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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3865_Библиотеки_им_академика_М_И_Перельмана
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300 Anticoagulation Therapy
https://t.me/med1917
2.5 mg
twice daily,
initiated
12–24 hr
after surgery
10 mg once
daily initiated
6–10 hr after
surgery
110 mg initiated
1–4 hr after
surgery, then
220 mg once
daily*
Initiated pre-
operatively or the
evening of the
surgical day with
adjusted-dosing to
achieve a target INR
of 2.5 ± 0.5
2.5 mg
twice daily,
initiated
12–24 hr
after surgery
10 mg once
daily initiated
6–10 hr after
surgery
110 mg initiated
1–4 hr after
surgery, then
220 mg once
daily
Initiated pre-
operatively or the
evening of the
surgical day with
adjusted-dosing to
achieve a target INR
of 2.5 ± 0.5
Insufficient
evidence
Insufficient
evidence
Insufficient
evidence
Initiated pre-
operatively or the
evening of the
surgical day with
adjusted-dosing to
achieve a target INR
of 2.5 ± 0.5
2.5 mg sub-Q q
24 hr initiated
6–8 hr after
surgery
VTE Prophylaxis in Orthopedic Surgery
75 units/kg sub-Q
q 24 hr initiated
the evening
prior to surgery
or 12–24 after
2,500 units sub-Q
given 6–8 hr after
surgery, then 5,000
units sub-Q q 24 hr*
Enoxaparin Dalteparin Tinzaparin Fondaparinux Warfarin Dabigatran Rivaroxaban Apixaban
30 mg sub-Q q
12 hr initiated
12–24 hr after
surgery
Orthopedic
Indication
Knee
replacement
TABLE 12-12: VTE Prophylaxis in Orthopedic Surgery
surgery
2.5 mg sub-Q q
surgery*
75 units/kg sub-Q
2,500 units sub-Q
30 mg sub-Q q
Hip
24 hr initiated
6–8 hr after
surgery
q 24 hr initiated
the evening prior
to surgery or 12–
given 4–8 hr after
surgery, then 5,000
units sub-Q q 24 hr
12 hr initiated
12–24 hr after
surgeryor40 mg sub-Q q
replacement
surgery
2.5 mg sub-Q q
24 hr initiated
24 hr after surgery*or4500 units sub-Q
q 24 hr initiated 12
hr prior to surgery*
evidence
or
5,000 units sub-Q
q 24 hr initiated the
evening prior to
surgery
Insufficient evidence Insufficient
24 hr initiated
10–12 hr prior
to surgery
30 mg sub-Q q
12 hr initiated
Hip fracture
surgery
6–8 hr after
surgery
12–24 hr after
surgery*
VENOUS THROMBOEMBOLISM PREVENTION 301
Pharmacologic prophylaxis is generally not recommended unless patients have addition risk factors of advanced age, malignancy, neurologic deficit,
previous VTE, or an anterior surgical approach. Based on the lack of clinical trials, pharmacologic prophylaxis recommendations are general and include
LMWH: low molecular weight heparin, q: every, sub-Q: subcutaneous, UFH: unfractionated heparin, units: International Units, VTE: venous thromboembolism
*Not approved by the U.S. FDA.
https://t.me/med1917
VTE Prophylaxis in Orthopedic Surgery
Enoxaparin Dalteparin Tinzaparin Fondaparinux Warfarin Dabigatran Rivaroxaban Apixaban
Orthopedic
Indication
TABLE 12-12: (Continued)
sub-Q UFH or a LMWH.
Spine
surgery
302 Anticoagulation Therapy
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• Dabigatran is now available in the United States
for VTE prevention in patients undergoing hip
replacement surgery, but not for knee replacement
surgery. Dabigatran was found to be inferior
to enoxaparin 30 mg twice daily in patients
undergoing knee replacement surgery.
• Rivaroxaban has demonstrated a superior
reduction in VTE events compared to enoxaparin
40 mg once daily in hip replacement surgery and
enoxaparin 40 mg once daily and enoxaparin
30 mg twice daily in knee replacement surgery.
Although major bleeding was not significantly
increased in these studies, it should be noted that
the definition of major bleeding did not include
surgical site bleeding (considered non-major
bleeding).
Apixaban has demonstrated a superior reduction
•
in VTE events compared to enoxaparin 40 mg
once daily in hip and knee replacement surgery
with no significant increase in major bleeding.
Apixaban was not non-inferior to enoxaparin
30 mg twice daily in knee replacement surgery,
although the event rates were similar (9%
apixaban vs. 8.8% enoxaparin).
difference in major bleeding was observed, the
combination of major and clinically relevant
nonmajor bleeding was significantly reduced with
the use of apixaban.
21
22
Although no
22
• Timing of initiation of VTE prophylaxis after
surgery is an important and complicated issue.
The risk of thromboembolic events begins
immediately after surgery; therefore, VTE
prophylaxis is generally more effective when
started earlier rather than later. The challenge
comes in that early VTE prophylaxis is also
associated with increased bleeding compared to
VTE prophylaxis started later.
• Initiation of VTE prophylaxis after elective spinal
surgery can typically start 12-24 hours postoperatively. Prophylaxis may need to be delayed if
the surgical site remains open.
VENOUS THROMBOEMBOLISM PREVENTION 303
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• The frequency and severity of complications
using non-neuraxial techniques (plexus or
peripheral delivery) are influenced by the size
of the catheter and degree of anticoagulation.
The most serious complication from excessive
anticoagulation using non-neuraxial techniques
appears to be blood loss rather than loss of
neural function.
VTE Prophylaxis in Critically Ill Patients
See Table 12-13.
TABLE 12-13: VTE Prophylaxis in Critically Ill Patients
Critical Care
Setting
UFH LMWH Fondaparinux
VTE Prophylaxis in Critically Ill Patients
Trauma Insufficient evidence Dalteparin 5,000 units
Acute spinal
cord injury
Burns 5,000 units sub-Q q 8
Critical care 5,000 units sub-Q q 8
HIT: heparin-induced thrombocytopenia, sub-Q: subcutaneous, units: International Units, VTE:
venous thromboembolism
5,000 units sub-Q q 8 hr Enoxaparin 30 mg
23
hr or
5,000 units sub-Q q
12 hr
hr or
5,000 units sub-Q q
12 hr
sub-Q q 24 hr or
Enoxaparin 30 mg
sub-Q q 12 hr
sub-Q q 12 hr or
Enoxaparin 40 mg
sub-Q q 24 hr
Dalteparin 5,000 units
sub-Q q 24 hr or
Enoxaparin 40 mg
sub-Q q 24 hr
Dalteparin 5,000 units
sub-Q q 24 hr
Enoxaparin 30 mg
sub-Q q 12 hr or
Enoxaparin 40 mg
sub-Q q 24 hr
Insufficient evidence
Insufficient evidence
Insufficient evidence
Insufficient evidence
2.5 mg sub-Q daily
may be an option in
suspected HIT
304 Anticoagulation Therapy
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• Trauma
Meta-analysis has demonstrated UFH to be
no more effective than control.
24
Enoxaparin 30 mg twice daily has
demonstrated better efficacy to UFH 5,000
units twice daily.
25
Evidence for dalteparin is based on
observational data.
Pharmacologic prophylaxis can be safely
started within 24 to 36 hours. Patients with
acute spinal cord injury may need to be
delayed for 48 to 72 hours.
Patients with severe trauma (injury severity
score >23) may present with antithrombin
deficiency; therefore, sub-Q prophylaxis may
be insufficient.
26
Although not prospectively
evaluated, an option may be to use an UFH
infusion while the patient is in the intensive
care unit early in the course of events. Only
a slight bump in the aPTT (35–45 seconds)
would be targeted since VTE prevention is the
goal.
• Acute spinal cord injury
UFH three times daily demonstrated similar
rates of DVT and bleeding compared
to enoxaparin twice daily, but there
was a significant reduction in PE with
enoxaparin.
While enoxaparin 30 mg twice daily should
27
be used during the acute injury period (about
2–3 weeks), either regimen could be used
during the rehabilitation period.
In a retrospective case-control study,
dalteparin 5,000 units daily failed to
demonstrate non-inferiority to enoxaparin
30 mg twice daily in prevention of VTE
(9.7% vs. 1.6%).
28
dalteparin and tinzaparin are warranted.
Further investigations of
VENOUS THROMBOEMBOLISM PREVENTION 305
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• Burns
The recent evidence in burn patients currently
comes from only observational studies with
UFH, enoxaparin, and dalteparin. The most
commonly used regimen is UFH 5,000 units
sub-Q every 12 hours.
•
Critical care
In medically ill or post-operative general
surgery patients, UFH or a LMWH can be
used. In orthopedic surgery or trauma, a
LMWH is preferred.
If mechanical prophylaxis is selected due
to high risk of bleeding, the patient should
be frequently re-evaluated and switched
to pharmacologic prophylaxis when the
bleeding risk decreases.
Some pharmacodynamic studies suggest that
critical care patients with significant edema
or receiving vasopressors may not achieve
detectable anti-Xa levels with LMWH.
In the largest trial of VTE prevention in
critical care patients, dalteparin 5,000 units
sub-Q once daily provided similar protection
against proximal DVT, better protection
against PE, similar bleeding, and less HIT
compared to UFH 5,000 units twice daily.
Dalteparin has been shown to not have
significant accumulation in critical care
patients with renal insufficiency.
A retrievable IVC filter may be considered
30
for PE prophylaxis, but it should be noted
that this practice has limited evidence and is
controversial. See the IVC discussion earlier
in this chapter.
29
306 Anticoagulation Therapy
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Travel Prophylaxis Strategies
See Table 12-14.
TABLE 12-14: Travel Prophylaxis Strategies
Indications Persons with previous VTE, thrombophilic disorders, severe obesity,
recently active cancer, pregnancy, estrogen use, advanced age, or
recent major surgery or trauma, who are traveling on flights >6 hr
Non-pharmacological Hydration
Pharmacological LMWH before takeoff on the outgoing and return flights
LMWH: low molecular weight heparin, VTE: venous thromboembolism
In-route exercises
Foot lifts: Place your heels on the floor, and bring your toes up as
•
high as you can. Then put both feet back flat on the floor. Then
pull your heels up while keeping the balls of your feet on the
floor.
• Ankle turns: Lift your feet off the floor and move your toes in
a circle, one foot moving clockwise and the other foot moving
counterclockwise. Change direction and repeat direction.
Frequent travel breaks every 1–2 hr
Avoid restrictive clothing (tight clothes, belts, etc.)
Avoid or limit alcohol and caffeine prior to travel
Airline, bus, or train aisle seating
Graduated compression devices
• Below knee compression devices with ≥15–30
mmHg graduated pressure are recommended for
travel prophylaxis.
• Compression devices should be placed 3–4 hours
before departure and removed upon arrival.
• Pharmacological therapy should be administered
2–4 hours prior to departure.
•
The ACCP provides a recommendation (Grade
2C) against the use of LMWH in this setting.
Contrary to this recommendation, some will give
a single prophylactic dose of LMWH. The only
trial mentioned in the ACCP guidelines that used
a LMWH gave sub-Q enoxaparin 1 mg/kg.
• Aspirin has been shown to be ineffective in this
setting.
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Duration of VTE Prophylaxis
See Table 12-15.
TABLE 12-15: Duration of VTE Prophylaxis
Indication Duration
General medically ill patients LMWH/UFH: 6–14 days as long as immobile during
Major general surgery Until hospital discharge
Major general surgery in patients with
previous venous thromboembolism
Surgery for gastrointestinal,
genitourinary, or gynecologic cancer
Total knee replacement surgery At least 10 days
Total hip replacement surgery 4 to 6 weeks*
Hip fracture surgery 4 to 6 weeks*
Critical care patients For the duration of the intensive care unit stay, with
Major trauma Until hospital discharge and continued prophylaxis in
Spinal cord injury patients Until hospital discharge in patients with incomplete
acute illness; betrixaban: 35–42 days
Beyond hospital discharge for up to 28 days
Beyond hospital discharge for up to 28 days
re-evaluation when the patient is transferred to the
general medical ward
patients with impaired mobility who undergo inpatient
rehabilitation (up to 8 weeks)
injuries
For 8 weeks in patients with uncomplicated complete
motor injury
For 12 weeks or discharge from rehabilitation in
patients with complete motor injury and other risk
factors
*While the average time from surgery to VTE in knee replacement surgery is 7 days, the average
time to VTE with hip procedures is delayed to 17 days.
Pharmacological Prophylaxis in Special Populations
Severe Renal Insufficiency
•
Patients with renal insufficiency are at higher risk of bleeding regardless of the
anticoagulant used.
•
Patients with a serum creatinine >2.5 mg/dL have been excluded from most
clinical trials.
•
Enoxaparin should be dosed at 30 mg sub-Q once daily regardless of the indication with CrCl <30 mL/min.
•
Dalteparin and tinzaparin do not seem to significantly accumulate in patients
with severe renal insufficiency when prophylaxis doses are used.
31
308 Anticoagulation Therapy
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•
Fondaparinux, dabigatran, and rivaroxaban are contraindicated in patients with
a CrCl <30 mL/min. Apixaban should not be used in patients with a CrCl <25
mL/min.
•
Patients on hemodialysis (renal failure) should receive sub-Q UFH.
Obesity
•
ACCP guidelines recommend possible weight-adjusted dosing in obese patients,
but the guidelines provide no insight at what weight this should be considered,
or what the “adjusted” dosing should be. Obese patients are at considerable
risk of PE, but data from clinical trials on drug dosing are limited.
•
Enoxaparin 40 mg sub-Q twice daily has demonstrated better efficacy than 30
mg sub-Q twice daily in bariatric surgery patients.
•
Injections of enoxaparin into the thigh in obese patients have a lower bioavailability compared to injections into the abdomen.
•
One study suggests that the typical dose of a LMWH may have to be higher in
patients with a body mass index ≥40.
•
Dalteparin 7,500 units daily has been evaluated in a retrospective study using
anti-Xa levels in patients undergoing bariatric surgery.
•
Efficacy and safety of direct oral anticoagulants in obese patients is similar to
non-obese patients with the heaviest patients studied ranges from 150 to 190 kg.
•
Optimal dosing of any agent for VTE prophylaxis in the morbidly obese patient is
unclear; clinicians need to use discretion weighing thrombosis versus bleeding.
32
18
33
Pregnancy34 (see Chapter 19 for more information)
•
Warfarin has been associated with congenital abnormalities when used during
the 1st trimester, and is therefore contraindicated. While warfarin could be used
during the 2nd trimester, it is typically avoided throughout pregnancy.
•
A LMWH or UFH can be used throughout pregnancy.
•
LMWHs (or fondaparinux) are not contraindicated in the 3rd trimester of
pregnancy and can be used in the early 3rd trimester. During the peripartum
period, many prefer to use UFH due to the shorter half-life and risk of bleeding
during delivery.
•
DOACs have not been evaluated in pregnancy and should not be used.
HIT (see Chapter 18 for more information)
•
Meta-analysis demonstrates a risk of HIT of 2.6% for UFH and 0.2% for LMWH
when prophylaxis doses are used.
•
Due to a cross-reactivity of 80-90%, a LMWH cannot be used as a substitute for
UFH in patients who develop HIT.
•
Although fondaparinux may be an option in patients with a history of HIT due
to low cross reactivity, case reports of HIT with fondaparinux have been noted.
•
DOACs have not been reported to cause HIT but have not been evaluated in
the management of HIT at this time.
For information on neuraxial anesthesia/analgesia, see Chapter 10.
35
VENOUS THROMBOEMBOLISM PREVENTION 309
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Quality Improvement
See Table 12-16.
TABLE 12-16: Quality Improvement Strategies
Strategy Description
Educational initiatives Peer-led presentations and inservices
Decision support tools Electronic alerts and reminders
Audit and feedback process Quality indicators and reports
Organizational changes Integrated care pathways
Standardized dosing times Utilize pharmacologic prophylaxis options that require less
Regulations and policy
changes
Mailings
Risk assessment models and prophylaxis reminders in
admission charts
Benchmarking against outcomes from highest performing
provider
Changing from paper to computer-held patient records
frequent dosing to avoid possible missed doses.
Utilize a standard dosing time in the evening (i.e., 2100) to
avoid missing morning dosing due to patients being off the
floor.
Reimbursement schemes including fee-for-service
Required assessment policy
REFERENCES AND KEY ARTICLES*
*1. Dobesh PP, Wittkowsky AK, Stacy ZA, et al. Key articles and guidelines for the
prevention of venous thromboembolism. Pharmacotherapy. 2009;29:410-458.
2. Kahn SR, Lim W, Dunn AD, et al. Prevention of VTE in nonsurgical patients. Chest.
2012;141(Suppl 2):e195S-e226S.
3. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical
patients. Chest. 2012;121(Suppl 2):e227S-e277S.
4. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery
patients. Chest. 2012;141(Suppl 2):e278S-e325S.
*5. Lyman GH, Khorana AA, Falanga A, et al. American Society of Clinical Oncology
guideline: Recommendations for Venous Thromboembolism Prophylaxis and Treatment
in Patients with Cancer. J Clin Oncol. 2007;25:5490-5505.
6. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism.
Chest. 2008;133:381S-453S.
7. Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a
predictive model for chemotherapy-associated thrombosis. Blood. 2008;111(10):4902-
4907.
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