Chapter 34: Anticoagulation Flashcards
Coagulation involves activation of ____ & ____
Platelets
the clotting cascade
All of the clotting factors have an inactive and active form. Once activated, a clotting factor will activate the next clotting factor in the sequence until ___ is formed
fibrin
a = active
Which drugs are direct factor Xa inhibitors
rivaroXAban
apiXAban
edoXAban
betriXAban
Which drug is an indirect factor Xa inhibitor
Fondaparinux
Which drugs are IV direct thrombin inhibitors & which drug is an oral direct thrombin inhibitor
IV - argatroban, bivalirudin
PO- dabigatran
What are the major differences between warfarin and DOACs
- DOACs = less DDI, less or comparable bleeding, and a shorter half-life compared to warfarin
- DOACs are dosed based on the indication and kidney/liver function while warfarin is dosed based on INR
- Use DOACs for stroke ppx in AFib if the CHA2DS2-VASc score is >/= 2 (men) or >/= 3 (women); BUT if there is moderate-severe mitral stenosis or mechanical heart valve, use WARFARIN
- use DOACs in VTE prevetion except in anti-phospholipid syndrome use warfaring
Primary organization that publishes guidelines for anticoagulation
American College of Chest Physicians (CHEST)
Warfarin drug class
Vitamin K antagonist
Vitamin K is required for the carboxylation (activation) of which clotting factors
II, VII, IX and X
2, 7, 9, 10 - all inhibited by warfarin
INR is affected by many drugs and changes in
dietary vitamin K
UFH, LMWH, and fondaparinux MOA
work by binding to antithrombin (natural anticoag) –> increase activity of antithrombin –> inactivates thrombin (factor IIa) and other proteases (like factor Xa) involved in blood clotting & prevents the conversion of fibrinogen to fibrin
LMWH inhibit Xa > UFH
Fondaparinux is selective towards Xa
Direct thrombin inhibitors MOA
block thrombin directly (factor IIa), decreasing the amount of fibrin available for clot formation
Why are the IV direct thrombin inhibitors (argatroban and bivalirudin) clinically important?
They do not cross-react with HIT antibodies
What is the DOC once HIT develops in the hospital setting
IV argatroban
Dabigatran brand name
Pradaxa
Which organization requires policies and protocols to properly initiate and manage anticoagulant therapy
The Joint Commission’s National Patient Safety Goals
Which lab could signify that bleeding is occurring while on an anticoagulant
an acute drop in hemoglobin
≥ 2 g/dL
Which drugs/conditions can cause bruising
Chronic steroids, thrombocytopenia/clotting disorder, Cushing’s syndrome, malnutrition, fracture/sprain, infection
Which drugs/conditions can cause a hematoma
on abdomen from LMWH injection that was rubbed (do not rub), or an epidural or spinal hematoma in a patient using LMWH or DOAC who is given neuraxial anesthesia or a spinal punture
Esophageal bleeding occurs from
varices (bleeding veins, with liver cirrhosis), chronic reflux (esophagitis, Barrett’s)
How does duodenal bleeding occur
from ulcers (e.g., H. pylori-induced)
The farther the bleeding site is from the anus, the ___ (lighter/darker) the stool
darker
UFH prophylaxis of VTE dose
5000 units SC Q8-12H
UFH treatment of VTE dose
80 units/kg IV bolus; 18 units/kg/hr infusion
UFH treatment of ACS/STEMI dose
60 units/kg IV bolus; infuse 12 units/kg/hr
Which weight is used for dosing UFH & LMWH
TBW
UFH CI
uncontrolled active bleeding
hx of HIT, HSR pork
UFH side effects
bleeding (epistaxis, ecchymosis, gingival, GI), thrombocytopenia, HIT, hyperkalemia
UFH monitoring
aPTT or anti-Xa level, platelets, Hgb, Hct
check 6h after initiation & q6h until therapeutic
When should you check aPTT level while using UFH
6 hours after initiation and every 6 hours until therapeutic
then q24h
What is the therapeutic range of aPTT
1.5-2.5 x control
A decrease in platelets > __% from baseline suggests HIT
50%
UFH antidote
protamine
Continuous IV infusions are common for treating VTE and ACS because heparin has
a very short half-life
What is HepFlush used for
to keep IV lines open
UFH warnings
Fatal medication errors, especially in neonates, occurred when the incorrect heparin strength (higher dose) was chosen
The anti-factor ___ activity in LMWH is much greater than the anti-factor __ activity
Xa
IIa
Enoxaparin ppx of VTE dose & dose if CrCl < 30 mL/min
- 30 mg SC Q12H or 40 mg SC daily
- CrCl < 30 mL/min: 30 mg SC daily
Enoxaparin treatment of VTE and UA/NSTEMI & dose if CrCl < 30 mL/min
1 mg/kg SC Q12H
(or 1.5 mg/kg SC daily only for inpatient VTE treatment)
-CrCl < 30 mL/min: 1 mg/kg SC daily
using TBW
LMWH treatment for STEMI in patients:
< 75 years
CrCl < 30 mL/min
- 30 mg IV bolus plus a 1 mg/kg SC dose (then 1mg/kg q12h)
- CrCl < 30 mL/min: 30 mg IV bolus plus a 1 mg/kg SC dose (then 1mg/kg qd)
using TBW
LMWH treatment for STEMI in patients:
> 75 years
- > 75 years: NO bolus (0.75 mg/kg q12h)
- CrCl < 30 mL/min: 1 mg/kg SC daily
LMWH CI
Hx of HIT, active major bleed
LMWH boxed warnings
risk of hematomas and subsequent paralysis with neuraxial anesthesia (epidural, spinal)
LMWH side effects
Bleeding, anemia, injection site rxns (e.g., pain, bruising, hematomas), ↓ platelets
____ level monitoring is recommended in pregnancy with LMWH
Anti-Xa
no monitoring required in most patients
Obtain peak anti-Xa levels __ hours post SC dose for enoxaparin
4
LMWH antidote
protamine
T/F: the air bubble from LMWH syringe should be expelled
False (can cause loss of drug)
HIT is an immune-mediated __ drug reaction that has high risk of venous and arterial thrombosis.
IgG
If left untreated, HIT can lead to a ____ state causing many complications including heparin-induced thrombocytopenia and thrombosis (HITT). HITT leads to amputation, post-thrombotic syndrome and/or death.
prothrombic
How is a diagnosis of HIT made
an unexplained drop in platelet count (>50% drop from baseline)
If a patient is on warfarin and diagnosed with HIT, what should be done
d/c the warfarin and administer Vitamin K
wait until Plts > 150,000 before restarting
In patients with HIT, which anticoags are recommended
non-heparin anticoagulants (in particular, argatroban)
In a patient with HIT, warfarin should not be started until the platelets have recovered to
≥ 150,000/mm3
overlap with non heparin AC
In patients with HIT, what is the preferred anticoag if urgent cardiac surgery or PCI is required
bivalirudin
Fondaparinux is a synthetic ____
pentasaccharide
Apixaban brand name
Eliquis
Rivaroxaban brand name
Xarelto
If taking rivaroxaban 15 mg BID and miss a dose, how can it be taken?
two 15 mg tabs taken at once (take immediately together to ensure intake of 30 mg/day)
then resume regular schedule
Apixaban dosing for nonvalvular AFib (stroke ppx)
5 mg BID
2.5 mg BID if patient has at least 2 of the following:
- age ≥ 80
- ≤ 60 kg
- SCr ≥ 1.5 mg/dL
Apixaban dosing for treatment of DVT/PE
10 mg PO BID x 7 days, then 5 mg PO BID
Rivaroxaban doses ≥ ___mg must be taken with food
15 mg
Rivaroxaban dosing for treatment of DVT/PE
& dosing for CrCl < 30 mL/min
- 15 mg PO BID x 21 days, then 20 mg PO daily
- Avoid use in CrCl < 30 mL/min
When should edoxaban dosing for nonvalvular AFib (stroke ppx) be avoided
CrCl > 95 mL/min
Treatment of DVT/PE with edoxaban should be started after ___-___ days of parenteral anticoagulation
5-10 days
Boxed warning for all DOACs, fondaparinux, oral direct thrombin inhibitors & LMWH
patients receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk of hematomas and subsequent paralysis
Boxed warning for Edoxaban only
reduced efficacy in nonvalvular AFib patients with CrCl > 95 mL/min
DOACs are not recommended with
prosthetic heart valves or antiphospholipid syndrome
T/F: DOACs do not require monitoring of efficacy
True
What is the antidote for apixaban and rivaroxaban
andexanet alfa (Andexxa)
Fondaparinux CI
CrCl < 30 mL/min
Avoid use of apixaban & rivaroxaban with strong dual inducers of ____ & ____
CYP3A4 and P-gp (e.g, carbamazepine, phenytoin, rifampin, St. John’s Wort)
Avoid use of rivaroxaban with strong inhibitors of ____ & ____
3A4 and P-gp (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir and conivaptan)
Converting from warfarin to another oral anticoagulant
Remember: READ
- Rivaroxaban when INR is < 3
- Edoxaban when INR is ≤ 2.5
- Apixaban when INR is < 2
- Dabigatran when INR is < 2
Converting from an oral Xa inhibitor (apixaban, edoxaban, and rivaroxaban) to warfarin:
- Stop Xa inhibitor. Start parenteral anticoagulant and warfarin at next scheduled dose
Converting from dabigatran to warfarin:
Start warfarin 1-3 days before stopping dabigatran
refer to dabigatran labeling for details
What should be done if one misses a dose of dabigatran
Take immediately unless it is within 6 hours of next scheduled dose
Dabigatran should be started for DVT/PE treatment __-__ days after starting parenteral anticoagulation
5-10
Dabigatran CI
mechanical prosthetic heart valve
Dabigatran SE
Dyspepsia, gastritis-like sx, bleeding (including GI bleeding)
T/F: dabigatran does not require monitoring of efficacy
True
Dabigatran should be dispensed ____ and discard ___ months after opening
in its original container
4
T/F: dabigatran capsules should not be broken, chewed, crushed or opened
True
Dabigatran should not be administered via
NG tube
Argatroban and bivalirudin are used in patients at risk for ___
HIT
Warfarin MOA
Competitively inhibits the C1 subunit of the VKORC1 enzyme complex, thereby reducing the regeneration of vitamin K epoxide and causing depletion of active clotting factors II, VII, IX and X and proteins C and S
Warfarin brand name
Coumadin and Jantoven
Which enantiomer of warfarin is more potent
S-enantiomer
Warfarin dosing for healthy outpatients
≤ 10 mg daily for first 2 days, then adjust dose per INR values
Lower doses of ≤ 5 mg of warfarin are indicated for which patients
elderly, malnourished, taking drugs which can ↑ warfarin levels, liver disease, HF, or have a high risk of bleeding
Warfarin CI
Pregnancy (except with mechanical heart valves at risk for thromboembolism)
Warfarin warnings
Tissue necrosis/gangrene, HIT, presence of 2C9*2 or *3 alleles and/or polymorphism of VCORC1 gene may increase bleeding risk
Warfarin SE
Bleeding/bruising, skin necrosis, purple toe syndrome
What is the goal INR of warfarin for most indications (DVT, AFib, biprosthetic mitral valve, mechanical aortic valve, antiphospholipid syndrome)
2-3
What is the goal INR of warfarin for high-risk indications such as a mechanical mitral valve or 2 mechanical heart valves
2.5-3.5
Warfarin antidote
Vitamin K
Warfarin tablet colors
- Remember: Please Let Greg Brown Bring Peaches To Your Wedding*
- Pink (1mg)
- Lavender (2 mg)
- Green (2.5 mg)
- Brown/Tan (3 mg)
- Blue (4 mg)
- Peach (5 mg)
- Teal (6 mg)
- Yellow (7.5 mg)
- White (10 mg)
Which foods are high in vitamin K
- Broccoli
- Brussel sprouts
- Cabbage
- Spinach
- Tea
Warfarin is a substrate of CYP
2C9
interactions with 2C9 have greatest impact on warfarin
Which drug can cause a large decrease in INR
rifampin
When starting amiodarone, the dose of warfarin should be decreased by
30-50%
Which key drugs can increase INR
Amiodarone, fluconazole, metronidazole, TMP/SMX
Which dietary supplement can decrease effectiveness of warfarin
St. John’s Wort
2C9 inducer
Which dietary supplement can increase the bleeding risk of warfarin
- “The 5 Gs”: garlic, ginger, gingko, ginseng, glucosamine
- High doses of fish oils, willow bark and wintergreen oil
In patients with acute DVT/PE, start warfarin on the same day as the parenteral anticoagulant (e.g., enoxaparin or UFH) and continue anticoagulants for a minimum of __ days and until the INR is > __ for at least __ hrs. Both criteria must be met
5
2
24
For patients with consistently stable INRs on warfarin therapy, INR testing can be done up to every __ weeks rather than every 4 weeks
12
Antidote for LMWH/UFH reversal
Protamine sulfate
For IV UFH reversal, 1 mg of protamine will reverse ~__ units of heparin
100
Since UFH has a very short half-life, reverse the amount of heparin given in the last __-__ hours; max dose __ mg
2-2.5h
50 mg
For LMWH (enoxaparin) reversal, __ mg of protamine per __ mg of enoxaparin
1:1
What is the antidote for dabigatran reversal
Idarucizumab
Idarucizumab brand name
Praxbind
Antidote for apixaban and rivaroxaban reversal
Andexanet alfa
Andexanet alfa brand name
Andexxa
Vitamin K or phytonadione brand name
Mephyton
Vitamin K or phytonadione BW
hypersensitivity reactions
Why is the SC and IM route of Vitamin K not recommended
- SC: variable absorption
- IM: risk of hematoma
use PO or IV
Warfarin antidotes for reversal
Vitamin K or phytonadione, Kcentra, NovoSeven RT
Factor VIIa Recombinant brand name
NovoSeven RT
KCentra must be administered with
Vitamin K
KCentra contains
Factors II, VII, IX, X, Protein C, Protein S
IV injection of Vitamin K must be
infused slowly
Vitamin K oral dose range
2.5-5 mg
What to do with Vitamin K if INR is above therapeutic range but < 4.5 without bleeding
Reduce or skip warfarin dose. Monitor INR
What to do with Vitamin K if INR is 4.5-10 without bleeding
Routine use of vitamin K is not recommended if no evidence of bleeding. Hold 1-2 doses of warfarin
What to do with Vitamin K if INR is >10 without bleeding
Hold warfarin. Give oral vitamin K 2.5-5 mg even if not bleeding
What to do with vitamin K if patient has major bleeding from warfarin
Hold warfarin therapy. Give vitamin K 5-10 mg by slow IV injection and four-factor prothrombin complex concentrate (PCC)
Stop warfarin therapy approximately __ days before major surgery
5
In patients with a mechanical heart valve, AFib or VTE at high risk for thromboembolism, bridging therapy with ___ or ___ is recommended
LMWH or UFH
D/c therapeutic-dose SC LMWH __ hrs before surgery
24
DVTs can be diagnosed with
an ultrasound
RF for the development of VTE
- Acute medical illness, Immobility, Previous VTE
- Cancer or chemo
- Pregnancy and postpartum period
- Estrogen-containing meds or SERMs
- EPO-stimulating agents
- Obesity
- surgery, trauma
- Inherited or acquired thrombophilia (e.g., antithrombin deficiency, Factor V Leiden, antiphospholipid syndrome, Protein C or S deficiency)
Any VTE that is caused by surgery or a reversible risk factor should be treated for __ months
3
For pts without cancer, which drugs are preferred over warfarin for the first 3 months of tx for a DVT in the leg or a PE
dabigatran and the oral Factor Xa inhibitors (rivaroxaban, apixaban and edoxaban)
for cancer patients what oral anticoagulants should be used
Factor Xa inhibitors are preferred
Patients with mechanical heart valves have the highest risk for clotting/strokes and are treated with
warfarin
Anticoagulation for patients with AFib who will undergo cardioversion:
* AFib > 48 hrs or unknown duration: anticoagulation (if warfarin, target INR 2-3) for at least __ weeks prior to and __ weeks after cardioversion when normal sinus rhythm is restored
3
4
Anticoagulation for patients with AFib who will undergo cardioversion:
• AFib = 48 hrs duration undergoing elective cardioversion: start full therapeutic anticoagulation at presentation, do cardioversion, and continue full anticoagulation for at least __ weeks while pt is in normal sinus rhythm
4
CHA2DS2-VASc Scoring System
C – CHF…………………………………………………1 H - HTN…………………………………………………1 A – Age > 75 years …………………………….2 D – Diabetes ………………………………………..1 S2 – Prior stroke/TIA ………………………….2 V – Vascular Disease…………………………..1 (prior MI, PAD, aortic plaque) A – Age 65-74 years …………………………..1 S – Sex category, female…………………….1
HAS-BLED scoring system
H - HTN (1)
A - abnormal liver or kidney fxn (1-2)
S - prior stroke (1)
B - bleeding tendency or predisposition (1)
L - labile INR (if on warfarin) (1)
E - elderly (> 65 years) (1)
D - drugs (asa, NSAIDs), excessive alcohol use (1-2)
Which CHA2DS2-VASc Score indicates oral anticoagulation is recommended. DOACs recommended over warfarin
≥ 2 in males ≥ 3 in females
Where should lovenox be injected
abdomen
Important counseling point for lovenox
do not rub the site of injection
