Hematology & Oncology

First Aid Express 2016 workbook: HEMATOLOGY & ONCOLOGY page 1

How to Use the Workbook with the Videos

Using this table as a guide, read the Facts in First Aid for the USMLE Step 1 2016, watch the corresponding First Aid Express 2016 videos, and then answer the workbook questions.

Facts in First Aid for Corresponding First Aid Workbook the USMLE Step 1 2016 Express 2016 videos questions 378.1–381.1 Anatomy (2 videos) 1–10 381.2–385.2 Physiology (2 videos) 11–14 386.1–404.2 Pathology (9 videos) 15–30 405.1–413.4 Pharmacology (3 videos) 31–35

Questions

ANATOMY

1. Define the following terms. (p 378) A. Anisocytosis ______B. Poikilocytosis ______C. Thrombocytopenia ______

2. What do the dense granules of platelets contain? (p 378) ______

3. What do the α-granules of platelets contain? (p 378) ______

4. List the types of white blood cells in order of decreasing prevalence. (pp 378) ______

______

5. What conditions can cause hypersegmentation of neutrophils? (p 378) ______

______

6. CD14 is a cell surface marker for which cell type? (p 379) ______

7. What five conditions can cause eosinophilia? (p 379) ______

8. What molecules are released by basophils? (p 379) ______

______

9. B lymphocytes are produced in the ______(bone marrow/thymus) and mature in the ______(bone marrow/thymus). T lymphocytes are produced in the ______(bone marrow/thymus) and mature in the ______(bone marrow/thymus). (p 380)

10. What type of cell has an off-center nucleus, abundant RER, and a clock-face chromatin dis- tribution? (p 381) ______

PHYSIOLOGY

11. Why are Rh-negative mothers given RhoGAM? (p 382) ______

______

12. In the chart, check which coagulation factors are in the intrinsic vs. the extrinsic coagulation pathways. (p 384)

Factor Extrinsic Pathway Intrinsic Pathway Both Pathways I II V VII VIII IX X XI XII

13. Which factors are vitamin K dependent? How does warfarin inhibit the activation of these factors? (p 384) ______

______

14. Describe the four steps of primary hemostasis and platelet plug formation. (p 385) ______

______

PATHOLOGY

15. Identify each cell type and its associated pathology. (pp 386-387)

A. B. C. D. E. F.

A. ______D. ______B. ______E. ______C. ______F. ______

16. In α-thalassemia, what is the condition called when all four α-globin genes are deleted? When three are deleted? When one or two are deleted? (p 388) ______

17. Indicate whether the lab findings in the chart are elevated, decreased, or normal. (pp 388, 389, 391, 393)

Anemia of Iron Pregnancy/ Hemo- Lab Value Chronic Deficiency OCPs chromatosis Disease Ferritin Serum iron Transferrin % Transferrin

18. In lead poisoning what enzymes are affected and what substrates are accumulated? (p 389) ______

19. What clinical manifestations do folate deficiency and vitamin B12 deficiency have in common? What sets them apart? (p 390) ______

20. What are four causes of aplastic anemia? (p 391) ______

21. Match the intrinsic hemolytic normocytic anemia with its characteristic. (p 392) _____ A. G6PD deficiency 1. GLU  LYS mutation _____ B. HbC defect 2. GLU  VAL mutation _____ C. Hereditary spherocytosis 3. Heinz bodies _____ D. Paroxysmal nocturnal hemoglobinuria 4. Howell-Jolly bodies _____ E. Pyruvate kinase deficiency 5. Increased incidence of acute leukemias _____ F. Sickle cell anemia 6. Rigid RBCs

22. Which autoimmune hemolytic anemias are warm and which are cold? (p 393) ______

______

23. What are the “5 P’s” of acute intermittent porphyria? (p 395) ______

______

24. Indicate whether the lab findings in the chart are elevated, decreased, or normal. (pp 396-398)

Platelet Bleeding Disorder PT PTT Count Time

DIC Glanzmann thrombasthenia Hemophilia TTP Vitamin K deficiency von Willebrand disease

25. Which type of Hodgkin lymphoma is equally prevalent in men and women? (p 399) ______

26. What type of cell is shown by the arrow in the image? In what condition is this cell seen? (p 399) ______

27. Match the disease with the genetic translocation most closely associated with it. (pp 400-403) _____ A. Burkitt lymphoma 1. t(8;14) _____ B. Chronic myelogenous leukemia 2. t(9;22) _____ C. Follicular lymphoma 3. t(11;14) _____ D. M3 AML 4. t(14;18) _____ E. Mantle cell lymphoma 5. t(15;17)

28. What will serum protein electrophoresis reveal in a patient with multiple myeloma? What will be seen in the urine? (p 401) ______

29. What are the four major groups of leukemia? Which type is at risk for DIC upon initiation of treatment and why? (p 402) ______

______

30. Indicate whether the lab findings in the chart are elevated, decreased, or normal. (p 404)

Chronic Myeloproliferative Platelets RBCs WBCs Disorder CML Essential thrombocytosis Myelofibrosis Polycythemia vera

PHARMACOLOGY

31. What is the mechanism of action of heparin? How is overdose treated? (p 406) ______

______

32. What is the mechanism of action of warfarin? How is overdose treated? (p 406) ______

______

33. Indicate how the drugs in the chart affect the lab findings. (pp 406-407)

Bleeding Platelet Drug PT PTT Time Count

Aspirin Clopidogrel/abciximab Heparin Warfarin

34. Match the drug with its target. (pp 409-413)

_____ A. Abciximab 1. ADP receptor (platelets) _____ B. Clopidogrel 2. B cells (CD20) _____ C. Etoposide 3. bcr-abl tyrosine kinase _____ D. 5-Fluorouracil 4. Estrogen receptor _____ E. Imatinib 5. Glycoprotein IIb/IIIa receptor _____ F. Rituximab 6. HER2 (erb-B2) _____ G. Tamoxifen 7. Plasminogen _____ H. tPA 8. Thymidylate synthase _____ I. Trastuzumab 9. Topoisomerase II _____ J. Vincristine 10. Tubulin

35. Match the patient with the drug he or she is most likely taking. (pp 409-410) _____ A. Patient preparing for bone marrow transplantation has 1. Bleomycin PFTs consistent with restrictive lung disease 2. Busulfan _____ B. Patient with colon cancer has myelosuppression 3. Cyclophosphamide not reversible with leucovorin 4. Doxorubicin _____ C. Patient with non-Hodgkin lymphoma is having 5. 5-Fluorouracil hemorrhagic cystitis 6. Methotrexate _____ D. Patient with leukemia is having myelosuppression reversible with leucovorin _____ E. Patient with solid tumor is having dilated cardiomyopathy _____ F. Patient with testicular cancer has PFTs consistent with restrictive lung disease

Answers

ANATOMY

1. A. Anisocytosis: Cells vary in size. B. Poikilocytosis: Cells vary in shape. C. Thrombocytopenia: Decreased number of platelets.

2. ADP and calcium.

3. von Willebrand factor, fibrinogen, and fibronectin.

4. Neutrophils, lymphocytes, monocytes, eosinophils, and basophils.

5. Vitamin B12 and folate deficiency.

6. Macrophages.

7. Neoplasia, asthma, allergic processes, chronic adrenal insufficiency, and parasites (invasive).

8. Histamine, heparin, and leukotrienes.

9. Bone marrow; bone marrow; bone marrow; thymus.

10. Plasma cell.

PHYSIOLOGY

11. To prevent the development of anti-Rh IgG, which can cause erythroblastosis fetalis in a subsequent fetus.

12. Factor Extrinsic Pathway Intrinsic Pathway Both Pathways I √ II √ V √ VII √ VIII √ IX √ X √ XI √ XII √

13. Factors II, VII, IX, X, and proteins C and S. Warfarin inhibits the enzyme vitamin K epoxide reductase, which is necessary to convert vitamin K to its reduced form so that it can go on to activate these factors.

14. 1. Injury: Endothelial damage occurs.

2. Exposure: Prompts vWF binding to exposed collagen.

3. Adhesion: Platelets bind vWF via the GpIb receptor and release ADP/Ca2+.

4. Activation: ADP binds the ADP receptor, and GpIIb/IIIa is expressed. Aggregation: Fibrinogen binds GpIIb/IIIa and links platelets.

PATHOLOGY

15. A = Degmacyte (bite cell): G6PD deficiency. B = Ringed sideroblast: sideroblastic anemia. C = Schistocyte: microangiopathic hemolytic anemia (DIC, TTP, HUS). D = Dacrocyte (teardrop cell): bone marrow infiltration or myelofibrosis. E = Target cell: HbC disease, asplenia, liver disease, thalassemia. F = Heinz bodies: α-thalassemia, G6PD deficiency.

16. Four deletions: Hb Barts; three deletions: HbH disease; one or two deletions: less clinically severe.

17. Anemia of Iron Pregnancy/ Hemo- Lab Value Chronic Deficiency OCPs choromatosis Disease Ferritin ↑ ↓ normal ↑ Serum iron ↓ ↓ normal ↑ Transferrin ↓ ↑ ↑ ↓ % Transferrin normal ↓↓ ↓ ↑↑

18. Enzymes: Ferrochelatase and ALA dehydratase. Substrates: Protoporphyrin and δ-ALA (blood)

19. Both folic acid and vitamin B12 deficiency can cause megaloblastic anemia. Only vitamin B12 deficiency, however, is associated with neurologic symptoms, such as subacute combined degeneration. Also B12 deficiency is associated with increased methylmalonic acid, unlike folic acid deficiency.

20. Idiopathic, radiation and drug exposure, viral agents, and Fanconi anemia.

21. A-3, B-1, C-4, D-5, E-6, F-2.

22. Warm (IgG): SLE, chronic lymphocytic leukemia, and certain drug reactions. Cold (IgM): chronic lymphocytic leukemia, Mycoplasma pneumoniae infection, and infectious mononucleosis.

23. Painful abdomen, Port wine-colored urine, Polyneuropathy, Psychological disturbances, and Precipitated by drugs (eg, cytochrome P-450 inducers), alcohol, and starvation.

24.

Platelet Bleeding Disorder PT PTT Count Time DIC ↓ ↑ ↑ ↑ Glanzmann thromboasthenia normal ↑ normal normal Hemophilia normal normal normal ↑ TTP ↓ ↑ normal normal Vitamin K deficiency normal normal ↑ ↑ von Willebrand disease normal ↑ normal ↑

25. Nodular sclerosing.

26. Reed-Sternberg cell; Hodgkin lymphoma.

27. A-1, B-2, C-4, D-5, E-3.

28. An M-spike, representing a monoclonal antibody; IgG light chains (Bence Jones proteins).

29. AML, ALL, CML, and CLL. AML can be associated with DIC upon initiation of treatment because the leukemia cells contain Auer rods composed of the enzyme peroxidase, which is released into the bloodstream when treatment causes cells to lyse.

30.

Chronic Myeloproliferative Platelets RBCs WBCs Disorder CML ↑ ↓ ↑ Essential ↑ — — thrombocytosis Myelofibrosis variable ↓ variable Polycythemia vera ↑ ↑ ↑

PHARMACOLOGY

31. Heparin activates antithrombin, decreasing thrombin and Xa. Treat heparin overdose with protamine sulfate.

32. Warfarin interferes with normal synthesis and γ-carboxylation of vitamin K-dependent clotting factors. You can treat warfarin overdose with intravenous vitamin K and fresh frozen plasma.

33.

Bleeding Platelet Drug PT PTT Time Count

Aspirin ↑ normal normal normal Clopidogrel/abciximab ↑ normal normal normal Heparin normal normal normal / ↑ ↑ Warfarin normal normal ↑ normal / ↑

34. A-5, B-1, C-9, D-8, E-3, F-2, G-4, H-7, I-6, J-10.

35. A-2, B-5, C-3, D-6, E-4, F-1.