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USMLE Step 1 > Hematopoietic & Lymphoreticular > Flashcards

Hematopoietic & Lymphoreticular Flashcards

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USMLE® Step 1 flashcards
1
Q

t(9;22)

A

Chronic myelogenous leukemia (CML)

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2
Q

t(12;21)

A

B-cell acute lymhocytic leukemia (ALL)

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3
Q

t(14;18)

A

Follicular lymphoma

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4
Q

t(15;17)

A

Acute promyelocytic leukemia (APL)

Translocation of retinoic acid receptor alpha gene (chromosome 17) and promyelocytic leukemia gene (chromosome 15)

Auer rods (see picture)

Tx: all-trans retinoic acid

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5
Q

Composition of platelet granules

A

Dense granules: ADP, calcium

α granules: vWF, fibrinogen

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6
Q

Bernard-Soulier syndrome

A

Deficiency of GpIb decreases platelet-to-vWF adhesion

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7
Q

von Willebrand disease

A

AD deficiency in von Willebrand factor prevents platelet adhesion and inhibits intrinsic pathway (vWF carries/protects factor VIII)

Dx: negative ristocetin test, increased BT and PTT

Tx: DDAVP (releases stored vWF from endothelial cells)

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8
Q

Glanzmann’s thromboasthenia

A

Deficiency of GpIIb/IIIa prevents platelet-to-platelet aggregation

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9
Q

Ticlopidine

Clopidogrel

Prasugrel

Ticalgrelor

A

Inhibits ADP-induced expression of GpIIb/IIIa inhibiting platelet aggregation

Indicated for ACS, coronary stending

SA: neutropenia (ticlopidine), TTP/HUS

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10
Q

Abciximab

Eptifibatide

Tirofiban

A

Inhibits GpIIb/IIIa directly preventing platelet aggregation

Indicated for unstable angina, angioplasty

SA: bleeding, thrombocytopenia

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11
Q

Vitamin K associated factors

A

II, VII, IX, X, C, S

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12
Q

Factor V Leiden

A

Mutant factor V is resistant to degradation by activated protein C → pro-thrombotic

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13
Q

β-thalassemia

A

Decreased synthesis of β globin chain due to point mutation in splice sites and promoter sequences (normally 2 genes on chromosome 11)

β-thalassemia minor (heterozygote): can be asymptomatic

β-thalassemia major (homozygote): severe anemia, HbA2, HbF, marrow expansion, extramedullary hematopoiesis

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14
Q

α-thalassemia

A

Decreased synthesis of α globin chain due to gene deletion (normally 4 genes on chromosome 16)

cis deletion in Asian populations (more severe disease in offspring)

Trans mutation in African populations

4 deletions: Hb Barts (γ2γ2), fetal hydrops

3 deletions: HbH (β2β2)

1-2 deletions: asymptomatic

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15
Q

Paroxysmal nocturnal hemoglobinuria

A

Acquired defect in myeloid stem cells resulting in absent glycosylphosphatidylinositol (GPI) anchoring protein → inability to bind DAF allows complement-mediated damage to RBCs, WBCs, and platelets

Hemolysis occurs at night when shallow breathing → acidosis → complement activation

Triad: Coombs - hemolytic anemia, pancytopenia, venous thrombosis

Labs: lack of CD55/59 (DAF)

Tx: eculizumab

A/w acute leukemias

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16
Q

G6PD deficiency

A

X-linked recessive disorder characterized by decreased half-life of glucose-6-phosphate dehydrogenase → reduced production of NADPH → reduced glutathione regeneration → RBCs become susceptible to oxidative stress

Findings: Heinz bodies, bite cells

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17
Q

Hereditary spherocytosis

A

Inherited defect of RBC cytoskeleton-membrane tethering proteins (ankyrin, spectrin, band 3.1, protein 4.2)

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18
Q

Autoimmune hemolytic anemia

A

Warm agglutinin (IgG): SLE, CLL, drugs

Cold agglutinin (IgM): CLL, Mycoplasma pneumonia, infectious mononucleosis

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19
Q

Immune thrombocytopenic purpura (ITP)

A

Autoantibody mediated destruction of platelets (typically IgG directed against GPIb or GPIIb/IIIa)

Increased megakaryocytes on bone marrow biopsy

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20
Q

Thrombotic Thrombocytopenic Purpura (TTP)

A

Deficiency of ADAMTS13 → reduced degradation of vWF multimers → accumulation of multimers promotes platelet activation and aggregation → microthrombi

Characterized by neurologic and renal symptoms, fever, thrombocytopenia, and microangiopathic hemolytic anemia

Tx: exchange transfusion and steroids

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21
Q

Disseminated intravascular coagulation (DIC)

A

Widespread activation of clotting leads to deficiency in clotting factors

Causes: sepsis (gram -), trauma, obstetric complications, acute pancreatitis, malignancy, nephrotic syndrome, transfusion

Labs: increased BT, PT, PTT, and fibrin split products (D-dimer), decreased platelets, fibrinogen, factors V and VIII

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22
Q

Hemophilia

A

Hemophilia A: defect in factor VIII

Hemophilia B: defect in factor IX

Both increase PTT and cause hemarthroses, easy bruising

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23
Q

Protein C or S deficiency

A

Reduced ability to inactivate factors V and VIII

Increased risk of thrombotic skin necrosis with hemorrhage following administration of warfarin

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24
Q

Which coagulation factors are activated by FVIIa?

A

IX, X

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25
Q

Which coagulation factors are activated by FIIa (thrombin)?

A

XI, VIII, V, XIII, activates platelets

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26
Q

Which coagulation factors require Vitamin K?

A

II (thrombin), VII, IX, X (2-7-9-10), protein C, and protein S

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27
Q

Which coagulation factors are found in cryoprecipitate?

A

I (fibrinogen), VIII, XIII, vWF, fibronectin

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28
Q

Which coagulation factor is produced outside of the liver in addition to within the liver?

A

Factor VIII is produced by endothelial cells

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29
Q

Which coagulation factors are inhibited by antithrombin III?

A

Inhibits thrombin and serine protease inhibitors (serpins) Potentiated by heparin XII, XI, IX, X, II (thrombin) 9-10-11-12 + 2 (thrombin)

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30
Q

Which coagulation factors are inactivated by the protein C and S complex?

A

Factors Va and VIIIa

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31
Q

What is Bernard-Soulier syndrome?

A

Bleeding disorder caused by genetic deficiency of GPIb –> prevents platelet adhesion

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32
Q

What is Glanzmann thrombasthenia?

A

Bleeding disorder caused by genetic deficiency of GPIIb/IIIa –> prevents platelet aggregation

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33
Q

What is HbH?

A

α-Thalassemia (three gene deletion) β2β2 hemoglobin

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34
Q

What is HbF?

A

Fetal hemoglobin α2γ2

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35
Q

What is HbA?

A

Normal adult hemoglobin α2β2

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36
Q

What is Hb Barts?

A

α-Thalassemia (four gene deletion) γ2γ2

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37
Q

What is HbA2?

A

Increased in β-thalassemia α2δ2

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38
Q

How many genes encode hemoglobin α chains and on which chromosome are they?

A

4 genes on chromosome 16

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39
Q

How many genes encode hemoglobin β chains and on which chromosome are they?

A

2 genes on chromosome 11

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40
Q

Which anemias results in extramedullary hematopoiesis (e.g. hematopoiesis moves into skull –> crew-cut x-ray, facial bones –> chimpmunk facies, liver, spleen –> hepatosplenomegaly)?

A

β-thalassemia major Sickle cell anemia

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41
Q

How do you diagnose specific thalassemias?

A

Gel electrophoresis α-thalassemia: HbH (β2β2) or Hb Barts (γ2γ2) β-thalassemia minor: reduced HbA (α2β2), increased HbA2 (α2δ2), increased HbF (α2γ2) β-thalassemia major: no HbA (α2β2), increased HbA2 (α2δ2), increased HbF (α2γ2)

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42
Q

Where is iron, folate, and vitamin B12 absorbed?

A

Duodenum, jejunum, and ileum, respectively

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43
Q

What is anisocytosis?

A

Variations in the size of RBCs

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44
Q

What is poikilocytosis?

A

Variations in the shape of RBCs

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45
Q

What are Howell-Jolly bodies?

A

Fragments of DNA left in RBCs that are usually removed by the spleen Associated with hereditary spherocytosis (treated with splenectomy), sickle cell anemia (autosplenectomy)

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46
Q

What is the difference in the gene mutation for sickle cell anemia and hemoglobin C?

A

A glutamic acid residue is replaced by valine in sickle cell anemia and lysine in hemoglobin C

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47
Q

What is CD55?

A

CD55 is decay accelerating factor (DAF) which is absent in paroxysmal nocturnal hemoglobinuria

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48
Q

What is a Heinz body?

A

Precipitated hemoglobin due to oxidative stress

G6PD deficiency

Heinz bodies are removed by splenic macrophages resulting in bite cells

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49
Q

Which diseases are associated with target cells?

A

Thalassemias

Hemoglobinopathies (sickle cell, HbC)

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50
Q

Which neoplasia is associated with t(12;21)?

A

B-cell acute lymphoblastic leukemia (B-ALL)

Good prognosis, more common in children

51
Q

Which neoplasia is associated with t(9;22)?

A

Philadelphia chromosome –> BCR-ABL fusion protein –> increased tyrosine kinase activity –> treat with imantinib

B-cell acute lymphoblastic leukemia (B-ALL); poor prognosis, more common in adults

Chronic myeloid leukemia (CML)

52
Q

Which neoplasia is associated with t(15;17)?

A

Acute promyelocytic leukemia

The retinoic acid receptor (RAR) on chromosome 17 is translocated to chromosome 15

RAR disruption blocks maturation and promyelocytes accumulate (Auer rods)

Treat with all-trans-retinoic acid (ATRA) –> vitamin A derivative

53
Q

Which neoplasia is associated with t(14;18)?

A

Follicular lymphoma

Diffuse large B-cell lymphoma (most common type of NHL)

BCL2 on chromosome 18 translocates to the Ig heavy chain locus –> overexpression of Bcl2 (inhibits apoptosis)

54
Q

Which neoplasia is associated with t(11;14)?

A

Mantle cell lymphoma

Cyclin D1 gene on chromosome 11 translocates to Ig heavy chain locus –> overexpression of cyclin D1 –> promotes G1/S cell cycle transition –> neoplastic proliferation

CD5+

55
Q

Which neoplasia is associated with t(8;14)?

A

Burkitt lymphoma (B cells CD20+)

C-MYC on chromosome 8 translocates to Ig heavy chain locus –> overexpression of c-myc oncogene

Associated with EBV

African form → jaw

Sporadic form → abdomen, pelvis

Histology: “starry-sky”

56
Q

Which neoplasias are associated with lytic bone lesions?

A

Adult T-cell lymphoma

Multiple myeloma

57
Q

Which neoplasias are CD5+ and CD20+

A

CLL/SLL Mantle cell lymphoma

Langerhans cell histiocytosis

58
Q

What diseases are associated with ineffective hematopoiesis?

A

Megaloblastic anemia

Hemolytic anemia

β-Thalassemia

59
Q

What diseases are associated with tear-drop RBCs?

A

Extramedullary hematopoiesis (β-Thalassemia, sickle cell anemia)

Myelophthisic process

Myelofibrosis

60
Q

What does tissue factor pathway inhibitor inhibit?

A

TF-VIIa complex and Xa

61
Q

How do endothelial cells inhibit platelet activation and aggregation?

A

PGI2, NO, ecto-ADPase

62
Q

Melphalan

A

Nitrogen mustard derivative bifunctional alkylating agent Alkylates DNA resulting in breaks and cross-linking

63
Q

Chlorambucil

A

Nitrogen mustard derivative bifunctional alkylating agent Alkylates DNA resulting in breaks and cross-linking

64
Q

Cyclophosphamide

Ifosfamide

A

Nitrogen mustard derivative bifunctional alkylating agent

Alkylates DNA resulting in cross-linking at guanine N-7

Must be activated by the liver

Side effects: hemorrhagic cystitis, myocardial necrosis, myelosuppression

Partially prevented with mesna

65
Q

Carmustine

A

Nitrosurea alkylating agent

Alkylates DNA resulting in breaks and cross-linking

Can penetrate CNS

Can be used as implantable wafer

66
Q

Lomustine

A

Nitrosurea alkylating agent

Alkylates DNA resulting in breaks and cross-linking

Can penetrate CNS

67
Q

Cisplatin

A

Platinum alkylating agent

Cross-links DNA

Side effects: nephrotoxicity (prevent with amifostine and chloride diuresis), ototoxicity

68
Q

Oxaliplatin

A

Platinum alkylating agent Cross-links DNA Side effects: neurotoxicity Treats colorectal cancer

69
Q

Carboplatin

A

Platinum alkylating agent

Cross-links DNA

70
Q

Procarbazine

A

Nonspecific alkylating agent Treats non-Hodgkin lymphoma Side effects: MAOI (eat less tyramine)

71
Q

Vincristine

A

Binds to tubulin, prevents polymerization into microtubules, arrests cells in M-phase

Side effects: neurotoxicity (areflexia, peripherla neuritis), paralystic ileus

72
Q

Vinblastine

A

Binds to tubulin, prevents polymerization into microtubules, arrests cells in M-phase

Side effects: neurotoxicity, mucositis, myelosuppression

73
Q

Paclitaxel

A

Promotes polymerization and stability of microtubules and inhibits disassembly (prevents anaphase)

Side effects: neutropenia, mucositis, alopecia

74
Q

Docetaxel

A

Promotes polymerization and stability of microtubules and inhibits disassembly Affect G2/M-phase Side effects: neutropenia, mucositis

75
Q

Ixabepilone

A

Binds β-tubulin and promotes polymerization and stability of microtubules and inhibits disassembly Affect G2/M-phase Side effects: neutropenia, cardiotoxicity, peripheral neuropathy

76
Q

Etoposide

A

Inhibits topoisomerase II and increases DNA degradation

Affects G2/S-phase

Side effects: myelosuppression

77
Q

Teniposide

A

Inhibits topoisomerase II and increases DNA degradation

Affects G2/S-phase

Side effects: myelosuppression

78
Q

Irinotecan

A

Inhibits topoisomerase I and prevents DNA unwinding and replication

Affects S-phase

Side effects: neutropenia, diarrhea

79
Q

Topotecan

A

Inhibits topoisomerase I and prevents DNA unwinding and replication

Affects S-phase

Side effects: neutropenia, diarrhea

80
Q

Daunorubicin

A

Anthracycline antibiotic: 1) intercalates in DNA inhibiting DNA and RNA polymerase 2) induces free radical formation which breaks DNA 3) inhibits DNA topoisomerase II

Side effects: cardiotoxicity (dilated cardiomyopathy from free radical damage), myelosuppression, alopecia

Dexrazoxane (iron chelator) may reduce cardiac damage

81
Q

Doxorubicin

A

Anthracycline antibiotic: 1) intercalates in DNA inhibiting DNA and RNA polymerase 2) induces free radical formation which breaks DNA 3) inhibits DNA topoisomerase II

Side effects: cardiotoxicity (dilated cardiomyopathy from free radical damage), myelosuppression, alopecia

Dexrazoxane (iron chelator) may reduce cardiac damage

82
Q

Dexrazoxane

A

Iron chelator inhibits free radical formation and reduces cardiac damage associated with daunorubicin and doxorubicin (anthracycline antibiotics)

Affects G2-phase

83
Q

Bleomycin

A

Forms DNA-bleomycin-Fe complex that is oxidized –> free radicals break DNA

Affects G2-phase

Side effects: pulmonary fibrosis, hyperpigmentation of hands, mucositis

84
Q

Methotrexate

A

Competitively inhibits dihydrofolate reductase: 1) prevents formation of dTMP 2) decreases synthesis of purine ring structure

Affects S-phase

Side effects: myelosuppression, mucositis, hepatotoxicity (high dose), abortifacient

Can use leucovorin (folinic acid) to reverse side effects

85
Q

5-fluorouracil

A

Pyrimidine analogue converted to 5-FdUMP which inhibits thymidylate synthase; 5-FdUTP incorporated into RNA resulting in defective transcripts

Side effects: myelosuppression, photosensitivity

Rescue with uridine

86
Q

Capecitabine

A

5-FU prodrug whose final set of activation is catalyzed by thymidine phosphorylase, and enzyme elevated in tumor cells

87
Q

Cytarabine

A

Cytidine analogue converted to Ara CTP which inhibits DNA polymerase and causes DNA chain termination when incorporated

Causes pancytopenia

88
Q

Gemcitabine

A

Cytidine analogue inhibits DNA polymerase and ribonucleotide reductase

89
Q

Azacitidine

A

Pyrimidine nucleoside analog gets incorporated into RNA and inhibits processing and function Treats myelodysplastic syndrome

90
Q

6-mercaptopurine

A

Purine analogue: 1) inhibits de novo purine synthesis 2) competitively inhibits biosynthetic reactions 3) incorporated into DNA and RNA

Side effects: myelosuppression, hepatotoxicity, increased toxicity with allopurinal (metabolized by xanthine oxidase)

91
Q

6-thioguanine

A

Purine analogue: 1) inhibits de novo purine synthesis 2) competitively inhibits biosynthetic reactions 3) incorporated into DNA and RNA

Side effects: myelosuppression, hepatotoxicity

92
Q

Asparaginase

A

Catalyzes conversion of asparagine to aspartate to inhibit protein synthesis (asparagine levels are low in tumor cells) Side effects: reduced protein synthesis (clotting factors, insulin, albumin), hypersensitivity reactions, hepatotoxicity

93
Q

Imatinib mesylate

A

Competitively blocks ATP-binding side of c-abl tyrosine kinase Inhibits c-kit and PDGF-associated tyrosine kinases Treats CML and Ph+ ALL Side effects: myelosuppression and CHF

94
Q

Erlotinib

A

Inhibits EGF receptor-associated tyrosine kinase Side effects: CHF

95
Q

Gefitinib

A

Inhibits EGF receptor-associated tyrosine kinase Side effects: CHF

96
Q

Vemurafenib

A

Inhibits B-raf serine-threonine kinase with V600E mutation

Treats melanoma

97
Q

Cetuximab

A

Antibody against EGF receptor

98
Q

Trastuzumab (Herceptin)

A

Inhibitor of HER2 tyrosine kinase receptor (extracellular domain)

SA: cardiotoxicity

99
Q

Bevacizumab

A

Antibody against VEGF –> inhibits angiogenesis

100
Q

Rituximab

A

Anti-CD20 antibody that promotes complement-mediated lysis of malignant B cells

May cause reactivation of HBV, increases risk of progressive multifocal leukoencephalopathy (a/w JC virus)

101
Q

Ipilimumab

A

Antibody against CTLA-4 that blocks inhibitory activity Treats malignant melanoma

102
Q

Pembrolizumab

A

Bind to PD-1 receptor on T cells

103
Q

Gamtuzumab ozogamicin

A

Antibody against CD33 (myeloid surface antigen)

104
Q

Bortezomib

A

Proteasome inhibitor Treats multiple myeloma and mantle cell lymphoma

105
Q

all-trans-retinoic acid

A

Treats promyelocytic leukemia by causing blasts to mature

106
Q

Heparin

A

Anticoagulant

Activates antithrombin –> inactivates thrombin and factor Xa

Indicated for PE, ACS, MI, DVT; safe during pregnancy (highly water soluble so doesn’t cross the placenta)

Monitor with PTT

Can reverse with protamine sulfate

Can cause heparin-induce thrombocytopenia –> IgG develops against heparin bound to platelet factor 4 –> activates platelets –> thrombosis and thrombocytopenia

107
Q

Warfarin (Coumadin)

A

Inactivates vitamin K epoxide reductase –> reduced gamma-carboxylation of factors II, VII, IX, X, proteins C and S

Monitor with PT/INR

Contraindicated in pregnancy (highly lipophilic and crosses placenta)

May cause tissue necrosis

Give vitamin K or FFP for reversal

108
Q

Smudge cells

A

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

109
Q

TRAP +

A

Hairy cell leukemia

110
Q

Enoxaparin

A

Low-molecular weight heparin (acts more on factor Xa)

Better bioavailability, 2-4 times longer half-life, can be administed subcutaneously and without laboratory monitoring

111
Q

Dalteparin

A

Low-molecular weight heparin (acts more on factor Xa)

Better bioavailability, 2-4 times longer half-life, can be administed subcutaneously and without laboratory monitoring

112
Q

Argatroban

A

Inhibits thrombin directly (derived from leeches)

Indicated for anticoagulation in patients with HIT

113
Q

Bivalirudin

A

Inhibits thrombin directly (derived from leeches)

Indicated for anticoagulation in patients with HIT

114
Q

Apixaban

A

Directly inhibits Xa

Indicated for stroke prophylaxis in patients with afib

Don’t require coagulation monitorng

115
Q

Rivaroxaban

A

Directly inhibits Xa

Indicated for stroke prophylaxis in patients with afib, treatment and prophylaxis for DVT and PE

Don’t require coagulation monitorng

116
Q

Alteplase (tPA)

Reteplase (rPA)

Tenecteplase (TNK-tPA)

A

Aids conversion of plasminogen to plasmin which cleaves thrombin and fibrin clots (↑ PT and PTT)

Indicated for early MI, stroke, severe PE

SA: bleeding

Treat toxicity with aminocaproic acid (fibrinolytic inhibitor), FFP, cryoprecipitate

117
Q

Azathioprine

A

Purine analogue: 1) inhibits de novo purine synthesis 2) competitively inhibits biosynthetic reactions 3) incorporated into DNA and RNA

Side effects: myelosuppression, hepatotoxicity, increased toxicity with allopurinal (metabolized by xanthine oxidase)

118
Q

Dactinomycin

A

Intercalates in DNA

SA: myelosupression

119
Q

Hydroxyurea

A

Inhibits ribonucleotide reductase to decrease DNA synthesis

120
Q

Imantinib

A

Tyrosine kinase inhibitor of brc-abl (Philadephia chromosome fusion gene in CML) and c-kit

Indicated for CMG, GI stromal tumors

SA: fluid retention

121
Q

Common chemotoxicities

A
122
Q

Rasburicase

A

Recombinant version of urate oxidase, and enzyme that converts uric acid into more soluble metabolites to prevent hyperuricemia from tumor lysis syndrome

123
Q

Pure reb cell aplasia

A

Associated with parvovirus B19 infection, thymomas, or lymphocytic leukemias

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