caner of what cells

A

plasma cells

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24
Q

Blood group A

A

A antigen on RBC surface and anti B antibody in plasma

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25
Q

Blood group B

A

B antigen on RBC surface and Anti A antibody in plasma

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26
Q

Blood group AB

A

A and B antigen on RBC surface; no antibodies in plasma; universal recipient of RBCs; universal donor of plasma

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27
Q

Blood group O

A

Neither A or B antigen on RBC surface; both anti A and anti B antibodies in plasma; universal donor of RBC, universal recipient of plasma.

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28
Q

Rh factor

A

Rh antigen on RBC surface. Rh- mothers exposed to fetal Rh + blood (often through delivery) may make anti-Rh IgG. In next pregnancies anti Rh IgG can cross placenta causing hemolytic disease of the newborn (erythroblastosis fetalis) in the next Rh+ fetus. treat with Rho(D) immune globulin

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29
Q

What does Rho(D) immune globulin do

A

For mother who is Rh-. Protects against initial sensitization of Rh- mom.

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30
Q

Hemophilia A is a deficiency in

A

Factor VIII

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31
Q

Hemophilia B is a deficiency in

A

Factor IX

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32
Q

Vitamin K deficiency

A

decreased synthesis of factors II, VII, IX, X, protein C, protein S.

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33
Q

vWF carries/protects what factor?

A

VIII

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34
Q

Protein C pathway for anticoagulation

A

Protein C goes through Thrombin-thrombomodulin complex (endothelial cells) to become activated protein C. Protein S takes Activated C and cleaves and inactivates Va and VIIIa

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35
Q

Plasminogen pathway for anticoagulation

A

Plasminogen is activated to plasmin via tPA causing fibrinolysis (cleavage of fibrin mesh and destruction of coagulation factors)

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36
Q

Antithrombin inhibits what

A

inhibits active forms of factors II, VII, IX, X, XI, XII; antithrombin activity is enhanced several fold by heparin; Principal targets of antithrombin are thrombin and factor Xa

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37
Q

Go through primary hemostasis (platelet plug formation)

A

1) injury (vWF binds to exposed collagen upon endothelial damage); 2) Adhesion (platelets bind vWF via GpIb receptor at site of injury (specific), platelets release ADP and Ca, ADP helps platelets adhere to endothelium and ADP helps with activation; 3) ADP binding to receptor induces GpIIb/IIIa expression at platelet surface; 4) Aggregation (fibrinogen binds GpIIb/IIIa receptors and links platelets and this temporary plug stops bleeding but it is held by a balance of pro-aggregation factors and anti-aggregation factors)

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38
Q

Primary hemostasis: Pro-aggregation factors

A

TXA2 (released by platelets), Decreased blood flow, Increased platelet aggregation

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39
Q

Primary hemostasis: Anti-aggregation factors

A

PGI2 and NO (Released from endothelial cells), increased blood flow, decreased platelet aggregation

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40
Q

Aspirins effect on thrombogenesis

A

Inhibits cyclooxygenase (which stops TXA2, which is a pro-aggregation factor)

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41
Q

Ticlopidine

A

inhibit ADP induced expression of GpIIb/IIIa; can cause neutropenia (use clopidogrel instead); synergistic with aspirin

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42
Q

Clopidogrel

A

inhibits ADP induced expression of GpIIb/IIIa; synergistic with aspirin

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43
Q

Abciximab

A

inhibits GpIIb/IIIa directly

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44
Q

Ristocetin

A

Activates vWF to bind to GpIb. Useful for diagnosis: normal platelet aggregation response is not seen in willebrand disease

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45
Q

Erythrocyte sedimentation rate

A

Acute phase reactants in plasma (e.g. fibrinogen) can cause RBC aggregation, thereby increasing RBC sedimentation rate (RBC aggregates have a higher density than plasma).

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46
Q

Decreased ESR is a sign of

A

polycythemia, sickle cell anemia, CHF, microcytosis, hypofibrinogenemia

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47
Q

Increased ESR is a sign of

A

infection, autoimmune disease, malignant neoplasms, GI diseases, pregnancy

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48
Q

Acanthocyte

A

RBC pathology
AKA a spur cell;
Associated with liver disease, abetalipoproteinemia (cholesterol dysregulation);
Acantho means spiny, looks like red ball with spikes

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49
Q

Basophilic stippling

A

pathologic RBC, round dark RBC, spotted with dark granules;
Associated with Anemia of chronic disease, alcohol abuse, lead poisoning, Thalassemias (BASIClly, ACiD alcohol is LeThal)

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50
Q

Bite cell

A

pathologic RBC

Associated with G6PD deficiency

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51
Q

Elliptocyte

A

pathologic RBC

Associated with Hereditary elloptocytosis! Never would have guessed!

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52
Q

Macro-ovalocyte

A

pathologic RBC
Associated with megaloblastic anemia (also get hypersegmented PMNs), marrow failure;
Bot blueish circular RBC

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53
Q

Ringed sideroblast

A

pathologic RBC
Sideroblastic anemia, excess iron in mitochondria=pathologic;
Looks like normal RBC but with tons of dark dots around mitochondira

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54
Q

Schistocyte, Helmet cell

A

pathologic RBC, looks like evil characters from pac-man;

Associated with DIC, TPP/HUS, traumatic hemolysis (like a mechanical heart valve)

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55
Q

Spherocyte

A

pathologic RBC;
Just a red ball with no central pallor;
Hereditary spherocytosis, autoimmune hemolysis

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56
Q

Teardrop cells

A

pathologic RBC;
look like fat sperm;
Associated with bone marrow infiltration (like myelofibrosis);
RBCs “shed a tear” because it’s been forced out of its home in the bone marrow”

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57
Q

Target cell

A

pathologic RBC
Literally looks like the Target Store Logo;
Associated with HbC disease, Asplenia, Liver disease, Thalassemia;
“HALT, I have you targeted!”

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58
Q

Heinz bodies

A

pathologic RBC;
RBC with big spots of blue in it;
From the oxidation of hemoglobin sulfhydryl groups leading to denatured hemoglobin precipitation and phagocytic damage to RBC membrane causing bite cells;
Visualized with special stains like crystal violet;
Seen in G6PD deficiency;

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59
Q

Howell-Jolly Bodies

A

pathologic RBC;
Looks like RBC with 1 singular blue splotch;
Basophilic nuclear remnants found in RBCs. Normally Howell-Jolly bodies are removed by splenic macrophages;
See in patients with function hyposplenia or asplenia.

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60
Q

Differential Diagnosis for anemia with MCV being less than 80

A

Microcytic anemia; iron deficiency, Anemia of chronic disease, Thalassemias, Lead poisoning, sideroblastic anemia

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61
Q

Iron deficiency anemia

A

Decreased iron due to increased bleeding (GI loss or menorrhagia), malnutrition/absoprtion disorders or increased demand (e.g. pregnancy) causing decreased final step in heme synthesis;
Findings: increased TIBC, Decreased ferritin, fatigue, conjunctival pallor, microcytosis and hypochromia of RBCs. May present as plummer Vinson syndrome

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62
Q

What is the triad of plummer vinson syndrome

A

Iron deficiency anemia, esophageal webs, atrophic glossitis

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63
Q

Alpha thalassemia

A

Defect in alpha globin gene deletions causing decreased alpha globin synthesis;
Cis deletion prevalent in Asiain populations; trans deletion prevalent in african populations;
Get 4 allele deletion: no alpha globin, excess gamma globin froms gamma4 (Hb Barts). Will die (hydrops fatalis)
Get 3 allele deletion: HbH disease. Very little alpha globin, excess beta globin (beta 4 or HBH). Get heinz bodies;
Get 1-2 deletion; nothing significant (with 2 may get hypochromic microcytic anemia that shows some target cells, maybe)

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64
Q

Beta thalassemia

A

Point mutation in splice sites and promoter regions leading to decreased beta globin synthesis; prevalent in mediterranean populations.

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65
Q

Beta thalassemia minor

A

Heterozygote; beta chain is underproduced;
Usually asymptomatic;
Diagnosis confirmed by increased HbA2 (>3.5%) on electrophoresis

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66
Q

Beta Thalassemia major

A

homozygote;
Beta chain is absent causing severe anemia requiring blood transfusions (get secondary hemochromatosis);
Get Marrow expansion causing skeletal deformities (crew cut on skull x ray (also seen in sickle cell), chipmunk face)
Get extramedullary hematopoiesis: leads to hepatoosplenomegaly. Increased risk of parvovirus B19 induced aplastic crisis.
Increased HbF (alpha2gamma2) is protective in infant and disease becomes symptomatic after 6 months

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67
Q

Lead poisoning

A

Lead inhibits ferrochelatase and ALA dehydratase leading to decreased heme synthesis and increased RBC protoporhyrin;
Also inhibits rRNA degradation, causing RBCs to retaion aggregates of rRNA (basophilic stippling);
High risk in old houses with chipping paint
Treat: Dimercaprol and Succimer used for chelation in kids.

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68
Q

Lead poisoning: physical exam findings

A

Lead lines on gingivae (burton lines) and on metaphyses of long bones on x ray;
Encephalopathy and Erythrocyte basophilic stippling;
Abdominal colic and sideroblastic anemia.
Drops of wrist and foot.

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69
Q

Sideroblastic anemia

A 
Defect in heme synthesis;
Hereditary: X linked defect in delta ALA synthase gene;
Causes of it: genetic, acquired (myelodysplastic syndromes) and reversible (alcohol is most common, lead, vit b6 deficiency, copper deficiency, and isoniazid);
Ringer sideroblasts (iron in mitochondria) seen in bone marrow. Increased Iron, Normal TIBC, increased ferritin. 
Treatment with pyridoxine (b6, cofactor for delta-ALA)
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70
Q

Folate deficiency

A

Macrocytic anemia
Caused by: malnutrition, malabsorption, anitfolates (methotrexate, trimethoprim, phenytoin), increased requirement (e.g. hemolytic anemia, pregnancy)
See: hypersegmented PMNs, glossitis, decreased folate, increased homocysteine but normal methylmalonic acid. No neurologic symptoms (distinguishes from B12 deficiency)

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71
Q

B12 Deficiency

A

Macrocytic anemia
Caused by: insufficient intake (strict vegans), malabsorption (e.g. crohns), pernicious anemia, Diphyllobothrium latum (fish tapeworm), PPI’s
Get: hypersegmented PMNs, glossitis, decreased B12, increased homocysteine, increased methylmalonic acid

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72
Q

What are the neurologic symptoms of B12 deficiency

A

Subacute combined degeneration (due to involvement of B12 in fatty acid pathways and myelin synthesis: Peripheral neuropathy with sensorimotor dysfunction, Dorsal columns (vibration/proprioception), Lateral corticospinal (spasticity), Dementia

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73
Q

Orotic aciduria

A

Megaloblastic anemia;
Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) because of defect in UMP synthase. Autosomal recessive. Presents in children as megaloblastic anemia that cannot be cured by folate or B12 with failure to thrive. No hyperammonemia (vs. ornithine transcarbamylase deficiency which increases orotic acid with hyperammonemia)
See: hypersegmented PMNs, glossitis orotic acid in urine;
Treatment: Uridien monophophate to bypass mutated enzyme.

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74
Q

Nonmegaloblastic macrocytic anemias

A

Macrocytic anemia in which DNA synthesis is not impaired. Caused by: liver disease, alcoholism, reticulocytosis leading to increased MCV; drugs (5-FU, zidovudine, hydroxyurea)
Macryocytosis and bone marrow suppression can occur in the absence of folate/B12 deficiency.

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75
Q

Intravascular hemolysis

A

See normocytic, normochromic anemia;
Findings: decreased haptoglobin, increased LDH, schistocytes and increased reticulocytes on blood smear; and urobilinogen in urine; e.g. paroxysmal nocturnal hemoglobinurea, mechanical destruction, microangiopathic hemolytic anemias

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76
Q

Extravascular hemolysis

A

See normocytic, normochromic anemia;
Findings: macrophage in spleen clears RBC. Spherocytes in peripheral smear, increased LDH plus increased unconjugated bilirubin, which causes jaundice (e.g. hereditary spherocytosis)

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77
Q

Anemia of chronic disease

A

Non hemolytic, normoctyic anemia;
inflammation leads to increased hepcidin (released by liver, binds ferroportin on intestinal mucosal cells and macrophages, this inhibiting iron transport) leading to decreased release of iron from macrophages;
Labs Show: decreased iron, decreased TIBC, increased ferritin, can become microcytic, hypochromic with time

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78
Q

Aplastic anemia

A

Nonhemolytic, normocytic anemia;
Caused by failure or destruction of myeloid stem cells due to: Radiation or drugs (benzene, chloramphenicol, alkylating agents, antimetabolites), Viral agents (parvovirus B19, EBV, HIV, HCV), Fanconi anemia (DNA repair defect), Idiopathic (immune mediated, primary stem cell defect), may follow acute hepatitis;
See all bone cell lines decreased, fatty marrow, fatigue, easily bleeds/bruises

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79
Q

Hereditary spherocytosis

A

Extravascular anemia;
Defect in proteins interacting with RBC membrane skeleton and plasma membrane (e.g. ankyrin, band 3, protein 4.2, spectrin). Less membrane causes small and round RBCs with no central pallor (increased MCHC, increased RBC distribution width) causing premature RBC removal by spleen;
Splenomegaly, aplastic crisis with parvoB19 infection, gallstones made of black pigment;
Labs: osmotic fragility test +, Eosin-5-maleimide binding test useful for screening, normal to decreased MCV with abundance of cells, masks microcytia;
Treat: splenectomy

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80
Q

G6PD

A

intra and extravascular anemia;
most common enzymatic deficiency in RBCs;
X linked recessive;
Defect in G6PD leads to decreased glutathione causing increased RBC susceptibility to oxidant stress. Hemolytic anemia following oxidant stress (sulfa drugs, antimalarials, infections, fava beans);
Back pain and hemoglobinuria a few days after stressor;
Labs: blood smear shows RBCs with Heinz bodies and bite cells.

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81
Q

Pyruvate kinase Deficiency

A

Extravascular anemia;
Autosomal Recessive;
Defect in pyruvate kinase leading to decreased ATP causing rigid RBCs;
Get hemolytic anemia in a newborn

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82
Q

HbC defect

A

Extravascular anemia;
Glutamic acid to lysine mutation at residue 6 in beta globin;
Patients with HbSC (1 of each mutant gene have milder disease than have HbSS patients)

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83
Q

Paroxysmal nocturnal hemoglobinuria

A

Intravascular anemia and you urinate dark red/brown;
Increased complement mediated RBC lysis (impaired synthesis of GPI anchor for decay-accelerating factor that protects RBC membrane from complement-CD55/59). Acquired mutation in a hematopoietic stem cell. Increased incidence of acute leukemias.
Triad: Coombs negative hemolytic anemia, Pancytopenia, and venous thrombosis, increased chance of pigmented gall stones;
Labs: CD55/59 Negative RBCs on flow cytometry.
Treat: eculizumab

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84
Q

Sickle cell anemia

A

Extravascular anemia;
HbS point mutation (substitution of glutamic acid with valine) in beta chain at position 6;
Pathogenesis: Low O2, dehydration, or acidosis precipitates sickling (deoxygenated HbS polymerizes), which results in anemia and vasc-occulsive disease, Spleen will be enlarged in first decade then atrophy due to infarcts and become small, bone marrow expansion to increase RBC #;
Newborns usually have HbF so they don’t show symptoms;
Heterozygotes resistant to malaria, 8% of blacks carry HbS trait
Diagnose: hemoglobin electrophoresis
Treat: hydroxyurea (increase HbF), and bone marrow transplant

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85
Q

Complications with Sickle Cell

A

Aplastic crisis (due to parvoB19);
Autosplenectomy (howell-jolly bodies) causing increased risk of infection by encapsulated organisms; early splenic dysfunction happens in childhood;
Splenic sequestration crisis;
Salmonella osteomyelitis;
Painful crisis: dactylitis, acute chest syndrome (most common cause of death in adults), avascular necrosis, stroke;
Renal papillary necrosis (Due to low O2 in papilla, also seen in heterozygotes) and microhematuria (medullary infarcts).

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86
Q

Where in the Kidneys is a sickle cell anemia likely to infarct

A

Vasa recta has increased osmolarity (cells sickle with increased osmolarity); the renal medullar shows patchy papillary necrosis causing proteinuria, renal scarring.

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87
Q

Autoimmune Hemolytic anemia: Warm agglutination

A

IgG, chronic anemia seen in SLE, CLL, and drugs (like alpha methlydopa), Warm Weather is GGGreat;
Coombs +

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88
Q

Autoimmune hemolytic anemia: cold agglutination

A

acute anemia triggered by cold; seen in CLL, mycoplasma pneumonia infections, or infectious mono

89
Q

Microangiopathic anemia

A

pathogenesis: RBCs are damaged when passing through obstructed or narrowed vessel lumina. Seen in DIC, TPP-HUS, SLE an malignant HTN.
Find: schistocytes (helmet cells) seen on blood smear due to mechanical damage to RBCs

90
Q

Macroangiopathic anemia

A

Prosthetic heart valves and aortic stenosis may also cause hemolytic anemia secondary to mechanical destruction.
Schistocytes on peripheral blood smear.

91
Q

Labs in iron deficiency anemia

A

Decreased serum iron, Increased TIBC (indirectly measures transferrin), decreased Ferritin, Decreased % transferrin saturation

92
Q

Labs in anemia of chronic disease

A

Decreased serum iron, increased ferritin, decreased TIBC (measures transferrin indirectly)

93
Q

Labs in anemia due to hemochromatosis

A

Increased serum iron, Decreased TIBC, increased ferritin, increased %transferrin saturated

94
Q

Labs in anemia due to pregnancy or OCPs

A

increased transferrin/TIBC, decreased % transferrin saturation.

95
Q

Neutropenia: what is it, cause

A

Neutrophil count

96
Q

Lymphopenia: what is it, cause

A

Lymphocyte count

97
Q

Eosinopenia: causes

A

Cushing syndrome, corticosteroids

98
Q

Lead poisoning: enzymes and effects

A

Effects the ferrochelatase and ALA dehyratase enzymes;
Accumulation of protoporphyrin delta-ALA (blood);
Presents as Microcytic anemia, GI and kidney disease. Children get exposure and have mental issues, Adults get headache, memory loss, demylination

99
Q

Acute intermittent porphyria: enzymes and effects

A

Effects the Porphobilinogen deaminase enzyme;
Accumulation of Porphobilinogen, delta ALA, coporphobilinogen (in urine);
Symptoms are the 5 Ps: Painful abdomen, Port wine colored urine, Polyneuropathy, Psychological disturbances, Precipitated by drugs, EtOH, starvation
Treat: Glucose and heme, which inhibit ALA synthase

100
Q

Porphyria cutanea tardia: enzymes and effects

A

effects Uroporphyrinogen decarboxylase enzyme;
leads to accumulation of uroporhyrin (tea-colored urine);
Blistering cutaneous photosensitivity. Most common porphyria

101
Q

PT test does what

A

Tests function of common and extrinsic pathway (I, II, V, VII, and X). Defect leads to increased PT

102
Q

PTT test does what

A

Tests function of common and intrinsic pathways (tests everything BUT VII and XIII)

103
Q

Hemophilia A and B lead to what changes in PT and PTT

A 
No change in PT (extrinsic pathway is fine)
Increased PTT (intrinsic is not okay);
Hemophilia A is defect in VIII;
Hemophilia B is defect in IX;
Why you get easy to bruise and bleeding into joints
104
Q

Vit K deficiency leads to what changes in PT and PTT

A

Increased PT and PTT;
General coagulation defect, but bleeding time is normal. Decreased synthesis of factors II, VII, IX, X, protein C and S;
Just like a patient on Warfarin

105
Q

Defects in platelet plug formation lead to an increase in

A

bleeding time

106
Q

Bernard-Soulier Syndrome

A

Decreased Platelet count, increased Bleeding time;

Defect in platelet plug formation; decreased GpIb causing defect in platelet to vWF adhesion

107
Q

Glanzmann thrombastenia

A

no change in platelet count, increased bleeding time;
Defect in platelet plug formation, decreased GpIIb/IIIa causing defect in platelet to platelet aggregation;
Labs: blood smear shows no platelet clumping

108
Q

Idiopathic (immune) thrombocytopenia purpura

A

Decreased platelet count and increased Bleeding time;
Defect: anti-GpIIb/IIIa antibodies causing splenic macrophage consumption of platelet/antibody complex. May be triggered by viral illness (acute version). Decreased platelet survival;
Labs: increased megakaryoctyes on bone marrow biopsy

109
Q

Thrombotic Thrombocytopenic purpura

A

Decreased Platelet count, increased bleeding time;
Inhibition or deficiency in ADAMTS13 (vWF metalloprotease) causing decreased degradation of vWF multimers.
Pathogenesis: Increased large vWF multimers cause increased platelet adhesion causing increased platelet aggregation and thrombosis. Decreased platelet survival.
Symptoms: pentad of neuro and renal symptoms, fever, thrombocytopenia, and microangiopathic hemolytic anemia.
Treat: exchange transfusion and steroids

110
Q

von Willebrand Disease

A

Intrinsic pathway coagulation defect: decreased vWF causing normal to increased PTT(because it carries factor 8); Defect in platelet plug formation (decreased vWF causes decreased vWF to platelet adhesion);
Autosomal dominant, most common inherited bleeding dysorder;
Labs: normal platelet count, increased bleeding time, normal PT, increased or normal PTT
Diagnosed by ristocetin cofactor assay (see decreased agglutination)
Treat: DDAVP, which releases vWF stored in endothelium

111
Q

DIC

A

Widespread activation of coagulation cascade leading to deficiency in clotting factors, which creates a bleeding state.
Causes: sepsis (gram -), Trauma (cytokine release), Obstetric complication, acute Pancreatitis, Nephrotic syndrome, Transfusion
Labs: Schistocytes, increased fibrin split products (D-dimers), decreased fibrinogen, decreased factors V and VIII.
See: decreased platelet count, increased bleeding time, increased PT, increased PTT.

112
Q

Factor V Leiden Disease

A

Production of mutant Factor V that is resistant to degradation by activated protein C. Most common cause of inherited hypercoagulability in whites.

113
Q

Prothrombin gene mutation

A

Mutation in 3’ untranslated regions causing increased production of prothrombin leading to increased plasma levels and venous clots

114
Q

Antithrombin deficiency

A

Inherited deficiency of antithrombin: has no direct effect on PT or PTT or thrombin time, but diminishes the increase in PTT following heparin administration.
Can also be acquired: renal failure/nephrotic syndrome causes antithrombin loss in urine causing increased factors II and X

115
Q

Protein C and S deficiency

A

Decreased ability to inactivate factors V and VIII. increased risk of thrombotic skin necrosis with hemorrhage following administration of Warfarin. Skin and subcutaneous tissue necrosis after warfarin administration, think protein C deficiency.

116
Q

Packed RBCs

A

Increases Hb and O2 carrying capacity;

Used for acute blood loss, severe anemia

117
Q

Platelets given IV

A

Increases platelet counts (~5000 per unit given);

stop significant bleeding

118
Q

Fresh frozen plasma

A

Increase coagulation factor levels;

Used for DIC, cirrhosis, Warfarin overdose, exchange transfusion in TPP/HUS

119
Q

Cryoprecipitate

A

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

120
Q

Leukemia Vs. Lymphoma

A

Leukemia is Lymphoid or myeloid neoplasms with widespread involvement of bone marrow. Tumor cells are usually found in peripheral blood;
Lymphoma is discrete tumor masses arising form lymph nodes. Presentations often blur definitions

121
Q

Leukemoid reaction

A

Acute inflammatory response to infection. Increased WBC count with increased neutrophils and neutrophil precursors such as band cells (left shift); increased leukocyte ALP. contrast with CML (also increase WBC count with left shift, but decrease leukocyte ALP)

122
Q

Hodgkin Lymphoma

A

Localized, single group of nodules; extranodal rare; contiguous spread (stage is strongest predictor of prognosis). Prognosis is much better than non-hodgkin.
Characterized by Reed-Sternberg cells;
Bimodal distribution with young adulthood and >55 years; more common in men except for nodular sclerosing type;
50% of cases associated with EBV;
Constitutional (“B”) symptoms: low grade fever, night sweats, weight loss

123
Q

Non-Hodgkin lymphoma

A

Multiple peripheral nodes; extranodal involvement common; noncontiguous spread;
Majority involve B cells (some are lymphoblastic T cell type);
Peak incidence for many subtypes is 20-40 years old;
May be associated with HIV and immunosuppression;
Fewer constitutional signs and symptoms

124
Q

Reed-sternberg cells

A

Distinctive tumor giant cell seen in Hodgkin disease; binucleate or bilobed with 2 halves as mirror images (“owl eyes”). RS cells are CD 15+ and CD 30+ B cell origin. Necessary but not sufficient for Hodgkin disease diagnoses. Better prognosis with strong stromal or lymphocytic reaction against RS cells. Nodular sclerosing form most common (affects genders equally). Lymphocyte rich form has best prognosis. Lymphocyte mixed or depleted forms have poor prognosis. “2 owl eyes x 15=30”

125
Q

Burkitt Lymphoma

A

Non hodgkin lymphoma: B cell origin
Occurs in: adolescents or young adults;
Genetics: (8;14) translocation of c-myc (8) (activation of c-myc) and heavy chain Ig (14);
“Starry sky appearance,” sheet of lymphocytes with interspersed macrophages and white clearings between;
Associated with EBV;
Jaw lesion in endemic form in Africa, and lesion on pelvis or abdomen (ovaries, bowel, retroperitoneum) in sporadic form

126
Q

Diffuse Large B cell Lymphoma

A

Non-hodgkin lymphoma: B cell origin
Usually older adults, but 20% are kids;
Genetics: t(14;18);
Most common type of non-hodgkin lymphoma in adults

127
Q

Mantle cell lymphoma

A

Non hodgkin lymphoma; B cell origin
Older males get this;
Genetics: t(11;14) translocation of cyclin D1 (11) and heavy chain Ig (14);
CD5+

128
Q

Follicular lymphoma

A

Non-hodgkin lymphoma; B cell origin
Adults get this;
Genetics: t(14;18) translocation of heavy chain Ig (14) and bcl-2 (18);
Indolent course; bcl-2 inhibits apoptosis. Presents with painless “waxing and waning” lymphadenopathy; Palpable spleen and liver, See CD10, CD19, CD29

129
Q

Adult T cell lymphoma

A

Non Hodgkin lymphoma; T cell origin;
Usually in adults;
Caused by HTLC-1 (associated with IV drug use);
Adults present with cutaneous lesions; especially affects populations in Japan, West africa, and the Caribbean;
Lytic bone lesions, hypercalcemia

130
Q

Mycosis fungiodes/Sezary syndrome

A

Non-hodgkin lymphoma; CD4+ T cell origin;
Usually in Adults;
Adults present with cutaneous patches/plaques/tumors with potential to spread lymph nodes and viscera. Circulating malignant cells seen in Sezary syndrome. Indolent.

131
Q

Multiple Myeloma: what is it, who gets it

A

Monoclonal plasma cell cancer that arises in the marrow and produce large amount of IgG (55%) or IgA (25%). Most common primary tumor arising within bone of the elderly (. 40-50 years old).

132
Q

Multiple myeloma: Associated with

A

Increased susceptibility to infection; Primary amyloidosis (AL); Punched out lytic bone lesions on x rays; M spike on serum protein electrophoresis; Ig light chains (most likely IgG light chains) in urine (Bence Jones protein); Rouleaux formation (RBCs stacked like poker chips in blood smear); Russel bodies in cytoplasm of plasma cells (white circular lesions made up of Ig)

133
Q

Multiple Myeloma: CRAB

A

hyperCalcemia, Renal insufficiency, Anemia, Bone lytic lesions/back pain;
Also Multiple Myeloma: monoclonal M protein spike

134
Q

Waldenstrom macroglobulinemia

A

It has an M spike like Multiple Myeloma but it is IgM; You get hyperviscosity symptoms, no lytic bone lesions

135
Q

Monoclonal gammopathy of undetermined significance (MGUS)

A

Monoclonal expansion of plasma cells with serum monoclonal protein

136
Q

Myelodysplastic Syndrome

A

Stem cell disorders involving ineffective hematopoiesis leading to defects in cell maturation of all non-lymphoid lineages. Caused by de novo mutations of environmental exposure (e.g. radiation, benzene, chemotherapy). Risk of transformation to AML.

137
Q

Pseudo-Pelger-Huet anomaly

A

neutrophils with bilobed nuclei (two nuclear masses connected with a thin filament of chromatin). Typically seen after chemotherapy.

138
Q

Lymphoma

A

Unregulated growth of leukocyte in bone marrow leading to increase or decreased number of circulating leukocyte in blood and marrow failure leading to anemia (decreased RBC), infections (decreased mature WBCs), and hemorrhage (decreased platelets); leukemic cell infiltrates in liver, spleen, and lymph nodes are possible

139
Q

Acute Lymphoblastic leukemia/lymphoma (ALL)

A

Lymphoid neoplasm

Age:

140
Q

Small lymphoblastic lymphoma (SLL)/ Chronic Lymphocytic Leukemia (CLL)

A

Age: >60 years old. CD20+, CD5+ B cell neoplasm. Often asymptomatic, progresses slowly, smudge cells in blood smear (leukocytes that are smashed open);
Autoimmune hemolytic anemia.
SLL same as CLL except CLL has increased peripheral blood lymphocytosis or bone marrow involvement.
Can progress to B cell lymphoma (Richter transformation)

141
Q

Hairy cell leukemia

A

Age: adults. Mature B cell tumor in the elderly. Cells have filamentous hair like prjections.
Get recurrent infections due to decreased WBC count; splenomegaly;
Neoplastic cells have positive B cell markers of CD19, 20, IgG surface molecules, kappa and lamda light chains and monocyte surface proteins of CD11c and CD25;
Stains TRAP (tartrate-resistant acid phosphate +). TRAP stain largely replaced by flow cytometry. Causes marrow fibrosis leading to dry tap on aspiration.
Treat: cladribine (2-CDA), and adenosine analog (inhibits adenosine deaminase)

142
Q

Acute Myelogenous Leukemia (AML)

A

Age: median onset 65 years;
See Auer rods, peroxidase + cytoplasmic inclusions seen mostly in M3 AML; Increased circulating myeloblasts on blood smear.
Risk factors: Exposure to alkylating chemo, radiation, myeloproliferative disorders, Down syndrome.

143
Q

AML with t(12;17)

A

M3 AML; Responds to all-trans retinoic acid (vitamin A) by inducing differentiation of myeloblasts. DIC is a common presentation in M3 and can be induced by chemotherapy due to release of Auer Rods.

144
Q

Chronic Myelogenous Leukemia (CML)

A

Age: peak incidence 45-85 years old. Median age is 64;
Defined by philadelphia chromosome (t(9;22), bcr-abl);
Myeloid stem cell proliferation;
presents with increased neutrophils, metamyelocytes (immature neutrophils), basophils; hepatosplenomegaly; may accelerate and transform to AML or ALL (“blast crisis”).
Very low leukocyte alkaline phosphatase (LAP) as a result of low activity in mature granulocytes (vs. leukemoid reaction, in which LAP is increased).

145
Q

t(9;22)

A

Philadelphia chromosome;
get CML;
bcr-abl hybrid

146
Q

t(8;14)

A

Burkitt lymphoma; (c-myc activation)

147
Q

t(11;14)

A

Mantle cell lymphoma (cyclin D1 activation)

148
Q

t(14;18)

A

Follicular lymphoma (bcl-2 activation)

149
Q

t(15;17)

A

M3 type of AML (responsive to all-trans retinoic acid)

150
Q

langerhans cell histiocytosis

A

Proliferative disorders of dendritic (langerhans) cells from moncyte lineage. Presents in a child as lytic bone lesions and skin rash or as recurrent otitis media with a mass involving the mastiod bone. Cells functionally immature and do not efficiently stimulate primary T lymphocytes via antigen presentation. Cells express S-100 (mesodermal origin) and CD1a. Birbeck granules (“tennis rackets” on EM) are characteristic.

151
Q

Chronic myeloproliferative disorders

A

represent an often-overlapping spectrum, but there are classic findings. JAK2 is involved in hematopoietic growth factor signaling. Mutations are implicated in myeloproliferative disorders other than CML.

152
Q

Polycythemia vera

A

chronic myeloproliferative disorder;
Hematocrit >55%, somatic (non-hereditary) mutation in JAK2 gene. Often presents as intense itching after hot shower. Rare but classic symptom is erythomegalia (severe burning pain and reddish or bluish coloration) due to episodic blood clots in vessels of the extremities. Secondary polycythemia is via natural or artificial increase in EPO levels.
In primary polycthemia vera there is a decreased EPO.

153
Q

Essential thrombocytosis

A

chronic myeloproliferative disorder;
similar to polycythemia vera, but specific for overproduction of abnormal platelets leading to bleeding thrombosis. Bone marrow contains enlarged megakaryocytes.

154
Q

Myelofibrosis

A

chronic myleoproliferative disorder;
Fibrotic obliteration of bone marrow. Teardrop RBCs and immature forms at the myeloid line. “bone marrow is crying because it’s fibrosed”

155
Q

Labs and genetics in polycythemia vera

A

increased RBCs; increased WBCs; Increased platelets; JAK2 mutation

156
Q

Labs and genetics in Essential thrombocytosis

A

Normal RBCs, Normal WBCs, Increased Platelets, increased JAK2 mutations (30-50%)

157
Q

Labs and genetics in Myelofibrosis

A

Decreased RBCs, Variable WBCs, Variable platelets, JAK2 mutations (30-50%)

158
Q

Labs and genetics in CML

A

decreased RBCs, Increased WBCs, Increased platelets, + philadelphia chromosome mutation.

159
Q

Heparin

A

cofactor for the activation of antithrombin, decreased thrombin, and decreased factor Xa, Short half life;
Used for immediate anticoagulation for PE, acute coronary syndrome, MI, DVT. Used during pregnancy (does not cross placenta. Follow aPTT.
Toxicity: bleeding, thrombocytopenia;

160
Q

Low molecular weight heparin

A

Enoxaparin, Dalteparin;
Act more on Factor Xa;
Better bioavailability and 2-4 times longer half life;
can be giving subcutaneously and without lab monitoring;
not easily reversed

161
Q

Heparin induced thrombocytopenia (HIT)

A

Development of IgG antibodies against heparin bound to platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets leading to thrombosis and thrombocytopenia. Give bivalirudin or argatroban after stopping heparin. May take a couple days to show up, but will look like purpuric non blanching lesions.

162
Q

Argatroban and bivalirudin

A

Derivatives of hirudin, the anticoagulant used by leeches;
inhibits thrombin directly;
Used instead of heparin for anticoagulating patients with HIT

163
Q

Mechanism of Warfarin

A

Interferes with norma synthesis of gamma carboxylation of vitamin K dependent clotting factors II, VI, IX, and X and proteins C and S (at therapeutic levels inhibits 7 (increased PT)
Metabolized by CYP450;
Has effect on Extrinsic pathway and increases PT

164
Q

Clinical use of Warfarin

A

Chronic anticoagulation after STEMI, venous thromboembolism prophylaxis, and prevention of stroke in A Fib.
Not used in pregnant women, crosses placenta;
Follow PT/INR values

165
Q

Toxicity of Warfarin

A

Bleeding, teratogenic, skin/tissue necrosis;
To reverse give Vitamin K, unless it is real bad then you give fresh frozen plasma.
At toxic levels it increases not only PT but also PTT,

166
Q

Direct Factor Xa inhibitor

A

Apixaban, Rivaroxaban;
Mechanism: bind and directly inhibit the activity of factor Xa;
Uses: Treat and prophylaxis of DVT and PE(rivaroxaban), stroke prophylaxis in patients with atrial fib. Do not need lab monitoring;
Toxicity would be bleeding and there are no reversal agents

167
Q

Thrombolytics

A

Alteplase (tPA), reteplase (rPA), tenecteplase (TNK-tPA);
Mechanism: directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots. Increased PT, Increased PTT, no change in platelet counts;
Used for: Early MI, early ischemic strokes, Direct thrombolysis of PE;
Toxicity: bleeding

168
Q

Thrombolytics are causing bleeding, how are you going to do to reverse it

A

aminocaproic acid which is an inhibitor of fibrinolysis;

Fresh frozen plasma and cryoprecipitate can also help.

169
Q

Aspirin

A

Irreversibly inhibits COX 1 and 2 by covalent acetylation;
increase bleeding time, decrease TXA2 and prostaglandins. No effect on PT or PTT;
Antipyretic, analgesic, anti inflammatory, antiplatelet (decreases aggregation);
Toxicity: GI ulceration, tinnitus (CN VIII), chronic use leading to acute renal failure, interstitial nephritis, upper GI bleed

170
Q

Reye syndrome

A

Give a kid aspirin when they have a viral infection;

Kids gets respiratory alkalosis early then a superimposed metabolic acidosis takes over.

171
Q

ADP receptor inhibitors

A

Clopidegrel, ticlopidine, prasurgrel, ticagrelor;
Mechanism: inhibit platelet aggregation by irreversibly inhibiting ADP receptors, inhibits fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen ;
Uses: acute coronary syndrome, coronary stenting. Decreased incidence or recurrence of thrombotic stroke.
Toxicity: Neutropenia (ticlopidine). TTP/HUS may be seen

172
Q

Cilostazol, dipyridamole

A

Phosphodiesterase III inhibitors; increase cAMP in platelets, thus inhibiting platelet aggregation; vasodilators.
Use: intermittent claudication, coronary vasodilation, prevention of stroke or TIAs (combined with aspirin), angina prophylaxis.
Toxicity: Nausea, headache, facial flushing, hypotension, ab pain

173
Q

GPIIb/IIIa inhibitors

A

Abciximab, eptifibatide, tirofiban;
Mechanism: bind to the glycoprotein receptor GP IIb/IIIa on activated platelets, preventing aggregation. Abciximab is made from monoclonal antibody Fab fragments.
Use: unstable angina, percutaneous transluminal coronary angioplasty;
Toxicity: Bleeding and thrombocytopenia

174
Q

What are the M phase cancer drugs

A

Vinca alkaloids and taxols

175
Q

What are the S phase cancer drugs

A

Etoposides and antimetabolites

176
Q

What are the G2 phase cancer drugs

A

Bleomycin and etoposides

177
Q

Methotrexate: mechanism

A

Antimetabolite (S phase)
Folic acid analog that inhibits dihydrofolate reductase leading to decreased dTMP causing decreased DNA and decreased Protein synthesis

178
Q

Methotrexate: clinical uses

A

Cancers: leukemias, lymphomas, choriocarcinomas, sarcomas

Non-neoplastic: abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis, IBD

179
Q

Methotrexate: toxicity

A

Myelosuppresion, which is reversible with leucovorin (folinic acid);
Macrovesicular fatty change in liver;
Mucositis;
Teratogenic

180
Q

5-fluorouracil (5-FU): mechanism

A

Antimetabolite (S phase)
Pyrimidine analog bioactivated to 5F-dUMP which covalently complexes folic acid.
This complex inhibits thymidylate synthase leading to an increase in dTMP causing decreased DNA and protein synthesis

181
Q

5-fluorouracil: uses

A

Colon cancer, pancreatic cancer, basal cell carcinoma (topical)

182
Q

5-fluorouracil: toxicity

A

Myelosuppression, which is not reversible with leucorvin.
Overdose treated with uridine;
photosensitivity

183
Q

Cytarabine (arabinofuranosyl cytidine): mechanism

A

Antimetabolite (S phase)

Pyrimidine analog causes inhibition of DNA polymerase

184
Q

Cytarabine (arabinofuranosyl cytidine): Uses

A

Leukemias, lymphomas

185
Q

Cytarabine (arabinofuranosyl cytidine): Toxicity

A

Leukopenia, thrombocytopenia, megaloblastic anemia

186
Q

Azathiprine, 6-MP, 6-thioguanine (6-TG): Mechanism

A

Antimetabolite (S phase);

Purine (thiol) analog leading to decreased de novo purine synthesis. Activated by HGPRT.

187
Q

Azathiprine, 6-MP, 6-thioguanine (6-TG): Uses

A

Prevents organ rejection, RA, SLE (azathioprine). Leukemia IBD (6-MP and 6-TG)

188
Q

Azathiprine, 6-MP, 6-thioguanine (6-TG): Toxicity

A

Bone marrow, GI, liver for all;

Azathiprine and 6-MP are metabolized by xanthine oxidase so both have increased toxicity when given with allopurinol.

189
Q

Dactinomycin

A

Antitimumor antibiotics, actinomycin D;
Mechanism: intercalates in DNA;
Uses: wilms tumor, Ewing sarcoma, rhabdomyosarcoma, Used for childhood tumors;
Toxicity: myelosuppression

190
Q

Doxorubicin, adriamycin, daunorubicin

A

Antitumor antibiotics;
Mechanism: generates free radicals and intercalates into DNA leading to DNA breaks and decreases replication;
Uses: Solid tumors, leukemias, lymphomas
Toxicity: Cardiotoxicity (dilated cardiomyopathy), myelosuppression, alopecia, toxic to tissues following extravasation (CHF, S3 heart sounds). Dexrazoxane (iron chelating agent) used to prevent cardiotoxicity

191
Q

Bleomycin

A

Antitumor antibiotic;
Induces free radical formation, which causes breaks in DNA strands.
Uses: testicular cancer, hodgkins lymphoma
Toxicity: pulmonary fibrosis, skin changes, minimal myelosuppression

192
Q

Cyclophosphamide, ifosfamide

A

Alkylating agent
Covalently X-linked (interstrand) DNA at guanine N-7. Require bio activation by liver.
Uses: Solid tumors, lymphomas, leukemias, and some brain cancers.
Toxicity: Myelosuppression, hemorrhagic cystitis, partially prevented with mesna (thiol group of mesna binds toxic metabolites)

193
Q

Nitrosoureas

A

Carmustine, lomustine, semustine, streptozocin;
Alkylating agents;
Require bioactivation, crosses BBB, Cross links DNA;
Uses: Brain tumors (including glioblastoma multiforme);
CNS toxicity (convulsions, dizziness, ataxia)

194
Q

Busulfan

A

Alkylating agent;
Cross links DNA;
Uses: CML, also used to ablate patient’s bone marrow before bone marrow transplant;
Toxicity: severe myelosuppression (in every case), pulmonary fibrosis, hyperpigmentation

195
Q

Name all the alkylating agents

A

Cyclophosphamide, Ifosfamide, carmustine, lomustine, semustine, streptozocin, busulfan

196
Q

Vincristine, Vinblastine

A

Microtubule inhibitors;
Vinca alkaloids (M phase) that bind Beta tubulin, inhibits its polymerization into microtubules, thereby preventing mitotic spindle formation (M phase arrest);
Uses: solid tumors, leukemias, and lymphomas
Toxicity: vincristine neurotoxicity (areflexia, peripheral neuritis), paralytic ileus. Vinblastine blasts bones marrow (suppression)

197
Q

paclitaxel, -taxols

A

Microtubule inhibitors;
M phase, Hyperstabilizes microtubules so that mitotic spindle cannot break down (anapahse cannot occur). “it is taxing to stay polymerized”
Uses: Ovarian and breast carcinomas;
Toxicity: Myelosuppression, alopecia, hypersensitivity

198
Q

Cisplatin, Carboplatin

A

Mechanism: Cross-links DNA;
Uses: Testicular, bladder, ovary, and lung carcinomas;
Toxicity: Nephrotoxicity and acoustic damage. Prevent nephrotoxicity with amifostine (free radical scavenger) and chloride diuresis.

199
Q

Etoposide, Teniposide

A

Mechanism: inhibits TOPOisomerase II leads to increased DNA degradation;
Uses: Solid tumors (particularly testicular and small cell lung cancer), Leukemias, Lymphomas
Toxicity: Myelosuppression, GI irritation, alopecia

200
Q

Irinotecan, topotecan, -tecan

A

Inhibit topoisomerase I and prevent DNA unwinding and replication;
Uses: colon cancer (irinotecan); ovarian and small cell lung cancers (topotecan);
Toxicity: severe myelosuppression, diarrhea

201
Q

Hydroxyurea

A

Mechanism: Inhibits ribonucleotide reductase leading to decreased DNA synthesis (S phase);
Uses: Melanoma, CML, Sickle cell disease (increases HbF);
Toxicity: Bone marrow suppression, GI upset

202
Q

Prednisone, prednisilone

A

Mechanism: may trigger apoptosis, may even work on non-dividing cells;
Uses: Most commonly used glucocorticoids in cancer chemo. Used in CLL, non-hodgkin lymphomas (part of combination chemotherapy regiment). Also used as immunosuppressant;
Toxicity: Cushings like symptoms, weight gain, central obesity, muscle breakdown, cataracts, acne, osteoporosis, HTN, peptic ulcers, hyperglycemia, psychosis.

203
Q

Tamoxifen, Raloxifene, -oxifen

A

Selective estrogen receptor modulators (SERMs)- receptor antagonists in breast and agonists in bone. Block the binding of estrogen to ER + cells;
Used for breast cancer treatment (tamoxifen) and prevention. Ralozifene also used to prevent osteoporosis;
Toxicity: tamoxifen is partila agonist in endometrium leading to increase risk of endometrial cancer and hot flashes, Raloxifene is endometrial antagonist

204
Q

Trastuzumab (herceptin)

A

Monoclonal antibody against HER-2 (c-erbB2), a tyrosine kinase receptor. Kills breast cancer cells that over express HER2 through inhibiting HER2 initiated cellular signaling and antibody dependent cytotoxicity;
Uses: HER2 + breast cancer and gastric cancer;
Toxicity: Cardiotoxicity
Remember tras2zumab (gastric and breast)

205
Q

Imatinib (gleevac)

A

Tyrosine kinase inhibitor of bcr-abl (philadelphia chromosome fusion gene in CML) and c-KIT (common in GI stromal tumors);
Uses: CML, GI stromal tumors;
Toxicity: fluid retention

206
Q

Rituximab

A

Monoclonal antibody against CD20, which is found on most B cell neoplasms;
Uses: Non-Hodgkin lymphoma, rheumatoid arthritis (with MTX), ITP;
Toxicity: Increased risk of progressive mutlifocal leukoencephalopathy

207
Q

Vemurafenib

A

Small molecule inhibitor of forms of the B-Raf Kinase with the V600E mutation.
Used for metastatic melanoma

208
Q

Bevacizumab

A

Monoclonal antibody against VEGF. inhibits angiogenesis;
Uses: Solid tumors (colorectal, renal cell carcinoma);
Toxicity: Hemorrhage and impaired wound healing

209
Q

Labs show what in DIC

A

Decreased fibrinogen, elevated fibrin degradation products, D-Dimers, and prolonged bleeding

210
Q

elevated D-Dimers mean what?

A

That clotting is taking place, or has taken place recently (clotting factors are being used)

211
Q

Difference between D dimer and Fibrin degradation products

A

D Dimer can only come from the degradation of fibrin clots, where as FDPs can come from fibrin clots or from the normal breakdown of fibrinogen

212
Q

Drugs that interfere with Warfarin

A

Drugs that also use CYP2C9 (so it increases Warfarin’s effect): Azoles, Cimetidine, cotrimoxazole, fluoxitine, Fluoroquinolones, marolides (but not azithromycine), metronidazole, sulfinpyrazone

213
Q

What is the name for “red dots in the cytoplasm of RBCs” and what does it mean

A

Probably Schuffner cells, means malaria

214
Q

When you treat a patient with chemotherapy that has M3 leukemia, what is a possible side effect you are worried about

A

They get DIC. You give all trans retinoic acid and that probably won’t happen (that is why we give ATRA)

215
Q

Serum Lactate Dehydrogenase will be increased when

A

It is the enzyme in glycolysis that will be elevated when you have cell lysis (mostly elevated when RBCs lyse, but lots of cells have this)

216
Q

Haptoglobin

A

Binds to hemoglobin when a RBC lyses its hemoglobin out. The serum haptoglobin will be decreased in cases of hemolytic anemia.

217
Q

Microspherocytes are what

A

they are small RBCs that have antibody coated portions of the RBC clipped off by macrophages.

218
Q

Direct coombs looks for

A

whether there are antibodies bound to RBCs

219
Q

What does an aPTT measure

A

measures the intrinsic and common pathway. Factors I, II, V, VIII, IX, X, XI, XII;
Used to monitor Heparin

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