Heme and Onc. Flashcards
What cell type contains dense granules? What are the two products of dense granules?
erythrocytes
ADP and calcium
What type of cell contains αgranules? What are the two products of αgranules?
erythrocytes
vWF and fibrinogen
In what organ is approximately 1/3 of platelet pool stored?
spleen
What is the vWF receptor?
GpIb
What is the fibrinogen receptor?
GpIIb/GpIIIa
What four enzymes are contained by neutrophils?
ALP
collagenase
lysozyme
lactoferrin
Do macrophages function via MHC II or MHC I?
MHC II
What type of nucleus do eosinophils possess?
bilobed
What two enzymes are produced by eosinophils granules?
histaminase and arylsulfatase
What are the three components of basophil granules?
histamine, heparin and leukotrienes
What form of leukemia can isolated basophilia be indicative of?
CML
What granulocyte binds Fc of IgE?
mast cell
What drug prevents mast cell degranulation?
cromolyn sodium
What two receptors do dendritic cells express?
Fc and MHC II
What are dendritic cells in the skin called?
Langerhans cells
What two CD molecules are expressed by B-lymphocytes?
19 and 20
What is the CD molecule required for T-cell activation?
CD28
Multiple myeloma is a cancer of what cell type?
plasma cells
If a person has type A blood, What antigen do they express on RBCs? What antibody is circulating?
A = RBC
Anti-B = circulating
If a person has type B blood, What antigen do they express on RBCs? What antibody is circulating?
B = RBC
anti-A = circulating
What type of immunoglobulin targets RBC antigens?
IgM
anti-Rh is what type of antibody?
IgG
If a person has type AB blood, What antigen do they express on RBCs? What antibody is circulating?
A and B = RBC
no circulating antibodies
What can people with AB blood universally donate?
plasma
What can people with AB blood universally receive?
blood
If a person has type O blood, What antigen do they express on RBCs? What antibody is circulating?
no antigen on RBCs
antigens to A and B in plasma
What can people with O blood universally donate?
blood
What can people with type O blood universally accept?
plasma
What three coagulation factors can thrombin activate?
V and VIII and thirteen
What coagulation factors activate factor X?
VIIa and VIIIa
Which three coagulation factors does Xa require? What is activated?
IIa and Va and VIIIa
What coagulation factor catalyzes the conversion of fibrinogen into fibrin?
IIa
Other than fibrinogen, what coagulation factor can thrombin activate?
XIII
What is the function of factor XIII?
cross-link fibrin
What cofactor requires only calcium?
XIII
What coagulation factors require calcium and phospholipid?
II, VII, IX, X
What two coagulation factors require thrombin for their activation?
five and eight
What is the function of plasmin?
to cleave fibrin
What complement can plasmin activate?
C3 to C3a
What clotting factor activates kallikrein?
XIIa
What two reactions does kallikrein catalyze?
HMWK to bradykinin
plasminogen to plasmin
What are the three functions of bradykinin?
increase permeability
pain
vasodilation
What three things can convert XII into XIIa?
collagen, basement membrane and activated platelets
What is the function of factor nine? What coagulation factors does factor nine need for its activation?
activate ten
seven and eight
Hemophilia A is a deficiency in what coagulation factor?
eight
Hemophilia B is a deficiency in what coagulation factor?
nine
What enzyme does warfarin inhibit?
Vitamin K epoxide reductase
What coagulation factor is carried by vWF?
VIII
Antithrombin inactivates which coagulation factors? What are the two primary targets of antithrombin?
two, seven, nine, ten, eleven, twelve
thrombin and Xa
Factor V Leidin disease produces a mutation in what clotting factor? What can’t this factor now be deactivated by?
Va
Activated protein C
Activated Protein C (APC) destroys which two coagulation factors?
Va and VIIIa
What are the two locations where vWF can be found?
endothelial cells and platelets
What is the receptor for vWF?
GpIb
What two products do platelets release in order to initiate the coagulation cascade?
ADP and Ca2+
What is the fibrinogen receptor?
Gp IIb/IIIa
What causes expression of GpIIb/IIIa? What is GpIIb/IIIa a receptor for?
ADP
fibrinogen
What thromboxane increases platelet aggregation? Where is this thromboxane released from?
TXA2
platelets
Decreasing what molecule does aspirin produce anticoagulation effects?
TXA2
What is the MOA of clopidogrel? What is another drug that produces this effect?
clopidogrel inhibits ADP induced expression of GpIIb/IIIa
Ticlopidine
What drugs inhibits GpIIb/IIIa directly?
Abciximab
eptifabitide
tirofiban
What is the MOA of Ristocetin?
induces vWF to bind GpIb
What receptor do clopidogrel and ticlopidine block?
ADP receptor
What protein is defective in Glanzmann Thrombasthenia?
GpIIb/IIIa
What is deficient in Bernard-Soulier?
GpIb
What are the two causes of acanthocytes?
abetalipoproteinemia
liver disease
What four conditions can produce basophilic stippling of RBCs?
anemia of chronic disease
alcohol abuse
Lead
Thalassemias
What is the acronym of basophilic stipling?
BASically, ACiD Alcohol is LeThal
What deficiency can lead to bite cells? What is removed?
G6PDase
oxidized Hb
What is the role of ferroportin?
to transfer iron out of a cell
What is the function of hepcidin?
to block ferroportin
Where are the two locations of ferroportin?
enterocytes of GI tract
macrophages
What disease produces a macroovalocyte?
megaloblastic anemia
What is a ringed sideroblast?
nucleated RBC with iron in mitochondria
Name for diseases where schistocytes are present?
DIC, TTP, HUS and traumatic hemolysis
What causes tear drop cells?
bone barrow infiltrate
What type of RBC features an increased cell membrane surface area?
target cells
What is the acronym do remember the causes of target cells?
HALT
What does the H in HALT stand for?
HbC
What does the A in HALT stand for?
Asplenia
What does the L in HALT stand for?
Liver disease
What does the T in HALT stand for?
Thalassemia
What type of prosthetic group is oxidized in Heinz bodies?
sulfhydryl
What type of stain is used to visualize heinz bodies?
crystal violet
What type of thalassemia produces Heinz bodies?
alpha-thalassemia
How do Howell-Jolly bodies stain?
basophilic
What are Howell-Jolly bodies composed of? What cell type?
nuclear remnants
RBCs
In what two circumstances do Howell-Jolly bodies arise?
asplenia or hyposplenia
What can cause an iron deficient anemia?
chronic bleeding
What is the triad of Plummer-Vinson Syndrome?
- esophageal webs
- Iron deficient anemia
- atrophic glossitis
Most microcytic RBCs also feature what?
hypochromia
In what population is the cis-deletion prevalent in alpha-Thalassemia?
Asians
In what population is the trans-deletion prevalent in alpha-Thalassemia?
Africans
What does four allele deletion alpha-thalassemia result in? What chain is present?
Hb barts
gamma chain
What does three allele alpha-thalassemia result in? What type of globin composes this?
HbH
β-globin
What type of mutation produces alpha-Thalassemia?
deletion
What type of population is β-thalassemia most commonly found?
Mediterranean
What type of mutation produces β-thalassemia? What two locations do these mutations occur?
point
promoter and splice site
What chains is HbH composed of?
four beta chains
β-thalassemia minor is characterized by what type of Hb? How much?
HbA2
> 3.5%
What happens to the β-chain in β-thalassemia minor?
β-chain is underproduced
What happens to the β-chain in β-thalassemia major?
β-chain is absent
What form of β-thalassemia produces a crew-cut on X-ray?
β-thalassemia major
What happens to bones during β-thalassemia major?
extramedullary hematopoiesis
A person with extra-medullary hematopoiesis is at risk of what viral infection?
Parvovirus B19
What form of hemoglobin predominates in β-thalassemia major?
HbF
What two enzymes are inhibited during lead poisoning?
ferrochelatase
ALA Dehydratase
What does the L of LEAD stand for?
Lead Lines on gingivae and metaphyses of long bones
What two locations do lead lines appear during lead poisoning?
metaphyses of long bones and gingiva
What does the E’s of LEAD stand for?
Encephalopathy and erythrocyte stipling
What does the A’s of LEAD stand for?
abdominal colic and sideroblastic Anemia
What does the D of LEAD stand for?
wrist and foot Drops
Dimercaprol and EDTA
What drug is used to chelate lead in children?
Succimer
What is the most commonly defective enzyme in Sideroblastic Anemia?
ALA Synthase
Other than iron, deficiency of what metal can cause sideroblastic anemia?
copper
What drug can cause sideroblastic anemia?
Isoniazid
What is the treatment for sideroblastic anemia? What enzyme will this restore activity to?
B6
ALA Synthase
What are the three antimetabolites that can cause megaloblastic anemia?
methotrexate
trimethoprim
phenytoin
What type of GI drug can cause a megaloblastic anemia?
PPIs
OTCase deficiency will increase what metabolite?
Orotic acid
What is the treatment for orotic aciduria?
uridine monophosphate
What is the function of haptoglobin?
to bind free Hb
Where is Hb-hemoglobin degraded?
Reticuloendothelial system
What are the two main laboratory markers of intravascular hemolytic anemia? What happens do their levels during hemolysis?
decreased haptoglobin
increased LDH
What is the breakdown of heme that is found in the urine?
urobilinogen
What destroys RBCs in paroxysmal nocturnal hemoglobinuria?
complement
Is paroxysmal nocturnal hemoglobinuria considered intravascular or extravascular hemolysis?
intravascular
What is the most commonly defective protein during PNH?
GPI anchor
What two CD molecules are most often mutated in PNH?
CD55/DAF
CD59
What is the function of CD55/DAF?
limit the formation of C3 convertase
What are the two functions of CD59?
bind MAC and prevent C9 from binding RBC cell membrane
Circulating Hb binds with what molecule? What does this lead to? How can this be treated?
NO
ED, esophageal spasm, abdominal pain
Sildenafil
Will unconjugated bilirubin increase during intravascular or extravascular hemolysis?
extravascular
What cell type is damaged during microangiopathic hemolytic anemia? What damages the RBCs?
endothelial cells
fibrin mesh
HUS is characterized by what triad?
hemolytic anemia
acute kidney failure
thrombocytopenia
What three bacteria can cause HUS?
E. coli O157:H7
Camplyobacter
Shigella
What toxin is implicated in HUS? What cell surface protein does this toxin bind? What is the net effect?
Shiga
Gb3
endothelial cells to become thrombogenic
What metalloprotinease is inactivated during HUS? What is the normal function of this protein?
ADAMTS-13
cleave vWF
Most cases of TTP arise due to inactivation of what protein? What is the normal function of this protein?
ADAMS-13
to cleave vWF
What is an inherited defect in ADAMTS-13 called?
Upshaw-Shulman Syndrome
What does myeloid mean?
granulocyte precursor
What are the four major granulocytes?
Neutrophil
Eosinophil
Basophil
Monocyte
Aplastic anemia is a destruction of what type of stem cells?
Myeloid
What four types of drugs can cause aplastic anemia?
benzene, chloramphenicol, antimetabolites, alkylating agents
What four virus can cause aplastic anemia?
B19, EBV, HCV and HIV
What type of anemia can cause aplastic anemia? Patients with this type of anemia are predisposed to develop what disease?
Fanconi anemia
AML
Idiopathic aplastic anemia may follow what infectious disease?
acute hepatitis
What are the three major blood cellular deficiencies of aplastic anemia?
pancytopenia (severe anemia)
thrombocytopenia
leukopenia
What are the two treatments for aplastic anemia?
immunosuppressive
G-CSF or GM-CSF
What four proteins are defective in hereditary spherocytosis?
ankyrin
spectrin
band 3
band 4.2
What is missing in RBCs with hereditary spherocytosis?
central pallor
What is the organ manifestation of hereditary spherocytosis?
splenectomy
What is used as a screening test in Hereditary Spherocytosis?
eosin-5-maleimide
What is the treatment of hereditary spherocytosis?
splenectomy
What product is decreased in G6PDase deficiency?
glutathione
How will a pyruvate kinase deficiency manifest in a new born?
hemolytic anemia
What substitution is present in a patient with HbC? What position?
glutamic acid to lysine in beta-globin
position six
What two complement proteins does DAF recognize and sequester?
C4b and C3b
What does the direct Coombs test detect?
IgG bound to RBCs
What does the indirect Coombs test detect?
circulating anti-RBC IgG
Would PNH have a positive Coombs test?
no
What is the function of CD59?
prevent formation of MAC
What is the treatment of PNH? What is the MOA of this drug?
eculizumab
terminal complement inhibitor
What glutamic acid substitution is prevent in HbS?
glutamic acid to valine
What two blood diseases will feature a ‘crew-cut’ Xray?
Thalassemia
HbS
Patients with an autosplenectomy are at an increased risk of what type of infection?
encapsulated bacteria
What disease can produce splenic sequestration crisis?
sickle cell anemia
What is the pneumonic for encapsulated bacteria?
Some Nasty Killers Have Some Capsule Protection
Salmonella osteomyelitis almost exclusively effects patients with what type of disease?
sickle cell anemia
What is the specific type of kidney damage seen in patients with sickle cell disease?
renal papillary necrosis
What is the drug Tx for sickle cell? Why?
Hydroxyurea
breaks down cells susceptible to sickle cell damage
What type of Hb does hydroxyurea increase?
HbF
Warm agglutinin detects what type of Ab? Against what antigen? Acute or chronic?
IgG
RBCs
chronic
Would autoimmune hemolytic anemia produce a positive or negative coombs?
positive
Other than hemolytic anemia, warm agglutinin test can detect the presence of what other two diseases?
SLE and CLL
Warm agglutinin test can be present if a patient is on what drug?
α-methyldopa
Cold agglutinin detects what antibody?
IgM
Is warm agglutinin chronic anemia or acute anemia? Cold agglutinin?
warm = chronic
cold = acute
What type of leukemia will produce a positive Cold Agglutinin test?
CLL
What type of bacterial infection will produce a cold agglutinin test?
Mycoplasma pneumoniae
What type of viral infection will produce a cold agglutinin test?
mononucleosis
Does serum iron increase or decrease in iron deficient anemia?
decrease
Does TIBC increase or decrease in iron deficient anemia?
increase
Does ferritin increase or decrease during iron deficient anemia?
decreases
Does % transferrin saturation increase or decrease during iron deficiency?
decrease
Does serum iron increase or decrease during ACD?
decrease
Does TIBC increase or decrease during ACD?
decrease
Does ferritin increase or decrease during ACD?
increase
Does TIBC decrease or increase during hematochromatosis?
decrease
Does pregnancy increase or decrease TIBC?
increase
What blood related protein increases during pregnancy and the use of oral contraceptives?
transferrin
What do corticosteroids do to neutrophils?
increase their count
What do corticosteroids do to eosinophils?
decrease
What do corticosteroids do to lymphocytes?
decrease
What B-vitamin is required for heme synthesis?
B6
What enzyme of heme synthesis is effected during sideroblastic anemia? How is this treated?
ALA synthase
B6
What are the two reactants of ALA Synthase?
glycine and succinyl-CoA
What are the two enzymes of heme synthesis that lead can interrupt?
ALA dehydratase
ferrochelatase
What enzyme is interrupted during Acute Intermittent Porphyria?
Porphobilinogen Deaminase
What enyzme of heme synthesis is interrupted during Porphyria Cutanea Tarda?
Uroporphyrinogen Decarboxylase
What two metabolites accumulate during lead poisoning?
aminolevulinic acid
Protoporphyrin
Does lead poisoning cause microcytic or macrocytic anemia?
microcytic
What are the two inhibitors of ALA synthase?
glucose and heme
What are the five P’s of AIP?
painful abdomen port wine urine Polyneuropathy Psychological disturbances Precipitated by alcohol/drugs/starvation
What metabolite accumulates during Porphyria Cutanea Tarda?
Uroporphyrinogen
What factors are measured by the prothrombin time?
one, two, five, seven and ten
What factors are measured by PTT?
all except seven and thirteen
What does GpIb bind? Name a disease defective in GpIb?
GpIb binds vWF
Bernard-Soulier disease
Immune thrombocytopenia features antibodies against what?
GpIIb/GpIIIa
What type of illness may trigger immune thrombocytopenia?
viral
What enzyme will be present in the serum during TTP?
LDH
vWF carries/protects what factor?
eight
What is the treatment of von Willebrand Disease? Why?
DDAVP
desmopressin increases vWF release from endothelial cells
What is the mnenomic for remember the causes of DIC?
STOP Making New Thrombi
What does the S of STOP Making New Thrombi stand for?
gram-negative sepsis
What does the T of STOP Making New Thrombi stand for?
trauma
What does the O of STOP Making New Thrombi stand for?
obstetric complications
What does the P of STOP Making New Thrombi stand for?
acute Pancreatitis
What does the M of STOP Making New Thrombi stand for?
Malignancy
What does the N of STOP Making New Thrombi stand for? Why does this happen?
nephrotic syndrome
lose antithrombin in urine
What does the 2nd T of STOP Making New Thrombi stand for?
transfusion
There is a widespread release of what clotting factor in DIC?
Tissue Factor
What two coagulation factors are most consumed in DIC?
five and eight
What part of coagulation does antithrombin deficiency effect?
diminishes the increase in PTT following heparin administration
What can cause acquired antithrombin deficiency?
nephrotic syndrome
Warfarin induced necrosis can be though of as a deficiency in what protein?
Protein C
What four clotting factors are contained in cryoprecipitate?
VIII, XIII, vWF and fibronectin
Is there an increase in leukocyte ALP durig active infection or CML?
active infection
Does Hodgkin lymphoma affect a single node or mutiple nodes?
single
Is Hodgkin or non-Hodgkin lymphoma characterized by Reed Sternberg cells?
Hodgkin
What type of cell are Reed-Sternberg cells derived from?
B-cells
What are Reed-Sternberg cells considered?
crippled germinal centers that have not undergone hypermutation to express their Ab
What are the two CD markers of Hodgkin Lymphoma?
CD15 and CD30
Which form of Lymphoma has non-contiguous spread?
non-Hodgkin
Which form of Lymphoma has a bimodal age distribution?
Hodgkin
What age does non-Hodgkin lymphoma usually strike?
20-40
What virus is often hypothesized to cause Hodgkin lymphoma?
EBV
Which has a better prognosis, Hodgkins Lymphoma with or without lymphocyte rich infiltrate?
rich in lymphocyte = better prognosis
Regarding cancer, what oncogenic protein is located on chromosome 8?
c-Myc
What translocation is present in Burkitt’s Lymphoma?
t(8;14)
Regarding cancer, what oncogenic protein is located on chromosome 14?
Ig heavy chain
What is the histological key word for Burkitt’s Lymphoma?
‘Starry Sky’
What virus is associated with Burkitt’s Lymphoma?
EBV
How does Burkitt’s arise in African? Sporadic form?
African = Jaw
Sporadic = Abdomen
What translocation takes place in diffuse large B-cell lymphoma?
t(14;18)
Where is the mantle zone located?
corona of germinal center
What translocation is present in a Mantle Cell Lymphoma?
t(11;14)
Regarding oncogenesis, what protein is located on chromosome 11?
Cyclin D1
What CD molecule is present on a mantle cell lymphoma?
CD5
What translocation is present during Follicular Cell lymphoma?
t(14;18)
Regarding oncogenesis, what protein is present on chromosome 18?
bcl-2
What type of non-Hodgkin lymphoma presents with waxing and waning lymphadenopathy?
follicular lymphoma
What is HTLV1 associated with?
IV drug use
What three populations are predisposed to HTLV1?
Japan, West Africa, Caribbean
What are three common presentations for HTLV1?
cutaneous lesions, bone lesions and hypercalcemia
What is mycosis fungoides?
cutaneous T-cell lymphoma
What type of T-cell is present in Mycosis Fungoides?
CD4+
What are the two locations where Mycosis Fungoides can spread?
lymph nodes and viscera
Are mutltiple myeloma monoclonal or polyclonal?
monoclonal
What two immunoglobulins are most often produced by Multiple Myeloma? Which more?
IgG and IgA
IgG
What type of spike takes place during Multiple Myeloma?
M spike
What are Bence Jones proteins composed of? Where are Bence Jones proteins found? What disease do Bence Jones proteins suggest?
Ig light chain
urine
multiple Myeloma
Clock face chromatin is indicative of what disease?
Multiple Myeloma
Which immunoglobulin is overproduced during Waldenstrom Macroglobulinemia?
IgM
How is Waldenstrom Macroglobulinemia differentiated from Multiple Myeloma?
WM does NOT have lytic bone lesions
What disease has Rouleaux formation? What are Rouleaux formations?
Multiple Myeloma
stacked RBCs
What disease is an asymptomatic precursor to Multiple Myeloma?
Monoclonal Gammopathy of Undetermined Significance
MGUS
What is a Pelger Huet anamoly? Caued by?
bilobed neutrophil
chemotherapy
Under what age is ALL most likely to arise?
15 years
Where can T-cell ALL create a mass?
thymus/mediastinum
Down Syndrome patients are at an increased risk of developing what two types of leukemia?
ALL and AML
What is the immunohistochemical marker for pre-T and pre-B cells? Function of this?
TdT+
VDJ rearrangement of TCR
What is the immunohistochemical for pre-B cells only?
CD10
What translocation has the best prognosis in ALL?
t(12:21)
What two immunohistochemical does CLL possess? Is CLL an expansion of B-cells or T-cells?
CD20 and CD5
B-cells
Hairy cell leukemia features what type of lymphocytes? Mature or immature?
Mature B-cell
What is the average age of onset of AML?
65 years
What type of leukemia stains with a TRAP stain?
hairy cell leukemia
What leukemia causes marrow fibrosis? What is the stain for this leukemia?
hairy cell
TRAP
What two drugs are used to treat Hairy Cell Leukemia? What is the MOA of these drugs?
Cladribine
adenosine analgoue that inhibits adenosine deaminase
What type of cells are Auer rods present? What disease features Auer rods?
leukemic blasts
AML
Patients with previous exposure to alkylating agents are at an increased risk of developing what type of leukemia?
AML
What type of leukemia responds to trans-retinoic acid? Why?
M3 AML
causes blasts to mature
DIC is a common presentation of what specific type of leukemia?
M3 AML
Which type of AML is most likely to cause DIC? Why?
M3
release of Auer rods due to chemo. agents
The Philadelphia Chromosome is possessed in what type of Leukemia?
CML
What type of translocation takes place in M3 AML?
t(15:17)
What three types of lymphocytes increase in number during CML?
neutrophils, metamyelocytes and basophils
What two diseases can CML transform into?
ALL or AML
Will there be a high or low level of leukocyte alkaline phosphatase during CML?
low
What is the tx of CML?
imatinib
Birbeck granules are indicative of what disease?
Langerhans Cell Histiocytosis
What precursor are Langerhans cells derived from?
monocytes
How does LCH present in child?
lytic bone lesions
What disease can be recurrent in LCH?
otitis media
S-100 is a marker for what cancer?
melanoma
S-100 is an IHC marker for what embryological origin?
mesoderm
What two IHC markers are expressed by LCH?
S-100 and CD1a
What cell signaling molecule is involved in myeloproliferative disorders?
JAK2
What does hematocrit have to be greater than to be considered polycythemia vera?
55%
What gene is mutated in polycythemia vera?
JAK2
How does polycythemia vera often present? Why?
intense itching after a hot shower
release of histamine
What hematological issue can present with gouty arthritis?
polycythemia vera
Why can essential thrombocytosis produce bleeding?
platelets sequester too much vWF
How do RBCs look during myelofibrosis?
tear drop
What drug inhibits heparin?
protamine sulfate
What is heparin bound to during HIT? What class of Ab?
PF4
IgG
What is the one draw back to LMW heparin?
not easily reversible
What two drugs are used in patients with HIT? What is their MOA?
Argatroban and Bivalirudin
inhibit thrombin directly
Which anticoagulant can cross the placenta?
warfarin
What drug is given to reverse warfarin OD?
vitamin K
What are the two direct inhibitors of Factor X?
apixiban and rivaroxaban
What are the three thrombolytics? What are their MOAs?
Alteplase, Reteplase and Tenecteplase
conversion of plasminogen into plasmin
What two proteins does plasmin cleave?
thrombin and fibrin
Name two common ADP receptor inhibitors
clopidogrel ticlopidine
Which ADP receptor antagonist can cause neutropenia?
Ticlopidine
What are the two PDE3 inhibitors?
Cilostazol and Dipyridamole
What antibody is a direct inihibitor of GpIIb/GpIIIa?
abciximab
What enzyme is inhibited by methotrexate?
DHFR
5-FU covalently complexes what molecule? What enzyme is inhibited?
folic acid
thymidylate synthase
What is given during a 5-FU overdose?
uracil
What enzyme does cytarabine inhibit?
DNA polymerase
What is the most notable side effect of cytarabine?
pancytopenia
Azathioprine/6-MP are analogues of what?
purines
What enzyme activates 6-MP into azathioprine?
HGPRTase
What drug can increase the toxicity of 6-MP and azathioprine?
allopurinol
What is the MOA of actinomycin (dactinomycin)?
intercalates DNA
What is the MOA of doxorubicin? What does this stop the progression of?
intercalates DNA
DNA topoisomerase
What type of toxicity does doxorubicin cause?
cardiac
What is the MOA of bleomycin?
free radical generation leadign to dsDNA breaks
What is the MOA of cyclophosphamide?
alkylating agent at guanine N-7
What is the toxicity of bleomycin?
pulmonary fibrosis
p450 is require to activate what type of anti-neoplastics?
Alkylating agents
What is the by-product of cyclophosphamide? What does this byproduct cause? What drug can overcome this?
acrolein
hemorrhagic cystitis
mesna
What is the main toxicity of cyclophosphamide?
myelosuppression
What is the MOA of nitrosureas?
cross-links DNA
What type of cancers are nitrosureas used for?
brain cancers
What are the main toxicities of nitrosureas?
CNS toxicity
What is the MOA of busulfan? What is it used for?
cross-links DNA
ablate bone marrow
What is the MOA of vincristine and vinblastine?
bind β-tubulin
What is the toxicity of vincristine?
peripheral neuropathy
What does vinblastine blast?
bone marrow
What is the MOA of paclitaxel?
prevent breakdown of mitotic spindle
What are the three main toxicitues of taxols?
myelosuppression
alopecia
hypersensitivity
What is the MOA for cisplatin/carboplatin?
cross-link DNA
testicular
What are the two toxicities caused by cisplatin?
nephrotoxicity and CN VIII damage
What drug is used to treat the nephrotoxicity associated with cisplatin?
amifostine
What is the MOA of etoposide/tenoposide?
inhibit topo. II
What drug can increase HbF?
sickle cell anemia
What is the MOA of irinotecan and topotecan?
inhibition of topo. I
What enzyme does hydroxyurea inhibit?
ribonucleotide reductase
Which SERM can be a partial agonist in the endometrium?
tamoxifen
What drug is used to target HER2+ tumors? What is the main toxicity of this drug?
trastuzumab
heart
What is another name for imatinib? What two neoplasias is imatinib used to treat?
Gleevec
Philadelphia chromosome CML and GI stromal
Rituximab is used to treat which three conditions?
all Bcell lymphomas
rheumatoid
ITP
Vemurafenib is used to treat what disease? Which specific marker?
malignant melanoma
B-raf kinase with V600E mutation
Bevacizumab is used to treat which two cancers?
colorectal
renal cell carcinoma
What is the toxicity of Methotrexate?
Myelosuppression
What four proteins are contained within neutrophils?
ALP, collagense, lactoferrin and lysozyme
What oxidative enzyme is contained within neutrophils?
myeloperoxidase
What two molecules are expressed by Thelper cells?
CD3 and CD4
What two molecules are expressed by cytotoxic Tcells cells?
CD3 and CD8
What are the two primary targets of antiheparin?
II and X
What molecule accumulates in hereditary sideroblastosis? What organelle?
Iron
mitochondria
What prosthetic group of Hb is oxidized in bite cells?
sulfhydryl
Where is a common location on the body for pallor to develop during iron deficient anemia?
conjuctiva
Lead poisoning inhibits the degradation of what sort of nucleic acid? What does this lead to?
rRNA
basophilic stipling
B6 is a cofactor for what enzyme of heme synthesis?
ALA synthase
Fanconi anemia features a decrease in what type of repair mechanism?
DNA
What are the two findings of G6PD deficiency?
back pain
hemoglobinuria
Non-Hodgkin lymphoma may be associated with what virus?
HIV
Which form of lymphoma presents with low-grade fever and night sweats?
Hodgkins
What three clotting proteins decrease during DIC?
fibrinogen, V and VIII
Auer rods contain what enzyme?
peroxidase
Does PCV have low or high EPO levels?
low
What clotting factor does LMW heparin bind to more?
ten
What is the MOA of argatroban and bivalirudin?
inhibit thrombin directly
How is warfarin metabolized?
CYP 2C9
Which anticoagulant is lipid soluble, warfarin or heparin?
warfarin
Which anticoagulant is given orally, warfarin or heparin?
warfarin
Which anticoagulant acts rapidly, heparin or warfarin?
warfarin
Which anticoagulant has a duration of hours, , warfarin or heparin?
heparin
What drug is used to treat an overdose of alteplase/reteplase/tenecteplase?
aminocaproic acid
What does 5-fluorouracil complex with? The production of what compound is inhibited? What enzyme is inhibited?
folic acid
dTMP
thymidylate synthase
Cytarabine is an analogue of purines or pyrimidines?
pyrimidnes
What is the side effect of cytarabine?
pancytopenia
What enzyme metabolizes azathioprine?
xanthine oxidase
What drug is used for childhood tumors?
dactinomycin
Which antineoplastic requires bioactivation by the liver?
cyclophosphamide
Drugs that inhibit microtubules prevent what phase of the cell cycle?
M phase
What is the most commonly used glucocorticoid for antineoplastic medicine?
Prednisone
In what tissue are SERMs an agonist?
bone
What two diseases can imatinib be used to treat?
CML and GI stromal tumors
What is the cofactor for myeloperoxidase?
heme
What is the function of CD40?
co-stimulatory molecule of APCs
Where are langerhans cells located?
areas of body in contact with external environment
What is the funtion of CD3?
to bind the T-cell recpetor
What is the function of Tregs?
help immune system differentiate self from non-self
What syndrome can develop if Tregs do not function properly?
IPEX syndrome
What txn factor is defective during IPEX syndrome?
FOXP3
What two compounds bind to protein C? What binds to activated protein C?
thrombin and thrombomodulin
protein S
What clotting factor binds exposed collagen?
vWF
What two hematological complications arise from Copper Deficiency?
anemia and neutropenia
How would a patient with subacute combined deficiency present with regards to their motor movement?
spastic movements
Is Hb released into the serum during extravascular hemolysis?
no
What type of infections are patients with a splenectomy predisposed to?
encapsulated organisms
What five conditions can produce microangiopathic hemolytic anemia?
DIC TTP HUS SLE malignant hypertension
What two parasite diseases can cause hemolytic anemia?
malaria and Babesia
Do corticosteroids cause neutropenia or neutrophilia?
neutrophilia
impair neutrophil migration out of vasculature
Do corticosteroids cause eosinopenia or eosinophilia?
eosinopenia
Do corticosteroids cause lymphopenia or lymphophilia?
lymphopenia
What drug is used to diagnose vWF Disease?
ristocetin
What is the most common cause of inheritable hypercoagulability in humans?
Factor V leiden deficiency
Warfarin induced necosis is exacerbated by what disease?
Protein C or S deficiency
What neoplasm has a ‘fried egg’ appearance on histlogy?
Multiple Myeloma
Myelodysplastic Syndromes have an increased risk of transforming into what disease?
AML
What are histiocytes?
activated macrophages or dendritic cells
What is Langerhans Cell Histiocytosis also known as?
Hand-Schuller-Christian Disease
What is the triad of LCH?
insipidus/exopthalmos/lytic bone lesions
What two types of cells compose histiocytes?
activated dendrites and macrophages
What three classes of cells are contained within pancytopenia?
erythroblasts
megakaryoblasts
granulocytes
What are the three toxicities of aspirin?
gastric ulceration
tinnitus (CN VIII)
interstitial nephritis
What is pulmonary side effect of aspirin overdose?
respiratory alkalosis
What is the main side effect of clopidogrel or ticlopidine?
acute coronary syndrome
What does increased cAMP in platelets do? What two drugs can cause an increase in cAMP in platelets?
inhibits aggregation
Cilostazol and Dipyridamole
What is the only drug that leucovorin can be used in combination with to prevent myelosuppression?
methotrexate
What is an overdose of 5-FU treated with?
uridine
What enzyme does 6-MP/azathioprine inactivate? What rxn is catalyzed by this rxn?
amidophosphoribosyltransferase
PRPP to PRA
What is the toxicity of rituximab?
multifocal leukoencephalopathy
Aminocaproic acid is an analogue of what amino acid?
lysine
What are the three causes of megaloblastic anemia?
B12, Folate and orotic aciduria
What type of drug can cause a B12 deficiency?
PPI
A patient with PNH has an increased liklihood of developing what disease?
acute leukemias
What three situations precipitate Hb Sickling?
hypoxemia, acidosis, dehydration
What are the two inhibitors of ALA Synthase?
glucose and heme
What cell would increase in number during Immune Thrombocytopenia in the bone marrow?
Megakaryocytes
What receptor is defective in Pelger-Huet Anamoly?
Lamin B receptor
What type of cell is present in CLL?
Smudge cell
Which anticoagulant is known to cause osteoporosis over long time use?
Heparin
What are the four ADP receptor inhibitors?
Clopidogrel, ticlopidine, prasugrel, ticagrelor
What drug is used in combination with doxorubicin to prevent cardiomyopathy?
Dexrazoxane
What is the antigen of Type A blood?
N-acetylgalactosamine
What is the antigen of Type B blood?
Galactose
Would an infection increase or decrease ESR?
increase
Would an auto-immune disease increase or decrease ESR?
increase
Would a neoplasm increase or decrease ESR?
increase
Would plycythemia vera increase or decrease ESR?
decrease
Would SSA increase or decrease ESR?
decrease
Would CHF increase or decrease ESR?
decrease
Would pregnancy have an increase or decreased ESR?
increased
Which three drugs can cause a non-megaloblastic macrocytic anemia?
hydroxyurea
5FU
zidovudine
What is the mode of inheritance for orotic aciduria?
autosomal recessive
What is the mode of inheritance for G6PDase Deficiency?
X-linked recessive
What is the mode of inheritance of Pyruvate Kinase Deficiency?
autosomal recessive
What is the most common cause of death in adults with SSA?
acute chest syndrome
What hematological abnormality can produce hemarthroses?
Hemophilia A and B
What type of RBC is created during TTP?
Schistocyte
Does TTP produce more renal or neurological symptoms?
renal
Does TTP produce a fever?
yes
What is the mode of inheritance for vWF disease?
autosomdal dominant
What two forms of Hodgkin Lymphoma does EBV produce?
mixed-cellularity
lymphocyte depleted
What gene is activated during EBV induced Hodgkins Lymphoma?
NF-KB
What cell is neoplastic during HTLV1?
CD4
What is the most common type of Hodgkins Lymphoma?
nodular sclerosing
Which form of myelogenous leukemia can produce splenomegaly?
CML
Other than crewcut/spleen/liver, where can extramedullary hematopoiesis take place?
serosal surfaces
What cell is over-produced during myelofibrosis? Which two cytokines released drive this process?
Megakaryocytes
PDGF and TGF
What non-kidney malignancy can produce an increase in EPO?
hepatocellular carcioma
Does warfarin monitor the extrinsic or intrinsic clotting cascade?
extrinsic
Which vitamin can potentiate the effects of warfarin?
vitamin E
Which endocrine disorder can potentiate the effects of warfarin?
Hyperthyroidism
Which fibrinolytic has the longest half-life?
Tenecteplase
What three types of tumors is doxorubicin used to treat?
solid tumors
leukemia
lymphomas
What two types of cancer is bleomycin used to treat?
Hodgkins
testicular cancer
What residue and position do nitrosureas alkylate?
O6 guanine
What cancer is busulfan used to treat?
CML
What four cancers are cisplatin/carboplatin used to treat?
Testicular
Ovarian
Breast
Lung
Which two cancers is Hydroxyurea used to treat?
melanoma and CML
In which two locations is tamoxifen an agonist?
bone and endometrium
What cancer is the ABVD regimen used for?
Hodgkins Lymphoma
What are the drugs of the ABVD regimen?
adriamycin/bleomycin/vinblastine/dacarbazine
What two cell lines express MPO?
neutrophils and monocytes
What three proteins can imatinib inhibit?
BCR/ABL
PDGF
c-Kit
Which leukemia can express CD52?
CLL
What drug targets CD52?
alemtuzumab
Which two neoplastic agents inhibit G1 and S?
Etoposide
Tenoposide
Which class of drugs are used during HIT?
Direct thrombin inhibitor
Do factor X Inhibitors require monitoring?
no
Are Langerhans cells during LCH mature or immature? What cant they do?
immature
activate Tcells
Which bone can be involved during LCH?
mastoid
What is seen in the bone marrow during Essential Thrombocytosis?
enlarged megakaryocytes
Does AML cause splenomegly?
no
Does Hairy Cell Leukemia have splenomegaly? Which pulp?
yes
white
What is a Stage One Lymphoma?
single node
What is a Stage Two Lymphoma?
two nodes on same side of diaphragm
What is a Stage Three Lymphoma?
both sides of diaphragm
What is a Stage Four Lymphoma?
invaded non-lymphoid tissue
Which two drugs can be used to turn down the immune response during Aplastic Anemia?
cyclosporine
antithymocyte globulin
Can be Lymphocytes function as an APC?
yes
What are eosinophils highly phagocytic for?
antigen/antibody complexes
What does anistocytosis mean?
different sizes
What does poikilocytosis mean?
different shapes
