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240 Anticoagulation Therapy
https://t.me/med1917
TRANSITIONING BETWEEN PARENTERAL
ANTICOAGULANTS
•
During hospitalization, patients may require transition between parenteral
therapies or as a bridge to VKA (Table 10-8).
•
Consider differences in pharmacokinetic properties of UFH and LMWH (or
fondaparinux).
•
Avoid concurrent use of parenteral anticoagulant agents to ensure safety.
•
When transitioning from IV UFH to an alternative parenteral anticoagulant agent
with rapid onset of activity, it may be preferable to wait a selected period of time
before initiating the alternative therapy in patients at increased risk of bleeding.
•
Because of potential distractions and logistic considerations, consider stopping
the UFH at the same time as initiating any new anticoagulant unless an atypical
clinical situation is present.
TRANSITIONING FROM PARENTERAL
ANTICOAGULATION TO ORAL VKA THERAPY
•
For patients with active thrombosis, UFH or LMWH is administered concurrently
and overlapped with warfarin for at least 5 days and until the INR has reached
a therapeutic range for 24 hours.
•
INR ranges will vary depending on indication for anticoagulation.
•
For warfarin-naïve patients, initiation nomograms can avoid excessive anticoagulation and rapidly achieve target INR with a starting dose between 5 and
36-38
10 mg.
•
For previously treated warfarin patients, re-initiate therapy at prior chronic
maintenance dose. When there is a desire for earlier “measured” INR response,
another option is to start with an increased dose for the initial 2 days (≈50-100%
increase in the maintenance dose), then follow with the usual maintenance dose.
•
Elderly patients with comorbidities or recent surgery should initiate warfarin
with a dose <5 mg.
•
For younger, healthier, heavier patients, may consider larger initial doses (7.5–10
mg).
•
Consider clinically significant disease states and drug–drug interactions.
•
INR monitoring starts, at the latest, after the initial 2–3 VKA doses. Unstable
patients in the hospital should have daily monitoring.
•
Warfarin maintenance doses are adjusted based on the cumulative weekly
dosage with increases or decreases of no more than 10–20% of the weekly dose.
Any variation in doses from day-to-day should be spread evenly over the week.
28
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TABLE 10-8: Practical Considerations for Transitioning Between
Various Parenteral Anticoagulants
Conversion from adjusted-dose
IV UFH infusion to adjusted-dose
sub-Q UFH
• Calculate the 24-hr IV UFH dose requirement needed
to maintain therapeutic aPTT.
Increase the total 24-hr UFH dose requirement by 10-
•
20% (sub-Q dosage requirements are higher than IV).
•
Divide the dose calculated above by 2 to determine
the initial q12 hr sub-Q dosing requirement.
Discontinue IV UFH and initiate the first sub-Q UFH
•
dose (as calculated above) within 1 hr.
Check aPTT or anti-factor Xa activity level at 6 hr after
•
first sub-Q dose.
Adjust further sub-Q UFH doses based on aPTT or
•
anti-factor Xa activity level.
Ensure a heparin 10,000- or 20,000-unit/mL
•
concentration is available (ensure your dispensing
procedures guarantee the safe use of these agents
due to the well-known neonatal intensive care heparin
errors).
Conversion from IV UFH infusion
to sub-Q LMWH (or sub-Q
fondaparinux)
Conversion from sub-Q LMWH
(or fondaparinux) to IV UFH
infusion
•
Calculate the appropriate LMWH (or fondaparinux)
dose based on the specific indication for use and
patient weight.
• Discontinue IV UFH.
• Initiate the first sub-Q LMWH (or fondaparinux) dose
within 1 hr.
If aPTT drawn within the last 6 hr is >100 sec or an
•
anti-factor Xa activity level >1 International Unit/
mL, wait 2 hr before administering LMWH (or
fondaparinux).
•
Calculate the appropriate IV UFH dose based on
indication for use and patient weight.
Discontinue sub-Q LMWH (or fondaparinux).
•
• Omit bolus or loading dose.
• Initiate IV UFH 1–2 hr before the next scheduled
LMWH or fondaparinux dose administration:
When switching from sub-Q LMWH given q 12 hr,
a.
initiate IV UFH at 10–11 hr after last LMWH dose.
b. When switching from sub-Q LMWH given q 24 hr,
initiate IV UFH at 22–23 hr after last LMWH dose.
c. When switching from sub-Q fondaparinux given
q 24 hr, initiate IV UFH at 22–23 hr after last
fondaparinux dose.
d. Evaluate patient’s renal status and if impaired, the
IV UFH dosing initiation intervals suggested in a–c
above need to be extended accordingly.
• Check aPTT or anti-factor Xa activity level at 6 hr after
initiating the IV UFH infusion.
• Adjust further UFH doses based on aPTT or anti-factor
Xa activity level and dosing nomogram.
(continued)
242 Anticoagulation Therapy
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TABLE 10-8: (Continued)
Conversion from sub-Q LMWH
(or fondaparinux) to adjusteddose sub-Q UFH
• Calculate the adjusted-dose sub-Q UFH dosing
requirements: The recommended initial dose is
250 units/kg sub-Q given q 12 hr.
•
Ensure a heparin 10,000- or 20,000-unit/mL
concentration is available (see the above precaution on
these dosing forms).
• Discontinue sub-Q LMWH (or fondaparinux).
Initiate sub-Q UFH at the time the next sub-Q
•
LMWH (or fondaparinux) dose is scheduled to be
administered:
a. When switching from sub-Q LMWH given q 12 hr,
initiate sub-Q UFH at 12 hr after last LMWH dose.
b.
When switching from sub-Q LMWH given q 24 hr,
initiate sub-Q UFH at 24 hr after last LMWH dose.
When switching from sub-Q fondaparinux given
c.
q 24 hr, initiate sub-Q UFH at 24 hr after last
fondaparinux dose.
d. Evaluate patient’s renal status; if impaired, the
sub-Q UFH dosing initiation intervals suggested in
a–c above need to be extended accordingly.
• aPTT or anti-factor Xa activity level should be drawn at
6 hr (mid-interval) after the first sub-Q UFH dose.
•
Subsequent sub-Q UFH doses should be adjusted
based on aPTT or anti-factor Xa activity level and
dosing nomogram.
Conversion between
prophylactic fixed dose UFH
to LMWH (or fondaparinux) or
LMWH (or fondaparinux) to UFH
aPTT: activated partial thromboplastin time, BID: twice daily, IV: intravenous, LMWH: low
molecular weight heparin, sub-Q: subcutaneous, UFH; unfractionated heparin
For patients receiving prophylactic sub-Q UFH q 8 or 12 hr,
discontinue UFH:
Evaluate patient’s renal status and determine
•
appropriate LMWH (or fondaparinux) dose and
interval.
• Administer LMWH (or fondaparinux) at the next
scheduled dose administration time.
• Continue LMWH dosing per prescribed regimen.
For patients receiving prophylactic sub-Q LMWH (or
fondaparinux) q 12 or 24 hr, discontinue LMWH (or
fondaparinux):
• Administer UFH at the next scheduled dose
administration time.
• Continue UFH dosing q 8 or 12 hr per prescribed
regimen.
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BRIDGING CONSIDERATIONS AND
RECOMMENDATIONS
Determine if patient is a candidate for bridging therapy:
•
Mechanical/bioprosthetic heart valves
•
Atrial fibrillation
•
Venous thromboembolism
Steps to consider in transitioning anticoagulation therapy for periprocedural
bleeding:
•
Operationalize an individualized plan for the patient (Figure 10-1).
34
Mechanical/Bioprosthetic Heart Valves
Considerations High Risk for
Patient characteristics •
Peri-op bridging
options
*When used within 3 months of surgery; not for patients with concurrent atrial fibrillation after this
period.
** Post-procedure DVT prophylaxis should still be considered in procedures that require routine
prophylaxis.
AF: atrial fibrillation, CHF: congestive heart failure, DM: diabetes mellitus, HTN: hypertension,
IV: intravenous, LMWH: low molecular weight heparin, TIA: transient ischemic attack, UFH:
unfractionated heparin
Thromboembolism
Any mitral valve
prosthesis
Older aortic
•
valves (cagedball or tilting
disc)
• Recent (within 3
months) stroke
or TIA
• Bioprosthetic
heart valve*
• IV UFH (should
be used for
all mechanical
mitral valves)
• Therapeutic
LMWH
Moderate Risk for
Thromboembolism
• Bileaflet aortic
valve prosthesis
AND one of the
following: AF,
prior stroke, or
TIA, HTN, DM,
CHF, age >75 yr
• Therapeutic
LMWH
IV UFH
•
Low Risk for
Thromboembolism
• Bileaflet aortic
valve prosthesis
without AF and
no other risk
factors for stroke
• Medtronic Hall
tilting disc valve
No bridging**
244 Anticoagulation Therapy
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(48–72 hours)
Resume OAC 6–8
hours postoperatively
Immediate
risk procedure
hemostasis, low
Delay OAC until
hemostasis achieved
high risk
procedure
Inadequate
hemostasis,
if high TE risk
such as heparin
Consider bridge with a
reversible anticoagulant
Procedure
No bridge
Consider bridge
HOLD OAC
HOLD OAC
lower intensity
uninterrupted or at
May continue VKA
No bridge
HOLD OAC
High TE risk
FIGURE 10-1. Individualized Periprocedural Plan
OAC: oral anticoagulant, TE: thromboembolism, VKA: vitamin K antagonist
and TE risk
Low bleeding
High bleeding risk
Assess the
following:
• Bleeding risk
• Thrombosis risk
• Patient
preference
• Physician
preference and
resources
35
TRANSITIONS IN CARE 245
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Atrial Fibrillation
•
No randomized data are available that demonstrate a benefit of LMWH in
reducing risk of stroke, systemic embolism, and transient ischemic attack (TIA)
caused by atrial fibrillation.
•
Summary of the BRIDGE trial:
LMWH bridging therapy compared to placebo showed no differ-
ence in the reduction of stroke, systemic embolism, and TIA, but
did demonstrate nearly a 3 x higher major bleeding rate.
Based on the results of the BRIDGE trial,
LMWH in patients with atrial fibrillation is discouraged. Individual
clinicians should evaluate groups that were not well represented
in the trial, such as recent stroke/TIA in previous 12 weeks, those
who are over 10% yearly risk (CHADS2VASc ≥7 or CHADS2 ≥5,
rheumatic valvular disease, and those who had a stroke with warfarin
interruption).
In the rare cases where clinicians choose to use bridging, thera-
peutic doses of LMWH/heparin should be used.
For many pacemaker (PPM) and implantable cardioverter-defibrilla-
tor (ICD) placement patients, warfarin should be continued based on
the BRUISE CONTROL study showing continued warfarin reduced
the risk of pocket hematomas with no difference in thrombotic
complications compared to bridging therapy with heparin.
Post-procedure DVT prophylaxis should still be considered in
procedures that require routine prophylaxis.
15
the use of periprocedural
16
Venous Thromboembolism
Considerations High Risk for
Patient
characteristics
Peri-op bridging
options
*Post-procedure DVT prophylaxis should still be considered in procedures that require routine
prophylaxis.
VTE: venous thromboembolism
Thromboembolism
• Recent (within 3
months) VTE
• Severe
thrombophilia
(deficiency of
protein C, protein
S or antithrombin,
antiphospholipid
antibodies,
or multiple
abnormalities).
• Therapeutic
LMWH
• IV UFH
Moderate Risk for
Thromboembolism
• VTE within the past
3 to 12 months
•
Nonsevere
thrombophilic
conditions
(heterozygous
factor V Leiden
mutation,
heterozgyous
factor II mutation)
• Recurrent VTE
• Active cancer
(treated within
6 months or
palliative)
No bridging* No bridging*
Low Risk for
Thromboembolism
• Single VTE
occurred >12
months ago AND
no other risk
factors
246 Anticoagulation Therapy
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Determine which bridging therapy is appropriate:
•
Therapeutic dosing of LMWH
•
IV UFH
Heparin infusion may be started targeting aPTT 1.5–2.5 x baseline,
while taking into account procedural and patient risk factors.
•
Prophylactic LMWH
Determine when to stop bridging therapy prior to surgery:
Bridging Therapy Discontinuation of Therapy Peri-Operatively
Therapeutic LMWH Last dose to be administered 24 hr prior to surgery/procedure
Prophylactic LMWH Last dose to be administered 12–24 hr prior to surgery/procedure
IV UFH Discontinue infusion 6 hr prior to surgery/procedure
Determine when to re-initiate anticoagulation therapy post-op:
•
In all cases, it is recommended to discuss re-initiation of anticoagulation therapy
with the surgeon/proceduralist.
•
Based on anticipated bleeding risk, hemostasis must be achieved before any
parenteral therapy.
Surgery/Procedure Bleeding
1
Risk
Low risk •
High risk The following options may be considered:
INR: international normalized ratio
Anticoagulation Re-Initiation Recommendation
Approximately 24 hr after (following day)
Warfarin may be initiated the evening of the procedure
•
at the patient’s previously determined maintenance
dose or a slightly increased dose about 50% higher than
previous dose.
•
Therapeutic LMWH/IV UFH re-initiation may be delayed
48–72 hr (POD 2 or 3) after procedure.
Prophylactic LMWH may be initiated until bleeding risk
•
subsides and then therapeutic LMWH can be started.
• All anticoagulant medications may be held.
•
Warfarin may be initiated the evening of surgery
(orthopedic surgeries) or delayed until bleeding risk
subsides.
TRANSITIONS IN CARE 247
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