Lecture 5-Hematology Flashcards
What are the (3) components of Virchow’s triad?—___ state, ___ wall injury, circulatory ___
Hypercoaguable state, vascular wall injury, circulatory stasis
Heparin affects ___ (bound clotting factors/unbound clotting factors/both)
UNBOUND clotting factors only—does not affect bound clotting factors/doesn’t break up existing clots
Heparin MOA = accelerates the rate at which ___ neutralizes ___ and ___; heparin binds ___ (reversibly/irreversibly) to ___ and induces a ___ change
Accelerates the rate at which antithrombin III (heparin cofactor) neutralizes thrombin (factor 2A) and factor 10A; heparin binds reversibly to antithrombin III and induces a conformational change
What system clears heparin from the body?
The reticuloendothelial system
Does heparin cross the placenta?
No
What test is often used to monitor heparin use?
ACT [activated clotting time]
ACT is used to measure heparin’s ___ (intrinsic/extrinsic) pathway activity
Intrinsic pathway activity
ACT is monitored in procedures with significant heparin use—T/F?
True
Heparin induced thrombocytopenia (HIT)—it is considered thrombocytopenia if platelets are < ___
< 100K
If there is a significant drop in platelet count from the patient’s baseline after heparin administration, you should consider the possibility of HIT (even if platelet count is not necessarily < 100K)—T/F?
True
HIT occurs ___-___ days after initiation of full dose or low dose heparin therapy, including heparin flush solution
5-15 days
HIT doesn’t occur immediately unless the patient has received heparin previously—T/F?
True
Type ___ (1 or 2) HIT occurs d/t heparin dependent antiplatelet ___ antibodies
Type 2 HIT occurs d/t heparin dependent antiplatelet IgG antibodies
Type ___ (1 or 2) HIT occurs d/t a direct, ___ effect on platelets
Type 1 HIT occurs d/t a direct, nonimmunogenic effect on platelets
How can HIT be reversed?
Stopping heparin therapy
In a minority of patients with HIT, it may be associated with thrombotic complications (“procoagulant state”), including arterial thrombosis and platelet-fibrin clots—if this occurs, what should you do?
Stop heparin and start patient on argatroban to prevent more clots from forming
Before diagnosing HIT, you should rule out other causes for thrombocytopenia—what two medications can cause thrombocytopenia? What disease state can cause thrombocytopenia?
Depakote and Pepcid can cause thrombocytopenia; sepsis can cause thrombocytopenia
HIT testing—___ testing picks up IgG antibodies; has very few false negatives; can get some false positives if it’s not the ___ specific antibody testing
ELISA testing picks up IgG antibodies; can get some false positives if it’s not the IgG specific antibody testing
HIT testing—___ = gold standard for HIT diagnosis; highly specific with very few false positives
Serotonin release assays
HIT treatment = stop ___ products; administer ___ anticoagulants (usually will use ___ or ___); add ___ to chart
Stop heparin products; administer non-heparin anticoagulants (usually will use argatroban or bivalrudin); add allergy to chart
What is the antidote for heparin?
Protamine sulfate
Protamine = cation, combines with strong anion heparin to form a stable salt (protamine NEUTRALIZES heparin)
Protamine can be used to reverse LMWHs—T/F?
False—LMWH are not as susceptible to protamine antagonism
If emergency reversal is needed for LMWH, protamine will neutralize about ___% of anti-Xa activity of LMWHs
65%
Protamine should be administered ___ (fast/slow)
SLOW
Rapid IV injection of protamine is associated with acute ___-related ___tension, ___cardia, ___ hypertension, transient ___, ___nea, respiratory ___
Acute histamine-related hypotension, bradycardia, pulmonary hypertension, transient flushing, dyspnea, respiratory distress
Patients may have a hypersensitivity reaction to protamine sulfate if they are hypersensitive to ___; have had previous ___ reversal; take protamine containing ___; or had previous ___
Hypersensitive to fish (protamine sulfate comes from salmon sperm); have had previous protamine reversal; take protamine containing insulin (NPH); or had previous vasectomy
To prevent hypersensitivity reaction to protamine, you can pre-treat patient with ___ and ___
Corticosteroid and antihistamine
Heparin rebound is ___ (common/rare) and is usually seen in patients who had ___ (little/massive) amounts of heparin
Heparin rebound is rare and is usually seen in patients who had massive amounts of heparin (i.e.: CPB cases)
What is heparin rebound?—a condition where patients ___ after ___ administration
A condition where patients re-anticoagulate after protamine administration
Heparin management [hold times prior to OR]—if patient is on IV heparin, stop ___-___ hours prior to procedure; if patient is on subQ heparin, stop ___ hours prior to procedure
If patient is on IV heparin, stop 4-6 hours prior to procedure; if patient is on subQ heparin, stop 12 hours prior to procedure
Heparin management [restart times after OR]—restart ___ hours post-op if patient is low risk for bleeding; restart ___-___ hours post-op if patient is high risk for bleeding (i.e.: liver disease, on other blood thinners, type of surgery puts them at risk for post-op bleeding)
Restart 24 hours post-op if patient is low risk for bleeding; restart 48-72 hours post-op if patient is high risk for bleeding (i.e.: liver disease, on other blood thinners, type of surgery puts them at risk for post-op bleeding)
Heparin management [catheter placement]—catheter should be placed ___ hour before heparin administration; catheter should be placed ___ hours before heparin administration if patient is going to have cardiac surgery
Catheter should be placed 1 hour before heparin administration; catheter should be placed 24 hours before heparin administration if patient is going to have cardiac surgery
Heparin management [catheter removal]—indwelling neuraxial catheters should be removed ___-___ hours after the last heparin dose and after their coagulation status has been evaluated
Should be removed 2-4 hours after the last heparin dose and after their coagulation status has been evaluated
LMWH MOA—inhibit factor ___ and ___—they are much more selective to factor ___ inhibition than ___
Inhibit factor Xa and IIa (thrombin)—they are much more selective to factor Xa inhibition than IIa
___ levels are the gold standard for monitoring LMWH therapy
Anti-Factor Xa levels
APTT and PT/INR are effective at monitoring LMWH therapy—T/F?
False—aPTT and PT/INR are insensitive to LMWH therapy
You should decrease the dose of LMWH in patients with chronic ___ insufficiency
Chronic renal insufficiency—because these drugs are renally eliminated
This anticoagulant is the most specific inhibitor of Factor Xa—no effect on factor IIa
Fondaparinux (Arixtra)
Black box warning for all LMWHs and fondaparinux (arixtra)—use of neuraxial blockade represents significant risk of ___; monitor for signs and symptoms of ___ damage
Use of neuraxial blockade represents significant risk of epidural hematoma; monitor for signs and symptoms of neurologic damage
Spinal/epidural hematoma risk for all LMWHs and fondaparinux—needle placement should occur at least ___ hours after last LMWH LOW dose or fondaparinux dose
Needle placement should occur at least 12 hours after last LMWH LOW dose or fondaparinux dose
Spinal/epidural hematoma risk for all LMWHs and fondaparinux—needle placement should occur at least ___ hours after last LMWH HIGH dose
24 hours
If epidural catheter is inserted, it should be done at least ___ hours prior to any dose of postoperative LMWH (single daily dosing)
4 hours prior to any dose of postoperative LMWH (single daily dosing)
Twice daily dosing of LMWH should be delayed until ___ hours post-op
Delayed until 24 hours post-op
Catheters should be removed prior to initiating ___ daily dosing
Twice daily dosing
Removal of epidural catheter should be done ___-___ hours before any dose of LMWH
2-4 hours before any dose of LMWH
Removal of epidural catheter should occur ___ hours after any dose and ___ hours before a subsequent dose
12 hours after any dose and 2 hours before a subsequent dose
What are (3) oral Xa inhibitors?
- Rivaroxaban (Xarelto)
- Apixaban (Eliquis)
- Edoxaban (Savaysa)
“Xa” in the name because they are oral Xa inhibitors
Hold time for dabigatran (pradaxa) with poor kidney function is ___-___ days; hold time for dabigatran (pradaxa) with normal kidney function is ___-___ days
3-5 days; 1-2 days
Xarelto only needs to be held for ___ hours prior to procedure
24 hours prior to procedure
For low risk bleeding, Xarelto should be held for ___ day; for high risk bleeding, xarelto should be held for ___ days
1 day; 2 days
Hold time for NOACs/DOACs is much ___ (more/less) than hold times for warfarin
Less than hold times for warfarin (5 days for warfarin vs. 1-2 days for NOACs/DOACs)
With NOACs, you don’t have to worry about starting the patient on bridge therapy or formation of clots while the medication is being held—T/F?
True, because the hold time is only 1-2 days (depending on low vs. high risk of bleeding)
All DOACs currently have available a BB warning for use with neuraxial anesthesia—T/F?
True
Dabigatran (pradaxa) should be held ___-___ days prior to neuraxial procedures
4-5 days prior to neuraxial procedures
Oral Xa inhibitors should be held ___-___ days prior to neuraxial procedures
3-5 days prior to neuraxial procedures
Dabigatran (pradaxa) and oral Xa inhibitors can be restarted ___ hours post-procedure if the patient is a low bleed risk; can be restarted ___-___ hours post-procedure if the patient is a high bleed risk
Can be restarted 24 hours post-procedure if the patient is a low bleed risk; can be restarted 48-72 hours post-procedure if the patient is a high bleed risk
Hemodialysis ___ (can/cannot) remove oral Xa inhibitors
Cannot
What is one reversal agent for oral factor Xa meds?
Andexanet alpha (andexxa)
Andexanet alpha (andexxa) was approved in January 2019 for reversal of Xa inhibitors; approved for what (2) oral Xa inhibitors?
- Xarelto
- Eliquis
Andexanet alpha (andexxa) is approved for reversal of edoxaban (savaysa)—T/F?
False—approved for reversal of xarelto and Eliquis only
Black box warning for andexxa—___ events, ___ events, cardiac ___, sudden ___; may also cause ___, ___onia, infusion related ___
Thromboembolic events, ischemic events, cardiac arrest, sudden death; may also cause UTIs, pneumonia, infusion related reactions
Argatroban = direct ___ inhibitor (factor ___)
Direct thrombin inhibitor (factor IIa)
Argatroban binds to both ___ and ___-bound thrombin
Both circulating and clot-bound thrombin
Argatroban has a ___ (lower/higher) risk of bleeding because it breaks up thrombin that is circulating and thrombin that is bound to clots
Higher risk of bleeding
Argatroban is used for the prevention/treatment of thrombosis in patients with ___
HIT
Argatroban ___ (does/does not) have a reversal agent
Does not have a reversal agent
(2) other direct thrombin inhibitors that are hirudin analogs
- Bivalrudin (angiomax)
- Lepirudin (refludin)
Hirudin comes from ___
Leech spit
Hirudin analogs bind ___ (reversibly/irreversibly) to both circulating and clot-bound thrombin; they are used as a heparin alternative if patient has ___
Irreversibly to both circulating and clot-bound thrombin; they are used as a heparin alternative if patient has HIT
Hirudin analogs ___ (do/do not) have a reversal agent
Do not have a reversal agent
Dose of hirudin analogs must be adjusted in ___ impairment
Renal impairment
Anti-hirudin antibodies form in ~___% of patients
~40% of patients
Anti-hirudin antibodies may be associated with an increased ___ effect of lepirudin; for this reason, ___ would be a safer choice
Anticoagulant effect of lepirudin; for this reason, argatroban would be a safer choice to treat patient with HIT
Dabigatran (pradaxa) is an oral direct ___ inhibitor
Oral direct thrombin inhibitor
HD will remove ___-___% of circulating dabigatran (unlike oral factor Xa inhibitors, Xarelto and Eliquis)
62-68% of circulating dabigatran
Antidote for dabigatran = ___
Idarucizumab (praxbind)
Warfarin antidote = ___
Vitamin K1
Warfarin antidote Vitamin K1 takes ~___ hours to see effects
~24 hours
Vitamin K1 should never be given ___
SubQ
Warfarin is pregnancy category ___
X—never give in pregnancy!
Warfarin drug interactions—anti___; other ___; ___s; ___; ___; anti___
Antibiotics; other blood thinners; NSAIDs; acetaminophen; supplements; antiepileptics
Most NOACs ___ (do/do not) require bridge therapy, as they are held ___-___ hours prior to procedure
do not require bridge therapy, as they are only held 24-48 hours prior to procedure
Warfarin management—goal INR is < ___
< 1.5
Warfarin should be held ___ days before procedure
5 days before procedure
Warfarin needs to be bridged with ___
LMWH (lovenox)
Oral anticoagulants like warfarin are falling out of favor—T/F?
True—d/t drug interactions, longer hold times, need for bridge therapy
Thrombolytic agents end in -___; what are (5) thrombolytic agents?
-ase
- alteplase
- reteplase
- tenecteplase
- streptokinase
- urokinase
Thrombolytic agents MOA—tPA binds to ___ and ___ and converts bound ___ogen to ___; ___ is our natural clot cleaver in the body, promotes the body to break down clots
TPA binds to fibrin and plasminogen and converts bound plasminogen to plasmin; plasmin is our natural clot cleaver in the body, promotes the body to break down clots
Thrombolytic agents put the body into a ___ state
“Systemo-lytic” state—activate plasmin to break down fibrin rich clots throughout the entire body; can be very dangerous
Is this an absolute or relative contraindication for thrombolytic therapy?—acute ICH
Absolute contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—history of ICH
Absolute contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—severe, uncontrolled HTN
Absolute contraindication—specifically, SBP 185 or greater, DBP 110 or greater
Is this an absolute or relative contraindication for thrombolytic therapy?—age > 75 yo
Relative contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—severe stroke or coma
Relative contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—recent major surgery
Relative contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—serious head trauma or stroke in previous 3 months
Absolute contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—arterial puncture of non compressible vessel within 7 days
Relative contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—platelets < 100,000
Absolute contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—systemic anticoagulation
Absolute contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—BG > 400 or < 50
Absolute contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—recent GI bleed within 21 days
Relative contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—seizure with stroke onset
Relative contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—recent MI within 3 months
Relative contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—CNS structural lesions
Relative contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—early radiographic ischemic changes
Absolute contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—active internal bleeding
Absolute contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—dementia
Relative contraindication
Is this an absolute or relative contraindication for thrombolytic therapy?—traumatic CPR
Relative contraindication
Dextran MOA—expands ___ by pulling in ___; prevents thromboembolism by decreasing blood ___
Expands intravascular volume by pulling in water; prevents thromboembolism by decreasing blood viscosity (dilution prevention)
Dextran side effects—allergic reactions d/t dextran-reactive ___ present in most adults; ___ formation may make subsequent ___ of blood difficult
Allergic reactions d/t dextran-reactive IgG antibodies present in most adults; rouleaux formation may make subsequent cross-matching of blood difficult
Aminocaproic acid (amicar) is used to treat ___
Excessive bleeding
How does amicar work?—inhibits activation of ___ to inhibit ___
Inhibits activation of plasminogen to inhibit fibrinolysis
Amicar load has to be given over ___
1 hour
Avoid rapid IV infusion of amicar secondary to ___tension, ___cardia, and/or ___mias
Hypotension, bradycardia, and/or arrhythmias
Risk of thrombosis with amicar is very ___ (low/high)
Low
TXA = ___ (anti/pro) coagulant
Procoagulant
TXA prevents bleeding by inhibiting ___/___
Plasminogen/fibrinolysis
TXA should be given ___ (slowly/quickly) d/t ___tension, just like what other drug?
Slowly d/t hypotension, just like amicar
Rapid administration of TXA can cause ___ d/t neuronal ___ and ___ inhibition of cerebral emboli
Seizures d/t neuronal GABA and glycine inhibition of cerebral emboli
What is raplixa?
Topical fibrin sealant
What are (3) components of platelet function?
- Adhesion
- Activation
- Aggregation
Platelet adhesion—___ factor promotes platelet adhesion to damaged vascular walls
VonWillebrand’s factor
What is the most common inherited coagulation defect?
VonWillebrand’s disease
Platelet activation—___ binds to receptor on platelet surface to activate platelet; binding results in ___ change; ___ change releases mediators involved in coagulation and healing—___ and ___
Thrombin binds to receptor on platelet surface to activate platelet; binding results in conformational change; conformational change releases mediators involved in coagulation and healing—Thromboxane A2 and ADP
Thromboxane A2 and ADP promote platelet ___
Aggregation
Aggregation—thromboxane A2 and ADP uncover ___ receptors; ___ attaches to its receptor, allowing platelets to link together
Thromboxane A2 and ADP uncover fibrinogen receptors; fibrinogen attaches to its receptor, allowing platelets to link together
What are two types of platelet aggregation inhibitors?
Aspirin and NSAIDs
Aspirin needs to be held for ___ days before surgery because it renders COX non-functional
7 days
Aspirin renders COX non-functional for the life of the platelet (8-12 days)—T/F?
True—have to wait for the body to make more platelets
NSAIDs need to be held for ___-___ hours before surgery
24-48 hours
NSAIDs depress platelet’s thromboxane A2 production but this is only temporary (24-48 hours)
(2) other platelet aggregation inhibitors (thienopyridine ADP-receptor antagonists) = ___ and ___
Clopidogrel (plavix) and ticagrelor (brilinta)
Ticagrelor (brilinta) ___ (is/is not) reversible
Is reversible
MOA of thienopyridine ADP-receptor antagonists—inhibit activation of the platelet ___ complex that is necessary for fibrinogen-platelet binding
Inhibit activation of the platelet glycoprotein (GP IIb/IIIa) complex that is necessary for fibrinogen-platelet binding
Thienopyridine ADP-receptor antagonists ___ (reversibly/irreversibly) modify the receptor
Irreversibly modify the receptor
Platelets exposed to thienopyridine ADP-receptor antagonists are affected for the remainder of their lifespan—T/F?
True
Aspirin and plavix should be held for ___ days before surgery
7 days
Brilinta should be held for ___ days before surgery
5 days before surgery (even though it is reversible)
Stop plavix ___ days prior to surgery
7 days prior to surgery
Ticlodipine (ticlid) is off the market; needed to be held ___-___ days prior to surgery
10-14 days
Stop prasugrel (effient) ___ days prior to surgery
7 days prior to surgery
Stop ticagrelor (brilinta) ___ days prior to surgery even though it is ___
5 days prior to surgery even though it is reversible
Aspirin, plavix, prasugrel need to be held for ___ days before surgery so that new platelets can be made
7 days
NSAIDs should be held for ___ days before surgery
2 days
Brilinta—even though it is ___, hold for ___ days
Even though it is reversible, hold for 5 days
Platelet function testing—VerifyNow P2Y12–measures percentage of platelet ___
Platelet inhibition
Platelet function testing—VerifyNow P2Y12–monitor antiplatelet therapy > ___% for clinical effect; determine when it is safe to proceed with surgery or regional anesthesia < ___%
> 80% for clinical effect; safe to proceed with surgery or regional anesthesia < 20%
Antiplatelet management—aspirin and NSAIDs ___ (do/don’t) have risk of epidural hematoma, so ___ (do/don’t) have to hold these medications for neuraxial blockade
Don’t have risk of epidural hematoma, so don’t have to hold these medications for neuraxial blockade
Antiplatelet management—hold clopidogrel/prasugrel for ___ days before neuraxial blockade is performed
7 days
Antiplatelet management—hold ticlodipine for ___ days before performing neuraxial blockade
14 days
Ticlid is off the market*
Antiplatelet management—hold brilinta for ___ days before performing neuraxial blockade
5 days
Platelet aggregation inhibitor—dipyridamole + aspirin = ___
Aggrenox
Have to hold dipyridamole/aspirin (aggrenox) for ___ days because of the aspirin
5 days
Vorapaxar (Zontivity)—no one really takes this medication at all, but terminal half-life is ~___ days
~8 days
Platelet aggregation inhibitors—prevent platelets from aggregating together by preventing ___ from binding to ___
Preventing fibrinogen from binding to Gp IIb/IIIa
(3) platelet aggregation inhibitors:
- Abciximab (repro)
- Eptifibatide (integrilin)
- Tirofiban (aggrastat)
Abciximab (repro) should be held ___-___ hours prior to procedure
24-48 hours prior to procedure
Eptifibatide (integrilin) should be held ___-___ hours prior to procedure
4-8 hours prior to procedure
Tirofiban (aggrastat) should be held ___-___ hours prior to procedure
4-8 hours prior to procedure
DDAVP (desmopressin) is a synthetic analog of ___ and is ___
Synthetic analog of ADH (posterior pituitary hormone) and is hemostatic
DDAVP increases ___ factor, tissue-type ___ activator, and ___
Increases vonWillebrand factor, tissue-type plasminogen activator, and prostaglandins
DDAVP promotes platelet adhesiveness to vascular endothelium—T/F?
True
DDAVP may minimize intraoperative blood loss and transfusion requirements in patients undergoing cardiac surgery or spinal fusion surgery—T/F?
True
Xigris (drotrecogin alpha) was removed from the market in 2011 because there was found to be no benefit for what patient population?
Sepsis patients
