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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3829_Библиотеки_им_академика_М_И_Перельмана
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Cancer patients undergoing surgery have a two- to ve-fold
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increased risk for postoperative VTE, compared with
28
noncancer patients undergoing the same procedures.
In
addition, among patients with DVT, those with cancer
have a more than two-fold higher risk for VTE recurrence
than those without cancer. In a retrospective study of 986
patients who underwent venous ultrasonography because of
suspected DVT, 12% of patients with con rmed DVT were
29
subsequently found to have cancer.
e likelihood for
development of VTE in cancer patients is increased among
those with more advanced clinical disease, and varies by
tumor type. Malignancies stemming from the uterus, brain,
ovary, pancreas, stomach, kidneys, and colon are among
those that have been associated with the highest relative risk
30
for VTE.
In a prospective multicenter registry from Italy
including more than 2,300 patients undergoing surgery for
cancer, PE was the main cause of postoperative death. In a
multivariable analysis from this study, ve independent risk
factors of VTE were identi ed:age above 60years, previous
VTE, advanced cancer, anesthesia longer than 2 h, and bed
31
rest longer than3d.
Acquired or inherited thrombophilia disorders can
also increase risk of VTE. Amutation in the factor V gene,
known as Factor V Leiden, is the most common cause of
32
familial thrombophilia.
is mutation can increase the
risk of VTE y- to eighty-fold over that of the general
population in individuals who are homozygous for the
mutation and three-fold in heterozygous individuals. e
second most common cause of familial thrombophilia is the
prothrombin 20210A mutation. is mutation is associated with a three-fold increase in the risk for VTE. Another
thrombophilia disorder is antiphospholipid antibody syndrome, including lupus anticoagulants and anticardiolipin
antibodies. romboembolic events are reported in approximately one-third of antiphospholipid-positive patients.
e risk of recurrent thrombosis in these patients ranges
33
from 22 to 69%.
Other thrombophilia disorders include
hyperhomocysteinemia; protein C, protein S, and antithrombin de ciencies; and elevated levels of coagulation
factors, including factors II, VIII, IX, and XI. Detection of
these disorders is critical for identi cation of a patient’s true
risk for VTE and should be a factor in a patient’s decision
regarding whether or not to undergo elective surgery.
VTE PROPHYLAXIS
Aside from early and frequent mobilization, the American
College of Chest Physicians does not recommend speci c
measures for general surgical patients at low risk for VTE
34
(Figures39.1 and 39.2).
Pharmacologic methods such as
unfractionated heparin (UFH) at doses of 5,000 U bid or
low molecular weight heparin (LMWH) at doses lower
than 3,400 U qd are recommended for the prevention of
VTE in patients at moderate risk (risk factor score of 2).
For patients at high risk (risk factor score of 3–4), both
UFH at doses of 5,000 U tid or LMWH (>3,400 U qd)
in combination with intermittent pneumatic compression
(IPC) boots are recommended for protection against VTE.
For patients at highest risk for VTE (risk factor score ≥ 5),
pharmacologic therapy using high-dose UFH or LMWH
doses are always recommended in the absence of contraindications, and the adjunctive use of mechanical prophylaxis
34
is also recommended.
NONPHARMACOLOGIC
INTERVENTIONS FOR THE
PREVENTIONOFV TE
Nonpharmacologic VTE prevention strategies are o en
appealing because they tend to be associated with a low risk
for bleeding; however, they have not been as extensively
studied as pharmacologic prophylaxis. It is recommended
that early and frequent ambulation be a routine part of
postoperative care in all patients unless there is an absolute
34
contraindication.
Although early mobilization following
surgery has been shown to signi cantly lower the risk for
postoperative VTE, it is recommended as the sole method of
prophylaxis only for low-risk patients:those under 40years
of age without any additional risk factors for VTE who are
undergoing minor surgery (outpatient surgery lasting less
than 45 minutes). For surgical patients at moderate risk
for VTE (major surgery with two additional risk factors),
mechanical methods of prophylaxis, including graduated
compression stockings (GCS) and IPC, have been very safe
and e ective modalities and have been very well accepted
in the United States, particularly in patients at high risk for
bleeding complications. Arecent epidemiologic study has
shown that around 10% of surgical patients at high risk for
9
VTE had contraindications for the use of anticoagulants.
e results of IPC have been variable, depending on the
type of surgery, patient’s risk factors, and end points used to
detect DVT. Overall, most studies show that IPC reduces
the incidence of DVT in general surgery, urology, neurosurgery, and orthopedic surgery. e systematic review by
35
Roderick etal.
identi ed nineteen trials assessing IPC as
monotherapy in 2,255 patients undergoing di erent types
of surgery. e results show that IPC signi cantly reduced
the incidence of DVT from 23.4% (268/1,147) in the control group to 10.1% (112/1,108) in the IPC group, a 66%
odds reduction (p < 0.0001). ere was no evidence that
sequential compression devices were more protective than
uniform compression machines, as their odds reductions
were 65% (six trials) and 66% (twelve trials), respectively.
A meta-analysis of the literature has reviewed een
randomized controlled trials with a total of sixteen treatment groups comparing IPC with controls in 2,270 surgical patients with objective diagnosis of DVT by imaging
techniques. In comparison to no prophylaxis, IPC reduced
308 • VENOUS THROMBOEMBOLISM
A1: Each Risk Factor Represents 1 Point
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Age 40-59 years
Minor surgery planned
History of prior major surgery
Varicose veins
History of inammatory bowel disease
Swollen legs (current)
Obesity (BMI > 30)
Acute myocardial infarction (< 1 month)
Congestive heart failure (< 1 month)
Sepsis (< 1 month)
Serious lung disease incl. pneumonia
(< 1 month)
Abnormal pulmonary function (chronic
obstructive pulmonary disease)
Medical patient currently at bed rest
Leg plaster cast or brace
Central venous access
Blood transfusion (< 1 month)
Other risk factor/s
A2: For Women Only (Each Represents 1 Point)
Oral contraceptives or hormone replacement
therapy
Pregnancy or postpartum (<1 month)
History of unexplained stillborn infant, recurrent
spontaneous abortion (≥ 3), premature birth with
toxemia of pregnancy or growth restricted infant
B: Each Risk Factor Represents 2 Points
Age 60-74 years
Major surgery (> 60 minutes)*
Arthroscopic surgery (> 60 minutes)*
Laparoscopic surgery (> 60 minutes)*
Previous malignancy
Morbid obesity (BMI > 40)
C: Each Risk Factor Represents 3 Points
Age 75 years or more
Major surgery lasting 2-3 hours*
BMI > 50 (venous stasis syndrome)
History of SVT, DVT/PE
Family history of DVT/PE
Present cancer or chemotherapy
Positive Factor V Leiden
Positive Prothrombin 20210A
Elevated serum homocysteine
Positive Lupus anticoagulant
Elevated anticardiolipin antibodies
Heparin-induced thrombocytopenia (HIT)
Other thrombophilia- Type
D: Each Risk Factor Represents 5 Points
Elective major lower extremity arthroplasty
Hip, pelvis or leg fracture (< 1 month)
Stroke (< 1 month)
Multiple trauma (< 1 month)
Acute spinal cord injury (paralysis) (< 1month)
Major surgery lasting over 3 hours*
TOTAL RISK FACTOR SCORE:
Figure39.1 rombosis risk factor assessment scoringsheet.
the risk of DVT by 60% (RR 0.40; 95% CI 0.29–0.56; p <
36
0.001).
Although there is strong evidence supporting the use of
IPC alone in moderate-risk patients, it has not been studied as thoroughly as pharmacologic agents and is only recommended as an adjunctive therapy in surgery patients at
high and highest risk for VTE or when anticoagulants are
34
contraindicated.
GCS have also been shown in meta-analyses to sub-
stantially reduce the incidence of lower extremity DVT in
37
patients who have undergone general surgery.
Asystematic
review from the Cochrane Collaboration analyzed seven
randomized controlled trials in surgery patients (four general surgery, one gynecologic surgery, one neurosurgery, one
orthopedic surgery). e incidence of lower-limb DVT in
patients who used GCS was signi cantly reduced, compared
with those who did not use this intervention (15% vs. 29%,
38
P < 0.00001).
In a meta-analysis of eleven studies that
investigated the prophylactic e cacy of GCS in patients
who had undergone moderate-risk surgery (nine abdominal
surgery, one gynecologic surgery, and one neurosurgery),
elastic stockings reduced the risk for lower limb DVT by
37
e current evidence suggests that GCS is e ective
68%.
in moderate-risk general surgery patients, but there is little
data exploring the e cacy of this intervention in high-risk
general surgery patients or surgery patients with cancer.
e main limitations of GCS include the lack of international standardization of their pressure pro les and the
di culty of tting patients with unusual leg sizes or shapes.
Patient compliance may be another limiting issue, especially with thigh-length stockings, as discussed above. e
most common reasons for noncompliance by patients and
nurses were that stockings were not reapplied a er cleaning
or bathing, or were removed because patients complained
from itching or heat. Compression stockings should not be
used in patients with peripheral arterial disease. erefore,
lack of foot pulses or an ankle-brachial index lower than 0.8
should be considered contraindications for their use, as well
as in patients with massive leg edema associated with cardiac
failure. Infectious dermatitis and fragile skin secondary to
diabetes are other contraindications to the use ofGCS.
Clinical trials have shown that combining GCS or IPC
with pharmacologic prophylaxis, such as heparin, results
in better protection against VTE than either of these
VTE PROPHYLAXIS IN THE GENERAL SURGICAL PATIENT • 309
VTE risk and suggested prophylaxis for surgical patients
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Total Risk
Factor
Score
0-1
2
3-4
5 or more
*30-day post-discharge clinically evident imaging proven DVT
IPC - Intermittent Pneumatic Compression; LDUH - Low Dose Unfractionated Heparin LMWH - Low Molecular Weight Heparin FXa I - Factor X Inhibitor
Prophylaxis Safety Considerations: Check box if answer is ‘YES’
Anticoagulants: Factor Associated with Increased Bleeding
Is patient experiencing any active bleeding?
Does patient have (or has had history of) heparin-induced thrombocytopenia?
Is patient’s platelet count <100,000/mm3?
Is patient’s taking oral anticoagulants, platelet inhibitors (e.g., NSAIDS, Clopidogre, Salicylates)?
Is patient’s creatinine clearance abnormal? If yes, please indicate value
If any of the above boxes are checked, then patient may not be a candidate for anticoagulant therapy and you should
consider alternative prophylactic measures such as IPC or FP.
Intermittent Pneumatic Compression (IPC)
Does patient have severe peripheral arterial disease?
Does patient have congestive heart failure?
Does patient have an acute supercial/deep vein thrombosis?
If any of the above boxes are checked, then patient may not be a candidate for intermittent compression therapy and you
should consider alternative prophylactic measures. (IVC lter?)
Figure39.2 Categories for risk for VTE in patients undergoing general surgery and recommended prophylactic regimens.
Incidence
of DVT
< 10%
10-20%
30-40%
40-80%
1-5% mortality
30-day
Proven DVT
Incidence*
0%
0.7%
0.97%
1.94%
Risk
Level
Low Risk
Moderate Risk
High Risk
Highest Risk
Prophylaxis Regimen
No specic measures; early
ambulation
IPC, LDUH (5000U BID), or
LWMH (<3400 U)
IPC, LDUH (5000U TID), or
LMWH (>3400U or FXa I
Pharmacological: LDUH, LMWH (>3400 U), Warfarin, or
FXa I alone or in combination with IPC
approaches used alone. 38 e incidence of DVT was only
1.5% in a group of 328 surgical patients who received a
pharmacologic and antistasis agent, compared with 26.8%
39
in a control group who did not receive prophylaxis.
In a
study in cardiac patients (N=2,551) randomized to receive
subcutaneous heparin alone or in combination with IPC,
the incidence of PE was 62% lower (1.5% vs. 4%) in those
40
who received combination therapy ( P < 0.001).
Similarly,
a review of the literature shows that combined modalities
are more e ective than single modalities in patients undergoing di erent types of surgery, with a mean reduction in
41
the incidence of postoperative VTE of69%.
Further support for the bene t of combined mechanical and pharmacological prophylaxis for the prevention of
VTE came from the APOLLO study. In this double-blind,
placebo-controlled trial, patients undergoing major abdominal surgery (N = 1,309) received IPC with or without
42
the Factor Xa inhibitor fondaparinux.
Combined IPC
and fondaparinux therapy produced a signi cant reduction in the incidence of all VTE from 5.3% (IPC alone)
to 1.7% ( P = 0.004). e rates of proximal DVT were
also signi cantly reduced in the combined therapy group
from 1.7% (IPC alone) to 0.2% ( P = 0.037). Patients
receiving fondaparinux treatment had signi cantly more
major bleeding episodes than IPC alone (1.6% vs. 0.2%,
P =0.006); however, none of these was fatal or involved
critical organs. In addition, a major bleeding rate of 1.6%
is comparable to the major bleeding rates observed with
abdominal surgery (colorectal surgery) with enoxaparin
43
and UFH.
Although patients might be at a higher risk for
bleeding with the addition of pharmacological anticoagulation treatments, combined therapy has been shown to be
signi cantly more e ective for the prevention of VTE following major surgery than mechanical prophylaxisalone.
Inferior vena cava (IVC) lters are not routinely used
for the prevention of DVT, but rather for the prevention
of PE in patients who either fail or have contraindications
to other prophylactic therapies, particularly anticoagulants.
Prophylactic use of IVC lters is indicated for patients with
an absolute contraindication to anticoagulation, serious
complication while on anticoagulation (i.e., hemorrhage,
thrombocytopenia, or drug reaction), or documented failure on anticoagulation. In addition, IVC lters can be e ective in patients with pelvic fractures or closed head injuries
who are at high risk for thrombosis or have had a previous
thrombosis.
IVC lters are generally safe, and have been shown to
reduce the incidence of PE and fatal PE to 2.6–3.8% and
310 • VENOUS THROMBOEMBOLISM
0.3–1.9%, respectively, in patients at risk for VTE. 44 An
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increase in recurrent DVT has been observed with IVC lters by Decousus and colleagues, who demonstrated a reduction in symptomatic and asymptomatic PE at 12days from
4.8 to 1.1% in patients with proximal DVT who received
lters, but at 2years the incidence of recurrent DVT was
signi cantly increased in these patients (20.8% vs. 11.6%,
45
P =0.02).
However, 8-year follow-up on these patients
was analyzed and while the signi cant reduction in the incidence of PE was maintained ( P =0.01), at 8years there were
no signi cant di erences in recurrent DVT ( P = 0.08),
PTS, or overall mortality with and without lters. Several
types of IVC lters are available, but the Green eld lter is
46
the only lter with good long-term follow-up.
Although
relatively rare, other complications associated with IVC lter placement and long-term use include migration of the
47
lter, post lter caval thrombosis, andPTS.
In summary, nonpharmacologic or mechanical prophylaxis modalities can be very e ective in reducing the incidence of DVT in general surgery patients at moderate risk
for VTE. However, they have not been as extensively studied as pharmacologic agents and are not recommended as
the sole method of prophylaxis in patients at higher risk for
VTE. However, in conjunction with pharmacologic agents,
mechanical prophylaxis can be very e ective in reducing
the incidence of VTE in these patients. On the other hand,
mechanical prophylaxis with GCS or IPC is recommended
in patients at high VTE risk who cannot receive anticoagu-
34
lants because of a high risk for bleeding.
PHARMACOLOGIC THERAPIES
FOR THE PREVENTIONOFVTE
Commonly used pharmacologic therapies for prevention
of VTE in patients undergoing general surgery include
subcutaneous UFH and LMWH (including enoxaparin,
dalteparin, fraxiparine, and tinzaparin). Low-dose subcutaneous UFH was the rst pharmacologic agent to be widely
investigated for prevention of VTE in patients undergoing
general surgery. In the 1970s, Kakkar and colleagues demonstrated that this therapy signi cantly reduced the risk for
both DVT and PE in this patient population. In a landmark
prospective randomized study of 4,121 patients undergoing major surgery (primarily abdominal, gynecologic, or
urologic surgery), UFH prophylaxis reduced the incidence
2
of DVT from 25 to 8% ( P < 0.005).
Patients treated with
UFH also had a signi cantly reduced incidence of PE
( P< 0.005) and death from PE (P < 0.005) compared with
control patients.
A subsequent meta-analysis of forty-six trials by Collins
and colleagues that included 16,000 patients who had
undergone general, orthopedic, or urologic surgery con rmed Kakkar’s results, with a DVT incidence of 27%
without prophylaxis compared with 10.6% with UFH and
an incidence of fatal PE of 3.4% and 1.7%, respectively.
3
e incidence of DVT was 8% (95% CI, 7% to 8%) with
UFH following general surgery in a recent meta-analysis of
forty-seven clinical studies. It has been suggested that the
administration of 5,000 U of UFH tid is more e ective
than 5,000 U bid, without increased bleeding, but no direct
comparison studies have been conducted. In general, UFH
can be given twice daily in moderate- to high-risk patients,
but should be given three times daily in higher risk patients.
Although UFH is e ective for prevention of DVT and
PE in general surgery patients, bleeding complications associated with this therapy present a serious safety concern.
Cancer patients may be at higher risk for hemorrhagic com-
48
plications with UFH than noncancer patients.
Another
limitation of UFH is its association with heparin-induced
thrombocytopenia (HIT). UFH used at therapeutic doses
has been associated with up to a 5% incidence of HIT, an
antibody-mediated process characterized by a dramatic
49
drop in platelets.
In 20% of cases, HIT develops into
thrombosis. UFH can also cause osteopenia by binding
to osteoblasts, which stimulates osteoclast activation and
results in bone breakdown when used long-term. e short
half-life of UFH (0.5–2 h) relative to other anticoagulants
is another limitation of UFH because it necessitates more
frequent dosing; however, the short half-life can also be an
advantage in the case of bleeding complications or for the
management of patients with renal failure. Another advantage of UFH is that an antidote, protamine sulfate, is available for situations where immediate reversal is required,
although reversal is not withoutrisks.
LMWHs appear to be at least as e ective as UFH for
the prevention of DVT in clinical trials of patients under-
50
going general surgery (Figure39.3).
Overall, the residual
incidence of VTE in abdominal surgery patients receiving LMWH ranges from about 5 to 15%, with the highest
51
rates in patients with cancer.
e incidence of DVT with
LMWHs following general surgery was 6% (95% CI, 6% to
7%) in a recent meta-analysis of twenty-one clinical studies.
Available LMWHs appear to be similarly e ective for the
prevention of VTE. Both enoxaparin and dalteparin have
been shown to reduce the incidence of DVT in patients
undergoing general surgery to rates of approximately 6
to 8%; however, direct comparison studies have not been
52,53
conducted.
LMWHs appear to be e ective in VTE prophylaxis, even
in patients with cancer. e incidence of VTE in patients
with cancer given enoxaparin was slightly lower than that
observed in patients given UFH (14.7% vs. 18.2%) in a study
of patients undergoing abdominal surgery for malignant
51
disease (N=1,115).
In addition, when patients undergoing planned curative surgery for abdominal or pelvic cancer
were given LMWH for 6 to 10 d and then randomized to
receive extended prophylaxis with LMWH or placebo for
21 d, the incidence of venographically demonstrated VTE
at 3 months was signi cantly reduced (5.5% vs. 13.8%,
VTE PROPHYLAXIS IN THE GENERAL SURGICAL PATIENT • 311
30
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25
20
15
25
14
10
5
Total DVT incidence (%)
0
GCS
Placebo/control
*All incidences are for DVT after general surgery based on meta-analyses from Geerts WH et al (2001)
except the incidence for Factor Xa inhibitor, which includes venographically proven DVT, symptomatic DVT,
and PE and is based on the results from Agnelli G et al (2005).
Figure39.3 Incidence of VTE with currently available prophylactic therapies following general surgery.* *All incidences are for DVT a er general surgery based on
meta-analyses from Reference 4 except the incidence for Factor Xa inhibitor, which includes venographically proven DVT, symptomatic DVT, and PE and is based on the results from Reference72.
P =0.01) with extended prophylaxis. 54 ere was no signi cant increase in bleeding with extended prophylaxis. ese
results suggest that LMWH is at least as e ective as UFH in
general surgery patients with cancer and that extended prophylaxis with LMWH is safe and can signi cantly reduce
the incidence of VTE in general surgery patients with
cancer. Recent meta-analyses demonstrate that extending
prophylaxis with LWMW for 28 d a er abdominal cancer
surgery reduces the risk of postoperative VTE by more than
50% compared to standard prophylaxis for 7–10 d.
It has been suggested that survival may be increased in
patients with cancer who receive LMWH compared with
55,56
UFH
8
6
LMWH
4.6
Factor Xa inhibitor
3
IPC
include speci c binding to ATIII, better bioavailability at
low doses, no monitoring required, and a longer half-life
(4 h vs. 0.5–2 h), allowing for once-daily dosing in some
patients. However, a long half-life can sometimes be a disadvantage in the case of bleeding complications. In addition,
LMWHs are incompletely reversed by protamine sulfate.
Other disadvantages of LMWHs include renal excretion,
precluding use in patients with renal failure, and increased
cost relative to UFH. Furthermore, LMWHs also carry a
risk for HIT and should not be used in patients at risk for
HIT, although they appear to be associated with a lower
49
incidence thanUFH.
UFH, although the reason for this is not clear. In women
with previously untreated breast and pelvic cancer who had
undergone primary surgery, those who received LMWH
(n=160) had signi cantly better long-term survival at 650
d than those who received UFH (n=164, P =0.0066).
57
Asigni cant survival bene t (12.6% vs. 27%, P =0.041)
was also observed with LMWH in a subset of patients
with cancer who were treated for DVT with a LMWH or
58,59
UFH.
In a randomized controlled study where patients
with advanced cancer (N=385) were randomized to receive
a LMWH once daily for 1year or placebo, there was no signi cant di erence in survival at 1, 2, or 3years; however, in
a subset of patients with a better prognosis, survival was signi cantly ( P =0.03) improved at 2 and 3years (78% vs. 55%
60
and 60% vs. 36%, respectively).
ese results suggest that
there may be some survival bene t of LMWH in patients
with cancer, particularly those at early stages of malignancy.
61
Although there is some evidence that LMWH therapy
may lead to fewer bleeding complications than observed
with UFH, results from clinical studies have been inconsistent, and bleeding remains an important safety concern
associated with LMWH, particularly when it is used at
higher doses.
50,51,53,62–65
Advantages of LMWH over UFH
Fondaparinux is a novel synthetic pentasaccharide that
selectively binds to antithrombin III with selective neutralization of factor Xa.
than LMWH in VTE prophylaxis following total joint
replacement
evaluated for VTE prophylaxis in patients undergoing
general surgery. In the Pentasaccharide in General Surgery
Study (PEGASUS) study, the e cacy and safety of postoperative fondaparinux (2.5 mg once daily) was compared
with that of the LMWH dalteparin started preoperatively
in high-risk abdominal surgery patients.
randomized, double-blind study included 2,900 high-risk
abdominal surgery patients, in which high risk was de ned
as patients older than 60years of age or older than 40years
of age with 1 or more risk factors including cancer, obesity
(BMI > 30 for men and 28.6 for women), history of VTE,
heart failure (NYHA grade III or IV), chronic obstructive pulmonary disease, or in ammatory bowel disease.
PEGASUS showed that the rates of VTE (venographically
N E W E R A N T I C O A G U L A N T S :
SELECTIVE FACTOR XA INHIBITORS
67
It has demonstrated better e cacy
68–70
and hip fracture surgery 71 and has been
72
is multicenter,
66
312 • VENOUS THROMBOEMBOLISM
proven DVT, symptomatic DVT, or fatal or nonfatal PE)
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up to day 10 among patients treated with fondaparinux and
dalteparin were 4.6% and 6.1% ( P = 0.14), respectively,
representing a 24.5% reduction in the incidence of VTE in
favor of fondaparinux (Figure39.4A). At postoperative day
32, symptomatic DVT was seen in 0.8% of patients treated
with fondaparinux and 1.0% of patients who received
dalteparin. e di erence in the incidence of major bleeding between the two treatment groups was not signi cant
(3.4% fondaparinux vs. 2.4% dalteparin, P =0.12). ese
results demonstrate that fondaparinux is at least as e ective as, if not more than, UFH and LMWH in preventing VTE in general surgery patients. Based on this data,
fondaparinux was recently approved for VTE prevention in
abdominal surgery patients undergoing general anesthesia
for more than 45 minutes who are over 40years of age and
have additional risk factors. Apost hoc analysis was performed to compare the e ects of the two therapies in the
68% of the evaluable study population who underwent surgery for cancer. In the cancer subpopulation, fondaparinux
signi cantly reduced the incidence of VTE compared with
dalteparin from 7.7% to 4.7% ( P = 0.02), representing a
39% reduction in the incidence of VTE (Figure39.4B). e
incidence of major bleeding was similar between groups
(3.4% fondaparinux vs. 2.5% dalteparin). ese preliminary
ndings suggest that postoperative fondaparinux is at least
as e ective and safe as preoperative dalteparin for the prevention of VTE a er abdominal surgery, and signi cantly
A
7.00%
6.00%
5.00%
4.00%
3.00%
% VTE
2.00%
1.00%
0.00%
B
9.00%
8.00%
7.00%
6.00%
5.00%
4.00%
% VTE
3.00%
2.00%
1.00%
0.00%
Figure39.4 (A) VTE reduction with fondaparinux versus dalteparin
in high-risk abdominal surgery patients. (B)VTE reduction with
fondaparinux versus dalteparin in high-risk abdominal surgery patients
with cancer.
4.10%
47/102
Fondaparinux
4.70%
33/696
Fondaparinux
P = 0.14
Fondaparinux Dalteparin
P = 0.02
Fondaparinux Dalteparin
6.10%
62/102
Dalteparin
7.70%
55/712
Dalteparin
more e ective than dalteparin in cancer patients undergoing the same procedures.
Another advantage of fondaparinux is that, unlike
UFH and LMWH, it has not been associated with HIT.
Because the fondaparinux molecule does not bind to platelet factor 4, it cannot form the complex that reacts with
the platelet-activating antibody and it does not cross-react
with HIT antibodies from patients with con rmed type II
73,74
HIT.
Fondaparinux has also been shown to be safe for
extended prophylaxis (4 weeks) although this was shown
in patients who had undergone hip fracture surgery, not in
general surgery patients. In addition, because fondaparinux
does not interfere with thrombin binding, it has no negative e ect on wound healing. Further, fondaparinux has a
17-h half-life, which allows for once-daily dosing and there
is no dose alteration required in patients weighing less than
50kg or renally impaired patients. However, no antidote is
available and a long half-life can also be a disadvantage in
the case of bleeding complications. Fondaparinux is renally
excreted and should not be used in patients with kidney failure and should be avoided in patients undergoing neuraxial
anesthesia, as there is the potential for epidural hematoma
formation.
In summary, there are a variety of agents available for
the prevention of VTE in patients undergoing general
surgery. No one agent is optimal for all patients. Di erent
agents should be used in patients at di erent levels of risk,
and patient characteristics and comorbid conditions can
make one agent more appropriate than another in a certain
patient. e strati cation of general surgery patients by risk
for VTE can guide surgeons in their selection of appropriate VTE prophylaxis.
RISK STRATIFICATION
e risk for VTE ranges from low to very high in patients
undergoing general surgery. Risk category placement is
dependent on the presence of factors that in uence the
risk for VTE, including type of surgery, age, immobilization, and comorbidities. It has been demonstrated that up
to 36% of general surgery patients had three or more risk
factors, placing them in the high or highest risk groups.
75
ese are groups in which pharmacologic VTE prophylaxis
is strongly recommended. e number of factors that can
in uence the risk of VTE and the variety of agents available
for VTE prophylaxis can make risk assessment and management di cult.
Risk strati cation has been suggested as a means of
determining the risk for VTE in patients undergoing surgery and for guiding the selection of appropriate prophylactic measures. Risk assessment models, like the one pictured
in Figure39.1, can be used to assign each patient a total risk
factor score, which can then be used to categorize patients
into one of four risk categories (low, moderate, high, and
VTE PROPHYLAXIS IN THE GENERAL SURGICAL PATIENT • 313
highest). 76 An appropriate method of VTE prophylaxis can
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be chosen based on the patient’s level of risk, taking into
consideration any contraindications to prophylaxis that
may be present (Figure39.2).
is risk assessment model has recently been validated
in a series of 8,216 surgical patients as part of the National
Surgical uality Improvement Program (NSQIP).
22
Patients had risk scores calculated by administrative data
using the electronic medical record and these were correlated with clinically evident imaging-proven VTE events
at 30 d.Statistically signi cant correlation of these VTE
events with the risk score occurred, including identifying a
low-risk group where the risk of anticoagulation is greater
than the anticipated clinical incidence of VTE. In those
with a very high score (>8), the 30-d proven VTE risk
was 6.5%. is score enables the clinician to suggest continuing prophylaxis beyond hospital discharge for these
thrombosis-prone individuals.
e incidence of VTE in patients in the low-risk category (one risk factor) is so low that prophylactic measures
would most likely not further reduce the risk. us, no
measures above early and frequent ambulation are recommended in this patient population (Figure 39.2). Elastic
stockings and IPC reduce the incidence of DVT to 14%
and 3% (Figure39.3), respectively, and can be used alone
in moderate-risk patients (two risk factors). Although IPC
has been shown to reduce the incidence of DVT to 3% following general surgery, it has not been extensively studied in
general surgery and is not recommended as the sole method
of prophylaxis in patients at greater than moderate risk
forVTE.
Subcutaneous UFH (5,000 U bid), LMWH (≤3,400
U qd), or fondaparinux (2.5 mg qd) can be used in patients
at moderate and high risk (Figure39.2). In patients at the
highest risk for VTE (≥5 risk factors) higher doses of both
subcutaneous UFH (5,000 U tid) and LMWH (>3,400
U qd) or fondaparinux (2.5 mg qd) should be used.
Although fondaparinux has not been as extensively studied
as UFH or LMWHs in general surgery patients, the results
of the above-mentioned PEGASUS study suggest that
fondaparinux is e ective for VTE prophylaxis in this patient
population and may be particularly e ective in patients in
the highest risk category. In addition, for patients at highest
risk for VTE, mechanical prophylaxis combined with pharmacologic prophylaxis can be more e ective than pharmacologic prophylaxis alone. e recent APOLLO trial results
emphasize the value of combined prophylaxis since in that
trial the incidence of venographically positive DVT was
42
1.7% in moderate and high-risk general surgery patients.
As an alternative to a risk assessment model, it has been
suggested that appropriate thromboprophylactic measures
be used in all but very low risk general surgery patients.
In a recent editorial comment, Goldhaber suggests using
pharmacological prophylaxis for all hospitalized patients,
according to easily implemented protocols. For those
patients with contraindications to receive anticoagulants,
77
mechanical methods should be used.
C O N C L U S I O N S
Although the development of VTE is relatively common in
the postoperative setting and is a common cause of sudden
postoperative death, VTE prophylaxis remains underutilized. Because VTE is o en asymptomatic, or when present,
symptoms are nonspeci c, surgeons may feel that they do
not o en see VTE in their practice. However, signs of VTE
include leg pain, leg swelling, chest pain, shortness of breath,
transient orthostatic hypotension, narcotic excess, fainting
spell, hypoxia, sudden death, postoperative stroke, suspected
myocardial infarction, PTS at 5 years, and postoperative
pneumonia, and most surgeons would agree that many of
these conditions are relatively common following surgery.
Due to the signi cant morbidity and mortality that is
associated with VTE, the risk of VTE must be considered
in all general surgery patients. In this population, nearly
40% of patients are at high or highest risk for VTE (three
or more risk factors) and, therefore, require pharmacologic
VTE prophylaxis. Risk strati cation schemes may help to
guide intensity of clot-preventing measures. Risk strati cation schemes like the one in Figure39.1 may be helpful for
assessing VTE risk in general surgery patients. Together with
the consideration of any contraindications or precautions,
risk strati cation can be used to guide surgeons in selection
of the optimal prophylactic therapy for each patient.
Clinical data suggest that using nonpharmacologic measures, such as GCS and IPC, can be e ective in low and
moderate-risk patients and can further enhance protection
against VTE in high-risk patients when used in combination with pharmacologic agents. Pharmacologic therapies,
including UFH and LMWH, are recommended for use
in all high-risk (three or more risk factors) general surgery
patients. In addition, fondaparinux is an important treatment option for higher risk patients undergoing abdominal
surgery. It has been demonstrated that extended pharmacologic prophylaxis (up to 4 weeks) can signi cantly reduce
the incidence of VTE events compared with prophylaxis for
1 week. Based on these data, it is suggested that high-risk
patients receive extended pharmacologic prophylaxis.
UFH is the least expensive pharmacologic agent and is
safe for use in patients with renal failure and those undergoing neuraxial anesthesia. However, it is associated with
HIT and must be given three times daily in patients at high
risk for VTE. LMWH has been shown to be at least as safe
and e ective as UFH, is associated with a lower incidence
of HIT, can be given once or twice daily, and may improve
survival in patients with cancer. LMWH should be used
with caution in patients with renal failure or in those undergoing neuraxial anesthesia. Prophylactic administration of
a novel factor Xa inhibitor, fondaparinux, has been shown
314 • VENOUS THROMBOEMBOLISM
to be as safe and at least as e ective as UFH and LMWH
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for the prevention of VTE a er abdominal surgery, and
signi cantly more e ective than LMWH in cancer surgery
patients. In addition, there is an apparent lack of association
with HIT with fondaparinux, and it can be given once daily.
Fondaparinux has a long half-life, allowing for once-daily
dosing, but this can be a disadvantage in the event of bleeding complications. It cannot be used in patients with renal
failure or those undergoing neuraxial anesthesia.
ere is no one method of VTE prophylaxis that is optimal for every patient. e bene ts and risks of each agent
should be considered for each patient so that the safest,
most e ective therapy is initiated. As yet, little is known as
to the appropriate duration of these measures; however, in
selected patients at high risk for VTE, extended prophylaxis
is recommended.
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