Oncology Flashcards
what is diff btwn 1o & 2o hemostasis
Primary = Platelets (number and function) &
formation of platelet plug
Secondary = Fibrin mesh that stabilizes the
platelet plug
so why aren’t we 1 super huge clot?
there are anti-clotting factors at play
what are coag defects that cause clinical bleeding
defects in 1mary = decr platelets/ thrombocytopenia
poorly functional platelets
lack of vWF (platelet & collagen derived)
defects in 2dary = lack of 1 or more coag factors
CS of 1mary defect
petechia
ecchymosis
oozing from mucosal sites
Cs of 2dary defects
bleeding into body cavity
Lg SQ hematomas
what is this?
scleral hemorrhage
1mary defect
what type of defect are:
melena
mucosal & gingival petichia & epistaxis
1mary
what type of defect would pleural bleeding be
2dary
how to dx 1mary hemostatis
platelet count
norm = >140,000
ALWAYS assess slide manually (platelet clumping will decr = artifact
how low a platelet count before we are concerned
20-30,000
how low platelets before we worry about spontaneous bleeding
<10,000
how to asses platelet function
BMBT
norm canine = <3.5 min
feline = <2.5 min
rapid POC test to assess 2dary hemostasis
Activated clotting time
only assesses intrinsic pathway
which test assesses intrinsic pathway
aPTT
which test assesses extrinsic pathway
PT
which test assesses common pathway
fibrinogen
what is dime store mnemonic
it’s not 12 but 11.98
intrinsic factors:
XII, XI, IX, VII
thrombocytopenia
1mary disorder
not generating enough = BM dz - mild to severe thrombocytopenia
leaving circ too quick = consumption (DIC) - mild to severe t-penia
destruct/immune mediated - severe t-penia
immune mediated thrombocytopenia (IMTP)
aka ITP (idiopathic t-penia purpura (human term)
platelet ct <15,000
can be 1mary IMTP = idiopathic
or 2dary
causes of 2dary IMTP
rickettsial dz
vx/meds w/i 30 days
systemic lupus erthematosus
2dary to neoplasia
what are addtl diag for IMTP
antiplatelet antibody testing (like Coombs for platelets)
antinuclear antibody (ANA) - used to screen for SLE (lupus)
Coombs - if concurrent IMTP w/ IMHA (Evans syndrome)
what is serologic test & why done
screen for rickettsial cause
Snap 4DX (HW, E. canis, Lyme, E. equi (Anaplasma phagocytophilium))
+ test = exposure NOT infection
need serial titer levels (4 fold incr)
Tx for IMTP
tx empirically w/ doxycycline while waiting for lab results
then immunosuppressants:
glucocorticoids
vincristine
human immoglobulin
mycophenolate
what happens with immunosuppressive doses of glucocorticoids
side effects
results in decr phagocytosis
Mainstay of tx for immune mediated dz
PP, PU, PD, wt gain
what is vincristine & how work
chemotherapy
causes premature release of platelets from marrow
how does human IVIG work
temp block of Fc receptors of phagocytes
what is mycophenolate mofetil
alternative to azathioprine
enzyme suppressor
leads to depletion of guanosine
short term Px for IMTP
short term = w/i 1 mo of dx
good w/ immunosuppression & supportive care
relapses can occur
name 1mary hemostasis disorder
2dary
vWF
Vit K rodenticide toxicity
Tx for DIC
get rid of underlying dz, +/- plasma, +/- heparin
what toxin causes Vit K antagonism
warfarin or related compounds
the 4 Vit K dependent coag factors
1972 = X, IX, V!!, II
if Factor VII has shortest t1/2 what will be prolonged 1st
PT & more severly incr
tx for 2dary hemostasis disorder rodenticide toxicity
Vit K & blood product w/ coag factors
IMHA
immune mediated hemolytic anemia
AB are directed at antigens on surface of RBCs promotin accelerated destruction
CS IMHA
lethargy, weakness, tachypnea/tachycardia
icterus
how IMHA dx
clinical & lab evidenc of hemolytic anemia w/ regenerative response
evidence of accelerated immune-mediated destruction of RBCs
classic signalment for IMHA
young to middle age
dog = female, cat = either
Am. Cocker Span.
3 tests commonly used to id accelerated immune destruction of RBCs
Coombs
auto agglutination
blood smear = presence of spherocytes
what is prevalence of 1mary IMHA v 2dary
causes
2/3 of IMHA 1mary = genetic predisp, acquired disreg
1/3 of IMHA 2dary = infection, neoplasia, drugs
addtl tests to Dx & Tx goals IMHA
serum biochem
coag panel
radiographs
BM cytology
titers for rickettsial dz
specific, supportive, symptomatic
steps in the diagnostic work up of the cancer patient
Hx
PE
+/- imaging
FNA & cytology
Bx & histopathology
methods, limitations and advantages of different tumor sampling techniques and how to choose between them for a given patient.
methods:
FNA & cytology
- Adv: least invasive, inexpensive, quick, safe
- Disadv: can’t grade, false +, false -
must consider results in clincal context “ biological behavior trumps grade”
needle core bx
- trucut needle
- adv: bigger sample than FNA
- disadva: seed tumor in bx track
punch bx
Jamshidi bone bx
surgical bx - incisional vs excisional
how the biologic behavior of a tumor influences the diagnostic testing that is required for patient evaluation
biological behavior trumps grade
techniques for collection and assessment of cytology specimens.
non-aspiration
- first attempt
- LN
- round cell tumors
- highly vascular tumors
aspiration
- hard/firm lesions
- very sm lesions whre multiple passes = impossible
- 2nd attempt
diff btwn clinical stage and histological grade
Clincal stage = extent of body affected, determined by clinician w/ diag testing
Grade = hisotpathologic scoring by pathologist
information desired in a pathology report, understand how to interpret the information, understand the limitations of pathology
dx
grade, if applicable for tumor type
margin assessment
prognostic factors - when evidence based
what is incisional bx
bx of a selected portion of lesion
what is excisional bx
removal of mass primarily for diagnostic purposes
equiv to “narrow excision
what can be seen with cytology of epithelial tumors
types
exfoliate easily, cellular
- sheets, clusters, acinar
- round, cuboidal, polyhedral
- Vacuoles = adenocarcinoma
adenoma, carcinoma
what can be seen with cytology of mesenchymal tumors
types
exfoliate poorly
- individual, loose aggregates
- spindle, stellate, round
- indistinct cell margins
sarcomas
what can be seen with cytology of Round cell neoplasia
types
exfoliate easily, highly cellular samples
- individual, round or oval cells
histiocytoma
lymphoma
plasmacytoma
MCT
TVT
sometimes melanoma
indications for chemotherapy
Patients with measurable tumor known to be sensitive to chemotherapy.
Adjuvant therapy to suppress occult micrometasisafter local therapy.
Palliate unresectableor metastatic cancer.
Occasionally, to downstage/reduce a chemosensitivetumor before definitive therapy (i.e. surgery).
Occasionally, to sensitize tissues to radiation.
hematopoietic cancers (usually systemic) - highly responsive to chemo tx
- lymphoma
- leukemia
- myeloma
solid tumors - adjunctive to sx a/o radiation
- carcinomas
- sarcomas
principles of applying chemotherapy
As a result of the Goldie Coldman Hypothesis and what we know from the Gompertzian Growth…
Chemotherapy should be initiated as early in the course of the disease (before obvious metastasis are apparent).
Due to the likelihood of mutated/“resistant” cancer cells, a protocol containing multiple agents is ideal
general mechanisms of chemotherapy
General characteristics of tumor cells:
- Loss of growth control
- Rapid proliferation
DNA or cell division mechanism-ultimately leading to apoptosis
Cell cycle specific drugs and nonspecific drugs
Rationale for combination chemotherapy
Different drugs exert their effect through different mechanisms and at different stages of the cell cycle, thus maximize cell kill
general toxicities with chemotherapy
Dose dependent
Self-limiting in most cases
Rapidly dividing tissues –non-selective
- Bone marrow - cytopenia
- Hair follicles - alopecia
- GI tract - v/d
“BAG”of adverse effects
Toxicity = patient dependent, drug dependent, and dose dependent
unique toxicities with chemotherapy
Vomiting - cisplatin, strepsitatoci, decarbazine
tx w/ maropitant (cerenia), metaclopramide (reglan), ondansetron (zofram)
diarrhea - (colitis) - doxorubicin
tx w/ metronidazole
dog breeds with MDR1 mutation - Vincristine & vinblastine, doxorubicin & mitoxantrone
measures to safely handle & administer chemotherapy
prevent aerosolization
- closed system
- Phaseal system
- Equashield
PPE
NEVER split/open tablets/capsules
NO LIQUID/ORAL FORMULATIONS
discuss the individual categories of traditional chemotherapy drugs
Alkylating agents:
- Cyclophosphamide
- Chlorambucil
- CCNU
MOA: induce apoptosis
Platinums
- cisplatin
- carboplatin
MOA: cause crosslinks
Antimetabolites
Antitumor antibiotics/ anthracyclines
- Doxorubicin
- Mitoxantrone
MOA: cell membrane damage
spindle toxins:
-
vinca alkaloids
- periwinkle
- vincristine
- vinblastine
- taxanes
- pacific yew tree
- paclitaxel, docetaxel
misc
cylclophosphamide toxicity
BAG
sterile hemorrhagic cystitis
CCNU toxicity
BAG
2/3 of dogs develop neutropenia
hepatotoxic
Doxorubicin “red death” toxicity
BAG
irreversible Cardiotoxicity in dogs (cumulative dose)
nephrotoxicity in cats
histamine release
extravasation injury
Spindle toxin toxicity
Vincristine:
BAG
ileus (common)
tx: metaclopramide
peripheral neuropathy (rare)
extravasation injury
Platinum toxicity
BAG
cisplatin : nephrotoxicity in dogs
FATAL idiosyncratic pulmonary edema in cats
(Cats go sPLAT!)
non-traditional systemic cancer therapy: immunotherapy/molecular targeted therapy/NSAIDs
NSAIDs: piroxicam w/ some carcinomas
immunotherapy: tumor vx ie. canine melanoma
targeted therapy: paladia for receptors on MCTs
Wht tx? What are the differences b/w surgical, radiation & chemotherapy tx for cancers
surgery cures more cancer than radioation or chemo/systemic tx
radiation used to control local recurrence or progression of certain tumors
chemotherapy suppresses cancer cells for some time, but cure rates are low
Preventative measures should be used to minimize exposure of chemotherapy agents to veterinary staff. The greatest risk of systemic absorption of chemotherapy agents by staff is via which of the following routes:
A: Absorption through the skin
B: Accidental injection
C: Inhalation of an aerosol
D: Accidental ingestion
Accidental injection
what is dose in radiation terminology
amount of radiation absorbed by the patient (Gray = Gy= 1 Joule/kg)
what is Fraction in radiation terminology
individual administration of dose of radiation
