VTE Part 3 Flashcards
Maintenance Dosing - Generalities
warfarin
• Maintenance Phase – when are you there?
– Clotting factors are at “steady state”
– Small warfarin dose changes in response to INRs out of range, unless changes that may impact warfarin are identified
• The full effect of a given dose may not be evidenced for 3 – 5 days
• Use weekly (even past 10 days) doses to guide future
change:
– Delayed effect of warfarin
– Response is NOT linear – if you double the dose, you won’t simply see a doubling of the INR
– Changes in dosing is slight (commonly 5 - 15% of weekly dose)
– Very common to take different amounts on different days
Dosing Chart (Target INR 2.5)
sklide 84
Factors Impacting the INR
Areas to Target for Patient Assessment
Assess:
- timing of impact
- chronicity of change
- Changes to Health - assess first
– Acute changes (fever, flu, diarrhea, etc.)
– Chronic Medical Condition Changes:
• Exacerbation of heart failure
• Alterations in thyroid function - Changes to Medications*
– Prescription, non-prescription, herbals
Drug Interactions:
1. Induction / Inhibition of
Cytochrome P450
• Major 2C9 –> know that inhibitors of 2C9 should not be used
• Minor 3A4, 1A2
2. Displacement of binding plasma proteins
3. Alterations in Vitamin K Status
4. Contributing to bleeding / clotting risk
- Changes to Lifestyle
– Vitamin K intake - impact INR, normal diet and if there is issue, then monitor diet
– Alcohol Consumption - drunk, INR get high, drink in moderation (1-2 drinks a day)
– Level of Activity - the more active, the more warfarin needed, significant changes
Warfarin Flow Sheet
don’t reduce more than 10% unless really sick
covid, reduce maintenance dose and check in 1 wk
MTh, monday, thursday
9 is all other days of wk
Reviewing the Individual Patient
• What is the most warfarin they have required? The
least? What is their ‘typical’ maintenance dose?
• Do they ‘bounce’ around in their therapeutic range?
• Are they typically ‘stable’ (within range) or not?
• Are there recurrent issues – frequent exacerbations of
CHF, ETOH use, non-compliance, etc.
1. Changes in health
2. Changes in medications
3. Changes in lifestyle
• HALLMARK Question: with the next INR, would you
rather have them come back a little high or a little low?
Generalities with Timing of INR
Assessment with Maintenance Dosing
• Make a conscious decision of interpretation, is it:
– reflective of a stable dose (most cases)
– clouded by a ‘hold’ or ‘bolus’ / ‘reload’ dose (if done within 7 days)
• Critically evaluate the timing between INRs
– My preference – if taking different doses 2-3 times per week, it will take 1.5 weeks (10 days) to see “steady state” or INR reflective of that maintenance dose
• Generally, if ‘stable’, INR testing is increased by 1 week intervals (maximum interval is 4-6 weeks)
– Reasons to test sooner – potential trend in results, result contradictory to clinical assessment
Critical INR Management
defined as?
Defined as an INR > 5.0
– Different labs, different cut-offs
• Laboratory pages ordering clinician
• WHO requires labs to perform QA testing between an INR of 1.5- 4.5 only
– What does an INR of 15.6 really mean???? instrumentaiton not acurate to report those
– Lab reports INR > 9
Critical INR Management:
3 things to look at
• Signs or symptoms of bleeding / unusual bruising or
Something more concerning ongoing
– Medical Attention vs. Ambulatory Management
• Clot vs Bleed Risk
– Immediate Critical INR Management
• Factor(s) Contributing to Critical INR
– Maintenance Dosing Post-Critical INR Management
Critical INR Management:
Ambulatory, Non-Bleeding Patient
4.5 - 10.0
> 10.0
the higher the INR, the longer it takes to decay, drop to therapeutic range
k2 antidotes
4.5 - 10.0: “… suggest against the routine use of Vitamin K.” (2B)
Omit 1-2 warfarin doses, consider Vitamin K PO 1-2.5 mg & reassess INR
> 10.0: “… suggest Vitamin K be administered.” (2C)
Hold warfarin, Vitamin K PO 2.5-5mg & reassess INR
Antidote for Warfarin Vitamin K Oral – works within 16-24 hours IV – begins to works in 6-8 hours SC – Not recommended IM – Not recommended
Prothrombin Complex Concentrate (factors II, VII, IX, X)
Temporary reversal of INR (within minutes)
Post-Critical INR Management
INR is now (near) Therapeutic, Then What?
• Acute, reversible cause identified – simply document an INR < 4.0 (depending on bleed & clot risk, whether vitamin K was given) and implement warfarin dosing similar to that prior to the inciting occurring [e.g., ethanol binge]
• Acute event that is now not reversible and going to continue (drug interaction) – document an INR < 4.0 (as above) and empirically decrease warfarin dosing based on experience / literature [e.g., fenofibrate initiation]
• No identifiable reason – document an INR < 4.0 (as above) then depending on clot vs bleed risk reduce maintenance dosing accordingly
– Generally speaking, frequency of assessment would differ amongst 3 strategies
Identify the incorrect statement.
Warfarin is an indirect anticoagulant that
has a delayed onset of action because:
1. It prevents the carboxylation of Vitamin K
dependent clotting factors, some of which
have long half lives
2. It only acts on clotting factors being
produced by the liver
3. It does not act on clotting factors already in
the circulation
4. It has a long half-life
- It has a long half-life
factor II has longest half life of 60 hours
Which statement is correct as it
applies to warfarin management?
- When newly starting warfarin, it is important to
check an INR once weekly. - Initiating warfarin alone in any patient creates a
hypercoagulable state. - Warfarin dose response is linear, if you double
the dose, you will essentially double the INR. - Changes in maintenance doses of warfarin
typically exceed 20%, allowing most patients to
take the same amount of warfarin each day.
. Initiating warfarin alone in any patient creates a
hypercoagulable state.
when is it clinically relevant
acute clot you are treating
Antithrombotic therapy for VTE
CHEST / ACCP Guidelines 2016
“In patients with DVT of the leg or PE and no cancer, as longterm (first 3 months) anticoagulant therapy, we suggest dabigatran, rivaroxaban, apixaban or edoxaban over VKA therapy (all Grade 2B). For those not treated with dabigatran, rivaroxaban, apixaban or edoxaban, we suggest VKA therapy over LMWH (Grade 2C)
DOAC is preferred
Oral Anticoagulation Therapy: Implementation
in Daily Practice
DOAC 12-14 hrs
warfarin no simple dosing
Monitoring with VTE
• Ensure appropriate drug / dose sequence, where applicable:
– Parenteral + Warfarin, then warfarin INR 2.0-3.0
– Rivaroxaban 15mg BID x 3 weeks then Rivaroxaban 20mg daily
– Apixaban 10mg BID x 7 days, then Apixaban 5mg BID
– LMWH x 5-10 days, then dabigatran 150mg BID (pharmacokinetic dose recommendation of 110mg BID if > 80yrs or >75 + risk factor)
– LMWH x 5-10 days, then edoxaban 60mg daily (30mg daily if CrCl 30-50mL/min or 15-30mL/min, < 60Kg or P-gp administration)
• Assessment of clinical improvement - ongoing:
– DVT: leg swelling, color, pain/tenderness, use/limitations
– PE: pain, breathing (SOB), right heart pressure, activity limitations
• Adherence, Reinforce Education, Labs (Renal Assessment, CBC- platelets if heparin)
• Duration of therapy evaluation (completion of long-term phase, what about the extension phase?)
