Anticoagulant Management of Patients Undergoing Elective Surgery

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Anticoagulant Management of Patients
Undergoing Elective Surgery
who Require Temporary Interruption
of Warfarin Therapy
James D. Douketis MD, FRCP(C)
Karen Woods RN
Mark A. Crowther MD, MSc, FRCP(C)
From the Department of Medicine, McMaster University and
St. Joseph's Healthcare, Hamilton, Canada.
June, 2005
Supported by an unrestricted educational grant
from LEO Pharma Inc.
innoMED Educational Service
Copyright: Minerva Communications Group Inc., 2005
All rights reserved. No part of this publication may be reproduced, stored in a retrieval
system, or transmitted, in any form or by any means, electronic, mechanical, photocopying,
recording, or otherwise, without prior written permission from the publisher.
Notice: The authors and publisher have made every effort to ensure that the patient care
recommendations herein, including choice or drugs and drug choices, are in accord with
the accepted standards and practices at the time of publication. However, since research
and regulations constantly change clinical standards, the reader is urged to check recent
publications and product monographs.
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Contents
Overview
3
Objectives
4
Frequently-Asked Questions
General Issues
Patient Stratification According to the Risk of Thromboembolism
Anticoagulant Management Before Surgery
Anticoagulant Management After Surgery
Specialized Patient Groups
Other Patient-related issues with Bridging Anticoagulation
Figure and Tables
Figure 1. Suggested Bridging Anticoagulation Patient Instructions
Figure 2. Sample Medical Record
Table 1. Physician Practice Patterns for Bridging Anticoagulation
Table 2. Arterial Thromboembolism and Major Bleeding in Trials
of Bridging Anticoagulation with LMWH
Table 3. Perioperative Anticoagulant Management in Patients
with a Mechanical Heart Valve
Table 4. Perioperative Anticoagulant Management in Patients
with Chronic Atrial Fibrillation
Table 5. Perioperative Anticoagulant Management in Patients
with Venous Thromboembolism
Table 6. Surgery Bleeding Risk Classification and Postoperative
Anticoagulation
5
5
7
9
11
14
17
19
19
20
23
Table 7.
Low-molecular-weight Heparin Dose Regimens
References
Abbreviations
aPTT
activated partial thromboplastin time
ASA
acetylsalisylic acid
CBC
complete blood count
DVT
deep vein thrombosis
INR
international normalized ratio
IU
international units
LMWH low-molecular-weight heparin
NSAID non-steroidal anti-inflammator y drug
2
TIA
transient ischemic attack
UFH
unfractionated (standard) heparin
VTE
venous thromboembolism (includes deep vein thrombosis
and pulmonar y embolism)
23
24
24
25
25
26
26/27
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Overview
The clinical management of patients who require temporary interruption
of warfarin or other coumarin derivatives because of surgery or a nonsurgical invasive procedure is a common and challenging clinical problem.
There are approximately 4 million people in Europe and North America
who are receiving long-term treatment with an oral anticoagulant such as
warfarin1. It is estimated that approximately 10% of such patients (or
400,000) are assessed annually for temporary interruption of oral anticoagulant therapy and possible 'bridging anticoagulation'.
Bridging anticoagulation with a short-acting heparin preparation, such as
unfractionated heparin (UFH) or low-molecular-weight heparin (LWMH),
is administered to minimize the period of time before and after surgery
that patients are not receiving therapeutic anticoagulation and, thereby,
minimize the risk of thromboembolism. Although the risk for thromboembolic events during temporary warfarin interruption is considered low
(i.e., <3%), these events can have devastating clinical consequences:
thrombosis of a mechanical heart valve is fatal in 15% of patients, and
embolic stroke results in a major neurological deficit or death in 70%
of patients 2,3.
There are no universally accepted recommendations regarding bridging
anticoagulation, and the aggressiveness of anticoagulation strategies
varies in published reviews of this topic 4-14. In general, most experts
recommend that patients at high risk for thromboembolic events should
receive therapeutic-dose (or full-dose) anticoagulant therapy during the
period before and after surgery, whereas recommendations in patients at
low or moderate risk for thromboembolism are less consistent. Recent
surveys of physicians' current practice patterns regarding bridging anticoagulation reflect these recommendations: over 90% of physicians prefer
bridging anticoagulation in patients at high risk for thromboembolism
whereas 50-80% of physicians prefer bridging anticoagulation to patients
at lower risk 15-18.
The overall objective of this monograph is to provide a practical guide for
the assessment and management of patients who require temporary
interruption of oral anticoagulant therapy for surgery or a non-surgical
invasive procedure. We acknowledge there are no randomized controlled
trials of bridging anticoagulation to provide definitive, evidence-based
practice recommendations. Nonetheless, there is evidence from recent
non-randomized trials of bridging anticoagulation that help to inform
clinical practice19-23. Our suggested guidelines are based on these studies
and on our clinical experience in managing patients who are considered
for bridging anticoagulation.
3
As a convention in this monograph, the term 'surgery' refers to patients
who are undergoing a surgical procedure that requires an anesthetic, or
a non-surgical invasive procedure, such as gastrointestinal endoscopy or
a dental procedure, in which a general anesthetic is not required. In
addition, we will use warfarin to represent oral anticoagulants (vitamin K
antagonists).
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Objectives
1) To provide a practical guide that clinicians and other health care
providers can use for the management of patients who require
temporary interruption of warfarin for surgery.
2) To identify patient groups at increased risk for thromboembolic
events, in whom peri-operative bridging anticoagulation with
LWMH or UFH should be considered.
3) To identify patient groups who are at increased risk for postoperative bleeding in whom anticoagulation should be used with
caution.
4) To address frequently encountered questions in patients who are
receiving warfarin therapy and require management of perioperative anticoagulation.
4
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Frequently-Asked Questions
General Issues
1) What is ‘bridging anticoagulation’?
Bridging anticoagulation refers to the administration of therapeutic-dose
(or full-dose) anticoagulant therapy with LMWH or UFH for the 8 to 10 day
period before and after surgery, during which time warfarin therapy is
interrupted and its anticoagulant effect is below the target therapeutic
range. The use of a short-acting anticoagulant, such as LMWH or UFH, in
the peri-operative period allows an anticoagulant effect to be present until
just before surgery, and allows the resumption of therapeutic anticoagulation
within 24 hours after surgery, at the earliest. This management approach
minimizes the time period that patients are not receiving therapeutic-dose
anticoagulation in the peri-operative period and, therefore, is intended to
minimize the risk of potentially devastating thromboembolic events due to
sub-therapeutic anticoagulation, such as a stroke, systemic embolism or
prosthetic heart valve thrombosis 24,25.
2) In which patients should bridging anticoagulation be considered?
There are no universally accepted guidelines as to which patients who
require interruption of warfarin therapy should receive bridging anticoagulation. In general, bridging anticoagulant should be considered in patients at
moderate or high risk for developing a thromboembolic event. Bridging anticoagulation is optional in patients at low risk for a thromboembolic event.
3) Can patients undergo surgery or other invasive procedure without
interruption of warfarin therapy?
Although there are no clinical trials addressing this issue, most surgeons
prefer that warfarin therapy is interrupted prior to a surgical or other nonsurgical invasive procedure to allow normal or near-normal hemostasis at the
time of the procedure and, thereby, minimize the risk for bleeding. However,
some physicians consider that the risk for bleeding has been overstated and
suggest that warfarin therapy does not require interruption prior to many
procedures 26. Ultimately, a discussion with the attending surgeon or interventionist will guide whether interruption of warfarin is required since for
many procedures, such as cataract surgery or dental extractions, warfarin
therapy can be continued without interruption 27-29.
4) What is the traditional approach to bridging anticoagulation?
This involves hospitalizing patients 4-5 days before surgery to stop warfarin
and start intravenous UFH while the anticoagulant effect of warfarin recedes.
UFH is stopped, typically, 3-4 hours before the procedure to avoid a residual
anticoagulant effect at the time of the procedure. After the procedure,
warfarin and UFH are resumed within 24 hours, the later for 4-5 days until
therapeutic anticoagulation with warfarin is re-established. Because of
unpredictable pharmacokinetics, use of UFH requires once- or twice-daily
laboratory monitoring with activated partial thromboplastin time (aPTT)
testing. Intravenous UFH is no longer widely used for bridging anticoagulation because of constraints on hospital bed availability and the increasing
number of surgical and other invasive procedures performed without
hospitalization or with a short, overnight, hospitalization.
5
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5) Why is a more novel approach to bridging anticoagulation with
LMWH more appealing?
LMWH therapy is more convenient for peri-operative anticoagulant management
because it can be administered as a fixed, weight-adjusted subcutaneous injection,
without the need for laboratory monitoring. Consequently, the use of LMWH as
bridging anticoagulant therapy obviates the need for hospitalization for perioperative anticoagulation, and can simplify patient care. Furthermore, this
strategy has the potential to substantially reduce health care costs 30,31.
6) What are current consensus recommendations regarding
bridging anticoagulation?
Consensus groups that include the American College of Cardiology /American
Heart Association Task Force on Practice Guidelines and the American College of
Chest Physicians recommend bridging anticoagulant therapy in patients at 'high
risk' for thromboembolism, although the definition of such 'high-risk' patients is
not clear 8,14. In patients at low or moderate risk for thromboembolism, there are
no clear guidelines regarding the need for bridging anticoagulation.
7) What are current recommendations from experts regarding
bridging anticoagulation?
Among thrombosis experts, there is no consensus as to which patients should
receive bridging anticoagulation. Some experts have argued that, with the
exception of a minority of patients who have had a thromboembolic event within
the preceding month, the risk of thromboembolism during the period of warfarin
interruption has been overstated, and is outweighed by the risk of postoperative
bleeding due to bridging anticoagulation 4,32. Other authorities do not specify
which patients should receive bridging anticoagulation. There is agreement,
however, on the need for randomized trials of bridging anticoagulation strategies
to better inform clinical practice.
8) What is the current practice of physicians in regards to
bridging anticoagulation?
Based on recent surveys of physician practices regarding bridging anticoagulation,
as outlined in Table 1, it appears that over 90% of physicians prefer bridging anticoagulation with therapeutic-dose LMWH or UFH in 'high-risk' patients, whereas
40-80% of physicians prefer bridging anticoagulation in low to moderate risk
patients 15-18.
9) What is the evidence that temporary interruption of warfarin increases
the risk for thromboembolism?
There are no prospective trials to assess the risk for thromboembolism
during temporary interruption of warfarin when bridging anticoagulation is
not administered. Consequently, there are no reliable estimates of the risk
for thromboembolism when warfarin is simply stopped and re-started but
without intervening bridging anticoagulation. It has been postulated,
however, that temporary interruption of warfarin or aspirin may result in a
rebound hypercoagulable state, through mechanisms that include increased
thrombin generation and platelet hyper-reactivity 33-35. Furthermore, such
effects may be compounded by the prothrombotic biochemical milieu that
can occur during the intra-operative and immediate post-operative period 35.
6
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10) Are there any clinical trials of bridging anticoagulation?
To date, there are no randomised controlled trials assessing different bridging
anticoagulation management strategies. In recent years, however, there have
been several non-randomised trials, summarized in Table 2, assessing the use
of LMWH as bridging anticoagulation in patients who require temporary
warfarin interruption 19-23. In general, these trials found that the use of LMWH
as bridging anticoagulation appears safe and there appears to be a low risk
(<2%) of thromboembolic events with this management strategy. The main
limitation of these studies is the lack of a comparison group in which a prespecified bridging anticoagulation strategy, such as pre- and post-operative
LMWH, is compared to other peri-operative management strategies.
Patient Stratification According to the Risk of Thromboembolism
11) What patient groups are considered to be at moderate to high risk of a
thromboembolic event, in whom bridging anticoagulation should be considered?
The risk of a thromboembolic event is dependent on the underlying disease
in which warfarin therapy is indicated, and the presence or absence of additional thromboembolic risk factors. Patients with a mechanical heart valve,
chronic atrial fibrillation, and venous thromboembolism are classified in
Table 3, Table 4, and Table 5, respectively according to the risk (i.e., high,
moderate, or low) of thromboembolism during temporary interruption of
warfarin therapy.
12) Should all patients with a mechanical prosthetic heart valve receive
bridging anticoagulant therapy?
Bridging anticoagulant therapy should be considered in patients with a
mechanical prosthetic heart valve who are at high or moderate risk for
stroke or valve thrombosis (Table 3). In such patients, the risk of a thromboembolic event is determined by the type and position of the prosthetic
valve, and the presence of additional risk factors for stroke and intra-cardiac
thrombosis 5,6,14,36.
In patients who are probably at high risk for thromboembolism, such as
those with a recent (within 3 months) stroke or transient ischemic attack
(TIA), a mitral valve prosthesis, or an older aortic valve prosthesis
(eg., caged-ball, tilting disc), bridging anticoagulation is recommended. In
patients at moderate risk for thromboembolism, such as those with a newer
aortic valve prosthesis (eg., bileaflet) and ≥2 stroke risk factors, bridging
anticoagulation should be considered. Finally, in patients who are probably
at low risk for thromboembolism, such as those with a newer aorti of INR
levels before surgery.
13) Should all patients with chronic atrial fibrillation receive
bridging anticoagulant therapy?
7
Bridging anticoagulation should be considered in selected patients with
chronic atrial fibrillation who are at high or moderate risk for stroke (Table
4). High-risk patients include those with a recent (within 3 months) stroke
or TIA, and patients with rheumatic valvular heart disease 37,38. Recently, a
scoring system (CHADs) was developed to assess risk for stroke in patients
with nonvalvular atrial fibrillation 39. The score is calculated based on the
number of risk factors a patient has: a prior stroke or TIA counts as 2
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points; congestive heart failure, hypertension, diabetes, and age >75 years
each count as 1 point. Bridging anticoagulation would be recommended in
patients with a CHADs score of 5-6, who are at high risk for stroke, and
should be considered in patients with a score of 3-4, who are at moderate
risk for stroke. In low-risk patients, with a score <3, bridging anticoagulation is optional and probably not needed.
CHADs Score
interval)
0
1
2
3
4
5
6
Risk Category
low
low
low
moderate
moderate
high
high
Annual (%) Risk for Score
(95% confidence
1.9 (1.2 - 3.0)
2.8 (2.0 - 3.8)
4.0 (3.1 - 5.1)
5.9 (4.6 - 7.3)
8.5 (6.3 - 11.1)
12.5 (8.2 - 17.5)
18.5 (10.5 - 27.4)
14) Should all patients with venous thromboembolism receive bridging
anticoagulant therapy?
Bridging anticoagulant therapy should be considered in selected patients
with venous thromboembolism (deep vein thrombosis and pulmonary
embolism) who are at high or moderate risk of disease recurrence (Table 5).
Bridging anticoagulation would be recommended in high-risk patients who
have had a recent (within
3 months) episode of venous thromboembolism 40,41, and considered in moderate risk patients who have an antiphospholipid antibody, a deficiency in protein C,
protein S or antithrombin, or active malignant disease (metastatic or treated
within 6 months) 41-43. In low-risk patients who do not satisfy these criteria,
bridging anticoagulation is optional and probably not needed.
15) What about patients who had thromboembolism during prior
interruption of warfarin therapy?
Such patients may warrant special consideration despite the lack of data pertaining to the risk of thromboembolism during subsequent episodes of warfarin interruption. Patient and physician concern about recurrent thromboembolism may warrant the need for bridging anticoagulation, irrespective
of the baseline risk as determined by discussed in Questions 12 to 14.
16) What patient groups are considered to be at increased risk of
postoperative bleeding?
The risk of postoperative bleeding in patients can be estimated based on surgical and non-surgical factors. Non-surgical factors include uremia, thrombocytopenia or a coagulation factor deficiency, active peptic ulcer disease and a
recent bleeding episode. The type of surgery is an important consideration in
determining a patient's postoperative bleeding risk 6. In Table 6, an overview
is provided of the bleeding risk associated with different types of surgery.
8
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Anticoagulant Management Before Surgery
17) When should patients be assessed for bridging anticoagulation?
Ideally, patients should be assessed 7-10 days prior to an elective surgical
procedure to allow enough time for the warfarin anticoagulant effect to
recede. Adequate time before surgery is also required to instruct patients
about LMWH self-injection and to arrange for laboratory testing on the day
before surgery, so as to ensure a normalized INR at the time of the procedure,
18) How many days prior to surgery should anticoagulant therapy be stopped so
there is no residual anticoagulant effect at the time of surgery?
Although the pharmacokinetic properties of warfarin differ between patients,
stopping warfarin 4 to 5 days before surgery will, in the vast majority of
patients, ensure that there is normal hemostasis at the time of surgery; with
an INR <1.3 44,45. Elderly patients may require a longer time for the INR to
normalize after warfarin is stopped. In patients who are receiving warfarin
with a target INR of 2.0 to 3.0, we recommend that warfarin is stopped 5 days
before surgery (see Figure 1).
19) What about stopping warfarin in patients who have a target INR of 2.5 to 3.5?
In such patients, warfarin should be stopped 6 days before surgery, especially
if the most recent INR was in the upper part of the therapeutic range or above
3.5. This will allow additional time for the INR to drift into the normal range.
20) What about patients who are receiving a coumarin derivative
such as phenprocoumon?
Although there is no known therapeutic advantage to using phenprocoumon
or other coumarin derivatives over warfarin, there are implications for bridging
anticoagulation. Phenprocoumon has a longer half-life than warfarin (~4 days
vs. ~2 days) and, consequently requires a longer time after treatment is
interrupted for its anticoagulant effect to be eliminated. In patients who are
receiving phenprocoumon and require surgery, this treatment should be
stopped 8 to 10 days prior to the procedure, thereby warranting consideration
for a longer period of bridging anticoagulation.
21) Should you always check the INR before surgery to make sure
that it has normalized?
We routinely measure the INR the day before surgery to make sure that it has
normalized (i.e., INR = 1.3) or is near normalized (i.e., INR = 1.4). This is
done because patients with a moderately elevated INR of 1.5 or higher are at
increased risk of postoperative bleeding complications 46. Thus, if the INR is
1.5 or higher, we administer 1 mg of vitamin K orally. This will ensure that
the INR normalizes by the time of surgery. Furthermore, this small dose of
vitamin K is not likely to interfere with re-anticoagulation when warfarin
therapy is resumed after surgery 47,48. In patients who receive vitamin K, it is
also reasonable to measure the INR on the morning of surgery to 'doublecheck' that the INR has normalized.
9
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22) Why not just measure the INR on the morning of surgery?
If the INR is measured only on the morning of surgery, there is a small
chance that a patient will have an INR level that is too high to allow surgery
(i.e., INR = 1.5). In such patients, vitamin K will not rapidly reverse the
elevated INR, and the patient will require 2 to 4 units of fresh frozen plasma
to normalize the INR. However, transfusion of blood products in this circumstance is avoidable with appropriate monitoring of INR levels before surgery.
23) If patients are also receiving an antiplatelet drug, when should this be stopped?
Patients who are receiving warfarin may also be receiving treatment with an
antiplatelet drug, usually ASA, 81 mg daily, or clopidogrel, 75 mg daily.
Since ASA and other antiplatelet drugs such as clopidogrel irreversibly
inhibit platelet function, ASA should be stopped 7-10 days (average lifespan
of a platelet) prior to the planned surgery or invasive procedure to ensure
normal hemostasis at the time of the procedure (see Figure 1).
24) If bridging anticoagulant therapy with LMWH is used, when should
it be started before surgery?
Bridging anticoagulation with LMWH, typically, is started 3 to 4 days before
surgery, when a patient's INR is below or is expected to be below the lower
limit of the target therapeutic range. In most patients with a mechanical
heart valve who have a target INR of 2.5-3.5, bridging anticoagulation can
be started when the INR is <2.5, whereas in patients with chronic atrial
fibrillation or venous thromboembolism, it can be started when the INR is <2.0.
In many instances, one will not know when the INR 'drifts below the therapeutic range', unless daily INR testing is done after stopping warfarin, which
is impractical. It is reasonable to estimate when the INR will be below the
therapeutic range, and when LMWH should be started. For example, if INR
testing is done 5 days before the planned surgery and the INR level is 3.0 on
that day, it is reasonable to assume that the INR level will be sub-therapeutic
(i.e., INR <2.5) 2 days later. Thus, LMWH can be started empirically 2 days
after warfarin is stopped.
LMWHs should be used with caution in patients with renal insufficiency.
LMWHs are primarily cleared by the kidney and may accumulate in patients
with impaired renal function, with the potential for an excessive anticoagulant effect and intra-operative bleeding 49. Thus, renal function should be
assessed in all patients who are being considered for bridging anticoagulation with LMWH. If LMWH is to be used in such patients, tinzaparin may be
the preferred LMWH based on studies in which tinzaparin was safely used for
the treatment of venous thromboembolism in patients with impaired renal
function. However, there are no studies assessing tinzaparin as bridging
anticoagulation in patients with impaired renal function.
25) When should the last dose of LMWH be administered before surgery?
10
If once-daily LMWH is used as bridging anticoagulant therapy (eg., tinzaparin, 175 IU/kg once-daily), the dose should be administered in the mornings, and with last pre-operative dose administered on the morning of the
day before surgery, and at least 24 hours before surgery. If twice-daily LMWH
is used (eg., enoxaparin, 1 mg /kg twice-daily), the evening dose on the day
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before surgery should be omitted. In this way, the last dose of LMWH will be
administered at least 24 hours before surgery.
26) Should the anticoagulant effect of the LMWH be measured on the day of
surgery to ensure no residual anticoagulant effect prior to surgery?
The anticoagulant effect of LMWH is measured by the anti-factor Xa (or antiXa) level. The aPTT does not reliably measure the anticoagulant effect of
LMWH. Anti-Xa level testing should not be routinely done in patients who are
receiving LMWH because this testing is not available in many hospital or clinic
laboratories and the results may not be available for several hours, which is
impractical in patients who are scheduled for surgery on the same day.
Furthermore, since LMWHs have a predictable pharmacokinetic profile and
elimination half-lives of 3-4 hours, there should not be a clinically important
residual anticoagulant when the last pre-procedure dose is administered 24
hours prior to surgery.
Anticoagulant Management After Surgery
27) When should LMWH be restarted after surgery?
The decision to resume LMWH after surgery is dependent on two factors: 1)
Whether there is adequate postoperative hemostasis, and 2) the risk of bleeding associated with the surgical procedure. If there is ongoing bleeding after
surgery, as detected by blood accumulation into a surgical drain, the start of
LMWH should be deferred until the bleeding has subsided. In general, most
postoperative bleeding will resolve within 24 hours after surgery.
If there is adequate postoperative hemostasis after surgery, the decision to
resume anticoagulant therapy will depend on the bleeding risk associated with
the surgical procedure. In Table 6, we classify different types of surgery according to their risk of postoperative bleeding (high, moderate, low). In patients
undergoing surgery that is associated with a high risk of bleeding, such as
urologic and neurosurgical procedures 6,19,50,51, the resumption of LMWH should
be deferred for at least 48-72 hours after surgery and, preferably, after discussion with the attending surgeon. In patients undergoing surgery that is associated with a moderate risk of bleeding, such as intra-abdominal surgery, the
resumption of LMWH should be delayed until 24-48 hours after surgery. In
patients undergoing surgery that is associated with a low risk of bleeding,
LMWH can be resumed 24 hours after surgery, usually the day after the procedure.
28) What dose of LMWH should be used after surgery?
In general, the same dose regimen used before surgery should be administered
after surgery, but the timing of when LMWH is to be resumed after surgery will
vary depending on whether there is adequate post-operative hemostasis and
risk of bleeding associated with the procedure.
29) Are there circumstances when LMWH should NOT be given after surgery?
11
There may be patients in whom bridging anticoagulation should be
considered before but not after surgery. Such patients include those who
have had excessive post-operative bleeding or have undergone a procedure
associated with a very high risk for bleeding (eg., intracranial neoplasm,
coronary artery bypass surgery). It is always helpful to discuss such high risk
patients with the attending surgeon to better understand patient-specific
issues relating to bleeding risk and to discuss the initiation of post-operative
anticoagulation.
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30) What about preventing deep vein thrombosis in patients in whom
post-operative LMWH is delayed or not given at all?
In patients who receive no post-operative LMWH as bridging anticoagulation
and in those in whom post-operative LMWH is delayed for 2-3 days or longer,
there may be concern that such patients may not be protected against DVT.
All patients will be resuming warfarin, administered to achieve a target INR
>2.0, and this treatment may be considered adequate prophylaxis against
DVT [52]. However, if there are concerns that warfarin alone may be insufficient as stand-alone treatment to prevent DVT, because of a delayed anticoagulant effect, it is reasonable to administer prophylactic-dose (or low-dose)
LMWH, assuming this does not pose a major bleeding risk, for the 3-5 days
after surgery until the INR is within the therapeutic range.
31) What is considered excessive post-operative bleeding?
The assessment of postoperative bleeding is subjective and will vary depending on the type of surgery 19,53. For example, patients who undergo prostatectomy routinely have postoperative hematuria, and this may persist for 24 to
72 hours after surgery. In such patients, it is prudent to withhold LMWH
until the hematuria is subsiding, that is, when the urine becomes pinkcoloured. In patients who undergo neurosurgery, a small amount of bleeding
may be associated with serious complications such as intracranial hemorrhage. In such patients, anticoagulation should be delayed for at least 24 to
48 hours after surgery. In general, we recommend consultation with the surgeon to assess if there is excessive bleeding after surgery, and to help guide
decisions about the resumption of anticoagulant therapy.
32) How should patients be managed when they have unexpected
postoperative bleeding?
In patients who develop postoperative major bleeding, defined by the need
for transfusion of >2 units of packed red blood cells, need for re-operation
or serious bleeding (eg., intra-cranial, intra-thoracic, retroperitoneal), all
anticoagulants should be withheld until the bleeding source has been identified and treated. Treatment to
reverse the effect of antithrombotic therapy may include one or
more of the following: fresh frozen plasma; recombinant coagulation factor
VII; platelets; protamine sulfate.
The resumption of anticoagulants is superseded by the need to prevent
further bleeding. If the cause of the bleeding is readily reversible, as with
the repair of a severed blood vessel that inadvertently occurred during
surgery, anticoagulants probably can be resumed within 24 hours. On the
other hand, if the bleeding is unlikely to resolve quickly, as with a large
gastric ulcer, the resumption of anticoagulants should be deferred for one
to two weeks, or longer, depending on the size of the ulcer and whether
there was active bleeding at the time of the gastroscopy 54,55. Repeat gastroscopy may be warranted 1-2 weeks after starting anti-ulcer therapy to
ensure ulcers have healed sufficiently and are unlikely to re-bleed if
anticoagulation is restarted.
12
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33) When should warfarin be restarted after surgery, assuming adequate
postoperative hemostasis?
In most patients, warfarin can be restarted on the evening after surgery.
A significant anticoagulant effect of warfarin will not occur for at least 24
hours after the initial dose of warfarin, and a full anticoagulant effect will
not occur for 4 to 5 days after the start of warfarin. Consequently, the
resumption of warfarin on the evening after surgery should not affect
postoperative hemostasis.
34) What is the usual starting dose of warfarin after surgery?
In general, we administer 5 mg of warfarin on the evening after surgery. If a
patient usually receives a higher or lower daily dose of warfarin, it is reasonable to start re-anticoagulation with that dose (see Figure 1).
35) What if a patient is using an irregular dose regimen of warfarin?
Some patients who receive warfarin therapy require an irregular dosing
regimen, such as 7.5 mg on Mondays, Wednesdays, and Fridays, and 5 mg
on the other days of the week. In such patients, it is reasonable to resume
warfarin so the usual day-to-day sequence of warfarin dosing is maintained.
For example, if the aforementioned patient had surgery on a Tuesday, the
first dose of warfarin would be 5 mg the evening after surgery, followed by
7.5 mg the next day. Resuming a patient's usual warfarin dose regimen after
surgery will minimize uncertainty about warfarin dosing for the patient, and
is less likely to result in dose errors.
36) Does the post-operative dose of warfarin change if a patient required
vitamin K before surgery?
If a patient received high-dose vitamin K before surgery (i.e., 5 to 10 mg), this
may result in resistance to re-anticoagulation when warfarin is resumed.
Because it is difficult to predict the warfarin dose requirements of such
patients, we administer double their usual dose of warfarin for two consecutive
days after surgery. In addition, we monitor the INR more frequently after
surgery to detect persistently low INR levels, if they occur, and to adjust the
dose of warfarin accordingly. If low-dose vitamin K is administered before surgery
(i.e., 1 to 2 mg), resistance to re-anticoagulation is unlikely. Nonetheless, it
is reasonable to double the first dose of warfarin in such patients, and to
resume the usual dose of warfarin on the following day.
37) When should the LMWH be stopped after surgery?
LMWH should be stopped when a patient's INR level is within the target
therapeutic range. Preferably, INR testing should be done on day 3, and day 5
after surgery. The timing of postoperative INR testing may vary by one day
earlier or later, depending on the day of the week that the surgery was done
and patient availability for blood testing. In most patients, with a target INR
of 2.0-3.0, LMWH will be required for 3 to 4 days after surgery, and in
patients with a target INR of 2.5-3.5, 4 to 5 days of LMWH will be required.
38) Is it necessary to measure the aPTT after surgery?
Measuring the aPTT testing after surgery is not necessary when a patient is
receiving LMWH because the aPTT test does not measure the anticoagulant
effect of LMWH.
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39) When should antiplatelet therapy be resumed after surgery?
In general, antiplatelet therapy such as ASA can be resumed on the same day
as warfarin.
Specialized Patient Groups
40) How do I manage anticoagulation in a patient who has an indwelling epidural
catheter that is used to administer analgesia after surgery?
The anticoagulant management of patients with an indwelling epidural
catheter is problematic because of concerns that such patients might develop
an epidural haematoma, which is a rare but devastating complication 56. In
general, the epidural catheter should be removed before LMWH is started
after surgery. In our practice, we are comfortable administering LMWH while
a patient is also receiving continuous epidural analgesia through an
indwelling epidural catheter if the following criteria are satisfied 57,58:
i) epidural catheter placement was not traumatic
ii) only low-dose, once-daily, LMWH is administered (as outlined in Table 5)
iii) warfarin therapy is not started until after the epidural catheter is removed
iv) the epidural catheter is removed during the trough anticoagulant effect
of the LMWH, corresponding to 18 to 22 hours after the preceding dose
v) other drugs that impair haemostasis, such as aspirin or NSAIDs, are
avoided until the epidural catheter is removed
41) What about anticoagulant management in patients who receive spinal (regional)
anaesthesia and have the epidural catheter removed immediately after surgery?
If the epidural catheter was used only to administer intra-operative anaesthesia and was removed after surgery, it is safe to resume anticoagulant therapy
within 12 hours of surgery. However, if the epidural catheter placement was
traumatic, the resumption of anticoagulant therapy probably should be
delayed for at least 24 hours after surgery.
42) Are there patients in whom one should consider UFH (standard heparin)
instead of LMWH for bridging anticoagulant therapy?
In patients with moderate-to-severe renal insufficiency, defined by a serum
creatinine >150 mmol/L or a creatinine clearance <40 mL/min, UFH is
the anticoagulant of choice because its clearance will not be significantly
impaired in the presence of renal insufficiency. On the other hand, LMWH is
eliminated primarily by the kidney and, therefore, can accumulate in
patients with renal insufficiency, with the potential to cause bleeding
complications after surgery.
14
If LMWH must be used in such patients with moderate-to-severe renal insufficiency, the anticoagulant effect of LMWH should be measured with anti-Xa
levels done 4 hours after the LMWH dose. The targeted therapeutic anti-Xa
level with LMWH is 0.5 to 1.0 anti-Xa units/mL. In regard to the choice of a
LMWH, there are differences in LMWH preparations that may favour the
use of tinzaparin in such patients. In 2 studies of elderly patients with ageassociated renal impairment, treatment with tinzaparin 175 IU/kg for
10 days was not associated with an excessive anticoagulant effect or an
increased risk for bleeding complications 59, 60. This observation is in contrast
to findings reported with other LMWH preparations, suggesting that the
renal clearance differs between LMWH preparations 49, 61.
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43) How does one manage peri-operative anticoagulation
in a patient with renal insufficiency?
If UFH is used for bridging anticoagulant therapy, the conventional approach
is to administer UFH intravenously in the peri-operative period, which
requires that patients are hospitalized for about 3 to 4 days before and 3 to
4 days after surgery. If intravenous UFH is used pre-operatively, the infusion
should be stopped at least 4 hours before surgery. In the post-operative
period, intravenous UFH can be resumed 12 to 24 hours after surgery.
However, we avoid using a standardized heparin nomogram because of the
unpredictable dose-response effect with UFH and the potential that patients
will develop a very high aPTT (i.e., >150 seconds) that might increase the
risk of bleeding complications [63]. Instead, we use a more conservative
dosing regimen of intravenous UFH, with a target aPTT of 45 to 60 seconds
rather than the target aPTT of 60 to 80 seconds as used with a heparin
nomogram.
The disadvantage of this approach is that it requires physician adjustment
of the UFH infusion rate. An alternative approach for peri-operative UFH
administration is to administer UFH with twice-daily subcutaneous
injections, which would allow outpatient treatment. However, this
management approach also requires daily aPTT testing 6 hours after
the morning UFH dose to monitor the anticoagulant effect, and to
adjust the dose of subcutaneous UFH 64.
44) What about the patient with renal insufficiency in whom
intravenous UFH is not feasible?
In such patients, management options include the use of subcutaneously
administered UFH. This can be done with by using a standard dose of 15,000
to 17,500 IU twice-daily and measuring the mid-interval aPTT 6 hours after
preceding dose of UFH, with the target aPTT 1.5-2.0 times the control value.
An emerging alternative approach to administer UFH is a weight-based,
fixed-dose regimen of UFH, 250 IU/kg, without the need to aPTT monitoring.
LMWHs can be administered with caution in patients who have impaired
renal function and, probably, with laboratory monitoring of anti-Xa levels
4 hours after the LWMH dose and with the anti-Xa level to not exceed
1.0 anti-Xa units/mL. If this is done, there is evidence that tinzaparin is
the LMWH-of-choice since it appears to be safer in patients with impaired
renal function, possible because it is less dependent on renal elimination
than other LMWHs 59, 60.
45) What about LMWH dosing in the obese patient?
In obese patients, who typically weigh >100 kg, there is uncertainty as to
whether the dose of LMWH for bridging anticoagulation should be 'capped'
at a maximum dose or if the dose should be based on body weight without
capping. For example, in a 120 kg person, the capped dose of the LMWH
tinzaparin would be 18,000 IU whereas the weight-based dose would be
21,000 IU. Although there are no studies comparing 'capped' vs. 'weightbased' dosing in obese patients, recent trials have found 'weight-based'
dosing with tinzaparin (175 IU/kg) was safe, with no increase in bleeding,
and not associated with an excessive anticoagulant effect 65,66. In the perioperative setting, most trials have used a 'capped' dosing, possibly because
of concerns of an excessive anticoagulant effect in a susceptible patient
group that is undergoing surgery.
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46) How do I manage the patient with a history of heparin-induced thrombocytopenia?
Heparin-induced thrombocytopenia (HIT) is an immune-mediated thrombocytopenia that occurs in patients who have received UFH and is associated
with thrombotic complications that include venous limb gangrene, stroke,
and myocardial infarction 67. In patients with prior HIT, all heparin preparations, including LMWHs, should be avoided. In such patients, danaparoid, a
low-molecular-weight heparinoid that has minimal cross-reactivity with UFH
is a safe alternative anticoagulant. The dose of danaparoid is 1250-2500 IU
twice-daily subcutaneously, starting on the day after surgery. One limitation
of danaparoid is that, like LMWHs, it is cleared by the kidneys and should be
avoided or used with caution in patients with renal insufficiency.
47) What other approved treatment options are available for the management
of patients with HIT?
Since danaparoid is not available in some countries, there are 2 alternative
anticoagulants for the treatment of HIT: argatroban and lipirudin 68,69.
Argatroban is a direct thrombin inhibitor that is given intravenously, with a
starting dose of 2 mg/kg/min, to achieve a target aPTT of 1.5- to 3.0-times
the baseline aPTT. Argatroban is cleared by the liver and should be avoided
or used with caution in patients with impaired hepatic function. It has a
half-life of 40-50 minutes, thereby allowing rapid elimination from the
circulation after the infusion is stopped. Because argatroban prolongs the
INR, care should be taken when argatroban is used as bridging anticoagulant
after temporary interruption of warfarin.
Lepirudin (recombinant hirudin) is a direct thrombin inhibitor that is given
intravenously or subcutaneously with a loading dose of 0.4 mg/kg over 15 to
20 minutes followed by a continuous infusion of 0.15 mg/kg/hr for 2-10 days.
Lepirudin can also be administered by subcutaneous injection. Lepirudin is
cleared by the kidney and should be avoided or used with caution in patients
with impaired renal function. It has a half-life of 80 minutes, thereby allowing
relatively rapid elimination after the infusion is stopped.
48) Does the overall anticoagulant management differ in patients who have
outpatient surgery and those who are hospitalized?
There should be no difference in the anticoagulant management of patients
who are hospitalized and those who have outpatient surgery. Hospitalized
patients are likely to undergo more frequent blood testing, as part of routine
postoperative care. Consequently, it is reasonable to perform more frequent
INR and hemoglobin testing while a patient is hospitalized. Peri-operative
management of anticoagulation in an outpatient setting has been shown to
reduce health care costs.
49) How should warfarin therapy be managed in patients at low risk of
thromboembolism in whom LMWH is not used as bridging therapy?
16
The management of warfarin therapy in low-risk patients who do not require
bridging anticoagulant therapy with LMWH is similar to that of patients who
receive bridging anticoagulant therapy. Thus, warfarin should be stopped 5 to
6 days before surgery, with INR testing performed on the day before surgery.
Warfarin can be restarted on the day of surgery if there is adequate postoperative hemostasis. The dose of warfarin after surgery should be the same as that
which the patient was receiving before its interruption.Because the INR level
will not be used to guide discontinuation of LMWH, these patients do not
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require INR monitoring as frequently after surgery. An INR test can be done 5
days after surgery to ensure that the INR is within the targeted therapeutic
range, and to allow subsequent warfarin dose adjustments.
50) What is the anticoagulant management in patients who have
major post-operative bleeding?
Patients who develop major postoperative bleeding while receiving bridging
anticoagulation should receive a transfusion of red blood cells and other
blood products as required after all anticoagulants are withheld. The source
of the bleeding should be identified and corrected whenever possible. In
patients who already have a prolonged INR due to postoperative warfarin,
should receive 2.5-5.0 mg intravenous vitamin K in addition to fresh frozen
plasma.
In patients who are receiving UFH or LMWH, protamine sulphate should be
given. The dose of protamine is determined by assuming that 1 mg of protamine will neutralize the anticoagulant activity of 100 IU of UFH. In most
patients who have received therapeutic-dose UFH, the dose of protamine is
25-50 mg by slow intravenous infusion. Protamine also can be given to
partially reverse the anticoagulant effect of LMWH, particularly in a bleeding
patient who has received a therapeutic dose of LMWH within 6 to 8 hours.
Since the half-life of protamine is less than that of LMWH, additional doses
of protamine may be required, every 3-4 hours, until the LMWH is cleared.
LMWHs differ in their ability to be neutralized by protamine sulphate due to
different degrees of sulfation content, with tinzaparin being most effectively
neutralized 62.
Other Patient-related Issues with Bridging Anticoagulation
51) How easy is it for patients to self-inject LMWH for bridging anticoagulation?
Most patients who are assessed for bridging anticoagulation can be taught to
self-inject LMWH and often find it easer than they expected. Showing patients
how to administer LMWH through pictures, short videos, or demonstrations
is essential to facilitate self-injection. To provide reassurance, patients may be
asked to administer the first dose of LMWH under observation of the nurse to
ensure that the proper technique is followed.
52) How does one manage patients who have persistently elevated INRs
on the day before surgery?
INR testing should be done, whenever feasible, on the day before surgery to
ensure a normal INR and to administer low-dose (1 mg) oral vitamin K in
patients with an INR >1.5. To facilitate this process, we routinely provide
patients with vitamin K (in tablet or liquid form). If INR testing, which is
typically done outside of the hospital clinic setting, reveals an INR >1.5 the
day before surgery, the patient is instructed to take the vitamin K, thereby
ensuring normal hemostasis on the day of surgery and avoiding the administration of blood products or cancellation of surgery if the INR is >1.5 on the
day of the procedure.
53) How does one facilitate communication between caregivers involved in a
patient who requires temporary interruption of warfarin and is receiving
bridging anticoagulation?
17
The care of patients who require temporary interruption of warfarin for surgery
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may involve one or more of the following health care providers: internist,
family physician, surgeon, anesthetist, nursing and other allied health care
staff. One way to maintain good communication is to transmit a record of the
patient assessment to these individuals promptly after the patient is assessed.
The increasing availability of an electronic medical record may facilitate this
process.
One approach is the use of a standardized computerized patient record which
can be completed while the patient is being assessed. This record estimates
the patient's risk for thromboembolism and bleeding and outlines the bridging anticoagulation management plan. This record can be sent by e-mail or
fax to all caregivers. A sample medical record is provided in Figure 2. This
approach also streamlines care for patients who are seen on multiple occasions for bridging anticoagulation (eg., yearly surveillance colonoscopy).
54) How can one ensure that patients follow the instructions for
bridging anticoagulation?
Having patients understand bridging anticoagulation can be challenging as
they must understand when to start and stop warfarin, as well as when to
start and stop LMWH the timing of the LMWH doses. To facilitate this and
minimize patient error, a patient instruction sheet can be provided. As outlined in Figure 1, this provides explicit instructions as to the timing and
dose warfarin and LMWH dose to be administered before and after surgery.
18
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Figure and Tables
Figure.1
Suggested Bridging Anticoagulation Patient Instructions
Days in
Date
relation to
(d/m/y)
surgery
-7
-6
-5
-4
-3
-2
-1
SURGERY
Anticoagulant Management
Blood
testing
STOP aspirin/clopidogrel/ticlopidine
STOP warfarin (i.e., no warfarin on this day)
LMWH
LMWH
LMWH
____ units, once- or twice-daily
____ units, once- or twice-daily
____ units, once- or twice-daily
(last dose 24 hours before surgery)
INR
INR
(at bedtime, when there is adequate postoperative
hemostasis)
warfarin ____ mg
+1
LMWH ____ units, once- or twice-daily
(at least 24 hours after surgery, when there is
adequate postoperative hemostasis)
warfarin ____ mg
+2
LMWH ____ units, once- or twice-daily
warfarin ____ mg
+3
LMWH _____ units, once- or twice-daily
warfarin ____ mg
+4
INR
CBC
LMWH _____ units, once- or twice-daily
(if required)
warfarin ____ mg
+5
LMWH _____ units, once- or twice-daily
(if required)
warfarin ____ mg
19
INR
CBC
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Figure 2. Sample Medical Record
Perioperative Bridging Anticoagulation Programme
St. Joseph's Healthcare, Hamilton
Patient Name
Today’s Date
Referring MD
ID:
Family MD
DOB:
Health Card #
INR Lab:
Telephone #
Allergies:
Date of surgery/procedure
History of presenting illness
Reason for Anticoagulation
DVT or PE
Atrial Fibrillation
Coronary Artery Disease
Peripheral Artery Disease
Stroke/Systemic Embolism
Bioprosthetic Heart Valve
Mechanical Heart Valve
Aortic
Mitral
Aortic + Mitral
Valve type and insertion date
Start of anticoagulation
Risk Factors for Thromboembolism
Stroke
Congestive Heart Failure
Thrombophilia
TIA
Peripheral Arterial Disease
Age >75 years
DVT
Coronary Artery Disease
Diabete Mellitus
PE
Hypertension
Prior TE in association with warfarin interruption
Remarks
20
Systemic Embolism
Active Cancer
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Risk Factors for Bleeding
recent (<6 mos) GI bleed
chronic renal disease
active peptic ulcer disease
recent bleed (other)
chronic liver disease
prior peptic ulcer disease
prior bleed (any kind)
thrombocytopenia
age >75 years
(<100)
prior bleed in association with surgery/bridging therapy
potential for spinal anesthesia
potential for post-procedure epidural analgesia
Remarks
Other Relevant Past Medical History
Antithrombotic Therapy
ASA
clopidogrel
NSAID
Other:
warfarin (current dose)
Other Medications
Physical Examination
H&N:
CHEST:
CVS:
ABD:
CNS:
SKIN:
Height:
Remarks
21
ticlopidine
Weight:
ASA-dipyridamole
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LMWH Administration
self inject
family member
requires nursing agency
Laboratory Results
Test
Date
Result
INR
Hemoglobin
Platelets
Creatinine
Thromboembolism Risk Assessment
Bleeding Risk Assessment
Low
Low
Moderate
Moderate
High
High
Assessment and Summary
Bridging Anticoagulation Recommendations
No bridging
Last antiplatelet dose
Last warfarin dose
Pre-procedure
Anticoagulation
Post-procedure
Anticoagulation
Signature
22 James D. Douketis MD, FRCP(C)
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Table 1. Physician Practice Patterns for Bridging Anticoagulation
Survey
Year
(reference)
1998
1
Pre-procedure preference
Patient
Group
mech. mitral valve
mech. aortic valve
Post-procedure preference
UFH or
LMWH
No bridging
therapy
UFH or
LMWH
No bridging
therapy
89–92%
61–66%
n/a
89–90%
51–72%
n/a
n/a
55–80%
n/a
38–77%
61–89%
61–72%
n/a
199816
atrial fibrillation
2002 17
mech. mitral valve
mech. aortic valve
95–96%
67–76%
n/a
200318
mech. mitral valve
mech. aortic valve
94–95%
53–65%
n/a
75–81%
32–45%
n/a
Table 2. Arterial Thromboembolism and Major Bleeding in
Uncontrolled Trials of Bridging Anticoagulation with LMWH
Number
of
patients
Patient
follow-up
(months)
Douketis 19
650
0.5
dalteparin
AF, MHV
0.6%
1.0%
Kovacs
224
3
dalteparin
AF, MHV
1.3%
6.9%
Dunn 21
200
1
enoxaparin
AF
2.3%
3.5%
Spyropoulos 22
595
1
tinzaparin,
dalteparin,
enoxaparin
AF, MHV
0.6%
3.3%
Turpie 23
220
3
enoxaparin
MHV
0.5%
3.5%
Study
(reference)
23
20
LMWH
Reason
Incidence Incidence
for
of major
of
anticoagulation
bleeding
ATE
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Table 3. Perioperative Anticoagulant Management in Patients
with a Mechanical Heart Valve
Thromboembolism
Risk Category
Patient
Characteristics
Suggested Anticoagulant
Management
High Risk
- recent (within 3 months)
stroke or TIA
- any mitral valve
- caged-ball* or tilting-disc†
aortic valve
- bridging anticoagulant
therapy strongly
recommended
Moderate Risk
- bileaflet‡ aortic valve and
≥ stroke risk factors
- bridging anticoagulant
therapy should be
considered
Low Risk
- bileaflet‡ aortic valve and
<2 stroke risk factors
- bridging anticoagulant
therapy is optional
Legend:
*Starr-Edwards valve; †Bjork-Shiley, Medtronic-Hall or Omnicarbon valve;
‡St.Jude or Carbomedics valve.
Stroke Risk Factors
• chronic atrial fibrillation • left ventricular dysfunction • • age >75 years
• hypertension • diabetes mellitus
Table 4.Perioperative Anticoagulant Management in Patients
with Chronic Atrial Fibrillation
Thromboembolism
Risk Category
Patient
Characteristics
Suggested Anticoagulant
Management
High Risk
- recent (within 3 month)
stroke or TIA
- rheumatic mitral valvular
heart disease
- CHADs score of 5 or 6
- bridging anticoagulant
therapy strongly
recommended
Moderate Risk
- CHADs score of 3 or 4
- bridging anticoagulant
therapy should be
considered
Low Risk
- chronic AF and
CHADs score of <3
- bridging anticoagulant
therapy is optional
Legend:
AF = atrial fibrillation, *stroke risk factors (see below).
Stroke Risk Factors
• previous stroke or transient ischemic attack • left ventricular dysfunction
• age >75 years • hypertension • diabetes mellitus
24
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Table 5. Perioperative Anticoagulant Management in Patients
with Venous Thromboembolism
Thromboembolism
Risk Category
Patient
Characteristics
Suggested Anticoagulant
Management
High Risk
- recent (within 1 month)
episode of VTE
- active cancer* or
antiphospholipid
antibody†
- bridging anticoagulant
therapy strongly
recommended
Moderate Risk
- VTE within 6 months
- bridging anticoagulant
therapy should be
considered
- previous VTE occurring
after surgery
Low Risk
- none of the above factors
present
- bridging anticoagulant
therapy is optional
Legend:VTE = venous thromboembolism (includes deep vein thrombosis and pulmonary embolism); *cancer
that has been treated within the past 6 months or is palliative; †anticardiolipin antibody or lupus anticoagulant.
Table 6. Surgery Bleeding Risk Classification
and Postoperative Anticoagulation
Bleeding Risk
Category
Surgery or Invasive
Procedure
Timing of
Postoperative Anticoagulation
Warfarin
25
LMWH
Very High Risk
- intracranial surgery
- spinal surgery
- coronary artery bypass surgery
- heart valve replacement
High Risk
- major vascular surgery
evening of the
- permanent pacemaker insertion
day of surgery
- internal defibrillator placement
- prostatectomy
- bladder tumour resection
- lung resection surgery
- hip/knee joint replacement surgery
- intestinal anastomosis surgery
- bowel polypectomy
- kidney or prostate biopsy
- cervical cone biopsy
Moderate Risk
- other intra-abdominal surgery
- other intra-thoracic surgery
- other orthopaedic surgery
- dental surgery
evening of the day 24 to 48 hours
of surgery
after surgery
Low Risk
- cataract extraction
- most cutaneous surgery
- laparoscopic cholecystectomy
or hernia repair
- single dental extraction
evening of the day
of surgery
first or second day >72 hours after
after surgery
surgery or consider
no post-operative
LMWH
24 to 48 hours
after surgery
24 after surgery
(ie., day after
surgery)
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Table 7. Low-molecular-weight Heparin Dose Regimens
LMWH
(generic name)
LMWH
(proprietary name)
Dose
(subcutaneous)
Dalteparin
Fragmin
100 IU/kg, twice-daily
Enoxaparin
Lovenox
1 mg/kg, twice-daily
Nadroparin
Fraxiparine
171 IU/kg, once-daily
Tinzaparin
Innohep
175 IU/kg, once-daily
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