Term
| Sequence of events leading to a clot from trauma to a vessel |
|
Definition
1. Reflex vasoconstriction
2. Platelets adhere
3. Tissue factor initiates extrinsic pathway |
|
|
Term
|
Definition
| found in the venous circulation, are composed of RBC's trapped in the fibrin meshwork, and usually contain few platelets |
|
|
Term
| What does factor XIIIa do |
|
Definition
| cross links fibrin stands to form a stable clot |
|
|
Term
| Collagen fibers will cause platelets to aggregate by stimulating them to secrete intracellular granular contents which include |
|
Definition
| adenosine diphosphate (ADP) and thromboxane A2. |
|
|
Term
| Adhesion of platelets to subendothelial collagen appears to require a plasma protein |
|
Definition
| von Willebrand factor (vWf) |
|
|
Term
|
Definition
| Tissue factor forms a complex w factor VII, which activates Factor X which along with its cofactor factor Va converts prothrombin to Thrombin (II), which cleaves fibrinogen to fibrin (I). |
|
|
Term
| What activates factor XIII |
|
Definition
|
|
Term
| Where does the common pathway start |
|
Definition
|
|
Term
|
Definition
| Surface complex (XII, Prekalikrein, HMW Kininogen, XI) Activates factor IX then another surface complex (IXa, VIIIa, phosphlipid, Ca2+) Activates Factor X then hits the common pathway. |
|
|
Term
| What factors are mostly associated with the extrinisic pathway |
|
Definition
|
|
Term
| Which factors are involved in the common pathway |
|
Definition
|
|
Term
|
Definition
extrinsic and common pathways. Isolated prolongation of the prothrombin time is seen primarily in two conditions:
i) vitamin K deficiency ii) liver disease.
In each disorder Factor VII is low, used to monitor warfarin activity. |
|
|
Term
| Partial thromboplastin time (PTT). |
|
Definition
| intrinsic and common pathways. Prolonged by heparin. screening test of hemophilia, Factor IX deficiency and von Willebrand's disease. Deficiency of Factors XII, XI, IX, VIII, V, X, II, fibrinogen, prekallikrein and high molecular weight kininogen will also prolong the PTT. |
|
|
Term
| Prolongation of both the PT and PTT is generally due to |
|
Definition
disorders in which multiple factor deficiencies occur, including:
i) Severe liver disease
ii) Disseminated intravascular coagulation (DIC)
iii) The anticoagulant warfarin
iv) Severe vitamin K deficiency |
|
|
Term
|
Definition
| used to detect inhibitors (antibodies) of clotting. Fifty percent of a coagulation factor is sufficient to give a normal PT or PTT. Abnormal plasma is mixed with normal plasma and if the PT or PTT is still abnormal it's a sign that there are antibodies/inhibitors in the abnormal plasma |
|
|
Term
|
Definition
| This vitamin K–dependent serine protease functions as a physiologic anticoagulant by inactivating Factors Va and VIIIa |
|
|
Term
|
Definition
| Protein S is also a vitamin K–dependent protein which serves as a cofactor for activated protein C. Protein S deficiency may result in thrombotic disease. Hereditary deficiency of protein C or protein S is transmitted in an autosomal dominant fashion |
|
|
Term
| activated protein C resistance. |
|
Definition
| mutant factor V molecule (factor V Leiden) that resists degradation by activated protein C |
|
|
Term
| There are 2 major etiologies for DIC |
|
Definition
a. DIC results from exposure of tissue factor to circulating blood.
b. DIC may also result from conditions leading to endothelial cell injury and/or Factor XII activation. There is a common association of gram–negative septicemia with DIC. |
|
|
Term
| Differential Diagnosis for increased PT in a patient with a bleeding disorder |
|
Definition
| Common: Factor VII deficiency (early liver disease, vitamin K deficiency, warfarin therapy) Rare: Factor VII inhibitor |
|
|
Term
| Differential Diagnosis for increased PTT in a patient with a bleeding disorder |
|
Definition
| Deficiency or inhibitor of Factors VIII, IX, or XI; vWD, heparin, lupus inhibitor with qualitative platelet defect |
|
|
Term
| Differential Diagnosis for increased PT and PTT in a patient with a bleeding disorder |
|
Definition
Common: Vitamin K deficiency, liver disease, warfarin, heparin
Rare: Deficiency or inhibitor of Factors X, V, prothrombin or fibrinogen; lupus inhibitor with hypoprothrombinemia; DIC |
|
|
Term
| Differential Diagnosis for increased PT and PTT and a decreased platelet count in a patient with a bleeding disorder |
|
Definition
| DIC, liver disease, heparin therapy with associated thrombocytopenia |
|
|
Term
| Differential Diagnosis for normal PT and PTT but a decreased platelet count in a patient with a bleeding disorder |
|
Definition
| Increased platelet destruction, decreased platelet production, splenomegaly, hemodilution |
|
|
Term
| Differential Diagnosis for only increased platelet count in a patient with a bleeding disorder |
|
Definition
| Myeloproliferative disorders |
|
|
Term
| Differential Diagnosis for normal PT, PTT and platelet count in a patient with a bleeding disorder |
|
Definition
Common: Variant vWD, acquired qualitative platelet disorders
Rare: Inherited qualitative platelet disorders, vascular disorders, fibrinolytic disorders, Factor XIII deficiency, autoerythrocyte sensitization |
|
|
Term
| Idiopathic thrombocytopenic purpura (ITP) |
|
Definition
| autoimmune disorder characterized by the development of antibodies to one's own platelets which are then destroyed in the spleen and/or liver. Childhood ITP frequently follows a viral infection. In children, the disease is self–limited and rarely requires treatment. In adults, treatment begins with corticosteroids. When remission is not sustained, splenectomy is the next form of therapy. Approximately 80% of patients will be cured by one of these modalities. The remainder have a chronic form of ITP |
|
|
Term
| Thrombotic thrombocytopenic purpura (TTP) |
|
Definition
| non immunologic disease characterized by thrombocytopenia, microangiopathic hemolytic anemia and neurologic abnormalities. Fever and renal abnormalities are also frequently present. Hyaline thrombi are found in small vessels of the involved organs. If untreated, most patients die within 3 months. Large–volume plasma or exchange will cure approximately 50% of patients. Splenectomy is useful for patients who relapse or who fail to respond to plasmapheresis. |
|
|
Term
| Acquired disorders resulting in abnormal platelet function |
|
Definition
i) Anti–inflammatory agents.
ii) Severe liver disease. In cirrhosis, platelet dysfunction has been related to high levels of fibrin (ogen) degradation products which interfere with normal platelet aggregation.
iii) Renal failure. Uremic metabolites are responsible for platelet dysfunction. Because the abnormalities in liver and renal disease are in the plasma, platelet transfusion is not usually beneficial for patients with these disorders. Hemodialysis is effective in treatment. |
|
|
Term
| Platelet and vascular type bleeding results in |
|
Definition
| petechiae, mucosal bleeding |
|
|
Term
| Coagulation type bleeding results in |
|
Definition
| ecchymoses and visceral bleeding |
|
|
Term
|
Definition
| natural anticoagulant. Inactivates factors IXa and Xa and thrombin |
|
|
Term
| Which factors are lacking in Hemophilia A and B. |
|
Definition
A: Factor VIII
B: Factor IX |
|
|
Term
|
Definition
| Autosomal dominant. Lacks vWfactor which is the carrier protein for factor VIII. von Willebrand factor is a plasma glycoprotein that is necessary for adhesion of platelets to subendothelial connective tissue. The manifestations of this disease differ from hemo-philia in that bleeding is predominantly into the skin and mucous membranes (epistaxis, bruising, and menorrhagia). The pattern of bleeding resembles that seen in platelet disorders, rather than coagulation disorders. In contrast to hemophilia, hemarthrosis is rare in vWD patients. |
|
|
Term
|
Definition
| Anticoagulant. Heparin is a catalyst which acts by enhancing the rate of inactivation of clotting factors by antithrombin III. Ordinarily, activated clotting factors are inhibited over a period of several minutes by antithrombin III. In the presence of heparin, inactivation occurs within seconds. |
|
|
Term
|
Definition
| Antibody to phospholipid, results in a prolonged PTT and positive mixing test. |
|
|
Term
| Myeloproliferative Disorders |
|
Definition
Definition: Clonal disorders of
pluripotent hematopoietic stem cells which can undergo complete differentiation. Usually tyrosine kinase defect.
Includes: Chronic myelogenous leukemia
Polycythemia vera
Essential thrombocytosis
Hypereosinophilic syndrome
Myelofibrosis
Chronic myelomonocytic leukemia |
|
|
Term
|
Definition
Dominant cell is neutrophil. Tip of 9 transferred to 22, philidelphia chromosome 210 KD protein (ALL 170 KD). Disease of adults,
Peak age of incidence 53 years,
Onset insidious,
Presents in chronic phase,
Splenomegaly related to WBC,
1/3 patients have no symptoms at diagnosis.
Imatinib (Gleevec),Dasatinib (Sprycel) are drugs of choice that inhibit the ATP binding domain. |
|
|
Term
|
Definition
Cause: Acquired somatic mutation of JAK2 kinase.
Erythrocytosis (dominant finding),
Thrombocytosis,
Leukocytosis,
Splenomegaly,
Erythropoietin independent erythropoiesis. |
|
|
Term
|
Definition
Phlebotomy (first choice)
Marrow suppression
hydroxyurea
32 P |
|
|
Term
|
Definition
Myeloproliferative disorder in which thrombocytosis predominates.
TPO independent platelet production.
Cause: Also a JAK2 mutation. |
|
|
Term
|
Definition
Marrow fibrosis with extramedullary hematopoiesis, stem cells are colonizing other organs (metastasize),
Splenomegaly and fibrotic marrow,
JAK2 V617F. Tear drop eryththrocytes. |
|
|
Term
| Heinz bodies associated with what disorder |
|
Definition
|
|
Term
| Hypereosinophilic Syndrome |
|
Definition
Eosinophilia,
Organ infiltration,
Activating mutation of a tyrosine kinase,
platelet derived growth factor receptor α |
|
|
Term
| Myelodysplastic Syndromes |
|
Definition
Stem cells don't fully differentiate. Anemia is macrocytic, disease of older adults.
1. Refractory anemia
2. Refractory anemia with ringed sideroblasts
3. Refractory anemia with excess blasts
4. Refractory anemia with excess blasts in
transformation
5. Chronic myelomonocytic leukemia |
|
|
Term
| heparin-induced thrombocytopenia |
|
Definition
| HIT. The heparin therapy activates the platelets and they all clot up and can increase the size of the original clot. Results in thrombocytopenia because the platelets are used up. |
|
|
Term
| anticoagulant factors that are also affected by warfarin |
|
Definition
| Protein C and Protein S. They have short half lives so they drop quickly and thrombi can form leading to dermal necrosis. |
|
|
Term
|
Definition
| synthetic compound based on the structure of Larginine, binds reversibly to the catalytic site of thrombin. It is administered intravenously and has an immediate onset of action. Indicated for patients with HIT |
|
|
Term
|
Definition
Direct thrombin inhibitors
indicated for patients with heparin-induced thrombocytopenia (HIT). should be used
cautiously in patients with renal failure, since it can accumulate and
cause bleeding in these patients. Patients may develop antihirudin
antibodies that occasionally cause a paradoxical increase in the
aPTT; therefore, daily monitoring of the aPTT is recommended.
There is no antidote for lepirudin. |
|
|
Term
|
Definition
produces irreversible, dose-dependent, intermediate reduction in thrombosis. Platelet response to clopidogrel is highly heritable (P < .001). CYP2C19*2 genotype is associated with
diminished platelet response to clopidogrel treatment and poorer
cardiovascular outcomes. |
|
|
Term
| What two genes contribute to Warfarin resistance and sensitivity. |
|
Definition
polymorphism in VKORC1 can lead to varying degrees of warfarin resistance.
polymorphisms in CYP2C9 are associated with
enhanced sensitivity to the drug, necessitating low doses, especially in
th case of CYP2C9*3 homozygotes |
|
|
Term
| Mechanism of action of warfarin |
|
Definition
exerts its pharmacological effect by
inhibiting VKORC1. VKORC1 is the vitamin K cycle enzyme controlling regeneration of reduced vitamin K, an essential cofactor that drives formation of the clotting factors. CYP2C9 is the major P450 enzyme that metabolizes S-warfarin to inactive metabolites. |
|
|
Term
| What is the main antiplatelet drug? What is it's alternative. |
|
Definition
|
|
Term
|
Definition
| Antibody to IIbIIIa receptor. used to prevent restenosis after an MI |
|
|
Term
|
Definition
�� Use: AML or the blastic phase of CML
�� Radiosensitizing effect, example of neoadjuvant therapy to treat head and neck carcinoma
�� Mechanism: Hydroxyurea blocks
ribonucleotide reductase, the rate-limiting enzyme of DNA synthesis.
�� Toxicity: Hematopoietic depression is the major toxic effect; UNCERTAIN risk of secondary leukemia; teratogen
�� Resistance: alterations in sensitivity of ribonucleotide reductase |
|
|
Term
| What are the three main groups among the alkylating cancer drugs? |
|
Definition
1. Nitrogen mustards
2. Nitrosoureas
3. Platinum compounds |
|
|
Term
| Which groups of alkylating agents are bifunctional |
|
Definition
�� Bifunctional: Nitrogen mustards & platinum
compounds
�� Monofuctional: Many Nitrosoureas |
|
|
Term
| Which alkylating agents show more renal toxicity? |
|
Definition
| The platinum compounds, but they also have less bone marrow suppression. |
|
|
Term
|
Definition
| Alkylator. Tissue selective nitrosourea used for Malignant pancreatic insulinoma, pancreatic carcinoid, doubles 1 yr survival rates |
|
|
Term
|
Definition
An Alkylator. Weak MAO inhibitor. Few reports
of cross resistance, minor toxicities (bone marrow
suppression), Use: Hodgkin’s Disease (MOPP protocol) |
|
|
Term
| Dacarbazine (DTIC) & Temozolomide |
|
Definition
metabolized to same active compound: 5-amino-imidizole-4 carboxamide -
thought to be the active alkylating species
�� DTIC Use: Melanoma, Hodgkin’s disease (ABVD)
�� Temozolomide Use: malignant gliomas |
|
|
Term
|
Definition
• ovarian, non-small cell and small cell lung cancers
• less toxic (~45×) than cisplatin but is generally less active |
|
|
Term
|
Definition
Extremely expensive.
• broad anticancer activity: colorectal, ovarian,
pancreatic, non-Hodgkins lym, breast, lung, prostate,
etc
• Lacks cross-resistance with other platinum
compounds
• Generally less toxic than other platinum compounds |
|
|
Term
|
Definition
�� Notable ADME: Cl- diuresis reduces toxicity
�� Use: testicular carcinoma - combination
therapy; Cisplatin (Platinol), etoposide, &
Beomycin (PEB).
�� Toxcitity: DLT - nephrotoxicity, neurotoxicity
& ototoxicity. Minimal marrow toxicity
�� Resistance: multiple mechanisms |
|
|
Term
| Most Common Nitrosoureas and there properties |
|
Definition
Carmustine (BCNU) and Lomustine (CCNU)
�� Notable ADME: extremely high oil-to-water partition coefficient
�� Used for glioblastoma
�� Toxicity: DLT: bone marrow suppression, may persist due to storage of the drug in adipose and liver tissues
�� Resistance: increased DNA repair
�� Being replaced by: Temozolomide |
|
|
Term
| Bendamustine hydrochloride |
|
Definition
�� Mechanism: bifunctional agent – both alkylator and purine-like (antimetabolite)
�� Uses: CLL and NHL
�� Toxicity: DLT –
hematopoietic toxicity
(myelosuppression, etc.), GI
toxicity, CNS toxicity (fever,
chills, fatigue)
�� Resistance: maybe only
partical cross resistance with
other alkylators |
|
|
Term
| Most Common Nitrogen Mustard and properties |
|
Definition
Cyclophosphamide (Cytoxan) – widely used agent
with activity against many tumors – Requires CYP
Bioactivation
�� Notable ADME: IV injection; does not cross BBB
�� Used in many combination therapies: CHOP, CMF
etc.
�� Toxicity: N&V, anaphalactoid rxns. DLT: bone
marrow suppression, max 10-12 days, recovery
by 21 days.
�� Acrolein – toxic byproduct
�� Mesna – traps acrolein
�� Resistance: cells may have aldehyde oxidase
�� Newer analog: Ifosphamide (Isophosphamide,
Ifex) |
|
|
Term
|
Definition
| Used in adjunct with cyclophosphamide to trap the active/toxic metabolite acrolein |
|
|
Term
|
Definition
prototype nitrogen mustards
�� Notable ADME: IV injection; T½ = <10 min
�� Used in combination therapy: MOPP
(Mechlorethamine, vincristine (Oncovin),
Procarbazine, Prednisone), 80% response, >50% cure for Hodgkin's disease.
�� Toxicity: Dose limiting toxicity (DLT) is bone marrow suppression – delayed-type suppression.
�� Resistance: increase drug inactivation & decrease uptake
�� Similar analogs: Chlorambucil |
|
|
Term
| Folate Antimetabolites and properties |
|
Definition
Methotrexate, Amethopterin
Trophoblastic choriocarcinoma, ALL, Burkitt’s lymphoma
•Mechanism: Dihydrofolate Reductase
inhibitor: inhibits dTMP synthesis.ADME
Methotrexate
•ADME: polyglutamation of MTX
concentrates drug in the cell
•Toxicity: bone marrow, GI, renal, alopecia, teratogen
•Resistance: increased/altered DHFR,
decreased uptake |
|
|
Term
|
Definition
Nucleotide analog.
Use: Colorectal, breast, gastric, pancreatic colon cancers (35% decrease in recurrence) Used topically for recurrence). premalignant skin lesions.
•Mechanism: irreversible inhibition of
thymidylate synthase. Incorporation into DNA/RNA. Kills in G1 and S-phases.
Penetrates CNS.
DLT: bone marrow suppression |
|
|
Term
|
Definition
| Oral analog of 5 fluorouracil |
|
|
Term
|
Definition
(reduced form of folic acid) is
commonly used to rescue cells exposed to folate antagonists (i.e., methotrexate) - does
not function as a cytotoxic chemotherapy agent.
�� Leucovorin promotes 5-FU inhibition of Thymidylate Synthase – used in colon cancer |
|
|
Term
| Cytosine arabinoside/Cytarabine |
|
Definition
Used for Acute myelogenous leukemia
•Mechanism: activated to ara-CTP (DNA
polymerase inhibitor) by dCMP kinase.
Kills in S-phase
•Toxicity: severe bone marrow
hypoplasia, GI |
|
|
Term
|
Definition
| Cytosine arabinoside analog used in solid tumors |
|
|
Term
|
Definition
Nucleotide analog. Used for Acute leukemias
•Mechanism: Feedback inhibitor of
purine synthesis. Hypoxanthine-guanine
phosphoribosyltransferase (HGPRTase)
makes the nucleoside phosphate from free base – incorporation into RNA/DNA
•Toxicity: bone marrow, nausea,
vomiting |
|
|
Term
|
Definition
Doxorubicin,
•Mechanism: DNA intercalator, DNA breaks by free radical damage and
Topo-interference.
Topo II •Toxicity: DLT - cardiotoxicity (total
dose, often irreversible),
myelosuppression |
|
|
Term
| Antibiotics Complex Glycopeptides |
|
Definition
Bleomycin, unique among natural products in that it's not susceptible to MDR1, and acts on the G2 phase.
•Mechanism: DNA & metal binding R
OH O
OH
O OH
NH2
O
Bleomycin A Bleomycin B2
region. DNA breaks by free radical
damage. Most susceptible in G2.
•Toxicity: Cardiotoxicity, edema, DLT lung and skin fibrosis; minimal
myelo- or immunosuppression |
|
|
Term
| Antibiotics – Cyclic Pentapeptide |
|
Definition
Actinomycin D. Extremely potent but not widely used.
•Mechanism: DNA intercalation;
inhibits transcription. RNA
polymerase much more sensitive
than DNA polymerase
•Toxicity: Myelosuppression, GI,
skin
Resistance: MDR efflux
transporters |
|
|
Term
|
Definition
Etoposide. DLT - bone marrow, nausea,
diarrhea |
|
|
Term
|
Definition
Irinotecan. DLT - bone marrow
suppression, but also GI toxicity, severe diarrhea. |
|
|
Term
| Microtubule Destabilizers |
|
Definition
Vincristine: DLT – peripheral neuropathy;
Vinblastin: DLT – bone marrow suppression |
|
|
Term
|
Definition
(vincristine and vinblastin) Don’t allow assembly of microtubules: cannot separate sister chromatids.
Cell senses too much DNA and enters death pathway(s). |
|
|
Term
|
Definition
Paclitaxel: DLT - Myelosuppression,
peripheral neuropathy, allergic
reactions to injection are a
problem.
Ixabepilone: diff binding spot. • Toxicity: Myelosuppression,
peripheral neuropathy, hypersensitivity
reactions.
• Resistance: LOW SUSCEPTIBILITY to
altered tubulin and the P-glycoprotein
and MRP1 efflux pumps |
|
|
Term
|
Definition
�� Mechanism: hydrolyzes L-asparagine to
aspartic acid and ammonia – depletes Lasparagine,. Cytotoxicity due to protein synthesis inhibition.
�� Resistance: expression of L-asparagine synthetase in tumor cells |
|
|
Term
|
Definition
Estrogen Receptor (ER) positive breast cancer, and breast cancer prevention
•Class: Antiestrogen SERMS (synthetic estrogen receptor modulators)
•Mechanism: Block estrogen response. Inhibits G1 to S transition.
•Toxicity: rarely severe adverse reactions to tamoxifen
but include vasomotor symptoms (hot flushes), N&V & vaginal bleeding . Tamoxifen also increases the incidence
of endometrial cancer by two- to threefold |
|
|
Term
|
Definition
aromatase inhibitor - effective
against ER positive breast cancer |
|
|
Term
|
Definition
�� Mech.: Acts on pituitary to inhibit
FSH and LH release
�� Use: Prostate cancer |
|
|
Term
|
Definition
GnRH antagonist
�� Immediate onset of action; more
rapid suppression of testosterone
than leuprolide
�� No initial testosterone surge
�� FDA-approved for prostate cancer |
|
|
Term
|
Definition
Flutamide: Inhibits the uptake and/or
nuclear binding of testosterone and
dihydrotestosterone by prostatic tissue -most effective when combined with LHRH agonists.
•Bicalutamide (Casodex) is a long lasting analog (once a day dosing) – also more selective for peripheral androgen receptor |
|
|
Term
| List the hormone related corticosteroids used to treat cancer |
|
Definition
Prednisone: Antianabolic effects
Diethylstibestrol, DES: Block androgen
dependence |
|
|
Term
| Antibodies used to treat cancer and their targets. |
|
Definition
�� Trastuzumab (Herceptin) – anti-HER2/neu
monoclonal (breast cancer)
�� Cetuximab (Erbitux) - anti-EGFR monoclonal
antibody (colon cancer)
�� Rituzumab (Rituxan) - anti-CD20 monoclonal
antibody (B-cell specific lymphomas)
�� Bevacizumab (Avastin) - anti-VEGF monoclonal
(colon cancer, breast cancer) |
|
|
Term
| �� Tyrosine Kinase Inhibitors |
|
Definition
�� Imatinib (Gleevec) – Bcr-Abl/c-kit kinase inhibitor (CML, GIST)
�� Sunitinib (Sutent) - broad spectrum Tyr-kinase
inhibitor (GIST and RCC)
�� Gefitinib (Iressa), erlotinib (Tarceva) - EGFR tyrosine
kinase inhibitor (non-small cell lung cancer) |
|
|
Term
|
Definition
inhibits signaling in both the Raf/MEK/ERK pathway (Ser/Thr kinase) and the VEGFR/PDGFR (Tyr kinase) pathway
�� Uses: Renal cell carcinoma, hepatocellular carcinoma, malignant melanoma, in trials for others
�� Metabolized by CYP3A4, inhibits several CYPs
�� DLT - bone marrow suppression, most
common toxicity is skin rash |
|
|
Term
|
Definition
Bortezomib
�� Uses: Multiple Myeloma, in trials for other leukemias
�� Mechanism: reversible inhibitor of the 26S
proteasome in mammalian cells
�� inhibit the activation of nuclear factor (NF)-κB |
|
|
Term
|
Definition
Tretinoin, ATRA (Altragen) - Retinoic Acid derivative
�� Uses: acute promyelocytic leukemia (APL) caused by PML/RARα fusion protein.
Arsenic trioxide (Trisenox)
�� Uses: Acute promyelocytic leukemia (relapsed or refractory); in trials for multiple myeloma
�� Mechanism: Not fully understood, but damages or degrades the PML/RARα fusion protein to enable partial differentiation and apoptosis; |
|
|
Term
|
Definition
Thalidomide (Thalomid)
�� Use: Multiple myeloma
�� Mechanism: angiogenesis inhibitor, TNF blocking agent |
|
|
Term
Diffuse Adenopathy:
Differential Diagnosis |
|
Definition
�� Infection
– EBV, CMV, hepatitis, other viral infxns, TB, HIV,
syphilis, toxoplasmosis, histoplasmosis
�� Immune Disorders
– Sarcoidosis
– SLE, other autoimmune disease
– Immunodeficiency disorders, e.g. CVID
�� Malignancy |
|
|
Term
| follicular lymphoma translocation |
|
Definition
t(14;18)» bcl-2 gene
» BCL-2 protein, anti-apoptosis signal, constantly expressed
» Cells don’t apoptose normallly
-40% of NHL, median age 55, bone marrow involvement is common. |
|
|
Term
| Burkitt’s lymphoma translocation |
|
Definition
t(8;14)» c-myc gene
» C-MYC protein, proliferation signal, over-expressed
» Cells proliferate at incredible rate |
|
|
Term
|
Definition
|
|
Term
| NHL Treatment: Aggressive |
|
Definition
�� R-CHOP is proven standard
�� Rituximab
�� Cyclophosphamide
�� Hydroxdaunomycin = doxorubicin
�� Oncovin = vincristine
�� Prednisone |
|
|
Term
|
Definition
|
|
Term
|
Definition
| Plasma cells in the bone marrow. Incidence increases with age peak 80yrs. Monoclonal antibodies seen on electrophoresis. Most have osteolytic lesions that lead to fractures. Shows multistep progression MGUS/smoldering to Intramedullary to malignant. Best to treat at intramedullary. beta-2 microglobulin above 5.5 mg/dL is marker for stage III, poor prognosis. Increased free light chains = poor prognosis. Cytogenetics is greatest prognostic factor. |
|
|
Term
| Multiple Myeloma treatment |
|
Definition
– Standard-dose chemotherapy, followed by
high-dose chemotherapy, followed by
autologous stem cell transplant |
|
|
Term
| Transfusion Related Acute Lung Injury (TRALI) |
|
Definition
Antibodies in donors blood, usually a woman that has been pregnant, or someone that's previously been transfused/shared needles.
�� Patient = neutrophils lining pulmonary capillaries
�� Donor = anti-HLA or neutrophil specific antibodies
�� Result = complement > neutrophil degranulation >
lysosomal enzymes and oxygen free radicals
�� pulmonary edema, acute dyspnea, fever, hypotension
�� Dx: Chest X-ray, r/o fluid overload |
|
|
Term
Immediate Generalized Reactions
(IGR) (transfusion) |
|
Definition
�� A.K.A. allergic>anaphylactoid>anaphylactic
�� Initiating event (theory)
�� Patient = performed IgE
�� Donor = allergen
�� histamine and enzymes released from mast cells |
|
|
Term
Non-hemolytic Febrile Reactions
(NHFR) (transfusion) |
|
Definition
�� A.K.A. Febrile or white cell reactions
�� Initiating event
�� Patient = anti-leukocyte antibodies (HLA or neutrophil)
�� Donor = white cell antigens OR
�� Cytokines produced during storage
�� Result
�� Fever > C up to 1-2 hours after transfusion
�� chills, rigors, anxiety, vital changes |
|
|
Term
| Hemolytic Transfusion Reactions |
|
Definition
| 1 in 38,000. ALmost always caused by clerical errors. Patients receiving mismatched blood. |
|
|
Term
| Platelet Transfusion: Summary (Test question) |
|
Definition
1. Patient with thrombocytopenia
�� Evaluate severity of hemorrhage
2. Determine etiology prior to platelet transfusion
�� Harmful - TMA, PTP
�� Helpful - Inadequate marrow production, DIC
�� Nothing - ITP, PTP
3. Check for refractoriness
�� Pre and Post platelet counts |
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Term
| Who should you use FFP for? |
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Definition
�� Replacement of multiple factor deficiencies in bleeding patients or in preparation for a surgical procedure
�� Examples include liver disease, DIC, massive transfusion.
Not for hemophilia or vW disease. |
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Term
| What is in cryoprecipate and what should it be used for? |
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Definition
Only use in patients to replace fibrinogen in patients with severe acute DIC.
�� Fibrinogen
�� Factor VIII coagulant
�� von Willebrand factor
�� Factor XIII
�� Only 40% of the fibrinogen in a unit of FFP is
harvested when making cryoprecipitate
�� Cryoprecipitate contains more fibrinogen per unit
volume compared to FFP
�� Fibrinogen can decrease dramatically in severe DIC |
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Term
|
Definition
| heterophile antibody test (monospot) |
|
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Term
| Small Lymphocytic Lymphoma (SLL) |
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Definition
| Type of NHL. Like CLL only in the tissue |
|
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Term
|
Definition
t(11;14) translocation results in
over- expression of cyclin D1 protein |
|
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Term
|
Definition
�� Reed-Sternberg cells (Owl)are the tumor cells CD30 and CD15 positive
�� Large numbers of “reactive” cells are also seen in the background |
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Term
| Cytologic Features Distinguishing Reactive Follicular Hyperplasia and Follicular NHL |
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Definition
Reactive Follicular Hyperplasia:
Cells: Polymorphic in germinal center
Mitotic act: Moderate to pronounced
Phagocytic act: prominent
Intrafollicular area: Reactive cells.
Follicular NHL:
Cells: monomorphic in follicle
Mitotic act: low
Phagocytic act: low
intrafollicular area: Neoplastic cells |
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Term
| Causes of follicular hyperplasia |
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Definition
�� Nonspecific
�� Autoimmune: rheumatoid arthritis
�� HIV (early stages)
�� Other infectious causes: toxoplasmosis, syphilis |
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Term
| Interfollicular Hyperplasia |
|
Definition
�� Polymorphous Immunoblastic Proliferations
�� Viruses
�� EBV (acute IM as prototype)
�� CMV
�� Other Herpes family viruses
�� HTLV-1
�� Drug Reactions – (anticonvulsants) regresses
following drug withdrawal
�� Vaccination
�� Dermatopathic Lymphadenopathy – reaction to draining melanin pigment from skin disruption |
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Term
| MIXED lymph node hyperplasia |
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Definition
Granulomas
�� Distinct type of immune reaction
�� Infectious – bacteria (ie. TB)
�� Non infectious – autoimmune (ie. sarcoid)
�� Localized aggregates of histiocytes
�� with suppuration: necrosis and neutrophils
�� ie. cat scratch disease
�� without suppuration |
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Term
| What tissue serves to provide the majority of blood cells in the mid-gestation fetus? |
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Definition
|
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Term
| A 29-year-old woman with a 13-week intrauterine pregnancy develops a deep venous thrombosis of the left lower extremity. What is the most appropriate treatment? |
|
Definition
| Heparin or low-molecular weight heparin |
|
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Term
| Therapeutic uses of ARTEMISININ AND DERIVATIVES |
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Definition
| initial treatment of severe P. falciparum infections, not used alone or for prophylaxis. |
|
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Term
| THERAPEUTIC USES Atovaquone |
|
Definition
| Used with proguanil to treat resistant falciparum. Combo can also be used for prophylaxis |
|
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Term
| Mechanism of chloroquine and related drugs |
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Definition
| Causes a failure to inactivate heme or even enhanced toxicity of drug–heme complexes is thought to kill the parasites via oxidative damage to membranes. |
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Term
|
Definition
At 2 days of age Newborn Hb level is ≥ 14.5gm/dL (mean 18.5 gm/dL)
At 2 weeks of age Newborn Hb level is ≥ 12.5gm/dL (mean 16.5gm/dL)
At 2 months of age Hb level is ≥ 9.0 gm/dL (mean 11.5gm/dL)
At 2–12 years of age Hb level is ≥ 11.5gm/dL (mean 12.5gm/dL)
At 12–18 y of age (males) Hb level is ≥ 13gm/dL (mean 14.5gm/dL).
At 12 –18y of age (females) Hb level is ≥ 12gm/dL (mean 14.0gm/dL) |
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Term
|
Definition
| LMWH, selective for Xa but still works through Antithrombin III. Low risk for HIT but renal excretion limits its use in those with renal failure. |
|
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Term
|
Definition
| Enoxaparin, dalteparin, tinzaparin.. All target Xa |
|
|
Term
| Antithrombin drug alternates to heparin. |
|
Definition
| Lepirudin, Bivalirudin, argotroban. All IV drugs |
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Term
|
Definition
recombinant form of activated protein C, inactivates factors Va and
VIIIa, used with organ dysfunction |
|
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Term
| Clopidogrel mechanism of action |
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Definition
| Antiplatelet. Irreversibly inhibits P2Y12 ADP receptor and inhibits activation of the glycoprotein IIb/IIIa pathway. |
|
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Term
| Glycoprotein IIb/IIIa Inhibitors |
|
Definition
| abciximab, eptifibatide, tirofiban |
|
|
Term
| List the Alkylating agents |
|
Definition
mechlorethamine
cyclophosphamide
bendamustine
streptozocin
cisplatin
carboplatin
oxaliplatin
carmustine
lomustine
procarbazine
dacarbazine
temozolomide |
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