UWorld- Heme/Onc Flashcards
taken 3/10/14
what kind of heparin (unfractionated, low molecular weight like enoxaparin or dalteparin, fondaparinux) is most effective at inactivating thrombin
unfractionated heparin; it has a long enough polysaccharide chain to form a ternary complex with antithrombin and thrombin to inactivate thrombin
what kind of drugs are argatroban and bivalirudin and what effect do they have on PT, aPTT and thrombin time (TT)
direct thrombin inhibitors (derived from hirudin from leeches);
they increase thrombin time, but have little effect on PT or aPTT
if a patient has a t(15;17) translocation what treatment would you provide?
what’s the disease?
treat with all-trans-retinoic acid (ATRA)
this patient has APML (which involves a defective retinoic acid receptor)
a patient for whom Heinz bodies are seen on blood smear and who tends to experience jaundice and dark urine after taking antimalarials and sulfonamides has inherited his/her disease via what inheritance pattern
G6PD deficiency is X-linked
nitrite poisoning will cause what to happen to PO2, % Hb sat, and O2 content
methemoglobinemia, caused by nitrite, which oxidize Fe2+ to ferric oxide (Fe3+) leads to:
- normal PO2 (amt. of O2 dissolved in the plasma is unchanged)
- decreased Hb saturation
- decreased O2 content
A patient with sore throat, malaise, persistent fever, cervical LAD, myalgias and splenomegaly has atypical cells on blood smear that have an eccentrically placed nucleus, ample cytoplasm and edges that seem to take the shape of the cells around them. What are these atypical cells?
What is the likely disease?
atypical CD8+ cytotoxic lymphocytes
EBV
A patient is on warfarin therapy after an acute cardiac incident. She says she’s taking her medications, but her PT is subtherapeutic. What other drugs might this patient be taking?
CYP450 inducers increase warfarin metabolism (removal)
ethosuximide, barbituates, phenytoin, chronic alcohol and smoking, St. John’s wort, glucocorticoids, carbamazepine, rifampin, griseofulvin
what kind of heparin is enoxaparin and how does it work
enoxaparin is a low molecular weight heparin that binds antithrombin to activate it, leading to inactivation of Factor Xa (preventing cleavage of prothrombin to thrombin)
A 5 year old had abdominal pain, diarrhea and fever. A few days later he presents with pallor and oliguria. Which lab findings would be decreased? Increased?
This patient probably has HUS.
increased: bleeding time, retic, LDH, BUN, Cr
decreased: platelets, Hgb, Hct, RBC count
note: PT and PTT are normal b/c no coag factor involvement
what are Nef and Tat? explain what they do.
Nef and Tat are HIV genes; Nef decreases MHC I expression on infected cell surfaces; Tat plays a role in viral replication
a patient with recurrent respiratory and GI infections is found to have low serum immunoglobulin;
what substructure in the lymph node is he/she likely lacking and what disease does this patient likely have
lacking germinal centers;
this patient has Bruton X-linked agammaglobulinemia which causes defective B cell maturation
what values are best for diagnosing/ confirming suspicion of hereditary spherocytosis
osmotic fragility test will indicate fragility of the membrane, characteristic of HS
also, mean corpuscular hemoglobin concentration will be increased due to membrane loss and dehydration of the cell
where is major basic protein found and what does it do
found in eosinophilic granules and protects against parasites
myeloperoxidase stains for what liquid cancer
AML
what is argatroban; name the drug type and others of its class
argatroban, along with hirudin and lepirudin, are direct thrombin inhibitors (they inhibit thrombin, but don’t affect factor Xa and they are used for anticoagulation as an alternative to heparin for patients with HIT)
explain the relative locations of HbA, HbH, HbC and HbS on hemoglobin electrophoresis
HbH moves farthest (tetramers of normal beta globin); then HbA (negative a.a. residues); then HbS (a valine aka neutral a.a. substitution); HbC moves the shortest distance (a lysine aka positive a.a. substitution)
what are the 5 steps of leukocyte accumulation in the tissues
- margination: vascular leakage allows leukocytes to contact endothelium
- rolling: selectins mediate loose binding to endothelium
- activation: while rolling neutrophils sample chemokines that activate integrins
- tight adhesion and crawling: integrins bound to ICAM promote tighter adhesion
- transmigration: in the periphery integrins and PECAM-1 promote extravasation into interstitium
what is the preferred route of iron administration
oral iron supplementation (parenteral iron is only given to patients who cannot take orally or need iron fast)
are most cases of B12 deficiency treated with oral or parenteral administration
parenteral: most cases of vit B12 deficiency are due to malabsorption so oral supplementation would be inadequate
the three symptoms eczema, thrombocytopenia and combine B and T cell deficiency (manifested as repeated infections) suggest what disease
Wiskott-Aldrich syndrome
why is vitamin K deficiency seen in preterm infants and what disease does it cause
preterm infants may have vitamin K deficiency due to immature liver, low vit K content in breast milk and meager intestinal microbiota;
vit K deficiency can cause hemorrhagic disease of the newborn due to low factors 2, 7, 9, and 10
name the chromosomes where the following genes are found:
bcl-2, c-myc, Ig heavy chain, kappa light chain, lambda light chain
bcl-2 = chromosome 18 c-myc = chromosome 8 Immunoglobulin heavy chain = chromosome 14 kappa light chain = chromosome 2 lambda light chain = chromosome 22
what is ticlopidine and what is a deadly, but rare side effect of its use
ticlopidine is an ADP antagonist (along with clopidogrel) and in rare cases it causes neutropenia (typically presenting with fever and mouth ulcers)
what are the most common ways to contract enterohemorrhagic E.coli
- undercooked beef
- person-to-person contact
- raw unpasteurized milk
gp41 mediates viral _________ while gp120 mediates viral __________
gp41 mediates viral entry while gp120 mediates viral attachment
what conditions make HbS RBC sickling more likely to occur
low oxygen levels, low volume (dehydration) and acidic environment
what molecular interaction allows fetal hemoglobin to have higher O2 affinity
impaired 2,3-DPG binding (2,3,-DPG effectively hinders O2 affinity)
if a cancer patient develops peaked T waves, elevated BUN/Cr, hypocalcemia and/or hyperphosphatemia what underlying condition would you suspect and how could it have been prevented
tumor lysis syndrome presents as hyperkalemia, hyperuricemia causing renal dysfunction, hyperphosphatemia and hypocalcemia
treat chemo patients with allopurinol, febuxostat, or rasburicase
differentiate Hodgkin’s from non-Hodgkin’s lymphoma
Hodgkin’s has Reed-Sternberg cells (giant bilobed or binucleate cells), better prognosis, more constitutional symptoms and is more localized to a single group of nodes
pol and env mutations in HIV allow for what modes of resistance, respectively
pol mutations allow for resistance to reverse transcriptase inhibitors
env mutations allow for resistance to host neutralizing antibodies
what CBC abnormalities would you expect for polycythemia vera and what is mutated to cause this condition
polycythemia, thrombocytosis, leukocytosis;
JAK2 mutation causes hyperproliferation of all three myeloid cell lines
bone marrow biopsy showing greater than 30% plasma cells is diagnostic of what condition
multiple myeloma
what does ristocetin do
ristocetin is used to test for vWF abnormalities;
ristocetin activates GP1b and so in normal blood adding ristocetin will promote increased platelet aggregation
in Hemophilia A and B patients, administration of what factor can allow for clotting
thrombin
in what conditions or cases would you see burr cells?
what are burr cells?
burr cells are RBCs with evenly spaced spikes;
seen as an artifact sometimes, but seen characteristically in PKD, microangiopathic hemolytic anemia, uremia and mechanical trauma
describe the effect of selective COX-2 inhibitors on inflammation, gastric mucosa and platelet aggregation
anti-inflammatory
no gastric mucosal disturbances as seen in NSAIDs
no disruption of platelet aggregation since platelets express mainly COX-1
explain the Haldane effect
as deoxygenated blood enters the alveolar capillaries, increased PO2 leads to increasing binding of oxygen to hemoglobin and consequent release of H+ and CO2 from hemoglobin
what gives reticulocytes their bluish color on Wright-Giemsa stain
ribosomal RNA that has not yet disappeared
what kind of drug is raltegravir and what does it treat
raltegravir is an HIV integrase inhibitor
which drugs are used for clot lysis in acute MI
fibrinolytics such as t-PA, alteplase, tenecteplase and recteplase
describe the mechanism by which paroxysmal nocturnal hemoglobinuria develops
deficiency of CD55 and 59 leads to inability to inactivate complement –> hemolysis that leads to hemoglobinuria
what are the three most common symptoms of paroxysmal nocturnal hemoglobinuria
hemolysis (intravascular), hypercoagulability, and pancytopenia
pure red cell aplasia commonly results from what underlying illnesses
thymomas and parvovirus B19 infection (because the virus preferentially infects proerythroblasts)
how does warfarin’s effects on vitamin K lead to down regulation of clotting factors
warfarin prevents vitamin K-mediated carboxylation of glutamate residues on factors 2, 7, 9, 10, Protein C and S
in aplastic anemia what replaces hematopoetic tissue in the bone marrow
fat cells and fibrous stroma
rat poison contains derivatives of 4-hydroxycoumarin; how does rat poison cause death
4-hydroxycoumarin is a vitamin-K antagonist
what is the primary cause of iron deficiency anemia
blood loss
why does myelofibrosis cause hepatosplenomegaly
decreased production of blood cells in the bone marrow leads to extramedullary hematopoesis
what defect causes myelofibrosis
a mutation causing valine to phenylalanine substitution in the JAK-2 kinase (a tyrosine kinase) leads to constitutive activation of the JAK-STAT pathway
what drug treats myelofibrosis and how
ruxolitinib is a JAK2 inhibitor
over what time period in childhood is fetal hemoglobin gradually replaced by adult hemoglobin
first 6 months of life
which anticoagulant is used to treat DVT in pregnant women
heparin
differentiate the location of positive and negative T-cell selection and when they occur in relation to each other
positive selection occurs first and takes place in the thymic cortex;
negative selection occurs after positive selection and takes place in the thymic medulla
what kind of blood problem does uremia cause
qualitative platelet disorder (note: platelet count is normal)
how does the JAK2 mutations seen in myeloproliferative disorders (except for CML) cause myeloproliferation
increased bone marrow sensitivity to growth factors
