March 28 - Heme/onc

Question 1

Azathioprine/ 6-mercaptopurine pathway

Answer 1

Azathioprine is prodrug activated to 6-mercaptopurine

6-mercaptopruine can be converted to active metabolites by HGPRT

Can be converted to inactive metabolites by xanthine oxidase or TPMT

Question 2

Factor Xa vs thrombin inhibitors

Answer 2

Direct factor Xa inhibitors: rivaroxaban and apixaban (X in name)

Direct thrombin inhibitors: Argatroban, bivalirudin, dabigatran. Drugs of choice in HIT

Question 3

Factors made in endothelial cells

Answer 3

vWF and VIII

Question 4

Tumor basement membrane penetration

Answer 4

1. Detach from surrounding cells by decreasing adhesion molecule expression (e-cadherin)
2. Adhere to BM by increaseing laminin and other adheion molecules
3. Invade BM by secreting proteolytic enzymes like metalloproteinases

Question 5

Proteosome inhibitors

Answer 5

Used in multiple myeloma, Causes accumulation of toxic intracellular proteins which leads to apoptosis of malignant plasma cells

Question 6

Burkitt lymphoma translocation

Answer 6

t(14;18). c myc and Ig heavy chain. Associated with EBV

Question 7

Cachexia

Answer 7

Anorexia, malaise, anemia, weight loss, and wasting seen in cancer. Mediated by TNF-alpha which is produced by some neoplastic cells

Question 8

TNF-alpha

Answer 8

In ifection, produced by macropahges and increases acute phase reactants.

In cancer, produced by neoplastic cells and causes chachexia

Question 9

Pure red cell aplasia

Answer 9

Hypoplasia of marrow erythroid elements with normal granulopoiesis and thrombopoiesis. Caused by inhibition of erythrocytic precursors and progenitors by autoantibodies and T cells. Associated with thymoma, parvovirus B19 infection

Question 10

Fanconi anemia

Answer 10

Inherited aplastic anemia + short stature + absent thumbs

Question 11

Angiogenesis

Answer 11

Caused by VEGF and fibroblast growth factor

Question 12

Warfarin-induced skin necrosis pathophys

Answer 12

Not an allergic reaction to drug. Seen due to deficiency of protein C or S when starting warfarin leading to transient hypercoagulability and thrombotic occlusion of the micrvasculature, causing skin necrosis

Question 13

Paroxysmal nocturnal hemoglobinuria: pathophysiology and presentation

Answer 13

Pathophysiology: Complement-mediated hemolysis. Caused by mutation in PIGA gene which helps to synthesize GPI anchor. GPI needed to attach CD55 and CD59 which inactivate complement. Thus, in their absence, get complement-mediated hemolysis.

Presentation: Hemolytic anemia. Thrombosis at atypical sites because lysed cells release prothrombotic factors. Pancytopenia due to stem cell injury. Hemosiderosis of kidney due to break down of iron-containing red cells and dposition in kidney

Question 14

vWF function

Answer 14

1. Promotes platelet adhesion by crosslinking platelet glycoproteins (GpIb) with exposed collagen on damaged endothelium
2. Carries factor VIII, increasing its half life

Question 15

Prostacyclin

Answer 15

Inhibits platelet aggregation

Question 16

CML vs leukemoid reaction

Answer 16

both increase WBCs and increase precursor forms

CML causes decreased leukocyte alk phos as cells are cytogenetically abnormal
Leukemoid reaction has normal to increased leukocyte alk phos

Question 17

Uremic platelet dysfunction

Answer 17

Seen in those with severe renal dysfunction. Accumulation of uremic toxins in circulation leads to decreased platelet aggregation and adhesion. This increases bleeding time but wiht normal platelet count.

Question 18

T-ALL presentation

Answer 18

Can present with large anterior mediastinal mass (where thymus is(. Can compress great vessels leading to superior SVC syndrome, compress esophagus leading to dysphagia, and compress trachea leading to dyspnea and stridor

Question 19

Thrombotic thrombocytopenic purpora pathogenesis

Answer 19

Decreased ADAMTS13 activity, either due to autoantibody or inerited defect. ADAMTS13 is a protease that normally vleaves vWF. Deficiency results in large vWF multimers that cause diffuse microvascular thrombi