Cancer Treatment Modalities: Onc Emergencies Flashcards
Disseminated Intravascular Coagulation =
A complex systemic disorder that involves activation of coagulation pathways, leading to thrombotic and hemorrhagic events
Conditions that have increased risk of developing DIC (9)
- Sepsis
- Some solid and hematologic cancers
- Trauma, (esp neurotrauma)
- Severe transfusion reaction
- Organ destruction
- Toxic reactions
- Heat stroke/hyperthermia
- Rheumatologic disorders
- Some obstetric complication
1) DIC causes ____coagulation, triggering the coagulation pathway to be initiated inappropriately.
Hyper
2) DIC cascade begins with the release of ____ ____, causing release of _____. This release then causes ______ to covert to _____, causing ______*.
tissue factor thrombin plasminogen plasmin FIBRINOLYSIS*
3) Fibrinolysis then causes excessive ______ (FDP’s), which causes ______.
The final result =
Fibrin degradation products
bleeding
Simultaneous hemorrhage and clot formation (life threatening)
Widespread activation of coagulation leads to high production of (2), which can then compromise =
Fibrinogen and FDPs
blood supply to organs
Clot formation =
Clot breakdown =
Thrombosis
Fibrinolysis
DIC imbalances
1) _____ thrombin
2) ______ anticoagulant pathways
3) _______ fibrinolysis
4) ________ response
1) Increased
2) Decreased
3) Dysfunctional
4) Inflammatory
DIC leads to the following
1) ____ deposits in vasculature
2) ______ fibrinolysis
3) _______ coagulopathy
4) Organ ____/_____
1) Fibrin
2) Dysfunctional
3) Consumptive (consumption of coagulation factors and platelets)
4) damage/hemorrhage
What is the most common underlying condition associated with acute (rapid onset) DIC?
Infection
Infx may produce a systemic inflammatory response, activating cytokine system that begins the hypercoagulation cascade
In onc, what condition is most associated with acute DIC?
Why?
Acute Promyelocytic Leukemia (APL) 85%
In APL, tissue factor released directly from promyelocyte blast cells in bloodstream
Hallmark sign of DIC
Bleeding that occurs simultaneously from at least 3 unrelated sites
Chronic DIC
1) Asctd with ____ thrombosis and _____ bleeding
2) Most often asctd with what type of Ca?
1) diffuse, minimal
2) Solid metastatic mucinous ADENOCARCINOMAs and tumors of prostate, breast, stomach, lung, and pancreas (prostate and breast most common)
DIC
Initial Sx
Bleeding
Occult/oozing to frank hemorrhage
DIC
Renal Sx
- Acidosis
- Hematuria
- Oliguria
- Uterine hemorrhage
DIC
Pulmonary Sx
- Dyspnea, hemoptysis, cough
- Tachypnea, diminished breath sounds
- Pleural friction rub
DIC
Integumentary Sx
- Jaundice
- Petachiae
- Skin necrosis of lower limbs
- Thrombosis
- Fever
DIC
Later stage Sx
Thrombus formations: organ dysfunction/failure (infarct, ischemia, necrosis)
Lab findings of DIC
Decreased results
- Platelets
- Fibrinogen
- Antithrombin III
- Plasminogen/Alpha 2 antiplasmin (degrades fibrin clots) -> hyperfibrinolysis
- Protein C
Lab findings of DIC
Elevated results
- FDPs
- D-dimer
- Thrombin
- Fibrinopeptide A level
Tx Goals of DIC
1) APL ->
2) Prostate Ca ->
3) Sepsis/infx ->
Early recognition and tx*
1) antineoplastic therapy
2) hormonal therapy
3) Antibiotics
Supportive Care of DIC
- Hospitalization for close monitoring
- Chronic DIC -> Anticoags, Blood products (antifibrinolytics)
- Care monitoring
Thrombotic Thrombocytopenic Purpura =
TTP a rare blood condition where there is excessive blood clot formation throughout the body, causing thrombocytopenia as platelets are consumed in the clotting process
2 types of TTP
Inherited
Acquired
Inherited TTP =
Primarily what age group?
What gene is faulty?
What syndrome happens typically?
- neonates and children
- ADAMTA13 gene
- Hemolytic uremic syndrome (HUS) - renal failure
Acquired TTP =
Primarily in adults bc of triggers that cause the body to produce antibodies against ADAMTS13 enzyme activity.
Development of these antibodies include some drugs/diseases gemcitabine, quinine or hormonal therapy/lupus or HIV, Bone marrow transplantation
Dx of TTP increases risk of (2)
- Hemolytic anemia
- DIC
Patho of TTP
ADAMST13 enzymes are key genes associated with blood ____
- Decreased or blocked activity of theses enzymes allows ->
- These thrombi further damage ->
Clotting
- loose strands of Von Willebrand factor (VWF) to damage platelets and rbc -> become lodged in small blood vessels
- plts exacerbating thrombocytopenia -> localize in organs such as lung, heart, brain
TTP
S/S
- Purpura
- Petechiae
- Pale skin or jaundice
- Fatigue
- Fever
- Tachycardia
- Tachypnea
- Oliguria
- Neuro changes
Lab findings in TTP
1) CBC/plts =
2) Smear =
3) Bilirubin =
4) Coombs test =
5) Lactate =
6) ADAMTS13 assay =
7) Urinalysis =
1) decreased
2) Schistocytes
3) increased
4) Negative (no antibodies)
5) increased
6) decreased activity
7) proteinuria, hematuria
Key features in dx of TTP (5)
1) hemolytic anemia w presence of shistocytes on peripheral blood smear
2) Thrombocytopenia
3) Renal dysfunction
4) Fever
5) Neuro changes
(more recent clinical consensus is that these findings are all rarely present)
Key features in dx of TTP now (2)
- Elevated LDH +
- Thrombocytopenia
these two factors alone considered highly suspicious of TTP
Tx for TTP
Inherited TTP =
Acquired TTP =
Plasma therapy
1) FFP (replaces dysfunctional or missing ADAMTS13 enzyme)
2) Plasmapheresis (removes antibodies that cause damage to ADAMTS13 enzyme and replaces it)
Tx for refractory TTP
Corticosteroids and/or Ritux to suppress immune system
Splenectomy
SIADH =
Endocrine based dysfunction causing abnormal release of ADH (arginine vasopressin) - usually released by pituitary gland in response to increased osmolality or decreased plasma volume -> causes kidneys to reabsorb water and concentrate urine to improve plasma volume
SIADH can be caused by? (4)
1) Nervous system disorders
2) Pulmonary disorders
3) Drug induced (chemo)
4) Neoplasms
Which cause of SIADH is often asctd w Cancer?
Endocrine paraneoplastic syndrome
- ADH release from tumor cells becomes unregulated by hormone negative feedback system mechanisms
Electrolyte imbalances in SIADH
Hyponatremia
Increased urine osmolality
Decreased serum osmolality
S/S of _____ SIADH
- r/t cerebral edema
- papilledema
- ataxia
- hypoactive reflexes
- seizures/psychosis
- coma
- death
- sodium levels < 120
Severe SIADH
S/S of ______ SIADH
- may be asymptomatic
- muscle cramps
- fatigue
- anorexia/n/v/ thirst
- headache
- sodium level 131-135
Mild or Chronic
S/S of ______ SIADH
- weight gain
- progressive NEURO Sx*
- Lethargy
- Abdominal cramping and diarrhea
- Oliguria/concentrated urine
- Hypoactive reflexes
- EXTRAPYRAMIDAL sx*
- Sodium 126-130
Moderate
Notably absent in SIADH are signs associated with ?
Fluid overload
- normal pulse, BP, mucous membranes, turgor, no peripheral edema
SIADH lab findings
1) Sodium
2) Potassium
3) Bicarb
4) Phosphorus
5) Serum osmolality
6) Serum BUN/Cr
7) Urinalysis
8) Renal and adrenal function
9) Thyroid function
1) decreased <130
2) normal
3) normal
4) normal or decreased
5) decreased <280mOsm/kg
6) may be decreased
7) NA >, specific gravity >, osmolality >
8) normal
9) normal
Best Tx for SIADH
Eliminate underlying cause
SIADH if unresponsive to fluid restriction consider ______
Demeclocyline
Tx for SIADH
- Fluid restriction
- treat underlying malignancy
- stabilize neuro sx
- ICU
- Hypertonic saline
- seizure precautions
- loop diuretics
- Vasopressin
Systemic Inflammatory Response Syndrome (SIRS) =
The systemic response to the presence of an infection in the blood
Includes: Sepsis, Severe Sepsis, Septic Shock
SIRS is defined as the presence of 2 or more of the following?
1) Temp =
2) HR =
3) RR =
4) WBC =
1) <36, >38 C
2) >90 bpm
3) > 20 bpm, PaCO2 <32mmHg
4) <4,000, >12,000, >10% bands
Infectious causes of SIRS
Bacterial sepsis Cellulitis Influenza Meningitis Pneumonia Toxic shock syndrome Urinary tract infections
Noninfectious causes of SIRS
Adrenal insufficiency Autoimmune conditions Burns Cirrhosis Hemorrhagic shock Hematologic malignancy Medications Myocardial infarction Seizure
Lab tests to evaluate for SIRS includes (5)
- CBC
- Urinalysis and culture
- Cardiac enzymes
- BMP
- Serum Lactate
SIRS Tx
Tx of underlying cause, early identification
Abx, glucose management, supplemental O2, consults
Sepsis =
Inflammatory response to bacteremia and manifests as at least two or more of SIRS criteria
Severe Sepsis =
Sepsis associated w hypotension, hypoperfusion of organs, organ dysfunction
Septic shock =
Severe sepsis that is unresponsive to fluid resuscitation and includes
(fever, chills, persistent hypotension, prolonged organ hypoperfusion, lactic acidosis, oliguria, tachycardia, tachypnea, mental status changes)
MODS =
(3) characteristics of MODS
Multiple Organ Dysfunction Sydrome = state in which lack of homeostasis is so severe that more than one organ system requires immediate intervention
- Metabolic acidosis
- Tissue hypoxia
- Decreased circulatory blood volume
S/S of Early Sepsis
- High cardiac output w normal or slightly elevated BP
- Capillary leak (edema)
- Subsequent hypotension
- Nausea
S/S of Severe Sepsis
- Hypotension causing hypoperfusion of organs
- Elevated temp
- Warm, flushed skin
- bounding pulse
- tachypnea, tachycardia
- decreased GI motility (n/v)
- abnormal hematologic status*
- hyperglycemia
- lactic acidosis
- oliguria
- mental status changes
S/S of Septic Shock (hypoperfusion)
- Cold, clammy skin
- lethargy, progressing to coma
- hypotension, tachycardia, weak pulse, tachypnea
- decreased breath sounds w pulmonary edema/rales
- renal failure
- persistent hematologic abnormalities
- hyperglycemia
- lactic acidosis
- hyponatremia
- hypokalemia
- hypocalcemia
- decreased albumin, magnesium, phosphate
Expected findings in CBC results during sepsis
1) WBC =
2) Hemoglobin =
3) Platelets =
1) increased or decreased
2) decreased
3) decreased
Expected findings in BMP results during sepsis
1) Glucose =
2) BUN/Cr =
3) Na =
4) K =
5) Ca =
6) Albumin =
7) Mg =
8) Phosphate =
1) increased generally, but decreased in prolonged septic shock
2) Increased
3) decreased
4) decreased
5) decreased
6) decreased
7) decreased
8) decreased
Lab findings in sepsis
1) Prothrombin =
2) lactate =
3) biochemical markers =
1) prolonged
2) elevation reflects tissue hypoperfusion
3) elevation reflects presence of sepsis
Sepsis Tx
1) _____ resuscitation
2) _____ support
3) __ __ __ prophylaxis
4) Anti____
5) Anti____
6) _____ products
7) E____ replacement
8) N____ and I____ support
9) Vaso_____ and ino___ drugs
10) Activated ______ _ replacement
1) fluid
2) respiratory
3) DVT
4) antibiotics
5) antifungals
6) Blood
7) Electrolyte
8) Nutritional, Insulin
9) pressors, inotropic
10) protein C
Severe sepsis/septic shock tax
1) admitted to ____
2) aggressive tx, ____ resususcitation, and continuous ____
3) require central venous _____ monitoring, o___ support, pulse _____
4) may require intubation and ventilation bc of ? (3)
5) > 50% will develop what syndrome? Which may develop into?
6) Supportive care: prophylaxis for (2), nutritional support, delirium, psychosocial support
1) ICU
2) fluid, monitoring
3) pressure, oxygen, oximetry
4) pulmonary edema, encephalopathy, coma
5) ARDS, lung fibrosis
6) stress ulcers, DVT
Tumor Lysis Syndrome =
Condition in which serious electrolyte imbalances occur in the body as a result of rapid cell death and necrosis of tumor tissue
TLS Patho
Tumor cells die -> intracellular components such as K phos and purine nuclei acids released in bloodstream -> high concentrations kidneys not able to eliminate quickly enough -> electrolyte and metabolic dysfunction
If TLS is not tx quickly can cause =
Neurological, GI, renal, cardiac failure -> eventual death
Usually occurs 48-72 hrs after tx
TLS is typically asctd with what types of cancer (3)?
1) Leukemia’s w high wbc
2) Non-Hodgkin lymphoma
3) Bulky, rapidly growing, tx responsive tumors
TLS risk factors (2) pre-tx
- elevated lactate
- renal dysfunction
Chemotherapies that can cause TLS
Ci Cy E P Flud H Intrathecal
Cisplatin Cytarabine Etoposide Paclitaxel Fludarabine Hydroxurea IT Methotrexate
Immunotherapies that can cause TLS
In
In
R
Tumor ____ factors
Interferons
Interleukins
Rituximab
Necrosis
What hormonal therapy drug can cause TLS
Tamoxifen
TLS can also occur from
1) Cort____
2) S_____
3) R____ therapy
1) Corticosteroids
2) Surgery
3) Radiation*
Electrolyte Imbalances in TLS (4)
Hyperuricemia
Hyperphosphataemia
Hyperkalemia
Hypocalcemia
TLS
Initial S/S
N/V Abdominal pain or dissension Dyspnea Dysrhythmias Edema Lethargy Muscle or join pain, muscle twitching
TLS
Progressive S/S
Increased GI
Sx
Oliguria, he matures, azotemia, progressing to Anuria
CHF (HTN, tachy/brady) progressin to ventricular arrhythmias
Progressive muscle weakness, parenthesis, tetany, seizures
TLS
Advanced S/S
AKI
Cardiac arrest
DIC
Death
For prevention and early detection of TLS pretx LAB Studies include (3)
Additional baseline data include (2)
Electrolytes
Renal function
Liver Function
Weight
Baseline EKG
TLS
Tx (6)
(Hint: what meds fix the electrolyte abnormalities?)
1) Hydration*
2) Allopurinol*
3) Rasburicase
4) Loop diuretics (prevents fluid overload and maintains UO)
5) Oral phosphate binding drugs -Urine alkalinization (controversial/rarely recommended bc can cause ca + pho precipitates)
6) Hemodialysis if renal failure occurs
Hypersensitivity =
Anaphylaxis =
A hypersensitivity reaction (HSR) is one in which the body mounts an immunologic response to a foreign substance or antigen resulting in local tissue injury
Anaphylaxis refers to an acute, severe inflammatory response that is sudden and systemic, caused by histamine release -> causes dyspnea, hypotension, LOC, death
What are the 4 categories of HSR?
1) Type 1: Anaphylactoid or anaphylactic
2) Type II: Cytotoxic
3) Type III: Immune-complex mediated
4) Type IV: Cell-mediated (delayed)