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Anticoagulants
Anticoagulants & Thrombolytics
187
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Graduate
07/15/2012

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Term
Definition of anticoagulants
Definition
drugs that delay or prevent the clotting of blood (no effect on clot after it is formed)
Term
what is this- prevents clot formation or extension of existing clot?
Definition
anticoagulants (Warfarin, Heparin)
Term
4 examples of antiplatelet agents
Definition
ASA, Plavix, Ticlid, Aggrenox
Term
what is the definition of antiplatelet agents?
Definition
reduce platelet aggregation, prevent stroke, MI, TIA
Term
What is the definition of direct thrombin inhibitors?
Definition
prevent clot formation
Term
what is an example of a direct thrombin inhibitor (Brand and Generic)
Definition
Dabigatran (Pradaxa)
Term
How does ASA work?
Definition
interferes with normal adhesion and aggregation of platelets
Term
True or false, fibronolytics possess inherent fibrinolytic effects or enhance the body's fibrinolytic system
Definition
false, thromobolytics
Term
At which tissue factor does the coagulation cascade merge together?
Definition
X to Xa
Term
What is the extrinsic pathway?
Definition
Ca + tissue factor VII
Term
Where in the cascade does LMWHeparin work?
Definition
X to Xa V FFP3 blockade
Term
Where in the cascade does Heparin work?
Definition
II to IIa (Prothrombin to Thrombin)
Term
what happens immediately after damage to a blood vessel?
Definition
platelets adhere and release chemicals to attract even more platelets
Term
what happens after platelet plug forms?
Definition
clotting factors, cause strands of fibrin to stick together and seal the inside of the wound
Term
what 3 things does clot formation require?
Definition
vascular endothelium, platelets, plasma-mediate hemostasis
Term
is tissue factor the intrinsic or extrinsic pathway?
Definition
extrinsic
Term
is factor XI intrinsic or extrinsic pathway?
Definition
intrinsic
Term
which pathway initiates plasma- mediated hemostasis and which amplifies the response?
Definition
tissue factor (extrinsic) initiates plasma mediate hemostasis and factor XI (intrinsic) amplifies the response
Term
what 3 ways do platelets participate in clot formation?
Definition
1. anchor sites for coagulation factor activation 2. delivery vehicles releasing hemostatically active proteins 3. major structural components of the clot
Term
true or false, coag studies are the most effective means for identifying bleeding and thrombotic tendencies
Definition
false, "a carefully performed history"
Term
What 2 hypercoagulable states require anticoag?
Definition
1. factor V leiden homozygous 2. antiphospholipid antibody syndrome
Term
How long is normal bleeding time?
Definition
3-10 minutes
Term
normal platelet count
Definition
150-400cells/ml
Term
PT normal time
Definition
12-14 seconds
Term
aPTT time
Definition
25-35 seconds
Term
Normal thrombin time
Definition
<30 seconds
Term
ACT normal time
Definition
80-150 seconds
Term
Normal fibrinogen levels
Definition
>150mg/dl
Term
where does Heparin bind?
Definition
antithrombin III
Term
Heparin enhances _____ times the ability of antithrombin to inactivate a number of coagulation enzymes
Definition
1,000 times
Term
heparin helps to inactivate a number of coagulation enzymes (5 examples are...)
Definition
thrombin, factor X, XII, IX, XI
Term
How does Heparin function as an anticoagulant?
Definition
accelerating the normally occuring antithrombin induced neutralization of activated clotting factor
Term
where does Heparin exist endogenously (3)?
Definition
basophils, mast cells and liver
Term
true or false, heparin think hepatic
Definition
true
Term
what does heparin block?
Definition
classic intrinsic and final common pathways
Term
Heparin is lipid soluble, true or false
Definition
false, poor lipid solubility
Term
is there an assay for heparin?
Definition
no, must monitor biologic activity
Term
if you increase the dose of heparin, what are you increasing?
Definition
the duration of action
Term
100units/kg IV elimination 1/2 time
Definition
56 minutes
Term
400 units/kg IV elimination 1/2 time
Definition
152 minutes
Term
true or false, hyperthermia increases elimination half time
Definition
false, decrease in body temp prolongs elimination 1/2 time
Term
why is it important to know that hypothermia prolongs heparin?
Definition
in CPB, we cool patients
Term
what is the goal aPTT for Heparin?
Definition
1.5-2.5 times pre drug value (30-35 seconds)
Term
when do you check ACT levels?
Definition
baseline, 3-5 minutes post administration, and 30min to 1 hour intervals post administration
Term
is Heparin metabolism reliable?
Definition
some people met Heparin faster
Term
what 4 things influence ACT?
Definition
hypothermia, thrombocytopenia, aprotinin, coagulation deficiences
Term
Control ACT is usually ______
Definition
90-120 seconds
Term
What is the goal ACT for CPB? when is it inadequate?
Definition
>400 seconds, <180seconds
Term
When is unfractionated heparin used?
Definition
when cost is an issue (Heparin is cheaper than Lovenox)
Term
What is the half life of UFH?
Definition
3 hours
Term
what is the onset of action of heparin?
Definition
immediate
Term
what is the SQ dose of Heparin?
Definition
250units/kg SQ QD
Term
How is Heparin suppiled?
Definition
5000units/ml or 10,000units/ml
Term
How does the size of Enoxaparin compare to the size of Heparin?
Definition
Enoxaparin is 1/3 the size of Heparin
Term
Why does Enoxaparin have more bioavailability?
Definition
less protein binding
Term
why does Enoxaparin have a longer elimination 1/2 time?
Definition
less binding to epithelial cells
Term
why is lovenox more convenient for patients?
Definition
more infrequent dosing
Term
which is more expensive- heparin or lovenox?
Definition
Lovenox
Term
Which is more predictable (pharmacokinetic response)- Heparin or Lovenox?
Definition
Lovenox
Term
which has fewer effects on platelet function?
Definition
Lovenox
Term
HIT is less likely with _____
Definition
Lovenox
Term
What is the Heparin dose for DVT Prophylaxis?
Definition
5,000 units SC every 8-12 hours
Term
What is the goal aPTT for DVT treatment?
Definition
1.5-2.5 aPTT
Term
How long before surgery should patient stop Coumadin?
Definition
5-7 days prior
Term
when does the patient start weight based dose of lovenox?
Definition
night before procedure
Term
what does the patient take morning of surgery?
Definition
no LMWH, no coumadin
Term
when does the Coumadin get restarted?
Definition
evening of surgery
Term
True or false, the day after surgery, restart LMWH, continue until INR therapeutic
Definition
true
Term
Vascular cases goal ACT
Definition
180-300 seconds
Term
What types of cases get DVT prophylaxis? 2
Definition
ERAS, Orthopedic
Term
What is the dose of Heparin given during aortic purse string sutures are placed during cannulation?
Definition
300-400units/kg
Term
How do you give Heparin? (route)
Definition
through a central line
Term
patients that have antithrombin deficiency- how does this affect Heparin? what do you do?
Definition
resistant to heparin bc there is nothing for heparin to bind to. Give 2 units FFP so Heparin can bind
Term
HIT- how does it cause thrombocytopenia?
Definition
agglutinate platelets
Term
If patient has a history of HIT- you can never give Heparin true or false
Definition
false, if remote history and no longer has antibodies, Heparin is safe
Term
What is the platelet drop after Heparin in HIT?
Definition
>50%
Term
What is the % chance of developing HIT after 5 days of Heparin?
Definition
5-28%
Term
3 alternative coagulants if patient has HIT
Definition
hirudin, bivalirudin, agatroban
Term
treatment for HIT
Definition
plasmapheresis
Term
If a patient receiving Heparin also takes ____, they are at higher risk for hemorrhage
Definition
ASA
Term
large doses of heparin can cause hypertension, true or false
Definition
false, hypotension
Term
chronic exposure of heparin leads to what?
Definition
reduction of antithrombin activity
Term
important risk factor for epidural hematoma
Definition
length and intensity of anticoag
Term
Heparin reversals x2
Definition
FFP, Protamine
Term
protamine is negatively charged and heparin is positvely charged- they form a stable complex, true or false
Definition
false, protamine positive
Term
how is the heparin-protamine complex removed?
Definition
reticuloendothelial system
Term
how do you dose protamine?
Definition
1mg for every 100units (1mg) of Heparin
Term
How do you inject protamine?
Definition
in PIV slowly over 5 minutes
Term
do not exceed _____mg of Protamine Sulfate in any ____ minute period
Definition
50mg in 10min period
Term
protamine- rapid IV push causes what?
Definition
HPN from histamine release, facial flushing, tachycardia
Term
How does protamine lead to Pulm HTN?
Definition
protamine heparin complex can result in complement activation and thromboxane release = pulmonary constriction
Term
If patients take ____ they are more likely to be allergic to protamine, why?
Definition
NPH insulin, chronic exposure produces antibodies against protamine
Term
there are approx ____mg protamine per ___units of isphane NPH insulin
Definition
0.5mg, 100units
Term
allergic reactions to protamine if ____ and ____
Definition
fish allergies, vasectomies/infertile males (antisperm antibodies)
Term
protamine comes from the sperm of salmon and other fish, true or false
Definition
true
Term
patient is allergic to protamine and needs CPB, what do you do?
Definition
pretreat, avoid protamine, admin alternative anticoag
Term
fondaparinux- what type of drug? what's it's other name?
Definition
DTI, arixtra
Term
Where does argatroban bind? is it reversible?
Definition
thrombin active site, yes it's reversible
Term
does argatroban require antithrombin III?
Definition
no
Term
how does argatroban exert its anticoag effects?
Definition
by inhibiting thrombin- catalyzed or induced reactions, including fibrin formation; activation of coag factors, protein C and platelet aggregation
Term
what is the bolus dose of argatroban?
Definition
350mcg/kg over 3-5 minutes
Term
what is the antidote to argatroban?
Definition
no specific antidote
Term
name 3 DTI's
Definition
1. hirudin 2. ximelagatran 3. argatroban
Term
when might you use a DTI?
Definition
CPB patients that have developed heparin resistance or HIT
Term
What is aprotinin?
Definition
an antifibrinolytic used for bleeding prophylaxis
Term
when is aprotinin used?
Definition
repeat operations, jehovahs, high risk of post op bleding, coagulopathies, long complicated procedures
Term
aprotinin preserves platelet function (Adhesion & aggregation), true or false
Definition
true
Term
test dose of aprotinin
Definition
1.4mg
Term
load dose of aprotinin
Definition
280mg over 20-30 minutes
Term
aprotinin infusion
Definition
70mg/h
Term
Is Amicar an antiplatelet?
Definition
no, antifibrinolytic
Term
dose of Amicar (bolus & infusion)
Definition
5-10g followed by 1g/hour
Term
what's the normal Coumadin dose?
Definition
5-10mg orally *dose varies among patients
Term
Coumadin competitively inhibits ____
Definition
Vitamin K dependent coagulation proteins
Term
What factors does Coumadin inhibit?
Definition
II, VII, IX and X
Term
What labs measure Coumadin coag?
Definition
PT/INR
Term
What is the goal INR for Coumadin?
Definition
INR 2.0-3.0
Term
why can't you use Coumadin in parturient?
Definition
crosses BBB
Term
Coumadin onset
Definition
3-4 days
Term
duration of single dose of coumadin
Definition
2-4 days
Term
half life of coumadin
Definition
40 hours
Term
when are coumadin effects seen in INR? why?
Definition
8-12 hours due to depletion of factor VII
Term
when are the full effects of coumadin seen?
Definition
not for several days
Term
How do you calculate INR?
Definition
patients PT/Control PT
Term
Normal INR range
Definition
0.9-1.2
Term
the INR is repeated every ___ weeks
Definition
4-6 weeks
Term
Goal INR is 2-3 for which conditions?
Definition
AFib, Treatment of VTE, Treatment of PE, Prevention of VTE in high risk surgery, tissue heart valves
Term
Goal INR is 2.5-3.5 for which conditions?
Definition
mechanical heart valve, prevention of recurrent MI, history of VTE with INR 2-3
Term
For minor surgery- when do you DC Coumadin for PT 20% within baseline?
Definition
1-3 days preop
Term
How do you reverse Coumadin for immediate surgery or active bleeding?
Definition
Vitamin K, 10-20mg orally or 1-5mg IV at a rate of 1mg/min
Term
after Vit K, PT to normal range within ____ hours
Definition
4-24 hours
Term
if the bleeding with Coumadin is an emergency- what is the treatment?
Definition
FFP
Term
what are thrombolytics used for?
Definition
restore circulation through a previously occluded vessel (ST elevation, CVA)
Term
Name 3 thrombolytics
Definition
streptokinase, urokinase, alteplase
Term
tpa- converts ______ to ______
Definition
plasminogen to the active form, plasmin
Term
what does plasmin do?
Definition
breaks down fibrin into fibrin degredation split products
Term
antithrombotics- what do they do?
Definition
suppress platelet function (inhibit platelet aggregation)
Term
3 examples of antithrombotics
Definition
ASA, Dipyridamole, Dextran 70
Term
how does ASA work?
Definition
inhibits thromboxane synthesis and release of adenosine diphasphate by platelets
Term
what is the life of a platelet?
Definition
8-12 days
Term
How does ASA affect COX
Definition
renders it non-functional, acetyl group of ASA causes acetylation of cyclooxygenase
Term
What does the ACETYLATION OF CYCLOOXYGENASE cause?
Definition
COX to be rendered non-functional
Term
What is cyclooxygenase?
Definition
the rate-limiting enzyme in the conversion of arachidonic acid to thromboxane A
Term
what is ASA primary and secondary prophylaxis?
Definition
primary is in the absence of diagnosis and secondary is treatment in the presence of overt CV disease or conditions
Term
How should primary ASA be used periop?
Definition
should be continued up to and day of but it may be held by surgeon for a few days prior
Term
when is primary ASA held?
Definition
intracranial, middle ear, posterior eye or intramedullary spine surgery, possibly in prostate surgery
Term
How should secondary ASA be used periop?
Definition
same as primary- stopping ASA for patients that need it requires an explicit discussion
Term
How does Plavix work?
Definition
inhibits platelet aggregation
Term
what class of ADP platelet receptors does Plavix work on?
Definition
P2Y12
Term
How is Plavix metabolized?
Definition
CYP450 enzymes to produce the ACTIVE METABOLITE that inhibits platelet aggregation
Term
How do NSAIDs work to depress platelets?
Definition
depress thromboxane A
Term
nsaids are more temporary- what is the doa?
Definition
24-48hours
Term
DDAVP causes release of _______
Definition
endogenous stored von willebrands
Term
what is the dose of DDAVP?
Definition
0.3mcg/kg IV infusion over 10-20 minutes
Term
after DDAVP- platelet adhesion increases within ____ minutes
Definition
30
Term
DDAVP wears off in _____ hours
Definition
4-6
Term
What is Factor VII
Definition
an initiator of thrombin
Term
what are the 2 pathways of factor VII
Definition
1. site of tissue injury combine with Tissue Factor 2. platelet surface
Term
why is factor VII good for trauma?
Definition
localizes to the site of injury
Term
what is the MOA of factor VII?
Definition
activates extrinsic pathway- forms a complex with tissue factor at the site of injury and activating factors IX and X
Term
Factor VIIa lowers the _______
Definition
prothrombin time
Term
You can use Factor VIIa in hemophilia A, B or C, true or false
Definition
false, only A & B
Term
What is the drug name for Factor VII?
Definition
NovoSeven
Term
what is the main benefit to Factor VII?
Definition
reduces the need for blood transfusion
Term
Factor VII comes with its own diluent- reconstitute with specific volume of ____ diluent
Definition
histadine
Term
what is the bolus dose for Factor VII?
Definition
90mcg/kg IV bolus
Term
how frequently can you re-dose Factor VII?
Definition
every 2 hours
Term
when do half of the spinal hematomas associated with heparinization occur?
Definition
at the time of catheter removal
Term
Heparin should be D/C'd ____ hours before catheter manipulation
Definition
2-4 hours
Term
How soon after catheter removal can you restart Heparin?
Definition
1 hour
Term
are patients that receive SQ heparin with 5000 units twice daily at risk for neuraxial techniques?
Definition
no, there is no contraindication
Term
remove catheters with INR < ____
Definition
1.5
Term
INR 1.5-3
Definition
caution removal
Term
INR > 3
Definition
decrease oral anticoag dose
Term
3 G's
Definition
garlic, ginkgo, ginseng
Term
true or false, all the herbals inhibit platelets but only ginkgo increases fibrinolysis
Definition
false, only garlic increases fibrinolysis
Term
time to d/c garlic
Definition
7 days
Term
time to d/c ginkgo
Definition
36 hours
Term
time to d/c ginseng
Definition
24 hours
Term
how soon after catheter removal before LMWH?
Definition
2 hours
Term
when do you d/c ticlid and plavix?
Definition
ticlid 14 days, plavix 7 days
Term
when do you d/c GP IIb-IIIa ?
Definition
8-48 hours in advance
Term
SQ lovenox- if patient got single 40mg SQ dose, the epidural cath can't be removed until _____
Definition
10-12 hours after the last dose
Term
before placing epidural cath, coumadin should be stopped _____
Definition
4-5 days
Term
before placing epidural cath, coumadin INR should be _______
Definition
less than 1.2
Term
anticoags should not be restarted for _ hours after removing the epidural cath
Definition
2 hours
Term
what does TEG measure x2
Definition
1. tensile strength of the clot 2. platelet aggregation/fibrin polymerization
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