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7 Perioperative Deep Vein Thrombosis Prophylaxis
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105
coagulation (bleeding, disseminated intravascular coagulation, and thrombosis) and
cancer have been a multidisciplinary challenge for physicians.
DVT in the postoperative period is frequently more in patients treated for malignancy than that in benign disease [6].
Liem etal. studied 372 patients with prior history of DVT who underwent subsequent surgeries. They concluded that perioperative symptomatic recurrence is frequent and related to high-risk procedures (Tables 7.1, 7.2, 7.3, 7.4, and 7.5). They
also found that the more time elapsed between a DVT episode and a subsequent
surgery, the less was the risk of recurrence [7].
Table 7.1 Surgical procedures classied into lower risk vs higher risk for venous
thromboembolism
Low VTE risk
Orthopedic Arthroscopy and arthroscopic
surgery
Hardware removal Knee arthroplasty
Elective spine surgery Hip fracture surgery
Lower extremity injuries below knee Pelvic reconstruction
Neurosurgical Elective spine surgery Procedures requiring craniotomy
Transphenoidal procedures Surgery for central nervous
Shunt procedures
Biopsics
General surgical Laparoscopic procedures Open procedures for benign
Open procedures for benign disease
<45min
Urologic Cystoscopy Open surgery for malignancy
Transurethral surgery Open prostectomy
Laparoscopic procedures Renal surgery/transplantation
Gynecologic Laparoscopic procedures Open surgery for benign disease
Open procedures <30min Open surgery for malignancy
Head and neck
surgical
Other Aortic and lower extremity arterial
VTE Venous thromboembolism
Open procedures for benign disease
<45min
reconstruction
Plastic and reconstructive surgery Open thoracic surgery
High VTE risk
Hip arthroplasty
malignancy
disease >45min
Open procedures for malignancy
Bariatric surgery
Radical cystectomy
Pelvic surgery
Urethral reconstruction
>30min
Open procedures for benign
disease >45min
Open procedures for malignancy
Major lower extremity
amputations
Coronary bypass surgery
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Table 7.2 Risk stratication for VTE in general gastrointestinal and abdominal-pelvic surgery
Risk
category
Very low <7 0 0 <0.5
Low 7–10 1–2 0.7 1.5
Moderate >10 3–4 1 3
High NA 5 or >5 1.9 6
NA not applicable, VTE venous thromboembolism
Table 7.3 Caprini risk assessment model
One point
Age 41–60years Age 61–74years Age >75years Stroke (<1month)
Minor surgery Arthroscopic
BMI>25kg/m
Swollen legs Laparoscopic
Varicose veins Malignancy Anticardiolipin antibodies
Pregnancy or
postpartum
History of
spontaneous
abortion
Oral contraceptives Central venous
Sepsis (<1month)
COPD, pneumonia
(<1month)
Abnormal PFTs
Acute myocardial
infarction
Congestive heart
failure
Inammatory
bowel disease
Bed rest
BMI body mass index, COPD chronic obstructive pulmonary disease, PFTs pulmonary function
tests, VTE venous thromboembolism
Rogers
score
3
Caprini
score
Two points Three points
surgery
Major open surgery
(>45min)
surgery (>45min)
Conned to bed
(>72h)
Immobilizing cast Heparin-induced
access
Observed risk of
VTE (%)
History of VTE Elective arthroplasty
Factor V Leiden Hip, pelvis, or leg
Lupus anticoagulant Acute spinal cord
Elevated serum
homocysteine
thrombocytopenia
Other congenital or
acquired thrombophilia
Estimated baseline risk without
prophylaxis (%)
M. R. Wehbe et al.
Five points
fracture
injury (<1month)
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Table 7.4 Risk assessment model from the patient safety in surgery study: Rogers score
General risk factor
Specic risk factor
Risk score points
Operation type Respiratory 9
Thoracoabdominal aneurysm 7
Abdominal aneurysm 4
Mouth, palate 4
Stomach, small/large intestine 4
Integument 3
Hernia 2
ASA 3, 4, 5 2
2 1
Female sex
Work RVU >17 3
10–17 2
2 point conditions Disseminated cancer 2
Chemotherapy within 30days 2
Preoperative serum sodium >145mmol/L 2
Transfusion >4units packed RBCs in 72h
2
within operation
Ventilator dependent 2
One point
Wound class 3 or 4 1
conditions
Preoperative Hct <38 1
Preoperative bili >1.0 1
Dyspnea 1
Albumin <3.5 1
Emergency 1
Zero point
ASA class 1 0
conditions
Work RVU <10 0
Male sex 0
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Table 7.5 Types of surgery
Type of surgery
General surgery Low-risk bleeding:
Orthopedic surgery Total hip or Total knee: preferable DOAC (if not ASA or LMWH)
Laparoscopic
cholecystectomy
Neurological
surgery
TURP or radical
prostatectomy
Vascular surgery If no other VTE risk factors: no prophylaxis
Trauma High risk of bleeding:
Recommendations
Pharmacological
prophylaxis LMWH/
LDUH
If no other VTE risk factors: no prophylaxis
Low risk for VTE: no
prophylaxis
If no other VTE risk factors: no prophylaxis
Mechanical prophylaxis
High-risk bleeding:
Mechanical
thromboprophylaxis
(ICD>GCS)
High risk for VTE and
high risk of bleeding:
Mechanical prophylaxis
Low risk of bleeding: Pharmacological prophylaxis
(LMWH)
Very high risk for VTE:
Combined pharmacological
and mechanical prophylaxis
High risk for VTE and low risk
of bleeding: Pharmacological
prophylaxis (LMWH)
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M. R. Wehbe et al.
Basis forVTE Prophylaxis
Most hospitalized patients present with a minimum of one risk factor for VTE,
while around 40% of them have three risk factors or more. Without an appropriate
prevention, the risk of DVT prevalence ranges from 10 to 80% among medical and
surgical patients [8]. Based on the American College of Chest Physicians (ACCP)
guidelines, the DVT prevalence among hospitalized patients varies according to
their hospitalization: medical patients 10–20%, general surgery 15–40%, major
gynecologic surgery 15–40%, neurosurgery 15–40%, stroke 20–50%, hip or knee
arthroplasty 40–60%, major trauma 40–80%, spinal cord injury patients 60–80%,
and critical care patients 10–80%.
A study done by Zhan etal. looking into 7.45 million American hospital discharges covering 944 acute care hospitals found the VTE (DVT+PE) was among
the top ve safety indicators causing excess charges, length of stay, and mor-
Moreover, the adverse consequences of unprevented VTE (symptomatic DVT,
symptomatic/fatal PE, cost of investigating symptomatic patients, risk and cost of
treating unprevented VTE, increased future risk of recurrent VTE and postthrombotic syndrome) all highlight the importance of thromboprophylaxis in hospitalized patients [10].
The literature over 30years sums up with concrete evidence that primary VTE
prophylaxis is effective and has become a must since PE is regarded as the most
common cause of preventable inpatient deaths, causing around 200,000 deaths
yearly in the United States alone [11].
Regular use of thromboprophylaxis has been highly effective at preventing VTE
and fatal PE, while at the same time has been repeatedly shown to be cost effective
[12]. On the other hand, the complications of thromboprophylaxis tend to set minimal or no increase on clinically major bleeding with the use of chemical thromboprophylaxis (LMWH, low-dose UH, warfarin) supported by several meta- analyses
and randomized controlled trials (RCTs) [13]. To sum up, VTE prophylaxis has
more benets than risks and is more cost effective when compared to the burden of
developing DVT or PE [14].
Risk Category
VTE prophylaxis is one of the key factors of patient safety in the perioperative
period. The VTE prophylaxis should be proportionate to the patient’s risk. The
cause of the patient’s admission to medical/surgical and his risk factors will determine his risk category for further prophylaxis. There are numerous VTE risk scores
published in the literature. The differences between them are mainly related to efcacy, safety, cost, and ease of implementation. The recent ACCP guidelines assess
risk category scores based on two proven methods: the Caprini score and the Rogers
score. The Caprini score assigns numerical points for risk factors (1 point to 5
points) and the sum of these points is categorized with the risk as very low (0–1
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point), low (2 points), moderate (3–4 points), and high (5 or more points). This scoring system was also validated and recommended support to the use of individual
patient VTE risk assessment up to 30days postoperatively [15]. From this retrospective validation study, the ACCP investigators concluded estimates of the baseline risk of VTE.These estimated risks were as follows: 0.5%—very low, 1.5%—low,
3%—moderate, and 6%—high risk.
On the other hand, the Rogers score was developed after studying data of more
than 183,000 patients who underwent vascular, general, or thoracic procedures.
From this data, points were assigned to variables that were found to be independent
predictors of VTE risk. The Rogers score was then calculated from these points and
the estimated risk of VTE was categorized into the following: 0.1%—very low,
0.5%—low, and 1.5% for the moderate score group [5].
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Venous Thromboembolism Prophylaxis
Thromboprophylaxis is essential in reducing morbidity and mortality of VTE.VTE
pathogenesis depends on three main factors: (1) venous stasis, (2) hypercoagulability, and (3) endothelial damage, which were demonstrated by Rudolph Virchow as
“Virchow’s triad.” Upon closer inspection of this triad, we nd that “hypercoagulability” and “stasis” were rst described by Richard Weisman, a surgeon to King
Charles II around 200years prior to Virchow, while the third factor “inammation
of the endothelium” was described in 1830 by the founder of hematology, Gabriel
Andaral [16].
Based on these ndings, preoperative VTE should target factors affecting venous
stasis, hypercoagulability, and endothelial damage. Venous stasis disrupts the normal balance of procoagulants and anticoagulants, leading to intravascular thrombus
formation. Venous stasis is encountered during bed rest/hospitalization, periods of
immobility, and having orthopedic casts. On the other hand, hypercoagulability is a
major occurrence after surgery, with extensive hemostatic system alterations beginning 2days postoperatively—especially in patients with malignancy, inherited and
acquired thrombophilia, sepsis, and trauma [17]. Moreover, a damaged endothelium
might contribute to Virchow’s triad by the inability to provide its anticoagulant and
antiplatelet surface diverting hemostasis toward coagulation [18]. This endothelial
damage might be due to several factors: direct trauma to major deep veins, iatrogenic injury, encircling tumors, and major orthopedic surgeries.
For all of the above-mentioned factors, VTE prophylaxis is a treatment directed
against the Virchow’s triad. This prophylaxis can be mechanical or pharmacologic,
and used as a single or combined treatment, depending on the patient’s risk factors.
Mechanical Methods ofThromboprophylaxis
Adequate but not excessive anesthesia, regional anesthesia, and hydration with
early ambulation are the oldest and simplest methods of thromboprophylaxis.
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Methods of mechanical thromboprophylaxis include graduated compression stockings (GCS), intermittent pneumatic compression (IPC) of the lower and upper
limbs, and foot compression devices. These methods tackle venous stasis by displacing blood from the distal to a more proximal venous system, hence increasing
the blood ow (volume and speed) in the deep venous system [19].
These methods, although not studied as extensively as chemoprophylaxis, are
acceptable alternatives to anticoagulants in patients with serious bleeding contraindications. They should also be used as adjuncts to chemoprophylaxis in high-VTE
risk patients.
These mechanical methods have several advantages and limitations. They might
decrease leg swelling and enhance the efcacy of chemoprophylaxis. One drawback
is that these mechanical methods were not adequately studied with respect to standards of use (e.g., size, pressure, and physiologic features), and the trials reporting
on them were mostly unblinded. They are also not as effective in high-VTE risk
groups and their effect on pulmonary emboli and death is still unknown. Finally, the
compliance of use by the patients and medical staff is often poor.
M. R. Wehbe et al.
Graduated Compression Stockings (GCS)
GCS exert the highest compression pressure at the level of the ankle, which gradually decreases up the stocking. In a systematic review of 18 randomized controlled
trials (RCTs) assessing the role of GCS in the prevention of DVT where GCS were
used alone or in addition to chemoprophylaxis, DVT developed in 13% with GCS
with chemoprophylaxis vs. 26% of those with GCS alone. In the remaining trials
where GCS were used in addition to chemoprophylaxis, DVT was found in 4% of
those with GCS combined with another method vs. 16% of those given the other
method alone. Other reviews stated an incidence reduction of DVT reaching 57%
with GCS. These studies prove the efcacy of GCS in low- and moderate-risk
patients, but don’t prove correct for high-risk patients undergoing malignancy and
major orthopedic surgeries.
Nevertheless, several restraints and contraindications of GCS use remain pertinent. These stockings are difcult to wear, especially in large sizes, unusual leg
shapes, and dermatitis, thus decreasing patients compliance. They are prohibited
from use in patients with peripheral arterial disease and ABIs of <0.8 [20].
Intermittent Pneumatic Compression (IPC)
IPC is the most studied and effective method of mechanical thromboprophylaxis.
This method consists of applying a selected pressure through sequential intermittent
air insufation using garments or a specic boot connected to a compressor, thus
preventing venous stasis. IPC also works on the coagulation cascade by increasing
several factors as prostacyclin, tissue factor pathway inhibitor, and tissue plasminogen activator.
RCTs of a variety of surgical patients (neurosurgical, orthopedic, urologic, and
general) show that IPC is more effective as a prophylaxis versus no prophylaxis at
all or GCS only. One of the largest stratied meta-analysis of IPC devices looking
into data from 16,164 hospitalized patients showed that IPC was more efcient in
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reducing VTE, with an absolute DVT risk reduction of 9.4%, and PE absolute risk
reduction of 1.6%. Additionally, IPC combined with chemical thromboprophylaxis
was found to be more efcient than IPC alone.
Similar to GCS, IPC use also has problems with compliance and size t. They
are also contraindicated in patients with peripheral arterial disease. Aside from its
contraindications, there are concerns regarding dislodging newly formed venous
thrombi in immobilized patients of >72 h after application of IPC. Ultrasound
examination prior to application may have a role in this dislodgment prevention, but
more studies are required in this aspect.
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Recommendations inSurgical Procedures
General Surgery
Recent general surgical procedures’ risk without thromboprophylaxis is unknown,
due to the lack of such protocols in the present literature. The risk of such procedures is based on older data that reports up to 30% risk of asymptomatic DVT and
up to 0.9% risk of a fatal pulmonary embolus in the absence of thromboprophylaxis
[21]. Such risk must have decreased in the present general surgical patients due to
several factors: earlier mobilization, abidance by thromboprophylaxis protocols,
and increase in the number of surgeries done under regional anesthesia. On the other
hand, a few factors increase the current risk of general surgical procedures’ VTE
such as: older patients requiring complicated surgeries, surgeries requiring intraoperative chemotherapy, and earlier discharges lacking accurate postoperative thromboprophylaxis. The type of surgery done remains the most important predictive
value for VTE risk. Same-day surgeries are among those with the lowest risk [22].
For example, a study done in Denmark concluded that a day-case hernia surgery
doesn’t require thromboprophylaxis after looking into the 30-day follow-up data of
2281 patients. In another study, it was found that in the absence of thromboprophylaxis, epidural anesthesia is safer than general anesthesia with respect to postoperative DVT [23].
Major general surgical procedures require routine postoperative thromboprophylaxis, according to data from different RCTs. The routine use of low-dose unfractionated heparin (LDUH) or low molecular weight heparin (LMWH) decreases the
risk of VTE by up to 60%. In several trials, LDUH is used as 5000IU up to 2h prior
to surgery and continued as TID (three times a day) doses for a week postoperatively. Based on indirect comparisons, most literature stated the TID dose was more
benecial than the BID (twice a day) dose. In an overview of results of 46 general
surgery randomized trials, the rate of DVT was signicantly reduced when using
LDUH as thromboprophylaxis versus none, with a decrease from 22 to 9%; odds
ratio (OR) 0.3, as were the rates of symptomatic PE from 2 to 1.3%; OR 0.5. But
this, on the other hand, was associated with a slight increase in mostly non-major
bleeding events’ rate from 3.8 to 5.9%; OR 1.6. The rate of major bleeding was
stable at 0.3% in both groups [24].
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LMWH thromboprophylaxis in general surgical procedures was also studied
thoroughly in the literature. Similar to LDUH, LMWH was found to reduce asymptomatic and symptomatic DVT by more than 60% [25]. When it comes to comparing both agents LDUH and LMWH, results in the literature didn’t show a signicant
difference in the rate of symptomatic VTE [26].
M. R. Wehbe et al.
Vascular Surgery
The majority of vascular patients are treated intraoperatively with anticoagulants
such as heparin or dextran at clamping time to achieve ACT >250. In addition, antiplatelet agents (aspirin and clopidogrel) are used in these patients pre- and postoperatively. These factors play a major role in thromboprophylaxis in this surgical
category [27]. Up to 25% of patients suffer from asymptomatic DVT after vascular
surgery if the appropriate prophylaxis wasn’t given [8]. A study done with 142 consecutive vascular patients for aortic aneurysm repair with pre- and 7- to-10-day
postoperative duplex ultrasound after receiving appropriate LDUH prophylaxis and
intraoperative sequential compressive device found that 9.8% had postoperative
DVT, with a single patient diagnosed with pulmonary embolus. In another study,
symptomatic DVT was <1% in a follow-up of up to 30days’ post-abdominal aortic
aneurysm repair or lower extremity bypass [28].
Thromboembolic risk appears to be higher in aortic aneurysm repair and aortofemoral bypass surgeries versus femoro-distal bypass surgery [29]. Moreover,
increased age, limb ischemia, and operative time were found to enhance thromboembolic risks in vascular surgery. Few RCTs discussed VTE prophylaxis after arterial surgery. Belch, et al. terminated their randomized double-blind control trial
after having bleeding risk outweighing their VTE prophylaxis benet. In their study,
they compared LDUH twice daily vs. placebo in elective aortic bifurcation surgery
of 45 patients. Their risk of DVT was higher in the placebo group, 24% vs. 4% [30].
Another study showed no benet of thromboprophylaxis in 24 vascular surgery
patients compared to 25 patients with no prophylaxis [31]. In the last study, 100
vascular patients undergoing aortic surgery were randomized into a group with
LDUH and graduated compression stockings versus another with no prophylaxis. In
this study, there was no differences between both groups, with each having 2% risk
of proximal DVT [32].
Urologic Surgery
VTE is a major concern after major urologic surgical procedures, with symptomatic
VTE risks reaching 5%. Increase in patients’ risk is seen with open procedures,
pelvic surgery, increase in age, lithotomy position intraoperatively, and malignant
pathologies. Most of this data in urologic procedures was withdrawn from open
prostatectomies. Moreover, several urologic procedures pose a risk of VTE, such as
major renal procedures, radical cystectomies, urethral reconstructions, and
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transplant surgeries that require prophylaxis. The literature poorly addressed VTE
in urology patients, with an unknown best practice. Based on this, most patients are
being given their prophylaxis according to general and gynecologic surgery prophylaxis guidelines. Low-risk urologic procedures, such as transurethral ones, are
advised to provide early postoperative ambulation rather than anticoagulation prophylaxis, due to the higher risk of bleeding. Similarly, laparoscopic urologic procedures face higher risk of bleeding, with thromboprophylaxis data scarce in the
literature to give recommendations. Conversely, the group of urologic surgeries
with high risk of bleeding is advised to use non-pharmacologic prophylaxis preoperatively, with the addition of LDUH or LMWH postoperatively, once the bleeding
risk declines [33].
113
Bariatric Surgery
Nowadays the number of yearly bariatric operations has increased tremendously for
morbidly obese patients. These procedures range from sleeve gastrectomy, biliopancreatic diversion, and Roux-en-Y gastric bypass. The majority of these procedures are done laparoscopically with a minimal postoperative hospital stay. Several
studies report thromboembolism complications after bariatric procedures. VTE was
reported over an 11-year period for more than 14,000 patients to be less than 0.2%
in the National Bariatric Surgery Registry. A different study showed only one PE
was found in 2000 consecutive patients undergoing Roux-en-Y gastric bypass in the
rst month postoperatively [34]. Similarly, a PE rate of 1% among 2011 bariatric
surgery patients was shown in 2002, when 69,072 patients underwent morbid obesity surgery, among which 0.34% had VTE after surgical discharge. Deadly PE was
detected in 0.2% within 1 month postoperatively after studying more than 5000
patients during a 24-year period [35]. VTE post bariatric surgery is increased in
those complicated by a leak, older population, and history of VTE [36]. VTE criteria
for bariatric surgery patients are not well known.
There is a single published RCT for VTE prophylaxis in morbid obesity surgery.
Sixty consecutive patients undergoing Roux-en-Y gastric bypass were randomized
to receive either 0.6mL or 1.0mL of nadroparin started pre-operatively and then
given once daily postoperatively until discharge. They concluded that 0.6mL of
nadroparin once daily is safe and as effective in prophylaxis of VTE as the higher
dose of 1mL.
In another RCT, 164 patients scheduled for gastric bypass were divided into
three groups depending on the dose of enoxaparin received: 4000, 6000, or twice the
4000IU.The objective was to determine the best regimen of enoxaparin providing
an antifactor Xa peak activity between 0.3 and 0.5IU/mL and to evaluate the course
of procoagulant microparticles (MPs). At the end of this study, they concluded that
a once-daily dose of 6000IU/day allowed the majority of the patients to sustain the
target range of antifactor Xa activity without increasing the bleeding risk [37].
Due to the small number of studies tackling VTE in bariatric surgery, some studies came across a regimen of low-dose continuous intravenous heparin as VTE
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prophylaxis with an outcome of low VTE and bleeding. This practice still lacks any
randomized controlled trials. Due to the scarcity of data among VTE prophylaxis in
bariatric surgery patients, their guidelines are also extrapolated from high-risk general surgery patients.
M. R. Wehbe et al.
Thoracic Surgery
Undervalued VTE risk in thoracic surgery is attributed to the low number of RCTs
reporting this issue. The majority of thoracic surgery patients have multiple VTE
risk factors such as old age, cancer, or decreased postoperative mobility. The risk of
PE after major thoracic operations is up to 5.2%, with a risk of mortality post major
thoracic surgery reaching 1.3% [38]. The rate of DVT could be as high as 14% if
screening duplex ultrasounds are used. The National Surgical Quality Improvement
Program diagnosed 1.6% of 13,000 patients undergoing lung resection with symptomatic DVT [28]. Pneumonectomy for malignancy with appropriate VTE prophylaxis of IPC and LDUH reported 7.4% symptomatic VTE in a retrospective review.
In an RCT comparing the common dose of heparin prophylaxis 5000U twice daily
versus a higher dose of 7500U twice daily in 100 consecutive patients having thoracotomies for lung or esophageal cancer, it was found that the 7500U heparin
doesn’t signicantly provide more prophylaxis compared to the lower 5000U dose
(22% versus 33% total DVT), but had signicant less extensive DVT (0% versus 4%
for popliteal DVT). Moreover, no postoperative excessive bleeding was noted in
either treatment group. In another RCT, 150 lung cancer resection patients were
allocated to two groups and followed up with routine duplex US at postoperative
day eight. The rst group received a xed low dose of Fraxiparine while the second
group received two higher doses in accordance with weight. This study concluded
no signicant difference of prophylaxis safety between the two groups; however,
there was a non-signicant higher bleeding risk with the higher dose of Fraxiparine.
VTE prophylaxis in thoracic surgery also lacks major denitive studies.
According to the ACCP guidelines, patients undergoing major thoracic surgery
require routine thromboprophylaxis with LMWH, LDUH, or fondaparinux, while
those with high risk of bleeding are recommended to have mechanical thromboprophylaxis only.
Coronary Artery Bypass Graft (CABG) Surgery
All cardiac bypass surgeries are done under systemic anticoagulation with heparin,
which almost eliminates the risk of thrombus formation intraoperatively.
Furthermore, these patients are prescribed postoperative antiplatelet therapy (aspirin and/or clopidogrel) with possible oral anticoagulation, which makes the need for
VTE prophylaxis debatable [39]. Data in this group of patients lacks RCTs and
most of the guidelines are extrapolated from retrospective studies that lack VTE
prophylaxis accuracy of dosage, results, and duration and entirety of patient-pool
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