Therapeutics I Exam III (Anti-Coagulation) Flashcards
Anti-Coagulation
What is the brand name for Apixaban?
Eliquis
What is the brand name for Colpidogrel?
Plavix
What is the brand name for Enoxaparin?
Lovenox
What is the brand name for Rivaroxaban?
Xarelto
What is the brand name for Warfarin?
Coumadin and Jantoven
What is normal body temperature?
98.6F
What is the normal respiratory rate?
12-18 breaths per minute
What does a basic metabolic panel evaulate?
Kidney function, blood acid/base balance, blood sugar, and electrolytes
What is the normal range for blood urea nitrogen (BUN)?
8-20 mg/dL
What is the normal range for carbon dioxide?
24-31 mEq/L
What is the normal range for Creatinine (SCr)?
0.6-1.2 mg/dL
What is the normal range for glucose?
Less than 100 mg/dL
What is the normal range for chloride?
95-105 mEq/L
What is the normal range for serum potassium?
3.5-5 mEq/L
What is the normal range for serum sodium?
135-145 mEq/L
What is the normal range for serum calcium?
8.5-10.2 mg/dL
Typically when calculating creatinine clearance, ideal body is used. What is used instead when calculating creatinine clearance for patients with obesity?
Use adjusted body weight
ABW= IBW +0.4(ABW-IBW)
What does a complete blood count (CBC) evaluate?
It tells information about cell counts in the blood. It is vital in monitoring anticoagulants and antiplatelets.
What do coagulation studies like prothrombin time (PT), International Normalized Ratio (INR), and aPTT tell us?
It measures how quickly the blood clots and it used to monitor anticoagulants.
What is the normal range for prothrombin time (PT)?
8.4-12.3 Seconds
What is the normal range for International Normalized Ratio (INR)?
0.8-1.2 for those not on any anticoagualtion
What is the normal range for activated/adjusted partial thromboplastin time (aPTT)?
25-36 seconds
What is the meaning of hemostasis?
To stop bleeding. This is the goal out body has when we start bleeding
The extrinsic pathway in the coagulation cascade is triggered by _____________ injury.
Endothelial
Tissue factor triggers coagulation once activated. It generates a small amount of _____________ and requires ___________ for the pathway to work.
Thrombin
Protein Disulfide Isomerase (PDI)
Tissue factor along with factor VIIa activate 3 substrates. What are those 3 substrates?
Obviously activates VII to VIIa
Activates IX to IXa
Activates X to Xa (inefficent)
When factor Xa and V bind to each other at the beginning of the common pathway, what is that complex called?
Prothrombinase complex
Thrombin converts fibrinogen to _________.
Fibrin (Ia)
Once hemostasis is reached after all the clotting cascades, tissue factor is _____________.
Inactivated and fibrin clot degrades through fibrinolysis.
What are the 4 main intrinsic anticoagulants that they body produces?
- Nitric oxide and Prostacyclin (inhibit platelet aggregation)
- Antithrombin (inhibits all coagulation cascades)
- Proteins C and S (degrade factor Va and VIIIa)
- Tissue factor pathway inhibitor (TFPI) ( inhibit factors Xa and VIIa)
The intrinsic anticoagulants nitric oxide and prostacyclin work by inhibiting __________ _____________.
Platelet aggregation
The intrinsic anticoagulant antithrombin works by inhibiting __________ pathways.
Coagulation
The intrinsic anticoagulants protein C and S work by degrading factors ______ and ______.
Va and VIIIa
The intrinsic anticoagulant tissue factor pathway inhibitor (TFPI) works by binding and inhibiting factors ______ and ______.
Xa and VIIa
What is really the only vitamin K antagonist medication that is still used today?
Warfarin
Vitamin K antagonist like warfarin inhibit factors _______, ______, _____, and _______, as well as proteins C and S synthesized in the liver.
II, VII, IX, and X
What is the MOA of vitamin K antagonists?
They inhibit vitamin K epoxide reductase which limits the production of factors II, VII, IX, and X as well as protein C and S made from the liver.
T or F: Vitamin K antagonists like Warfarin are not prodrugs.
False. This class of medications requires carboxylation to become active.
T or F: Warfarin can decrease clotting factors by 30-70%.
True! The actual amount varies from person to person.
How does vitamin K play a role in the coagulation cascade?
Vitamin K is crucial in the creating and activating clotting factors present in the coagulation cascade. Vitamin K antagonist inhibit the enzyme the recycles the oxidized vitamin K into reduced vitamin K so it no longer works in creating clotting factors.
T or F: Warfarin inhibits the oxidation of vitamin K.
True. It blocks VKOR from oxidizing vitamin K to stop its activity.
Warfarin is 99% _______ bound.
Protein bound. This means a person with low albumin per say will have more free drug in their body.
There are two stereoisomers for Warfarin (R,S)? Via which enzymes are each of the stereoisomers metabolized by?
R-warfarin is metabolized by CYP1A1, 1A2, and 3A4 while S-warfarin is metabolized by CYP2C9.
Warfarin is unique in the fact that dosing is based on _________ and not days.
Weeks
The half-life of warfarin is around 25-60 hours depending on genomics. The duration of the drug is around ____-_____ days.
2-5 days
T or F: Warfarin has a wide therapeutic index.
False! Warfarin has a very narrow therapeutic index
What determines the onset of action of vitamin K antagonists like Warfarin?
Onset of action is determined by the half life of the already present clotting factors.
Which clotting factor has the longest half-life?
Factor II (60 hours)
What is bridging?
This is a term used to describe the administration of Heparin or Enoxaparin after Warfarin administration in order to decrease the risk for clotting at the initiation of warfarin.
T or F: Right at initiation of Warfarin, the risk for clotting actually increases due to the long half-lifes of the clotting factors it inhibits.
True!! That is why bridging is done with IV anticoagulants to decrease the risk for initial clotting.
T or F: Warfarin is always given with a loading dose to get patients to therapeutic levels quicker.
False! Loading doses with Warfarin were only shown to decrease factor VII faster but not the others and it increases the risk for bleeding. Loading doses for Warfarin are typically not recommended.
T or F: INR is a standardized value that can be comparatively used to determine a patient’s adherence and response to Warfarin or other anticoagulants.
True!
A prothrombin time of _______ (INR 3.7-4) increases the risk for bleeding.
Two. A PT of over 2 is not wanted.
The odds of a subdural hemorrhage increase ________x as prothrombin time increases from 2 to 2.5.
7.6x
Based on clinical trials, the ideal INR for someone on Warfarin therapy is between ____-_____ with changes based on the condition.
2-3
What is the INR goal someone with a venous thromboembolism?
2-3
What is the INR goal for someone with a mechanical heart valve?
2.5-3.5
We go higher on this as those with these types of valves readily clot.
T or F: While on Warfarin therapy, patients need to consume the same amount of vitamin K per day.
False. Patients need to consume the same amount of vitamin K per week, not per day.
Increased vitamin K levels in the body lead to a __________ INR.
Decreased.
This makes sense as vitamin K aids in clotting so too much of it will overpower Warfarin anatongist properties and cause INR to decrease and therefore increase risk of a clot.
What is the typical dosing for Warfarin (Coumadin)?
5 mg PO per day
What are the factors that can influence sensitivity to warfarin?
75 and older, clinical congestive HF, Diarrhea, drug interactions, elevated baseline INR, fever (acute illnesses), hyperthyroidism, cancer (prothrombotic state), malnutrition, and CYP2C9 and VCOR polymorphisms.
What are the 6 main contraindications for Warfarin use?
- PREGNANCY
- Risk of hemorrhage
- Senility, alcoholism, psychosis (general lack of patient safety and ability to adhere to Warfarin therapy)
- Spinal puncture procedures with potential for bleeding
- Inability to go to lab for INR
- Frequent falls
What are the main side effects of warfarin?
Bleeding and necrosis
What is the black box warning for warfarin?
Bleeding risk
What is the antidote to warfarin?
Vitamin K
What are some risk factors that increase the risk for major bleeding?
Intense anticoagulation therapy, initiation of therapy, unstable INR, 65 and older, concurrent antiplatelet therapy, concurrent NSAID use, history of GI bleeds, recent surgery or trauma, high risk for falls, heavy alcohol use, renal failure, cerebrovascular disease, and cancer
What is the dosing for vitamin K when used as the antidote for warfarin?
1-10mg orally (preferred) or IV.
Oral is preferred as the liver synthesizes clotting factors and with oral 1st pass metabolism, it places vitamin K at the site of action to induce clotting.
A person has INR between 4.5-10 with no bleeding. Should they be treated with vitamin K therapy?
No.
A person has INR above 10 but with no bleeding. Should they be treated with vitamin K therapy?
Oral vitamin K should be administered
A person presents with major bleeding. What should be done?
- Rapid reversal of anticoagulation with four-factor PCC rather than plasma
- Use vitamin K, 5-10mg, via slow IV injection rather than coagulation factors alone
Febrile illness with warfarin therapy can increase INR via what mechanism?
Febrile illness can increase INR via increased catabolism of clotting factors.
Acute ethanol ingestion, liver disease, and/or heart failure with warfarin therapy can increase INR via what mechanism?
Inhibition of warfarin metabolism and diminished production of clotting factors
Malnutrition, lots of vomiting/diarrhea, and/or chemo-induced mucositis/stomatitis with warfarin therapy can increase INR via what mechanism?
Increased warfarin sensitivity due to decrease vitamin K intake and production and increased vitamin K removal from GIT. Low albumin levels which results in decreased warfarin binding so more free warfarin.
Chronic ethanol ingestion and/or tobacco smoking with warfarin therapy can decrease INR via what mechanism?
Induction of warfarin metabolism
Foods high in vitamin K, chewing tobacco, nutritional supplements, and/or enteral feedings with warfarin therapy can decrease INR via what mechanism?
Increased synthesis of clotting factors, increase vitamin K intake, decreased bioavailability of warfarin as it can bind to feeding tubes.
What are the two main drug CLASSES that interact with warfarin?
- CYP2C9/3A4/1A2/2C19 inhibitors (may increase INR and bleeding risk)
- CYP2C9/3A4/1A2/2C19 inducers
Do NSAIDs and aspirin interact with warfarin?
Yes!!
What is the FAB-Five for drugs that inhibit the metabolism of warfarin?
This is the way to memorize the top drug interactions with warfarin:
F- Fluconazole (Diflucan)/ Antifungals
A- Amiodarone (Cordarone)
B- Bactrim (TMP-SMX)
F- Flagyl (Metronidazole)
F- Fluoroquinolones
Why do fluoroquinolones (antibiotic class) lead to a massive increase in INR while on warfarin?
These antibiotics kill of the good gut bacteria that produce vitamin K. Without any vitamin K and the addition of warfarin, the INR increases rapidly which increases the risk for bleeding.
Fluconazole (Diflucan) inhibits what 3 CYP enzymes?
CYP2C9, 3A4, and 2C19
Amiodarone (Cordarone/Pacerone) inhibit what 2 CYP enzymes?
CYP2C9 and 3A4
Bactrim (TMP-SMX) inhibits which CYP enzyme?
CYP2C9
Flagyl (metronidazole) inhibits which CYP enzyme?
CYP2C9
The class of fluoroquinolone antibiotics inhibit which CYP enzyme?
Their drug interaction with warfarin is not CYP mediated.
What 5 medications interact with Warfarin by inducing their metabolism?
Carbamazepine
Phenytoin
Phenobarbital
Primidone
Rifampin
Carbamazepine induce which 2 CYP enzymes?
CYP3A4 and 1A2
Phenobarbital induces which 3 CYP enzymes?
CYP2C9, 3A4, and 1A2
Primidone induces what 3 CYP enzymes?
CYP2C9, 3A4, and 1A2
Phenytoin induces which 2 CYP enzymes?
CYP3A4 and 1A2
Rifampin induces which CYP enzymes?
CYP2C9, 3A4, 1A2, and 2C19
What are the herbal supplements that can increase the effects of warfarin?
Cranberry, tumeric and the 3Gs being garlic, ginkgo, and ginseng
What are the herbal supplements that can decrease the effects of warfarin?
St. John’s wort, CQ10, and green tea
T or F: Educating the patient on the color of their warfarin medication and how it is related to their dose is not important.
False. Patient need to know what dose they are on and it correlated color.
T or F: Patients on warfarin should be educated on the signs and symptoms of bleeding and thromboembolism.
True! These are the big warnings associated with warfarin use.
What are direct oral anticoagulants?
These are oral anticoagulants that are not warfarin
What is the MOA for the direct oral anticoagulant named Dabigatran (Pradaxa)?
It is a prodrug that once activated is a direct thrombin inhibitor
T or F: Dabigatran is not a prodrug.
False. Dabigatran is a prodrug that is rapidly hydrolyzed to its active form in the liver and plasma.
What is the brand name for Dabigatran?
Pradaxa
Does Dabigatran require renal dose adjustments?
Yes! Around 80% is excreted renally
What is the average bioavailability of Dabigatran?
3-7%
When is the peak concentration of Dabigatran reached?
1-2 hours
Is Dabigatran dialyzable?
Yes, this means that it can be eliminated via dialysis which may be beneficial in an overdose.
What is the half-life of Dabigatran?
12-17 hours
What is the dosing for Dabigatran in the case of prophylaxis for VTE (Venous Thromboembolism) following a total hip replacement?
110 mg orally for the first day about 1-4 hours after surgery followed by 220 mg once daily.
Avoid if CrCl is less than 30 ml/min
What is the dosing for Dabigatran in the case of treatment for a deep vein thrombosis (DVT) or a pulmonary embolism (PE)?
CrCl greater than 30? After 5-10 days of parenteral anticoagulation give 150 mg PO BID
(Avoid if CrCl is less than 30 ml/min)
What ages in the pediatric population can use Dabigatran?
8-18 years old. They use weight based dosing in this population.
What are the two common adverse effects associated with Dabigatran use?
Bleeding and dyspepsia
What is the antidote for Dabigatran overdose?
Idarucizumab (Praxbind)
It is a monoclonal antibody fragment that rapidly bind Dabigatran
What are the two black box warnings associated with Dabigatran use?
- Premature discontinuation can increase risk for clotting events
- Spinal/epidural hematoma risk while on this medication. Could lead to bleeding in that area eventually causing paralysis
What is unique about the drug interactions with Dabigatran?
The interactions are specific to the clinical indications for use so they vary from case to case.
When using Dabigatran during atrial fibrillation, what are the two instances of drug interactions?
- If using a p-glycoprotein inhibitor and patient has CrCl between 30-50, reduce the dose of Dabigatran or avoid it
- If using a p-glycoprotein inhibitor and patient has CrCl between 15-30, avoid Dabigatran
When using Dabigatran during DVT/PE, what is the one instance of drug interactions?
If using a p-glycoprotein inhibitor and the patient has a CrCl less than 50, avoid dabigatran.
What are the two p-glycoprotein inducers that interact with Dabigatran and concurrent use should be avoided?
Rifampin and St. John’s Wort
What other medications should be absolutely avoided with Dabigatran use?
Anticoagulants, antiplatelets, and NSAIDs
T or F: Dabigatran should be taken with a full glass of water and can be taken with food if dyspepsia is occuring.
True
What are the 3 medications that are direct oral anticoagulants but work by inhibiting factor Xa in the coagulation cascade?
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Edoxaban (Savaysa)
What is the brand name for Rivaroxaban?
Xarelto
What is the brand name for Apixaban?
Eliquis
What is the brand name for Edoxaban?
Savaysa
Do the oral Xa inhibitors require renal dosing adjustments?
Yes!
What is the bioavailability for Rivaroxaban and Apixaban?
Rivaroxaban is 80-100% while Apixaban is 50%
When do Rivaroxaban and Apixaban reach maximum concentrations in the body?
2-4 hours
Are Rivaroxaban and Apixaban highly protein bound?
Yes! Around 87% and higher
What is unique about the dosing for Rivaroxaban related to its half-life being 5-9 hours?
Rivaroxaban is only dosed once per day even though it has a moderately small half life
What is unique about the dosing for Apixaban related to its half-life being 12 hours?
Apixaban is dosed BID even though it has a longer half-life compared to Rivaroxaban which is only dosed once per day.
Rivaroxaban and Apixaban are metabolized by ________ enzymes while Edoxaban is mainly a substrate for ______________.
CYP (3A4)
P-glycoprotein
What are the only two indications for Edoxaban use?
Stroke prevention in atrial fibrillation and treatment of VTE
What are the 5 indications for Apixaban use?
- Stroke prevention in atrial fibrillation
- DVT prophylaxis in hip and knee replacements
- Treatment of VTE
- Prevention of recurrence of VTE
- Heparin induced thrombocytopenia (off-label)
T or F: Rivaroxaban is approved for use in the pediatric population.
True!!!!!!!!
What is the dosing for Rivaroxaban for someone getting treated for VTE prophylaxis for total hip/knee replacement or prophylaxis of VTE in acutely ill medical patients?
10 mg PO daily
Avoid if CrCl less than 30
What is Rivaroxaban dosing for the treatment of VTE, to reduce to risk of recurrence of VTE, and off-label use for heparin induced thrombocytopenia?
15 mg PO BID WF for 21 days for acute DVT/PE followed by 20 mg PO once daily WF
Avoid if CrCl less than 30
What is the dosing for Rivaroxaban to reduce the risk of recurrence of DVT and PE?
After 6 months of standard anticoagulant treatment in patients with continued risk:
10 mg PO daily with out without food
T or F: If a patient has a creatinine clearance less than 95 ml/min, we do not use Edoxaban.
False. We do not use Edoxaban if CrCl is GREATER than 95!!!
What are the black box warnings associated with oral factor Xa inhibitors like Rivaroxaban, Apixaban, and Edoxaban?
- Premature discontinuation can increase the risk for clotting
- Spinal/epidural hematoma
What are the adverse effects associated with oral factor Xa inhibitors like Rivaroxaban, Apixaban, and Edoxaban?
Bleeding
(Abnormal LFTs for Edoxaban as well)
What is the antidote for Rivaroxaban and Apixaban?
Andexanet alfa
What are the 6 warnings/precautions associated with factor Xa inhibitor use?
Bleeding risk, antiphospholipid syndrome (triple +), hepatic + renal impairment, GI diseases/bariatric surgery, prosthetic heart valves (DOACs are not used for mechanical valves)
If a person is taking a p-glycoprotein inhibitor and a strong CYP3A4 inhibitor, Rivaroxaban should be _______________
Avoided
Rivaroxaban should never be taken with ____________, _______________, and ___________.
Anticoagulants, antiplatelets, and NSAIDs
If a person is taking a p-glycoprotein inducer and a strong CYP3A4 inducers, Rivaroxaban should be _______________
Avoided
If a person is taking a p-glycoprotein inhibitor and a weak/moderate CYP3A4 inhibitor in patients with CrCl between 15-80 mL/min, Rivaroxaban should be _______________
Avoided
If a person is taking a p-glycoprotein inducer and a strong CYP3A4 inducer, Apixaban should be _______________
Avoided
If a person is taking a p-glycoprotein inhibitor and a strong CYP3A4 inhibitor, Apixaban should be _______________
Avoided or dose adjusted
Apixaban should never be taken with ____________, _______________, and ___________.
Anticoagulants, antiplatelets, and NSAIDs
T or F: Edoxaban use should be avoided in patients taking p-glycoprotein inducers (rifampin) and inhibitors.
True
Edoxaban should never be taken with ____________, _______________, and ___________.
Anticoagulants, antiplatelets, and NSAIDs
What is the Apixaban dosing for prophylaxis of DVT following total knee/hip replacement?
2.5 mg PO BID
What is the Apixaban dosing for the treatment of DVT or PE and possible off-label use of HIT?
- 10 mg PO BID for 7 days
- 5 mg PO BID after that
What is the Apixaban dosing for the reduction of risk of recurrence of DVT/PE following initial therapy?
2.5 mg PO BID after initial 6 months of treatment for DVT/PE
T or F: Food does not enhance the bioavailability of Rivaroxaban.
False. Food does enhance the bioavailability of rivaroxaban
What two medications need parenteral bridging for the treatment for DVT/PEs before taking the actual oral anticoagulation medication?
Dagibatran and Edoxaban
T or F: If the blood vessel is intact, platelet activation/ coagulation does not occur.
True!
Efficacy of antithrombin (a natural anticoagulant) has 1000x enhanced efficacy when ____________ sulfate proteoglycans are administered.
Heparan
The activation of Protein C&S (natural anticoagulant) is dependent on _______ binding to Gla residues.
Calcium
What are the 3 heparin derivatives?
- Unfractionated heparin (this is like THE heparin)
- Low molecular weight heparin (LMWH)
- Synthetic polysaccharide
Unfractionated heparin is a heterozygous mixture of sulfated ________________.
Mucopolysaccharides
What is the average molecular weight of unfractionated heparin?
5,000-30,000 daltons (very big)
T or F: Unfractionated heparin is commonly extracted from horse intestinal mucosa.
False. It is commonly extracted from porcine (pig) intestinal mucosa.
In order for unfractionated heparin to work it must bind to ___________.
Antithrombin
What is the MOA of unfractionated heparin?
Its pentasaccharide has to bind to antithrombin and makes a conformational change and then together they deactivate factor Xa. If the polysaccharide is greater than 18 saccharides it can also inactivate factor IIa.
What is the main difference between unfractionated heparin and low-molecular weight heparin?
LMWH cannot inactivate factor IIa while unfractionated heparin can inactivate factor Xa and IIa.
What is the onset of action for unfractionated heparin?
Immediate when given IV and around 30 minutes when given SubQ
T or F: There are renal adjustments for unfractionated heparin.
False. There are no renal adjustments for unfractionated heparin.
What are some blood tests that should be run to assess coagulation and monitoring while someone is on unfractionated heparin?
Baseline CBC, aPTT (hPTT)- activated partial thromboplastin time, and anti-Xa levels, signs and symptoms of disease progression, and adverse effects
What are the 6 adverse effects associated with unfractionated heparin?
Bleeding
Osteoporosis
Dermatological rxns
Alopecia
Hyperkalemia
Hypersensitivity
BODAHH
What is heparin-induced thrombocytopenia (HIT)?
This is a platelet count that has decreased 50% or more from baseline (less than 150 x 10^9) and/or thrombosis that occurs between days 5 and 14 following initiation of heparin.
This is a low platelet count that can be associated with immunity or can be non-immune. Non-immune mediated is more common than immune mediated.
If someone has immune HIT following heparin, how do we manage this?
Immune HIT has a delayed onset of action (4-14 days) as the body has to make antibodies for the heparin. We manage it by stopping the heparin, then giving parenteral direct thrombin inhibitors like Argatroban or Bivalirudin.
In HIT treatment, warfarin should not be given until platelets are above __________.
150,000
If someone has non-immune HIT following heparin, how do we manage this?
Non-immune HIT onset is less than 4 days and we manage this via observation.
What are the 6 indications for the use of heparin?
- TX for DVT, PE, peripheral arterial embolism, and acute coronary syndrome
- Prophylaxis for DVT
- A. fib with embolization
- Disseminated intravascular coagulation (DIC)
- Bridging to/from other anticoagulant (typically warfarin)
- Prevention of clotting during procedures
What are the 3 specific contraindications for unfractionated heparin?
- Prior HIT
- Hypersensitivity
- Active bleeding
Coagulation monitoring via aPTT while on unfractionated heparin is crucial. How often should aPTT be monitored?
At first, monitor every 6 hours for 24 hours and then daily if aPTT is in range. Monitor every 6 hours after a dose change of unfractionated heparin.
What is the dosing for unfractionated heparin for prophylaxis for VTE?
5,000 Units SubQ BID/TID (BID dosing used for super ill old people)
T or F: Anticoagulants do not burst clots, they keep clots from forming.
True
What is the dosing for unfractionated heparin for the treatment of VTE?
IV bolus of 80 units/kg followed by a continuous IV infusion of 18 units/kg/hr. Titrate based on aPTT
What is the dosing for unfractionated heparin from the treatment of acute coronary syndrome?
IV bolus of 60 Units/kg followed by continuous IV infusion 12-14 Units/kg/hr. Titrate based on aPTT.
What is the protocol for reversing an overdose on unfractionated heparin?
- Stop the heparin (check aPTT 1 hour after holding)
- Protamine sulfate administration to neutralize the heparin
- Whole blood transfusion if serious bleeding
What are the two available forms of low-molecular weight heparin?
Dalteparin (Fragmin) and Enoxaparin (Lovenox)
T or F: Low-molecular weight heparin has greater inhibition of factor Xa due to its shorter chain not allowing for factor IIa inhibition.
True! Its average weight is 5,000 daltons
What is the MOA of low-molecular weighted heparin?
Its smaller polysaccharide chain that with antithrombin binds and inhibits factor Xa.
IV enoxaparin (Lovenox) is indicated for _______ and _________ only.
STEMI and Percutaneous coronary intervention (PCI)
What is the onset of action for Enoxaparin (Lovenox)?
3-5 hours for the maximum effect
Enoxaparin (Lovenox) renal dosing is required for a CrCl less than __________ ml/min.
30
T or F: Enoxaparin (Lovenox) is okay to give in those with acute renal dysfunction.
False! Do not give!
Does LMWH heparin or unfractionated heparin have a greater risk for HIT?
Unfractionated heparin has a greater risk of HIT due to it being a larger molecule.
Heparin dosing uses ________ based dosing and ________ needs to be monitored while on this medication.
Weight
aPTT
LMWH heparin dosing uses fixed dosing for prophylaxis but uses weight based dosing for _________________. _______ needs to be monitored while on this medication.
Therapeutic treatment
Anti-Xa
How often does anti-Xa need to be monitored while on low-molecular weighted heparin?
Draw 4-6 hours after dose
What are the 3 indications for use for Dalteparin?
- DVT prophylaxis
- TX for VTE in cancer patients
- Prophylaxis of ischemic complications following acute coronary syndrome
What are the 4 indications for use for Enoxaparin?
- DVT prophylaxis
- Inpatient/outpatient treatment for acute VTE
- Prophylaxis for ischemic complications of unstable angina and MI
- TX for STEMI
What are the 4 adverse effects associated with low-molecular weighted heparins?
Bleeding, hypersensitivity, HIT, and osteoporosis
What are the 3 contraindications for low-molecular weighted heparin?
Active bleeding, past HIT, and hypersensitivity
What is the black box warning associated with the use of low-molecular weighted heparin?
Epidural/spinal puncture hematoma resulting in paralysis.
T or F: Low molecular weight heparin can absolutely not be used during pregnancy.
False!!!! LMWH heparin is actually the drug of choice for anticoagulation during pregnancy for the treatment and prophylaxis of DVT.
What is something that should be monitored when giving LMWH heparin to pregnant people?
Monitor anti-Xa due to the changing volume of distribution during pregnancy.
Also monitor CBC, SCr, aPTT, PT, and signs and symptoms of bleeding
What is the dosing for the LMWH called Enoxaparin (Lovenox) in cases of acute treatment for VTE?
1 mg/kg SubQ Q12H
OR
1.5 mg/kg SubQ Q24H
Cap dose at 150 mg or monitor anti-Xa more
What is the dosing for LMWH called Enoxaparin (Lovenox) in the cases of prophylaxis for VTE?
30 mg SubQ BID or 40 mg SubQ daily
(For obese patients: 40 mg SubQ BID or 0.5 mg/kg SubQ BID)
T or F: Enoxaparin has no renal adjustments to dosing for a CrCl less than 30 ml/min.
False. Enoxaparin absolutely needs dose adjustments for CrCl less than 30 ml/min
What is the renal adjustment dosing for a CrCl less than 30 for Enoxaparin for DVT prophylaxis?
30 mg SubQ once daily
What is the renal adjustment dosing for a CrCl less than 30 for Enoxaparin for VTE treatment?
1 mg/kg SubQ once daily
T or F: Enoxaparin is fine to use in those on dialysis.
FALSE. Do not use in those on dialysis
What is the protocol if someone were to overdose on LMWH heparin?
- Stop the LMWH
- Monitor for signs and symptoms of bleeding
- Transfuse PRN for major bleeding
- Protamine may partially neutralize the LMWH
What is the only synthetic pentaccarhide that is FDa approved for us?
Fondaparinux (Arixtra)
What is the brand name for the synthetic pentaccarhide, Fondaparinux?
Arixtra
What is the MOA for the synthetic pentaccarhide like Fondaparinux?
It binds to antithrombin and exclusively binds and deactivates factor Xa (not IIa as it is much too small to do that).
When is the peak concentration of Fondaparinux reached?
2-3 hours with 20ish hour half life
Fondaparinux is contraindicated for use if CrCl is less than _________ or the patient is on __________.
30 ml/min
Dialysis (ESRD)
What should be monitored while on Fondaparinux?
Anti-Xa levels (can be considered as machiene would need to be calibrated for this medication)
What are the main indications for use of Fondaparinux?
DVT and PE treatment and VTE prophylaxis
What are the two adverse effects associated with Fondaparinux?
Bleeding and thrombocytopenia (low platelets)
What is the black box warning associated with Fondaparinux?
Epidural/spinal puncture risk for hematoma
What are the 5 contraindications for Fondaparinux use?
- allergy to medication
- CrCl less than 30
- body weight less than 50kg (can’t use for prophylaxis)
- major active bleeding
- bacterial endocarditis
What should be monitored when a patient is on Fondaparinux?
CBC, aPTT, PT, signs and symptoms of bleeding
What is the dosing for Fondaparinux in VTE and HIT Treatment?
-less than 50 kg: 5 mg SubQ daily
- 50-100kg: 7.5 mg SubQ daily
- Greater than 100kg: 10 mg SubQ daily
What is the dosing for Fondaparinux in VTE prophylaxis?
2.5 mg SubQ daily and avoid if under 50 kg
What are the two direct thrombin inhibitors we need to know?
Argatroban (Acova) and Bivalirudin (Angiomax)
What is the brand name for the direct thrombin inhibitor Argatroban?
Acova
What is the brand name for the direct thrombin inhibitor Bivalirudin?
Angiomax
T or F: Direct thrombin inhibitors have very long half lifes.
False. They have very short half lives being 30-60 minutes
What are the two types of VTE?
DVT and PE
Why are hospitalized patients at risk for VTE?
They are typically immobile, have indwelling catheters, or are recovering from trauma.
Which surgery has the highest absolute risk for DVT?
Spinal cord surgery (60-80%)
When at the hospital should medications be given to prevent DVTs?
Basically all surgeries, major trauma, acutely ill and high risk patients, cancer patients, COVID-19 patients, and critically ill patients
What are some good non-pharmacological practices for VTE prevention?
Walking, graduated compression stockings, intermittent pneumatic compression, and venous foot pumps
What scoring system is used to assess risk for VTE in surgical patients?
Caprini score
What scoring system is used to assess risk for VTE in hospitalized patients?
Padua score
Per the CHEST 2016 guidelines on DVT prophylaxis, what should medical patients be given?
LMWH, unfractionated heparin, fondaparinux, or rivaroxaban
Per the CHEST 2016 guidelines on DVT prophylaxis, what should critically ill medical patients be given?
LMWH like Enoxaparin or unfractionated heparin
Per the CHEST 2016 guidelines on DVT prophylaxis, what should outpatient cancer patients with additional risk and solid tumors be receiving?
LMWH like Enoxaparin or unfractionated heparin
What are the additional risk factors in cancer patients that advise administering prophylactic medication for DVT?
Prior VTE, immobilization, hormone treatment, angiogenesis inhibitors, thalidomide or lenalidomide use.
What is the dosing for Enoxaparin in DVT prophylaxis use?
40 mg SubQ daily
(CrCl less than 30, do 30 mg SubQ daily)
Per the CHEST 2016 guidelines on DVT prophylaxis, what should someone at high bleeding risk or actively bleeding recieve?
Nothing!! Only use mechanical prophylaxis for these patients as you do not want them to bleed more.
T or F: Rivaroxaban can be used in DVT prophylaxis for hip fracture surgery.
False. Do not use rivaroxaban for hip fracture surgery in DVT prophylaxis.
Per the CHEST 2016 guidelines on DVT prophylaxis, what is the preferred DVT prophylaxis medication for those undergoing hip/hip fracture/knee surgery?
LMWH like enoxaparin. Can also use fondaparinux or dabigatran
What is the dosing for Fondaparinux (Arixtra) in DVT prophylaxis?
2.5 mg SubQ daily
At what weight can Fondaparinux no longer be used?
Less than 50kg
What is the dosing for dabigatran in DVT prophylaxis?
220 mg PO daily
For patients undergoing major orthopedic surgery (not knee/hip/etc), how long should VTE prophylaxis be?
Up to 35 days
What are the main differences between LMWH and unfractionated heparin?
LMWH is slightly more effective, has a longer half-life, and more expensive. Unfractionated heparin is reversible, less expensive, and preferred in end-stage renal disease. Both have similar bleeding risks.
What are the main differences between LMWH and Fondaparinux (synthetic pentasaccharide parenteral anticoagulant)?
Fondaparinux is more effective and only FDA indicated drug for hip fracture surgery, it is safe for HIT but it can’t be used in those below 50 kg and in those with CrCl less than 30.
How is LMWH monitored in prophylaxis patients?
Draw blood 4 hours after 3-4th dose and aim for peak goal of medication at 0.2-0.5 IU/mL. No need to monitor anti-Xa in most patients.
What is the guideline for VTE prophylaxis in covid-19 patients?
LMWH then unfrationated heparin
What is the clinical presentation of a DVT?
Skin discoloration or darkening, increased leg circumference, palpable cord, Homan’s sign (discomfort behind knee with foot dorsiflexion), and obviously pain, swelling, and warmth
What are the signs and symptoms of a PE?
Cough, chest pain, SOB, spitting up blood, palpitations, dizziness, tachycardia, tachypnea, rales lung sounds, sweaty, cyanotic, hypotensive
What is a saddle PE?
This is when the blood is stuck in the trachea before it splits into the two lungs
What are the other locations for PEs?
Lobar, segmental, and subsegmental
What are the 3 classifications for PE in terms of hemodynamic compromise?
Massive, submassive, and low-risk
What is categorized as a massive PE?
Sustained hypotension with systolic below 90 for 15+ minutes, pulselessness, or persistent profound bradycardia. If the pulmonary tree is blocked over 50%, or there is a high risk of mortality.
What is categorized as a submassive PE?
Hemodynamically steady (no hypotension) but often accompanied by right ventricle dysfnction.
What is categorized as a low-risk PE?
No right ventricular dysfunction present and a low risk of death.
What is D-dimer testing?
This is a test used that can rule out a DVT or PE
If someone is suspected of experiencing a VTE, what lab tests should be run to rule out a heart attack?
Cardiac troponins, B-natriuretic peptide, and D-dimer testing
What are the different VTEs we treat with anticoagulation?
Proximal DVT, PE, acute isolated distal DVT (with severe symptoms and high risk for clot extension), subsegmental PE (with high risk of recurrent VTE), incidental asymptomatic PE, cerebral vein/venous sinus thrombosis, and a superficial venous thrombosis.
What are the different VTEs that we do not treat with anticoagulation but solely monitor them?
Acute isolated distal DVT (without severe symptoms and low risk for extension) and subsegmental PE with low risk of recurrent VTE
If someone is a contraindication for the use of anticoagulation therapy, what device can be placed instead?
Inferior vena cava filter. It stops a clot from entering the lungs by catching it in the heart during movement.
What is the treatment for someone diagnosed with an extensive iliofemoral DVT or a massive/submassive PE?
- Thrombolytic/fibrinolytic like tenecteplase
- IV unfractioned heparin
What is the treatment dosing for unfractionated heparin?
IV bolus at 80 Units/Kg followed by continuous infusion at 18 Units/kg/hour. Titrate based on aptt.
What are the contraindications for the use of thrombolytics/fibrolytics?
- History of intracranial hemorrhage
- Structural intracranial cerebrovascular disease
- Intracranial malignancy
- active bleeding
- recent spinal canal or brain stroke surgery in last 3 months
- recent head trauma
If a hemodynamically unstable patient is contraindicated for thrombolytic/fibrinolytic use, what is done instead?
Thrombectomy/ embolectomy.
What is the dosing for the thrombolytic/fibrinolytic Tenecteplase for the treatment of an extensive iliofemoral DVT or massive/submassive PE?
30-50 mg bolus over 5-10 seconds (adjusted for BW, do not need to know the individual BW doses)
If someone is not have an extensive iliofemoral DVT or a massive/submassive PE but still experiencing some sort of PE or DVT, what are the treatment options?
There are 3 treatment options if a patient does not fall into the other category:
- Apixaban or Rivaroxaban
- Parenteral anticoagulation for 5-10 days bridged to dabigatran or edoxaban
- IV unfractionated heparin or LMWH or fondaparinux bridged to warfarin
What is the treatment dosing for rivaroxaban?
15 mg PO BID for 21 days then 20 mg once daily with food
What is the treatment dosing for apixaban?
10 mg PO BID for 7 days then 5 mg BID
What is the treatment dosing for fondaparinux?
<50 kg= 5 mg
50-100=7.5 mg
>100= 10 mg
What is treatment dosing for dabigatran?
150 mg PO BID
What is the treatment dosing for Edoxaban?
60 mg PO daily (after 5-10 days of parenteral anticoagulation)
(30 mg PO daily if CrCl 15-50, BW less than 60, or if p-glycoprotein inhibitors like verapamil or quinidine are present)
When should edoxaban be avoided?
If CrCl is too good and above 95 CrCl
How should parenteral agents and warfarin be bridged?
Parenteral agents and warfarin should overlap for 5 days with an INR of 2 or greater for 24 hours. Finally, there needs to be 2 INRs in therapeutic range 24 hours apart in order to go full warfarin.
Expect the greatest INR increase _____-_____ hours after initiating warfarin.
48-72 hours
If a person has renal disease and a CrCl less than 30, what anticoagulant is preferred?
Apixaban
In pregnancy, what is the only anticoagulant we can give?
LMWH
If someone has poor adherence to anticoagulation medications, what is the preferred medication to put them on and why?
Warfarin because it is based on weekly dosing so they could double up if they missed a day
What is the 1st line long-term anticoagulant preferred choice?
DOACs (basically all the oral ones except warfarin)
If a person with cancer is having a VTE, what is the preferred treatment?
DOACs are preferred
If a person has antiphospholipid syndrome, what anticoagulation medication is preferred?
Warfarin with target INR of 2.5
At minimum, during treatment phase after a VTE, a patient should be anticoagulated for at least __________ months. There is also an extended phase of anticoagulation which has no stop date.
3 months
T or F: DOAC dose reduction is now recommended during the extended phase of anticoagulation after a VTE.
True. Consider Rivaroxaban 10 mg daily and Apixaban 2.5 mg PO BID
If a patient had a VTE that was provoked by surgery, they need to be anticoagulated for at least ________ months.
3 months
If a patient had a VTE that was provoked by a non-surgical transient risk factor, they need to be anticoagulated for at least ________ months.
3 months
If a patient had an isolated distal DVT of the leg, they need to be anticoagulated for at least ________ months.
3 months
If a patient had an unprovoked VTE, they need to be anticoagulated for at least _____ months and ________ phase anticoagulation is recommended.
3 months
Extended phase
If someone had an unprovoked VTE and they have low-bleeding risk, they need to be on __________ therapy with anticoagulation while someone with a high bleed risk should be good with only ________ months of anticoagulation therapy.
Extended
3 months
What is the target INR goal for those on warfarin?
2-3
Is aspirin a good treatment option for VTE?
It is not a reasonable alternative to extended therapy but could help prevent recurrence of VTEs.
How is type 2 HIT categorized?
Immune-mediated type 2 HIT is categorized by a 50% decrease in baseline platelets and a plt nadir greater than 20.
How is HIT treated?
- Stop heparin
- Anticoagulate with Direct Thrombin Inhibitor like argatroban or bivalirudin)
- Avoid warfarin until plts are above 150,000
For the treatment of HIT, what is the dosing for Argatroban?
2 mcg/kg/min. Monitor aPTT, CBC, and body weight. aPTT goal is 1.5-3x baseline
How is argatroban transitioned to warfarin?
Decrease or keep argatroban at 2mcg/kg/min and initiate usual warfarin dose (5mg). Argatroban can be stopped one INR is greater than 4. Repeat INR in 4-6 hours, if it fell you can restart the argatroban. EXPECT HIGH INRs as argatroban and warfarin together will elevate INR.
What is the dosing for bivalirudin in the treatment of HIT?
0.15-0.2 mg/kg/hr
If CrCl is less than 30 start at 0.04-0/08 mg/kg/hr and if CrCl between 30-60, start at 0.08-0.12 mg/kg/hr.
In terms of platelet aggregation, what is released in the first step in response to injury or damage to the epithelium?
Collagen and von Willebrand factor
In platelet aggregation, PAR-1 and PAR-4 are activated by ____________ and go on to activate COX-1 and GpIIb/IIIa.
Thrombin (factor IIa)
________ is the major product of COX-1 activation in platelet aggregation.
TxA2 (Thromboxane)
_______ and ________ activate GpIIb/IIIa and COX-1 to promote platelet aggregation and secretion.
P2Y1 and P2Y12
________ is an endogenous compound that is secreted by endothelial cells and inhibits platelet activation.
Prostacyclin
________ and _______ that are activated during platelet aggregation by both PAR-1, PAR-4, GPVI, and P2Y1 and P2Y12 doing the platelet cross-linking.
GPIIb and GPIIIa
Aspirin targets what molecule in the platelet aggregation?
Aspirin irreversibly inhibits COX-1 which stops the production of TxA2 therefore inhibiting platelet aggregation and vasoconstriction.
What is unique about aspirin?
Aspirin irreversibly inhibits COX-1 on platelets meaning it will last for the lifetime of the platelet being around 7-10 days.
What are common adverse effects associated with aspirin use?
-Upper GI events due to depletion of prostaglandin for housekeeping
-Bleeding
- hemorrhagic events
- hypersensitivity
- Reye’s syndrome
What are the two irreversible P2Y12 inhibitors we need to know?
Clopidogrel (Plavix) and Prasugrel (Effient)
What are the two reversible P2Y12 inhibitors we need to know?
Ticagrelor (Brilinta) and Cangrelor (Kengreal)
The age cut-off for aspirin use is ______ years old.
18 years
Clopidogrel (Plavix) is one of the most commonly used antiplatelet agents. This drug is a ________________ prodrug.
Theinopyridine
What is the dosing for clopidogrel (Plavix)?
300-600 mg PO loading dose (typically given in cath lab) following by 75 mg PO daily with or without food.
Those who are poor _________ metabolizers cannot convert clopidogrel to it active form making this drug ineffective.
CYP2C19
What are the common adverse effects of clopidogrel?
Purpura (bleeding and clotting disorder), headache, chest pain, diarrhea, rash
What are the rare but serious adverse effects of clopidogrel?
TTP which is thrombotic thrombocytopenia purpura (purple rash like)
What is the black box warning associated with clopidogrel?
Poor CYP2C19 metabolizers have a greater risk for CV events following ACS or PCI.
What are the major drug interactions with clopidegrel?
Interacts with inhibitors of CYP2C19:
Omeprazole
Cimetidine
Esomeprazole
Fluvoxamine
Amiodarone
CCBs
Grapefruit juice
GAP CCF
__________ is also a thienopyridine prodrug.
Prasugrel
What is the brand name for prasugrel?
Effient
T or F: The onset of action for Prasugrel is dependent on the loading dose.
True. A 60 mg loading dose would work in less than 30 minutes
______ and ________ enzymes convert prasugrel to its active form in the liver.
CYP3A4 and CYP2B6
What is the main indication for use of prasugrel?
Reduce future thrombotic cardiovascular events in those with acute coronary syndrome managed with percutaneous coronary intervention (PCI).
What is the dosing for prasugrel?
10 mg daily after a 60 mg loading dose
(5 mg daily is BW less than 60 kg)
What are the 3 adverse effects associated with prasugrel?
Bleeding
TTP (thrombotic thrombocytopenic purpura)
Increased risk for intracranial hemorrhage
What is the main contraindication for the use of prasugrel?
Prior TIA or CVA
What is the black box warning associated with Prasugrel?
Bleeding risk and especially those with a history of TIA/CVA.
What is the MOA of reversible P2Y12 inhibitors like Ticagrelor and Cangrelor?
They are non-competitive and reversible inhibitors of the P2Y12 receptor on platelets.
Ticagrelor is a prodrug as well that is metabolized into its active metabolite via __________ and ________.
CYP3A4 and CYP3A5
T or F: The onset of action of Ticagrelor is dose dependent.
True. Typically a loading dose of 180 mg is given and it works in about 30 minutes.
What are the adverse effects associated with Ticagrelor?
Bleeding, dyspnea, ventricular pauses, dizziness, and nausea
What is the black box warning associated with Ticagrelor?
Do not use in patients with active bleeding or those who have history of an intracranial hemorrhage.
Aspirin doses above 100 mg daily reduces the effectiveness of ticagrelor and should be avoided.
T or F: Aspirin doses greater than 200 mg reduces the effectiveness of Ticagrelor and should therefore be avoided.
False. Aspirin doses greater than 100mg should be avoided with Ticagrelor.
What are the main drug interactions with Ticagrelor?
Avoid with strong CYP3A4 inducers and inhibitors
40 mg dose limit with lovastatin and simvastatin
Digoxin
Aspirin over 100 mg
T or F: There is no specific method for switching between the different P2Y12 inhibitors.
False. There is a chart method that is used to transition people to different medications within this class.
Why is dual-antiplatelet therapy often given Post-MI?
Stents placed after MIs are highly likely to trigger platelet aggregation at that site and giving two agents hitting two different targets can help decrease that risk.
What are the two typical combination therapies given post-MI for anti-platelet effects?
Thienopyridine (irreversible P2Y12 inhibitor) and aspirin
Ticagrelor and aspirin
What is the brand name for Ticagrelor?
Brilinta
What is the brand name for Cangrelor?
Kengreal
What is unique about the medication Cangrelor?
It has an onset of action of 2 minutes and a half-life of 3-6 minutes. This allows for platelet function to be restored 1 hour after discontinution.
What is the dosing for Cangrelor?
30 mcg/kg IV bolus followed by 4 mcg/kg/min IV infusion
What is the major drug interaction with Cangrelor?
Administer clopidogrel and prasugrel (irreversible P2Y12 inhibitors) AFTER a cangrelor infusion is discontinued.
What are the 4 common adverse reactions associated with cangrelor use?
Bleeding, dyspnea, worsening renal function, and hypersensitivty
What is the protease-activated receptor-1 (PAR-1) antagonist we need to know?
Vorapaxar (Zontivity)
What is the MOA of Vorapaxar, a PAR-1 antagonist working at the level of platelet aggregation?
It blocks thrombin and thrombin-receptor agonist peptide (TRAP) therefore reducing platelet aggregation.
What is unique about the drug Vorapaxar (Zontivity)?
It takes a long time for it to leave the body and it lasts a long time
What is the dosing for Vorapaxar?
2.08 mg PO daily
Typically used with aspirin or clopidogrel
What are the black box warnings associated with Vorapaxar?
Do not use in those with a history of stroke, TIA, intracranial hemorrhage, or active bleeding. This medication can increase the risk for fatal bleeding.
What drugs interact with Vorapaxar?
Strong CYP3A4 inducers and inhibitors
What are the two GbIIb/IIIa inhibitors we need to know?
Tirofiban (Aggrastat) and Eptifibatide (Integrilin)
What is the MOA of the GbIIb/IIIa inhibitors?
Tirofiban (Aggrastat) and Eptifibatide (Integrilin) inhibit GbIIb/IIIa on the platelets to stop cross-linkage.
What are the adverse reactions associated with GbIIb/IIIa inhibitors?
Bleeding, intracranial hemorrhage, stroke, and thrombocytopenia
What is the MOA for the medication called Dipyridamole (Persantine)?
This is an anti-platelet agents that is a vasodilator that inhibits platelet function by inhibiting adenosine uptake and cGMP phosphodiesterase complex.
What are the indications for use for Dipyridamole (Persantine)?
Cerebrovascular ischemia with aspirin
Prosthetic heart valves with warfarin
What is the dosing for Dipyridamole (Persantine)?
75-100 mg 4x day as an adjunct to usual warfarin therapy
What is the MOA for the medication called Cilostazol (Pletal)?
This is an antiplatelet agents that is a phosphodiesterase III inhibitor.
What is the dosing for Cilostazol (Pletal)?
It is used to treat intermittent claudication at doses of 100 mg PO BID
What is the contraindication and black box warning for Cilostazol (Pletal)?
Contraindicated for patients with heart failure of any severity.
What are the 3 fibrinolytic agents we need to know?
Alteplase (Activase/Cathflo)
Reteplase (Retavase)
Tenecteplase (TNKase)
What is the natural body process of breaking down a clot?
Normally the endothelial cells secrete tissue plasminogen factor (t-PA) at the site of injury which binds to fibrin. This action converts plasminogen to plasmin and the plasmin dissolves and digests the fibrin.
________ and ________ inactivate t-PA after a clot has been naturally busted.
PAI-1 and PAI-2
__________ inactivates plasmin to stop digesting fibrin in a clot.
alpha2-antiplasmin
Rank the 3 fibrinolytics from least to most selective.
Reteplase<Alteplase<Tenecteplase
What are the absolute 4 contraindications where fibrinolytics can not be used?
Active internal bleeding
Suspected aortic dissection
Known intracranial neoplasm (tumor)
History of hemorrhagic cerebrovascular accident (CVA) in the last 1 year
Factor I in the coagulation cascade is also known as __________.
Fibrinogen
Factor II in the coagulation cascade is also known as __________.
Prothrombin
Factor III in the coagulation cascade is also known as __________.
Tissue factor
Warfarin acts on what 4 factors in the coagulation cascade?
Factor II (prothrombin, 60 hr half life)
Factor VII
Factor IX
Factor X
What are the three type of thrombi?
White, red, and fibrin deposits in capillaries
What is a white thrombus?
White thrombi are platelet rich and typically seen in high pressure high flow arteries.
What is a red thrombus?
Red thrombi are mainly composed of RBCs and fibrin. They are typically seen in low pressure veins and slow flow areas.
What is the minimum amount of time when bridging to warfarin?
5 days. Make sure to check INR
How is Apixaban bridged to warfarin?
Start the warfarin and stop the apixaban 3 days later.
For continuous anticoagulation, stop the apixaban and start LMWH and warfarin at the time the DOAC would have been due. Stop the LMWH when INR is within therapeutic range.
How is rivaroxaban/ apixaban bridged to warfarin?
Can start to warfarin and stop DOAC 3 days later
or for continuous anticoagulation
Stop the DOAC and start LMWH and the warfarin at the time the DOAC would have been due. Then stop the LMWH when INR is within therapeutic range.
If it is just prophylaxis for VTE, how much apixaban is given?
2.5 mg PO BID
How should warfarin be transitioned to a DOAC?
Discontinue the warfarin and start the DOAC (once INR is less than 3) at the next time that the warfarin would have been due. If INR is greater than 3, stop the warfarin and check INR daily until less than 3 and then start the DOAC.
If someone has an active GI bleed and need to be anticoagulated, what medication can they be given?
NO medication. They need to stick to non-pharm options.
Which of the following is an intrinsic anticoagulant?
A. Factor II
B. Protein S
C. Fibrin
D. Thrombin
B. Protein S
What is the MOA of dabigatran?
Inhibits factor IIa (direct thrombin inhibitor)
Which of the following medications does not require renal dosing?
A. Enoxaparin
B. Heparin
C. Fondaparinux
D. Dabigatran
B. Heparin (used in dialysis)
If parenteral anticoagulation can not be used for someone with end-stage renal disease/ dialysis, what parenteral anticoagulant should be used?
Apixaban
What would be important to monitor in a pregnant woman on LMWH like Enoxaparin?
Anti-Xa. Pregnancy is a condition we want to monitor with this as volume of distribution is changing.
Which class of medications prevents platelet aggregation by serving as receptors for fibrinogen and vWF?
A. P2Y12 inhibitors
B. GP IIb/IIIa inhibitors
C. tPAs
D. PAR-1 antagonist
B. GP IIb/IIIa inhibitors
Which of the following is a symptom of a DVT?
A. Bilateral leg swelling
B. Elevated INR
C. Palpable cord
D. Post-thrombotic syndrome
C. Palpable cord
Select the appropriate DVT prophylaxis dosing?
A. Heparin 5000 units SubQ TID
B. Enoxaparin 10mg SubQ BID
C. Rivaroxaban 60 mg PO daily
D. Fondaparinux 20 mg PO daily
A. Heparin 5000 Units SubQ TID
Which of the following can be given as a continuous IV infusion?
A. Heparin
B. Warfarin
C. Enoxaparin
D. Fondaparinux
A. Heparin
Enoxaparin can be given IV but it is not continuous.
Which of the following medications requires 5-10 days of parenteral anticoagulation upon initiation?
A. Apixaban
B. Dabigatran
C. Rivaroxaban
D. Enoxaparin
B. Dabigatran
(TX for DVT or PE, if CrCl greater than 30, after 5-10 days of parenteral anticoagulation, begin 150 mg PO BID of dabigatran (Pradaxa).
Edoxaban is for this as well
Which of the following is true regarding extended therapy?
A. Increase dose after second VTE
B. Do not use for second VTE
C. Consider decreasing dose during extended therapy
D. Everyone should have extended therapy
C. Consider decreasing dose during extended therapy
Which of the following can be used for DVT prophylaxis when a patient has an active bleed?
A. Heparin
B. Sequential compression devices
C. Warfarin
D. IVC filter
B. Sequential compression devices
Which of the following is NOT a common location for a DVT?
A. Lower extremity
B. Upper extremity
C. Pulmonary arteries
D. Hemodialysis access sites
C. Pulmonary arteries
Which of the following is not a major risk factor for VTE?
A. Major surgery
B. Obesity
C. Pregnancy
D. Hypotension
D. Hypotension
Which of the following type of VTE is considered provoked?
A. VTE after recent surgery
B. VTE with no identifiable cause
C. VTE in patient with Factor V Leiden
D. VTE in person with history of clots
A. VTE after recent surgery
What clinical scoring system is commonly used to assess the risk of VTE in hospitalized medical patients?
Padua prediction score. High risk for VTE with the Padua score is 4 or higher.
What clinical scoring system is commonly used to assess risk of VTE in surgical patients?
Caprini Score
0-4 means low risk
5-8 means moderate risk
9 or greater means high risk
Which of the following can increase a patients sensitivity to warfarin?
A. Age greater than 75
B. Congestive HF
C. Malnutrition
D. All of the above
D. All of the above
What is the approved antidote for Rivaroxaban and apixaban overdose?
Andexanet alfa
Which of the following drugs strongly increases the effects of warfarin?
a) Fluconazole
b) Amiodarone
c) Bactrim (TMP-SMX)
d) All of the above
D. All of the above
Which of the following can reduce the effectiveness of warfarin?
a) Ginkgo biloba
b) St. John’s Wort
c) Garlic
d) Cranberry
D. St. John’s Wort
Which of the following DOACs require administration with food to ensure proper absorption?
a) Apixaban
b) Dabigatran
c) Rivaroxaban
d) Edoxaban
C. Rivaroaxaban
Which of the following anticoagulants should not be used in patients with a mechanical heart valve?
a) Warfarin
b) Apixaban
c) Edoxaban
d) Dabigatran
D. Dabigatran
A 68-year-old male with atrial fibrillation is started on warfarin. After five days of therapy, his INR is only 1.3. What is the most likely reason for this delayed response?
a) Warfarin primarily affects fibrinogen, which has a long half-life.
b) Factor II (prothrombin) has a long half-life, delaying full anticoagulation.
c) Warfarin is rapidly metabolized by CYP2C9, reducing its efficacy.
d) The patient likely has an undiagnosed vitamin K deficiency.
B. Factor II has a long half-life therefore delaying full anticoagulation till factor II is depleted.
A patient on warfarin for DVT prophylaxis has an INR of 6.2 but no active bleeding. What is the most appropriate management?
a) Administer IV vitamin K and fresh frozen plasma.
b) Hold warfarin and administer 1–2.5 mg of oral vitamin K.
c) Immediately administer prothrombin complex concentrate (PCC).
d) Continue warfarin at a reduced dose and recheck INR in 24 hours.
B. Hold the warfarin and administer 1-2.5 mg of oral vitamin K
Note this was at CHATGPT question. After further discussion with the entity, it was decided that holding warfarin and monitoring INR would be more appropriate as the patient is not actively bleeding.
Which of the following statements best explains why edoxaban should not be used in patients with CrCl > 95 mL/min?
a) Increased renal clearance leads to lower plasma concentrations, reducing efficacy.
b) Rapid metabolism by CYP3A4 causes subtherapeutic drug levels.
c) The drug is highly protein-bound, preventing renal elimination.
d) Edoxaban increases the risk of spontaneous bleeding in patients with high renal function.
A. Increased renal clearance leads to lower plasma concentrations, reducing efficacy.
A 72-year-old patient with a history of atrial fibrillation and chronic kidney disease (CrCl = 28 mL/min) is prescribed apixaban. What dose adjustment, if any, is required?
a) Reduce the dose to 2.5 mg BID if the patient also meets weight and age criteria.
b) Increase the dose to 10 mg BID for better efficacy.
c) No adjustment is needed for this renal function.
d) Discontinue apixaban and switch to warfarin.
A. Reduce the dose to 2.5 mg BID if the patient also meets weight and age criteria.
A patient with a history of HIT (heparin-induced thrombocytopenia) needs anticoagulation for DVT treatment. Which is the safest option?
a) Enoxaparin
b) Fondaparinux
c) Warfarin
d) Argatroban
D. Argatroban
A 56-year-old female with a mechanical heart valve and a history of DVT is switched from warfarin to a DOAC due to INR fluctuations. What is the most appropriate recommendation?
a) Switch to apixaban, as it has a lower bleeding risk than warfarin.
b) Switch to rivaroxaban, as it has been studied in mechanical heart valves.
c) Continue warfarin, as DOACs are contraindicated in mechanical heart valves.
d) Stop anticoagulation completely if the INR is well-controlled.
C. Continue warfarin, as DOACs are contraindicated in mechanical heart valves
A patient on apixaban is also taking a strong CYP3A4 and P-gp inducer. What is the most appropriate action?
a) Increase the apixaban dose to compensate for increased metabolism.
b) Continue apixaban at the same dose, monitoring renal function closely.
c) Switch to warfarin, as apixaban levels will be reduced.
d) Add an antiplatelet agent to maintain efficacy.
C. Switch to warfarin. APixaban and rivaroxaban should be avoided in those taking a strong p-gly and CYP3A4 inducer/inhibitor.
Which anticoagulant is most appropriate for a patient with cancer-associated VTE?
a) Warfarin
b) Low-molecular-weight heparin (LMWH)
c) Dabigatran
d) Aspirin
B. LMWH
A 72-year-old male with atrial fibrillation is started on warfarin for stroke prevention. His baseline INR is 1.0. After five days on 5 mg daily, his INR is 1.6. He has stable kidney function (CrCl = 65 mL/min) and no bleeding symptoms. What is the best next step?
a) Increase warfarin to 7.5 mg daily and recheck INR in 2 days.
b) Continue warfarin 5 mg daily and recheck INR in 3–5 days.
c) Discontinue warfarin and initiate a direct oral anticoagulant.
d) Administer a loading dose of 10 mg to reach therapeutic INR more quickly.
B. Continue warfarin 5 mg daily and recheck INR in 3-5 days.
A 65-year-old female with a history of DVT and chronic kidney disease (CrCl = 28 mL/min) is prescribed rivaroxaban. What is the most appropriate dosing recommendation?
a) Rivaroxaban 10 mg once daily
b) Rivaroxaban 15 mg once daily
c) Switch to warfarin due to renal dysfunction
d) No change; rivaroxaban does not require dose adjustment
C. Switch to warfarin due to renal dysfunction. Rivaroxaban is contraindicated in those with CrCl less than 30. Warfarin can be used but generally, apixaban is saved for those with severe renal dysfunction.
A 50-year-old patient with a newly diagnosed DVT is started on unfractionated heparin and warfarin simultaneously. After 3 days, his INR is 2.3. What is the most appropriate next step?
a) Discontinue heparin and continue warfarin alone
b) Continue both heparin and warfarin for at least 2 more days
c) Switch to a DOAC for better long-term adherence
d) Reduce warfarin dose and maintain heparin for 5 more days
B. Continue heparin and warfarin for at least 2 more days. This is because warfarin requires at least 5 days of overlap with heparin to ensure full anticoagulation due to it delayed effect on factor II.
How are DOACs bridged to parenteral anticoagulants?
Stop the DOAC and start the parenteral at the same time the DOAC would have been given.
T or F: FDA‐approved prescribing information requires no dose adjustment for apixaban in patients with renal impairment alone, including patients with end‐stage renal disease and those on hemodialysis. However, to qualify for apixaban dose adjustment, one must meet at least 2 of the following characteristics; just remember your ABCs:
1.Age ≥80 years.
2.Body weight ≤60 kg.
3.Creatinine (serum) ≥1.5 mg/dL.
True
Those with triple positive antiphospholipid syndrome will fail DOACs and need to be on ___________.
Warfarin
What symptoms are categorized as a massive PE?
- Sustained hypotension (less than 90 systolic for 15 + minutes)
- Pulselessness
- Persistent bradycardia
What symptoms are categorized as a submassive PE?
- Hemodynamically stable possibly with RV dysfunction
If a submassive PE is suspected, a stat _______ for a diagnosis needs to be done as well as an _________ for possible RV dysfunction.
CTPA
EKG
In those with cancer, ________ are preferred during the treatment phase after a VTE.
DOACs
In those with cancer, specifically if they have luminal GI malignancies, __________ or ___________ should be used to decrease the risk for bleeding.
Apixaban
LMWH
What is the first-line preferred medication for long-term anticoagulation?
DOACs
What is the second-line preferred medication for long-term anticoagulation?
Warfarin
What is the 3rd line preferred medication for long-term anticogaultion?
LMWH (anti-Xa goal 0.5-1)
The target INR for those with antiphospholipid syndrome on warfarin is ________.
2.5
An inpatient on warfarin needs to have their INR monitored at least _________.
Daily
A person on warfarin right after hospital discharge needs their INR checked if stable in ______-______ days. If unstable they need INR checked in 1-3 days after discharge.
3-5 days
During the first month on warfarin therapy, INR needs to be checked at least ________.
Weekly
If parenteral agents must be avoided for anticoagulation, what two medications are preferred for use?
Rivaroxaban and apixaban
If liver disease or coagulopathy, which anticoagulant is preferred?
LMWH like enoxaparin is preferred. If patient has child-pugh score of A, DOACs can be used.
T or F: In the extended phase of anticoagulation, DOAC dose reductions are now recommended. This include making apixaban 2.5 mg PO BID and rivaroxaban 10 mg PO daily.
True! After the first 3 months of therapy (treatment phase), it may be appropriate to lower the DOAC dose.
Provoked VTEs can be treated for only the treatment period (3 months). However, in what situation is extended therapy considered?
Unprovoked VTEs (High risk for bleeding is 3 months only but medium to low risk is extended therapy). Extended phase with DOACs is recommended.
Those with cancer and VTE should be on __________ therapy for anticoagulation.
Extended
T or F: Aspirin is reasonable therapy for an extended treatment period following a VTE.
False. Aspirin is not reasonable for this reason. Aspirin may help prevent the recurrence of VTEs.
In order to determine if a patient is experiencing type 2 immune-mediated HIT, _________ scoring is used.
4T
6-8= high likelihood
4-5= intermediate
0-3= low
What is the black box warning associated with warfarin?
Bleeding risk!
