Term
How should you treat asymptomatic hereditary spherocytosis?
What about symptomatic? |
|
Definition
Asx: trick question, no tx needed.
Sx: splenectomy, > age 5 if possible. |
|
|
Term
Cold agglutinin test looks for what type of antibodies in the patient's serum?
Is the severity of the disease related to the titer of autoantibody? |
|
Definition
Cold agglutinating IgM antibodies
Yes; severity related to titer and ability to activate complement |
|
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Term
| What is the difference between direct and indirect Coomb's test? |
|
Definition
| Direct: look for presence of IgG or complement bound to patient's RBC membranes. Indirect: Look for presence of anti-RBC IgG in patient's serum. |
|
|
Term
Warm Antibody AIHA and Cold Agglutinin AIHA: which is associated with IgG, which with IgM?
Which is a more common AIHA? |
|
Definition
Warm antibody: IgG
Cold agglutinin: IgM
Warm antibody AIHA is more common (70% v. 30%) |
|
|
Term
What is the main pathway for initiation of coagulation?
What is the amplification pathway? |
|
Definition
Initiation: extrinsic pathway (TF and VII)
Amplification: intrinsic pathway (XII, XI, IX) |
|
|
Term
| Protein C and S complex cleaves what factors? |
|
Definition
|
|
Term
| The activity of t-PA is multiplied x500 in the presence of what? |
|
Definition
|
|
Term
| Are red bruises on the arms and back of hands associated with coagulation deficiencies? |
|
Definition
No; they are associated with tissue weakness
- Cushing's
- Glucocorticoids
- "Senile purpura"
- Chronic sun exposure |
|
|
Term
| T/F: Hemoptysis, hematemesis, and melena are rarely the presenting symptom in patients with bleeding disorders. |
|
Definition
True.
Usually mucosal bleeds (vWF, platelet) or deep bleeds (clotting factors). |
|
|
Term
| What is the "classic pentad" of thrombotic thrombocytopenic purpura? |
|
Definition
Microangiopathic hemolytic anemia
Thrombocytopenia
Renal involvement
Neurological signs
Fever |
|
|
Term
TTP is cause by antibodies to what enzyme?
What is its normal function? |
|
Definition
ADAMTS13
Cleave vWF within thrombi |
|
|
Term
In trying to decide whether a patient has DIC or TTP, you order aPTT and PT tests. Both come back prolonged.
Which do you now suspect much more?
Why? |
|
Definition
DIC has prolonged aPTT and PT, as a dysfunction of the clotting cascade.
TTP does not - the dysfunction is at the level of vWF and platelet clotting. |
|
|
Term
| You are trying to determine whether a patient with a clotting factor disorder has a vitamin K deficiency, or liver disease in general. Which clotting factor level could help you distinguish? |
|
Definition
Factor V
V is synthesized by the liver, but it is not vitamin K dependent. Therefore, levels may remain high in K deficiency but will be low in liver disease. |
|
|
Term
| An elderly woman with a B cell malignancy has a bleeding disorder with a prolonged aPTT but normal PT. What is the likely problem? |
|
Definition
Antibodies to factor VIII.
Seen in elderly, connective tissue disorders, post-partum, and B cell lymphomas. |
|
|
Term
What is the normal range for platelet count?
What is the average lifespan of a platelet?
What proportion of platelets are normally in the spleen at any given time? |
|
Definition
150k-400k per uL
5-9 days
1/3 |
|
|
Term
| What is a common epitope for anti-platelet antibodies? |
|
Definition
| Surface glycoproteins, esp. GpIIbIIIa |
|
|
Term
Severe Heparin Induced Thrombocytopenia (SHIT!) is caused by heparin forming antigenic complexes with what other factor?
How does this cause SHIT? |
|
Definition
Platelet factor 4 (PF4)
IgG binds to Heparin-PF4 complex, activates Fc receptor on platelet and causes fruther degranulation and PF4 release --> vicious cycle (a SHIT storm) |
|
|
Term
This rare genetic disorder of platelet adhesion features giant platelets on a peripheral smear and a loss of response to Ristocetin in an aggregation test.
What is the defect? |
|
Definition
Bernard Soulier Syndrome.
Decrease in presence of GpIb-IX-V |
|
|
Term
This rare genetic disorder of platelet aggregation features platelets that do not aggregate in response to thrombin, ADP, epinephrine or collagen. However, aggregation in response to ristocetin is intact.
What is the disorder? |
|
Definition
Glanzmann's thrombocytopenia
Lack of GpIIbIIIa: no platelet-platelet adhesion.
(GpIb-IX-V is intact so adhesion to vWF and endothelial wall is present.) |
|
|
Term
| What is prothrombin 20210 mutation, what is its effect on coagulability? |
|
Definition
| Mutation in 3' UTR of prothrombin gene, leads to elevated prothrombin levels and hypercoagulability. |
|
|
Term
Mutations in Cystathionine Beta Sythase (CBS) lead to what condition?
Is this common or rare? |
|
Definition
CBS mutations lead to hyperhomocysteinemia.
This is a rare recessive autosomal disease. |
|
|
Term
| Hyperhomocysteinemia is associated with what conditions? |
|
Definition
| Premature atherosclerosis, intrauterine growth retardation, miscarriage, venous thromboembolism |
|
|
Term
Which of these drugs may influence warfarin effect?
A. Drug that increases insulin resistance
B. Drug that binds to plasma proteins
C. Drug that accelerates P450 metabolism
D. Drug that is renally excreted |
|
Definition
B and C
B: 99% of warfarin is bound to plasma proteins -- competition with other drugs may affect bioavailability
C: Warfarin is P450 metabolized |
|
|
Term
| T/F: Heparin can only inhibit soluble thrombin, not fibrin-bound thrombin. |
|
Definition
|
|
Term
| Heparin effect is monitored by repeated administration of what test? |
|
Definition
|
|
Term
| Which has a longer half-life, heparin or LMWH? |
|
Definition
|
|
Term
| Hirudin, Lepirudin, Bivalirudin, and Argatroban all inhibit what clotting factor? |
|
Definition
|
|
Term
| You can diagnose Hemophilia A at birth but not B. Why? |
|
Definition
| Vitamin K dependent factors are low at birth, IX activity assays unreliable. VIII should be normal. |
|
|
Term
| T/F: Maternal iron status has a big effect on fetal iron deficiency. |
|
Definition
| False - very little effect |
|
|
Term
What subtype of AML has distinctive heavily granulated promyelocytes and numerous Auer rods?
What is the characteristic chromosome abnormality?
What is the major clinical risk?
What is the best treatment? |
|
Definition
Acute promyelocytic leukemia (FAB M3)
t(15:17)
DIC
all-trans retinoic acid (ATRA) |
|
|
Term
| ALL and AML are more common in males or females? |
|
Definition
|
|
Term
| What virus is associated with T-cell ALL? |
|
Definition
HTLV-1
(human T cell leukemia/lymphoma virus) |
|
|
Term
| What subtype of leukemia commonly can present with DIC? |
|
Definition
| Acute promyelocytic leukemia (APL or M3-AML) |
|
|
Term
| Allopurinol and Rasburicase are used to treat what complication of ALL? |
|
Definition
Tumor lysis syndrome (causing hyperuricemia)
(Allopurinol inhibits xanthine oxidase)
(Rasburicase converts uric acid to allantoin) |
|
|
Term
Fanconi anemia is an inherited form of what kind of anemia?
What other abnormalities are present? |
|
Definition
Aplastic Anemia
Skeletal abnormalities, small stature, skin and nail changes |
|
|
Term
A pt comes to you with leukopenia. Smear shows cells with numerous Auer rods in the cytoplasm, staining strongly positive for MPO.
What complication are you concerned about in this patient?
What treatment would you start immediately?
What chromosomal abnormality would you expect to see? |
|
Definition
The patient may have acute promyelocytic leukemia
DIC
ATRA
t(15;17) |
|
|
Term
| Of the lymphomas derived from the germinal center of the lymph follicle (follicular, large cell, burkitt) which is the most aggressive/fast growing? |
|
Definition
| Burkitt - 100% germinating fraction, higher than even bacteria! |
|
|
Term
What lymphoma types express these markers?
CD5
CD10/Bcl-6
Cyclin-D1 |
|
Definition
CD5: CLL/SLL and Mantle cell
CD10/Bcl6: Follicular
Cyclin-D1: 90% Mantle cell, subsets of plasma cell and hairy cell |
|
|
Term
A lymphoma is CD5 positive. What are the possibilities?
What immunophenotype would help you distinguish? |
|
Definition
CD5: CLL/SLL or Mantle cell
Cyclin-D1 is positive in 90% Mantle cell, negative in CLL/SLL |
|
|
Term
| A lymphoma is CD10 and Bcl-6 positive. What is the most likely type? |
|
Definition
|
|
Term
Match the molecular/genetic abnormality to lymphoma type:
t(8;14)/c-myc;IgH
t(14;18)/IgH;bcl-2
t(11;14)/cyclin-D1;IgH |
|
Definition
t(8;14)/c-myc;IgH - Burkitt
t(14;18)/IgH;bcl-2 - Follicular
t(11;14)/cyclin-D1;IgH - Mantle cell |
|
|
Term
| How does Hodgkin's lymphoma spread differently than Non-hodgkins? |
|
Definition
| Hodgkins spreads lymph node to lymph node; NHL can spread hematologically and appear anywhere. |
|
|
Term
Rituximab attacks what membrane protein?
What type of lymphoma must it be to express this?
Is this single dose or maintenance dosing? |
|
Definition
CD20
B-cell lymphoma
Maintenance dosing |
|
|
Term
| What are 3 possible medical emergencies due to multiple myeloma? |
|
Definition
Hypercalcemia
Cord compression
Hyperviscosity syndrome (M protein > 10g/dL) |
|
|
Term
Mechlorethamine, Cyclophosphamide, Carmustine, and Lomustine are all work by what mechanism?
What is their dose limiting toxicity?
What is the difference in time delay? |
|
Definition
All are alkylating crosslinkers. Mechlorethamine and Cyclophosphamide are Nitrogen mustards, Carmustine and Lomustine are Nitrosoureas.
DLT is myleosuppression.
1-2 week nadir for NItrogen mustards,
4-6 week nadir for Nitrosoureas |
|
|
Term
Which of the alkylating crosslinkers has the strongest extravasation hazard?
Why does cyclophosphamide not have extravasation hazard?
What is its unique toxicity?
How is it protected against? |
|
Definition
Mechlorethamine has vesicant extravasation hazard.
Cyclophophamide must be P450 activated.
Has hemorrhagic cystitis hazard.
Use MESNA and irrigation/diuresis to prevent. |
|
|
Term
Non-alkylating crosslinkers all contain what metal?
What do their names end with?
How are they eliminated? |
|
Definition
Platinum
-platin (Cisplatin, Carboplatin, Oxaliplatin)
Renal excretion |
|
|
Term
Of the platinum agents, which have vesicant extravasation hazard?
Which has cumulative renal toxicity?
Which has cumulative neurotoxicity?
Which has myelosuppression and only irritant extravasation hazard? |
|
Definition
Vesicants: Cisplatin and Oxaliplatin
Cumulative renal: Cisplatin
Cumulative neural: Oxaliplatin
Myelo & Irritant: Carboplatin |
|
|
Term
What is the mechanism of Dacarbazine, Temozolomide, and Procarbazine?
Which has vesicant extravasation hazard? |
|
Definition
DNA methylation.
Darcarbazine is vesicant |
|
|
Term
What is the mechanism of Bleomycin and Dactinomycin?
Which has MDR resistance, cumulative pulmonary toxicity, and vesicant extravasation hazard? |
|
Definition
Oxygen free radical formation
Dactinomycin: MDR, cumulative pulmonary tox, vesicant |
|
|
Term
Fluorouracil, Capecitabine, Pemetrexed, and Methotrexate all have slightly different mechanisms but inhibit the same overall pathway. What pathway?
What is each mechanism?
How does this change the effect of leucovorin? |
|
Definition
Thymidine synthesis.
Fluorouracil: irreversibly inhibits thymidylate synthase
Capecitabine: Irreversibly inhibits thymidylate synthase after metabolism
Pemetrexed: Competitively inhibits thymidylate synthase at folate binding site
Methotrexate: competitively inhibits DHFR at folate binding site.
Leucovorin = reduced folate. INCREASES antitumor and toxic effects of fluorouracil and capecitabine, DECREASES antitumor/toxic effect of methotrexate (and prob pemetrexed too??) |
|
|
Term
What unusual toxicity is found among the thymidine nucleotide antagonists?
Which drugs specifically? |
|
Definition
GI mucositis, stomachitis.
Fluorouracil, Capecitabine, Methotrexate. |
|
|
Term
What are the 2 deoxycitidine nucleotide antagonists?
Which promotes radiosensitivity? |
|
Definition
Cytrarabine (Ara-C) and Gemcitabine
Gemcitabine promotes radiosensitivity |
|
|
Term
What is the mechanism of the Vinca Alkaloids?
All the names start with what?
What is the mechanism of resistance for all?
What is the extravasation hazard for all?
Which has neurotoxicity DLT? |
|
Definition
Inhibit microtubule polymerization
Vin- (Vincristine, Vinblastine, Vinorelbine)
MDR efflux resistance (ABCB1)
All are severe vesicants!
Vincristine has neurotoxicity DLT |
|
|
Term
What is the mechanism of action of Taxanes?
All the names end in what?
What is the resistance mechanism?
What is the extravasation hazard? |
|
Definition
Inhibit microtubule depolymerization
-taxel (Paclitaxel, Docetaxel)
MDR efflux (ABCB1)
Severe vesicants! |
|
|
Term
What is the mechanism of Camptothecins?
All names end in what?
What is resistance mechanism?
Which has GI mucocitis/stomachitis? |
|
Definition
Topoisomerase I inhibitors
-tecan (Topotecan, Irinotecan)
MDR efflux (ABCB1) and Topo1 mutations
Irinotecan has GI mucositis in addition to myelosuppression |
|
|
Term
Doxorubicin (Adriamycin) and Etopside work by what mechanism?
Which has a huge range of uses?
What is the resistance mechanism?
Which has cumulative cardiotoxicity, and vesicant extravasation hazard? |
|
Definition
Topoisomerase II inhibitors
Doxorubicin has huge range of uses
MDR efflux (ABCB1) - also antioxidant thiols for doxorubicin.
Doxorubicin has cumulative cardiotoxicity and vesicant extravasation hazard. |
|
|
Term
What are the 3 approved tyrosine kinase inhibitors?
What is mechanism of resistance?
What is the extravasation hazard? |
|
Definition
Imatinib, Nilotinib, Dasatinib
Bcr-Abl mutations, overexpression
None -- all oral drugs! |
|
|
Term
What are the 3 anti-angiogenesis drugs?
What are the mechanisms?
Are they high or low toxicity? |
|
Definition
Bevacizumab, Sunitinib, Sorafenib
Bevacizumab is an antibody to free VEGF; Sunitinib and Sorafenib block VEGF receptors.
All have relatively low toxicity. |
|
|
Term
| What 3 drug mechanism groups are affected by ABCB1 efflux? |
|
Definition
GENERALLY: Large, lipophilic molecules - the natural products
Reactive oxygen agents (Dactinomycin)
Microtubule organization inhibitors (Vinca alkaloids [Vincristine, Vinblastine, Vinorelbine] and Taxanes [Paclitaxel, Docletaxel])
Topoisomerase inhibitors (Camptothecins, Doxorubicin, Etopside) |
|
|
Term
All of the drugs that affect microtubules have what extravasation hazard?
Bonus points: name them! |
|
Definition
Severe vesicants!
Vinca alkaloids: Vincristine, Vinblastine, Vinorelbine
Taxanes: Paclitaxel, Docetaxel |
|
|
Term
| What do Mechlorethamine, Cisplatin, Oxaliplatin, Dacarbazine, Dactinomycin, and Doxorubicin have in common? |
|
Definition
Vesicant extravasation hazard
"OMC-tripleD" |
|
|
Term
This drug must be metabolically activated by P450, and has a risk of hemorrhagic cystitis which can be managed by MESNA.
What is it?
What is the mechanism? |
|
Definition
Cyclophosphamide.
Alkylating Crosslinker |
|
|
Term
| This is a platinum drug with cumulative renal toxicity and vesicant extravasation hazard. |
|
Definition
|
|
Term
| This is a platinum drug with cumulative neurotoxicity and vesicant extravasation hazard. |
|
Definition
|
|
Term
| This is an oxygen free radical drug with MDR resistance, cumulative pulmonary toxicity, and vesicant extravasation hazard. |
|
Definition
|
|
Term
| This is the only thymidine nucleotide antagonist that does not have GI/mucositis as a DLT. |
|
Definition
|
|
Term
This is the only drug shown to increase radiosensitivity.
What is it?
What is its mechanism? |
|
Definition
Gemcitabine
Deoxycitidine nucleotide antagnoist |
|
|
Term
| Which Vinca alkaloid has neurotoxicity as DLT? |
|
Definition
|
|
Term
| Which topoisomerase I inhibitor has GI mucositis as one of its DLTs? |
|
Definition
|
|
Term
This drug has a wide range of uses, MDR resistance, cumulative cardiotoxicity, and vesicant extravasation hazard.
What is it?
What is the mechanism? |
|
Definition
Doxorubicin
Topoisomerase II inhibitor |
|
|
Term
These two drugs bind VEGF receptor.
What are they?
What is the extravasation hazard? |
|
Definition
Sunitinib and Sorafenib
None! Oral drugs |
|
|
Term
| What do Cisplatin, Oxaliplatin, Dactinomycin, and Doxorubicin (Adriamycin) have in common? |
|
Definition
Cumulative toxicity
CODA (it's the end for you if you repeatedly use!)
Cisplatin: renal
Oxaliplatin: neuro
Dactinomycin: pulmonary
Adriamycin (Doxorubicin): cardio |
|
|
Term
What kinds of drugs are Carmustine and Lomustine?
When is myelosuppression expected? |
|
Definition
Alkylating crosslinkers: Nitrosoureas
nadir at 4-6 weeks |
|
|
