Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3865_Библиотеки_им_академика_М_И_Перельмана
.pdf
230 Anticoagulation Therapy
https://t.me/med1917
(continued)
dabigatran (27.5% vs 15.4% P<0.001)
bleeding than those not bridged (6.5% vs 1.8% P <0.001)
and not bridged groups did not differ for TE (1.2% vs 0.6%
P = 0.16), and stroke or systemic embolism (0.5% vs. 0.3%
P = 0.007)
bleeding (6.8% vs 1.6% P <0.001) and TE than those not
bridged (1.8% vs 0.3 P = 0.007); and not bridged did not
differ for stroke or systemic embolism (0.5% vs 0.2% P =
0.321)
• Dabigatran interruption: bridged patients had more major
• Bridging was used more during warfarin interruption than
Evaluated bridging strategies
in patients treated with
warfarin INR 2–3, dabigatran
110 mg BID, or 150 mg BID.
Bridging before and/or after
-VASc 3.6
2
DS
2
AF patients (n = 4,133),
average CHA
• Warfarin interruption: bridged patients had more major
procedure:
Enoxaparin 40 mg BID
• IV UFH
• Enoxaparin 1 mg/kg BID
•
• Enoxaparin 40 mg/day
• UFH SQ 5,000 units BID
CI, 0.42–1.54)
comparing bridged and nonbridged groups (OR 0.80;
There was no difference in the risk of TE events in 8 studies
CI 0.0.0–3.4) and 32 of 5,160 nonbridged patients (0.6%;
CI, 0.0–1.2)
•
TE events occurred in 73 of 7,118 bridged patients (0.9%;
IU/kg day or 100-120
IU/kg BID
day or 1 mg/kg BID
Warfarin INR 2–3 compared
AF patients (44%),
Dalteparin 200
with bridging IV UFH or
LMWH before and/or after
procedure:
•
mechanical heart valve
(24%), previous VTE (22%),
other (10%)
(n = 12,000)
• Enoxaparin 1.5 mg/kg
IU/kg BID
• Ardeparin 100–130
included
Tinzaparin 175 IU/kg day
•
• Prophylactic doses were
Pre-specified
sub study of the
Trial Study Design Population Intervention Outcome
Substudy
TABLE 10-3: (Continued)
of RELY
RELY (randomized
controlled trial)
)
15
(Douketis et
al.
Meta-analysis of 24
studies
18
Siegal et al.
-
molecular weight heparin; TE: thromboembolism; TIA: transient ischemic attack; UFH: unfractionated heparin; VTE: venous thromboembolism
https://t.me/med1917
2
DS
2
patients (5% vs. 1.3% adjusted OR 3.84, P<0.0001)
VASc scores (P=0.5)
Bridged patients were more likely to have cerebrovascular events
• Bleeding events more common in bridged vs. nonbridged
(22% vs. 15%, P=0.0003), and mechanical valve replacements
(9.6% vs. 2.4% P<0.0001); however, no difference in CHA
TRANSITIONS IN CARE 231
bleeding, hospitalization, or death within 30 days was also
significantly higher in patients receiving bridging (13% vs.
6.3%, adjusted OR 1.94, P=0.0001)
Incidence of MI, stroke or systemic embolism, major
•
Primarily warfarin INR 2–3
Registry data AF patients (n=10, 132),
19
Trial Study Design Population Intervention Outcome
TABLE 10-3: (Continued)
ORBIT-AF
• LMWH (73%)
with bridging before and/or
after procedure:
-VASc ~4, CHADS2
2
DS
2
2.3–2.5
CHA
(Steinberg
BA, et al.)
• Fondaparinux (1.1%)
• IV UFH (15%)
CHADS2: cardiac failure, hypertension, age, diabetes, and stroke (doubled); VAS: vascular disease; ICD: implantable cardioverter defibrillator; IV: intravenous; LMWH: low
232 Anticoagulation Therapy
https://t.me/med1917
• The use of DOACs as a bridge to therapeutic
warfarin is a controversial topic. While it should
be safe, in actual practice the lack of provider
recognition on how the DOACs affect INR and
knowledge of the correct timing of INRs (when
used in these patients) can lead to suboptimal
care. Due to this, using a parenteral agent with
warfarin for bridging may often still be the best
option. See Chapter 21 on DOAC effects on
coagulation laboratory tests for more information
(see Tables 10-4, 10-5, and 10-6).
TABLE 10-4: Periprocedural Management of Direct-Acting Oral
Anticoagulants
Calculated
CrCl (mL/min)
Dabigatran Low Risk of Bleeding High Risk of Bleeding
>50 24 hr
31–50 2 days
<30 4 days 5–6 days
Rivaroxaban, Apixaban, Edoxaban
>50 1 day 2 days
31–50 1–2 days 3–4 days
<30 2 days 4 days
CrCl: creatinine clearance, PI: prescribing information
1,9,39-43
Timing of Last Dose Before Surgery
(PI: Discontinue 1–2 days
before)
(PI: Discontinue 3–5 days
before if CrCl <50 mL/min)
2 days
(PI: Consider longer times if major surgery,
spinal puncture, spinal or epidural catheter,
patients in whom complete hemostasis may be
required)
5 days
(PI: Discontinue 3–5 days before if CrCl
<50 mL/min)
TRANSITIONS IN CARE 233
https://t.me/med1917
TABLE 10-5: Comparison of Pharmacodynamic Properties of
Direct-Acting Oral Anticoagulants
Agent Target Clotting
Rivaroxaban Xa Yes 1.25–3 7–7.6 36%
Apixaban Xa Yes 1–3 8–15 25%
Dabigatran IIa Yes 1.25–3 12–17.2 80%
Edoxaban Xa Ye s 1–2 10-14 35%
: time to reach maximum plasma concentrations, t½: half-life
t
max
Factor
Reversible Binding
to Catalytic Site
40-43
t
(hr) t½ (hr) Renal Excretion
max
of Active Drug
CONSIDERATIONS IN USING
ANTICOAGULANT THERAPY IN
CONJUNCTION WITH NEURAXIAL
ANESTHESIA
•
Ensure safe transition with anticoagulation through neuraxial (spinal or epidural)
procedural anesthesia (Table 10-7).
•
Avoid risks of spinal hematoma.
Incidence with no anticoagulant; 1:220,000 with epidural anesthesia
and 1:2,320,000 with spinal anesthesia
Incidence with heparin; 1:70,000 with epidural anesthesia and
1:100,000 with spinal anesthesia
• Many health systems choose to avoid LMWH
prophylaxis in conjunction with indwelling
epidural catheters due to the complex
requirements needed to do it safely. Many health
systems consider delaying warfarin/DOAC
re-initiation until catheter is removed to avoid
complications in catheter removal.
234 Anticoagulation Therapy
https://t.me/med1917
= 17–21 hr) sub-Q.
(continued)
41
= 45 min), IV.
½
½
= 6–7 hr), fondaparinux (t
½
for oral agent.
max
Stop IV UFH infusion.
Rivaroxaban, dabigatran, edoxaban, or apixaban:
Consider pharmacodynamics: IV UFH (t½ = 60 min).
32, 33, 39-43
Conversion from adjusted-dose IV
TABLE 10-6: Practical Considerations for Transitioning Between Various Direct-Acting Oral Anticoagulants or to
Parenteral Agents
1. Administer first oral dose of rivaroxaban, dabigatran, edoxaban, or apixaban at the time of UFH discontinuation.
Consider t
UFH infusion to oral rivaroxaban,
dabigatran, edoxaban, or apixaban
for oral agent.
max
Consider t
Rivaroxaban, dabigatran, edoxaban, or apixaban:
2. Continue direct-acting oral anticoagulant per prescribed regimen.
1. Give rivaroxaban, dabigatran, edoxaban, or apixaban when next LMWH (or fondaparinux) dose is due.
Consider pharmacodynamics: LMWH (t
Conversion from sub-Q LMWH (or
sub-Q fondaparinux) therapeutic
2. Stop all following parenteral doses.
dosing to oral rivaroxaban, dabigatran,
edoxaban, or apixaban
= 25 min) or argatroban (t
½
to correspond to direct thrombin inhibitor elimination.
max
for oral agent.
max
Continue direct-acting oral anticoagulant per prescribed regimen.
Administer rivaroxaban, dabigatran, edoxaban, or apixaban orally at the time of the next scheduled parenteral dose.
Stop current parenteral prophylaxis agent.
Rivaroxaban, dabigatran, edoxaban, or apixaban:
3.
1.
Converting from prophylactic dose
sub-Q UFH, LMWH (or fondaparinux)
to oral rivaroxaban, dabigatran,
Consider pharmacodynamics: bivalirudin (t
2. Continue direct-acting oral anticoagulant per prescribed regimen.
dose
edoxaban, or apixaban prophylactic
Converting from direct thrombin
Administer first rivaroxaban, dabigatran, edoxaban, or apixaban oral dose immediately at cessation of bivalirudin/
Rivaroxaban, dabigatran, edoxaban, or apixaban:
1.
Aim for oral agent t
Consider t
apixaban
inhibitor (bivalirudin or argatroban)
IV infusion to oral therapeutic dose
rivaroxaban, dabigatran, edoxaban, or
argatroban infusion.
Evaluate patient’s renal and hepatic status; if impaired, extend initiation interval accordingly.
2.
TRANSITIONS IN CARE 235
https://t.me/med1917
(continued)
For all DOACs:
1. Give final warfarin dose.
2. Wait 2–3 days.
Converting from warfarin to oral
rivaroxaban, dabigatran, edoxaban, or
TABLE 10-6: (Continued)
apixaban
For atrial fibrillation patients taking rivaroxaban, consider starting when INR <3.
For atrial fibrillation patients taking edoxaban, consider starting when INR <2.5.
When INR <2, give first dose of rivaroxaban, dabigatran, edoxaban, or apixaban:
3.
Begin a parenteral agent with warfarin when the next scheduled dose of rivaroxaban would be due.
Rivaroxaban:
1. Discontinue rivaroxaban.
2.
Dabigatran:
warfarin
Converting from oral rivaroxaban,
dabigatran, edoxaban, or apixaban to
For CrCl ≥50 mL/min, start warfarin 3 days before discontinuing dabigatran.
For CrCl 30–50 mL/min, start warfarin 2 days before discontinuing dabigatran.
For creatinine clearance 15–30 mL/min, start warfarin 1 day before discontinuing dabigatran.
2. Begin warfarin based on creatinine clearance:
1. Discontinue dabigatran.
For creatinine clearance <15 mL/min, no recommendations can be made.
Apixaban:
Begin a parenteral agent and warfarin when the next scheduled dose of apixaban would be due.
Discontinue apixaban.
2.
1.
236 Anticoagulation Therapy
https://t.me/med1917
(continued)
of edoxaban, reduce the dose to 15 mg and begin warfarin concomitantly. Once INR ≥2 is achieved, edoxaban should be
Edoxaban
Oral option:
1. For patients taking 60 mg of edoxaban, reduce dose to 30 mg and begin warfarin concomitantly. For patients taking 30 mg
Converting from oral rivaroxaban,
dabigatran, edoxaban, or apixaban to
TABLE 10-6: (Continued)
warfarin
discontinued and continue warfarin therapy.
All INRs done in this fashion must be immediately prior to an edoxaban dose.
2.
3. Patient compliance to this regimen may be extremely difficult, and may lead to improper levels of anticoagulation.
of edoxaban. Once the INR is ≥2, the parenteral agent should be discontinued and continue warfarin therapy.
Parenteral option:
1. Discontinue edoxaban and administer a parenteral anticoagulant and warfarin at the same time of the next scheduled dose
Calculate the appropriate IV infusion UFH dose based on indication for use and patient weight.
Check aPTT or anti-factor Xa activity level at 6 hr after initiating the IV UFH infusion.
Oral anti-Xa inhibitors (rivaroxaban, apixaban, edoxaban):*
1. Start when next dose of DOAC is scheduled.
Converting from oral therapeutic dose
rivaroxaban, dabigatran, edoxaban,
2.
3. Omit bolus or loading dose.
infusion
or apixaban to adjusted-dose IV UFH
*As noted above, in patients with high thrombotic risk, alternative UFH anticoagulation monitoring for 48-72 hours may be
needed (e.g., Xa inhibitor transitioning to UFH in hospital using anti-factor Xa levels for monitoring and using aPTT to guide
titrations); in high bleeding risk/low thrombosis risk situations and/or delayed DOAC clearance due to acute kidney injury,
heparin initiation may need to be delayed beyond standard recommendations to avoid over anticoagulation until the DOAC has
largely cleared; appropriate laboratory measures may help guide when to initiate UFH (e.g., waiting until an apixaban patient’s
4.
5. Adjust further UFH doses based on aPTT or anti-factor Xa activity level and dosing nomogram.
heparin correlated anti-factor Xa level is in the measurable range to start therapy).
TRANSITIONS IN CARE 237
https://t.me/med1917
<30 mL/min
Dabigatran:
1. Wait 12 hr for patients with a creatinine clearance ≥30 mL/min; wait 24 hr for patients with a creatinine clearance
TABLE 10-6: (Continued)
Calculate the appropriate IV infusion UFH dose based on indication for use and patient weight.
Evaluate patient’s renal status; if impaired, the IV UFH dosing initiation interval needs to be extended accordingly.
2.
4.
3. Omit bolus or loading dose.
5. Check aPTT or anti-factor Xa activity level at 6 hr after initiating the IV UFH infusion.
6. Adjust further UFH doses based on aPTT or anti-factor Xa activity level and dosing nomogram.
Discontinue direct-acting oral anticoagulant.
Consider peak activity for LMWH (3–5 hr) or fondaparinux (3 hr).
Calculate the appropriate LMWH (or fondaparinux) dose based on the specific indication for use and patient weight.
Oral anti-Xa inhibitors (rivaroxaban, apixaban, edoxaban):
1. Discontinue oral anti-Xa and start LMWH/fondaparinux at the next scheduled dose of DOAC.
2. Calculate the appropriate LMWH/fondaparinux dose based on indication for use and patient weight.
3. Evaluate patient’s renal status; if impaired, the LMWH dosing initiation interval needs to be extended accordingly.
Converting oral rivaroxaban,
dabigatran, edoxaban, or apixaban to
LMWH (or fondaparinux)
<30 mL/min.
Calculate the appropriate LMWH/fondaparinux dose based on indication for use and patient weight.
Wait 12 hr for patients with a creatinine clearance ≥30 mL/min; wait 24 hr for patients with a creatinine clearance
Dabigatran:
2.
1.
: time to reach maximum plasma concentrations, t½: half-life, UFH: unfractionated heparin
max
aPTT: activated partial thromboplastin time, CrCl: creatinine clearance, IV: intravenous, INR: international normalized ratio, LMWH: low molecular weight heparin, sub-Q:
subcutaneous, t
238 Anticoagulation Therapy
https://t.me/med1917
Therapy
Stop GP IIb/
IIIa inhibitors 8
hr (eptifibatide,
tirofiban) to 48
33,39-43
hr (abciximab)
prior to needle
placement.
Stop ticagrelor
5 days prior,
clopidogrel 5–7
days prior, and
prasugrel 7 –10
days prior to
needle placement.
Minimum hold
period for
vorapaxar has not
been established.
Avoid use.
Stop cilostazol
48–72 hr prior to
needle placement.
Stop ticlopidine
(continued)
14 days prior to
needle placement.
Oral Anticoagulation Antiplatelet
LMWH Prophylaxis LMWH
UFH Prophylaxis Intravenous
Warfarin: Stop warfarin at least
Therapeutic
Presence of blood during needle and
UFH
Delay heparin
5,000 units sub-Q
4–5 days prior to procedure.
INR should be checked prior to
insertion if warfarin given more
than 24 hr earlier.
INR must be normal prior to
needle placement.
Patients receiving warfarin
therapy during epidural
analgesia should have INR
monitored daily.
Dabigatran: Stop 4-6 days prior
to insertion.
Rivaroxaban: Stop at least 2–3
days prior to insertion. Can
consider stopping at least 4
Pre-op
LMWH
therapeutic
doses: Delay
needle
placement
by at least
24 hr after
LMWH dose;
indwelling
catheters
catheter placement delays initiation of
LMWH 24 hr.
Pre-op LMWH
prophylaxis dosing:
Delay needle
placement at least 12
hr after the LMWH
dose.
Post-op LMWH daily
dosing: Administer
first LMWH dose 6–8
hr post-op; administer
second dose no
administration
until 1 hr
after needle
placement.
BID dosing
is considered
acceptable.
The safety of
5,000 units sub-Q
TID dosing
has not been
established.
days prior if the patient has
impaired renal function or age
greater than 65.
Apixaban: Stop at least 3–5
days prior to insertion.
Edoxaban: Stop at least 3–5
days prior to insertion.
should be
removed
prior to
LMWH
initiation.
sooner than 24 hr after
the first dose.
Post-op LMWH BID
dosing: First LMWH
dose no earlier than 24
hr postop; indwelling
catheters should be
removed prior to BID
LMWH initiation.
Fibrinolytic
Therapy
Agent or Class
Neuraxial
TABLE 10-7: Guidelines for Regional Anesthesia with Anticoagulation or Antiplatelet Use
Anesthesia
Avoid fibrinolytic
administration
for at least
Technique
Epidural
or spinal
anesthesia
10 days after
puncture.
If patients
are to receive
fibrinolytic
needle or
catheter
insertion
therapy,
neuraxial
anesthesia
techniques
should be
avoided.
Agent or Class
Therapy
BID: twice daily, GP: glycoprotein, INR: international normalized ratio, LMWH: low molecular weight heparin, sub-Q: subcutaneous, TID: three times daily, UFH:
unfractionated heparin
https://t.me/med1917
Catheters must
Oral Anticoagulation Antiplatelet
Check INR prior to catheter
Catheter
Therapeutic
be removed
prior to initiating
eptifibatide,
tirofiban,
abciximab,
clopidogrel,
ticagrelor,
prasugrel,
cilostazol, or
removal.
Catheters should ideally be
removed when INR is below
1.5, but removal can be
cautiously considered if INR
removal a
minimum of
24 hr after
the last dose
of LMWH.
Dabigatran: Wait
1.5–3.
If a DOAC was started in the
event a catheter was placed:
•
TRANSITIONS IN CARE 239
ticlopidine. May
be considered if
last dose 8–12 hr
previously.
24–48 hr or longer before
removing.
longer before removing.
Rivaroxaban: Wait 18 hr or
Apixaban: Wait 24 hr or
•
•
longer before removing.
longer before removing.
Edoxaban: Wait 24 hr or
•
LMWH Prophylaxis LMWH
UFH Prophylaxis Intravenous
Fibrinolytic
TABLE 10-7: (Continued)
Neuraxial
UFH
Therapy
Anesthesia
Technique
Catheter removal a
minimum of 12 hr after
last LMWH dose.
Administer first dose
2 hr after catheter
removal.
Remove
indwelling
catheter 2–4
No
contraindications.
No
recommendation.
If fibrinolytic
Epidural
or spinal
anesthesia
1 hr after
hr after the last
heparin dose.
Reheparinize
therapy is
given, monitor
fibrinogen level
recovery as
catheter
removal
catheter
removal.
guidance.
Соседние файлы в папке Библиотека им академика М.И. Перельмана