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Table 5.1 Individual risk factors for VTE (Ref. [8])
Individual risk factors
• Advanced age
• Female gender
• Prior VTE or varicose veins
• Patient comorbidities (hypertension, infection, obesity, anemia, pulmonary, liver or renal
disease)
• Prolonged immobilization
• Major surgery
• Trauma
• Inherited thrombophilic factors
• Active malignant neoplasm with or without concurrent chemotherapy
• Central vein catheterization or transvenous pacemaker
• Neurological disease with extremity paresis
A. Falanga and V. Milesi
incident DVT or PE, VTE patients are still at risk of recurrence [4]. Consistently
across studies, the risk of recurrence is higher when risk factors are unknown (idiopathic VTE) or persistent as compared with risk factors that are transient. In general,
the greater the transient nature of the risk factor, the lower the risk for recurrence
after anticoagulant withdrawal. For example, Baglin and colleagues showed that in
patients with a rst episode of VTE, during a 2-year follow-up period, the incidence
of recurrent VTE was 0% with surgery-related VTE, 19.4% with unprovoked VTE,
and 8.8% with VTE associated with nonsurgical risk factors (fracture, illness,
immobilization, travel, or estrogen) [5].
VTE is a common complication among hospitalized patients. In the absence of
appropriate thromboprophylaxis, the reported incidence ranges from 10 to 40% in
medicine and general surgery populations and from 40 to 60% in patients undergoing major orthopedic surgery [6]. PE may occur in up to 5–10% of high-risk hospitalized patients and represents one of the most common causes of preventable
in-hospital death [7].
In order to improve survival, avoid recurrence, prevent complications, and reduce
health-care costs, the occurrence of VTE must be reduced. To achieve this goal, it is
very important that persons at risk for VTE are accurately identied. A number of
known individual risk factors for VTE are summarized in Table5.1 [8].
In this chapter, we will focus on the risk of VTE associated with surgery, especially
in elderly patients, and on the available tools for stratifying patients undergoing surgery according to their risk level. Furthermore, we will provide information on the
various forms of thromboprophylaxis and on the efcacy and safety of thromboprophylaxis in very high-risk type of surgery, i.e., orthopedic and oncological surgery.
5.2 Venous Thromboembolism inElderly Patients
The incidence of VTE increases signicantly with age for both idiopathic and secondary VTE, suggesting that the risk associated with advancing age may be due to
the biology of aging rather than simply an increased exposure to VTE risk factors
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with advancing age. Incidence rates of VTE increase dramatically at about age 55
and by age 80 are nearly 1in 100 per year, approximately 1000-fold higher than for
subjects aged 45 or younger [9, 10]. Furthermore, rates of PE rise faster than DVT
in the elderly so that the disease has a greater fatal impact.
Frequent VTE risk factors in older adults include recent hospitalization, recent
surgery, cancer (occult or active), infection, immobility, chronic cardiopulmonary
disease and exacerbation, and prior history of VTE.Frailty has also recently been
found to be a risk factor for VTE.Other less common, but actual, VTE risk factors
in older adults include nephrotic syndrome, myeloproliferative disorders, antiphospholipid antibody syndrome, and heparin-induced thrombocytopenia [11]. There
are also age-specic factors that are almost exclusively present in the older population, such as reduced muscle strength, endothelial dysfunctions, and venous insufciency. Overall muscle strength declines starting from the age of 50years [12]. It
is likely that this also affects the calf muscle pump. Although the role of muscle
strength of the lower limbs and the concomitant deterioration in the venous hemodynamics is not yet claried, diminished function or efcacy of the calf muscle
pump could lead to reux and stasis, which subsequently may predispose to thrombus formation. Also, the prevalence of chronic venous insufciency increases with
age. The pathophysiology of this functional disease consists of failure of valves
through dilation of the venous wall or remodeling of the valve leaets, which can
then lead to stasis and elevation of distal venous blood pressure.
Other common ndings with aging are important changes in the hemostatic balance, with appearance of a prothrombotic state, characterized by an increase in
plasma levels of brinogen, Factor VII, Factor VIII, brinopeptide A, D-dimer, and
PAI-1 and by an increased platelet activation invivo with changes in platelet function related to variation in the membrane lipid composition [13]. For example,
plasma brinogen levels increase with age, with an approximate 10mg/dL incremental rise per decade in healthy subjects, and in some settings correlate with VTE
risk in older adults. von Willebrand factor and FVIII levels also increase with aging
and may be associated with increased risk of thrombosis. Components of the brinolytic pathway, such as brinolysis inhibitors, show a true age-related increase,
which contributes to the overall thrombotic risk [
11]. Finally, in elderly subjects, the
occurrence of laboratory features of hypercoagulability, as shown by increased levels of circulating thrombotic markers, including D-dimer, underlies a prothrombotic
background.
5.3 Risk Stratification inSurgery
In surgical patients, indication for VTE prophylaxis varies according to the individual risk of VTE (Table 5.1) and the type of surgical procedures. As shown in
Table5.2, two types of surgery are distinguished based on the length of intervention
(i.e., greater or lower than 45min).
The risk for VTE is increased in all patients undergoing general surgery,
including elderly patients. However, the relative risk for postoperative
68
Table 5.2 Classication of surgical interventions
Minor surgery
• Radical neck dissection
• Inguinal hernia repair
• Appendectomy
• Laparoscopic cholecystectomy
• Transurethral prostatectomy
• Repair of a cystocele or rectocele
• Cruciate ligament repair
• Thyroid or parathyroid surgery
a
In case of interventions with a greater duration of 30–45min or associated with serious bleeding
or extended dissections, the risk becomes comparable to that of major surgery
a
Major surgery
Abdominal or thoracic surgery that requires
general anesthesia lasting ≥45min
A. Falanga and V. Milesi
development of this complication varies among individual patients based on several factors, i.e., the length of immobilization following surgery, the type of surgery performed, and the presence of comorbid conditions. Immobilization for an
extended period is a well- established risk factor for VTE, and early mobilization
following surgery has been shown to lower the risk for postoperative VTE [14].
There is also strong evidence that the type of surgical procedure is predictive of
the risk of postoperative VTE.Major general surgery (i.e., abdominal or thoracic
operations that require general anesthesia lasting ≥45min) is associated with a
high risk of VTE.Orthopedic surgery is associated with an even higher risk [15].
Other procedures associated with a substantially increased risk include major
vascular surgery, small or large bowel resection, gastric bypass, radical cystectomy, kidney transplantation, and below-the-knee amputation [16]. A lower risk
of VTE was reported with radical neck dissection, inguinal hernia repair, appendectomy, laparoscopic cholecystectomy, transurethral prostatectomy, repair of a
cystocele or rectocele, cruciate ligament repair, and thyroid or parathyroid surgery (Table5.2).
In recent years, risk stratication has been suggested as a means of determining
the risk for VTE in patients undergoing surgery and of guiding the selection of
appropriate prophylactic measures. Several risk assessment models that stratify
patients according to their risk of VTE have been published, the most notable
being the Caprini score, that estimates VTE risk by adding points for various VTE
risk factors (Table5.3). The Caprini score was introduced in 2005 to improve
compliance with VTE prophylaxis guidelines for surgical patients and uses a
point-scoring system; the relative scores for individual risk factors are summed to
produce a cumulative risk score that denes the patient’s risk level (low, moderate, high, or highest risk) and the associated prophylaxis regimen [17]. An appropriate method of VTE prophylaxis can be chosen based on the patient’s level of
risk, taking into consideration any contraindications to prophylaxis that may be
present.
Although this model was not developed using rigorous statistical methods, and
includes some variables that were later found not to be associated with VTE risk, it
is relatively easy to use and appears to discriminate reasonably well among patients
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Table 5.3 Caprini risk assessment model (Ref. [17])
1 point
Age 41–60years Age 61–74years
Minor surgery Arthroscopic
BMI >25kg/m
Swollen legs Laparoscopic
Varicose veins Malignancy Prothrombin 20210A Acute spinal cord
Pregnancy or postpartum Conned to bed
History of unexplained or
recurrent spontaneous
abortion
Oral contraceptives or
hormone replacement
Sepsis (<1month) Heparin-induced
Serious lung disease,
including pneumonia
(<1month)
Abnormal pulmonary
function
Medical patient at bed rest
Congestive heart failure
(<1month)
History of inammatory
bowel disease
Acute myocardial
infarction
2
2 points 3 points
Age≥75years
surgery
Major open surgery
(>45min)
surgery (<45min)
(>72h)
Immobilizing
plaster cast
Central venous
access
History of VTE Elective
Family history of VTE Hip, pelvis, or leg
Factor V Leiden Hip, pelvis, or leg
Lupus anticoagulant
Anticardiolipin
antibodies
Elevated serum
homocysteine
thrombocytopenia
Other congenital or
acquired thrombophilia
5 points
Stroke (<1month)
arthroplasty
fracture
fracture
injury (<1month)
69
at low, moderate, and high risk for VTE.The incidence of VTE in patients in the
low-risk category (1 risk factor) is so low (approximately 2%) that prophylactic
measures would most likely not further reduce the risk. Thus, no measures above
early ambulation are recommended in this patient population. The incidence of VTE
ranges from 10 to 80% in the remaining groups; therefore, prophylactic measures
are recommended in these groups. As opposed to an increasingly precise stratication and individual thrombotic risk, the denition of bleeding risk is instead limited
to suggestions, even in the latest guidelines. Furthermore, there are differences
between guidelines in the denitions of what are the contraindications to pharmacological anticoagulant prophylaxis. For example, concerning thrombocytopenia as a
known bleeding risk factor, the National Institute for Health and Clinical Excellence
(NICE) guideline [18] contraindicates the anticoagulant thromboprophylaxis in
case of platelet count <20,000/μL, while in other guidelines the cutoff value is
<50,000/μL.The decision to start or not pharmacological thromboprophylaxis must
necessarily be based on an individual assessment of the thrombotic/bleeding risk
balance.
70
A. Falanga and V. Milesi
5.4 Methods ofPerioperative Thromboprophylaxis
Methods of thromboprophylaxis are typically divided into mechanical and pharmacological modalities. It is recommended that early and “aggressive” ambulation be
a routine part of postoperative care in all patients unless there is an absolute contraindication. Although early mobilization following surgery has been shown to signicantly lower the risk for postoperative VTE [14], it is recommended as a single
method only for low-risk patients, those younger than 40years without any additional risk factor for VTE, and who are undergoing minor surgery (outpatient surgery lasting less than 45min). For surgical patients at moderate risk for VTE (major
surgery with 2 additional risk factors), mechanical methods of prophylaxis have
been safe and effective modalities.
Mechanical methods include:
• Graduated compression stocking
• Intermittent pneumatic compression
• Venous foot pump
These devices act by reducing venous stasis and increasing venous outow in the
lower extremities. Mechanical thromboprophylaxis is an attractive option for surgeons because it does not increase the risk for bleeding complications. However,
although these devices have been demonstrated to decrease the incidence of DVT,
they have not been shown to decrease the risk of PE or death [15]. For these reasons,
the 8th ACCP guidelines recommend the use of mechanical tools as a single method
of thromboprophylaxis exclusively in case of active bleeding or in presence of
extremely high risk of bleeding; otherwise, they recommend the medical methods
be used in association with pharmacological prophylaxis in patients at very high
risk of VTE.
Commonly used pharmacologic agents for prevention of VTE in surgery include
subcutaneous unfractionated heparin (UFH), low molecular weight heparins
(LMWH), fondaparinux, and oral anticoagulants.
Low-dose subcutaneous UFH was the rst pharmacologic agent to be widely
investigated for prevention of VTE in patients undergoing general surgery. It is generally administered subcutaneously at a dose of 5000I.U. every 8 or 12h, beginning
2h before the surgical procedure. Although UFH is effective for the prevention of
DVT and PE, bleeding complications associated with this regimen present safety
concerns. The short half-life of UFH (0.5–2h) as compared to other anticoagulants
is a limitation of UFH because it necessitates more frequent administrations; however, the short half-life can also be an advantage in case of bleeding complications
or renal failure.
LMWHs appear to be at least as effective as UFH for the prevention of DVT in
clinical trials of patients undergoing general surgery. It is produced by depolymerization of heparin into smaller molecules. These formulations have a more favorable
pharmacokinetic prole, including improved bioavailability, longer half-life allowing for one time daily administration, and decreased interindividual variability in
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71
anticoagulant response, thus obviating the need for therapeutic monitoring in most
patient populations. In summary, the advantages of LMWHs over UFH include a
higher anti-Xa activity compared with antithrombin activity, better bioavailability at
low doses, no monitoring required, and longer half-life (4–6h vs. 0.5–2h), oncedaily xed dosing. However, a long half-life can sometimes be a disadvantage in
case of bleeding complications.
Fondaparinux is the rst in a new class of antithrombotics known as factor Xa
inhibitors, which are characterized by targeted inhibition of coagulation. It is administered subcutaneously at the dose of 2.5 mg once a day. Similar to LMWH,
fondaparinux has the advantage of single-dose administration and seems not to be
correlated to heparin-induced thrombocytopenia.
The oral antivitamin K anticoagulants at low doses (INR 1.5) have a limited use
in surgery in Europe, whereas the new oral direct Factor X or Factor II inhibitors
(DOAC), including dabigatran, rivaroxaban, and apixaban, are currently indicated
for VTE prophylaxis in elective orthopedic surgery (i.e., replacements of prosthetic
hip and knee). Indeed, in this setting, DOAC can be a viable alternative to parenteral
anticoagulants, as shown by international randomized clinical trials of Phase II and
III, documenting that DOAC are as effective and safe as LMWH in the prevention
of VTE in orthopedic surgery.
5.5 Management ofThromboprophylaxis inSurgery
5.5.1 General Surgery
Based on the Caprini score, the 9th American College of Chest Physicians (ACCP)
guidelines have developed recommendations for thromboprophylaxis in general
surgery (Table 5.4) [19]. Indications for VTE prophylaxis vary according to the
individual risk of VTE and the surgical procedure.
The 9th ACCP guidelines do not recommend specic thromboprophylaxis for
low-risk surgery patients, such as ambulatory patients or those undergoing minor
procedures and without additional VTE risk factors. For these patients, only an early
mobilization is recommended. For patients at moderate or high risk of VTE who
undergo major general surgery, prophylaxis with LMWH, UFH, or fondaparinux is
recommended. The combination of either LMWH, UFH, or fondaparinux with
mechanical prophylaxis with graduated compression stockings and/or intermittent
pneumatic compression is recommended for general surgery patients with multiple
risk factors for VTE.The 9th ACCP guidelines recommend continuing prophylaxis
at least until patient discharge for patients undergoing major general surgical procedures. Extended prophylaxis for up to 28days should be considered for selected
high-risk patients, such as those undergoing oncological or orthopedic surgery.
For laparoscopic surgery, the routine use of thromboprophylaxis is not recommended, with the exception of patients with additional risk factors, for whom the
use of one among UFH, LMWH, fondaparinux, compression elastic stockings, or
intermittent pneumatic compression is recommended.
72
Table 5.4 Prevention of VTE in non-orthopedic surgical patients (modied from ACCP
Guidelines 2012) (Ref. [19])
Category of risk Recommendations
Very low risk (score 0) No specic pharmacologic (Grade 1B) or
Low risk (score 1–2) Mechanical prophylaxis, preferably with
Moderate risk (score 3–4) LMWH (Grade 2B), low-dose UFH (Grade 2B),
High risk (score≥5)
High risk (score≥5) in whom both
LMWH and UFH are contraindicated or
unavailable and who are not at high risk
for major bleeding complications
High-VTE-risk patients surgery for cancer Extended duration of pharmacologic prophylaxis
High-VTE-risk patients who are at high
risk for major bleeding complications
For all patients Inferior vena cava (IVC) lter should not be used
mechanical (Grade 2C) prophylaxis be used
intermittent pneumatic compression (IPC), over
no prophylaxis (Grade 2C)
or mechanical prophylaxis, preferably with IPC
(Grade 2C), over no prophylaxis
LMWH (Grade 1B) or low-dose UFH (Grade 1B)
over no prophylaxis. Mechanical prophylaxis with
elastic stockings (ES) or IPC should be added to
pharmacologic prophylaxis (Grade 2C)
Low-dose aspirin (Grade 2C), fondaparinux
(Grade 2C), or mechanical prophylaxis, preferably
with IPC (Grade 2C), over no prophylaxis
(4weeks) with LMWH over limited-duration
prophylaxis (Grade 1B)
Use of mechanical prophylaxis, preferably with
IPC, over no prophylaxis until the risk of bleeding
diminishes and pharmacologic prophylaxis may
be initiated (Grade 2C)
for primary VTE prevention (Grade 2C)
A. Falanga and V. Milesi
5.5.2 Oncological Surgery
There is a particularly strong association between cancer and VTE [20]. Clinically
apparent VTE is present in as many as 15% of all cancer patients, with much higher
incidences reported in postmortem studies. In addition, among patients with DVT,
those with cancer have a more than twofold increased risk for VTE recurrence than
those without cancer. The likelihood for the development of VTE in cancer patients
varies by tumor types and is increased among patients with more advanced disease
[21, 22]. Malignancies stemming from the uterus, brain, ovary, pancreas, stomach,
kidneys, and colon are among the tumor types that have been associated with the
highest relative risk for VTE [21].
Cancer patients undergoing surgery have a two- to vefold increased risk for
postoperative VTE, as compared with non-cancer patients undergoing the same procedures [23]. Regarding perioperative thromboprophylaxis, data show that LMWH
have the same efcacy as UFH in oncological surgery. In a large meta-analysis of
available randomized trials comparing LMWH, UFH, and placebo or no treatment,
LMWH appeared to be as safe and effective as UFH in reducing VTE, in both the
general population and a large subgroup of patients with cancer [24, 25]. In addition, the safety, assessed as the rate of bleeding complications, was similar between
the two types of heparins. For this and for their other several advantages (i.e., the
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once-daily administration, the favorable pharmacological prole, and the lower
association with heparin-induced thrombocytopenia), LMWH are increasingly used
in this area. The standard duration of thromboprophylaxis is about a week after
surgery or, in general, until discharge.
Several studies, however, have shown the efcacy of extended prophylaxis to
3–4weeks after hospital discharge. The prolonged prophylaxis not only reduces the
risk of thrombosis during the period of administration of heparin, but the benets
persist beyond 3months following surgery. In the ENOXACAN II study, patients
undergoing surgery for abdominal malignancy received 1week of LMWH prophylaxis and were then randomized to LMWH or placebo for another 21days [26].
Bilateral venography performed at the end of treatment period showed a statistically
signicant reduction in DVT from 12% with placebo to 4.8% with extended prophylaxis. Another study (FAME study) evaluated the efcacy and safety of thromboprophylaxis with LMWH, administered for 28 days after major abdominal
surgery compared to a 7-day treatment [27]. The cumulative incidence of VTE was
reduced from 16.3% with short-term thromboprophylaxis to 7.3% after prolonged
thromboprophylaxis. A third study to test the efcacy and safety of thromboprophylaxis in patients admitted for abdominal or pelvic surgery for cancer is the
CANBESURE study. Patients received LMWH once daily for 8days and were then
randomized to receive either LMWH or placebo for 20 additional days [28]. At the
end of the double-blind period, VTE occurred in 0.8 and 4.6% patients in the two
groups, respectively. The bleeding risk was not increased by extended LMWH
prophylaxis.
The American Society of Clinical Oncology (ASCO) guidelines recommend the
use of prophylactic anticoagulation in surgical patients. In particular, patients undergoing laparotomy, laparoscopy, or thoracotomy lasting more than 30min should
receive pharmacologic thromboprophylaxis with either low-dose UFH or LMWH
unless contraindicated because of ongoing active bleeding or a high risk for it [29].
Since these patients remain at elevated risk for VTE for an extended period of time
after hospital discharge, the ASCO panel recommends that prolonged prophylaxis
for up to 4weeks be considered in patients undergoing major abdominal or pelvic
cancer surgery with high-risk features, such as residual malignant disease postresection, obesity, or previous history of VTE [29]. The National Comprehensive
Cancer Network (NCCN) guidelines also recommend that all cancer patients with
high risk (age≥60years, advanced cancer, operative times more than 2h, previous
VTE, and >3days of bed rest) undergoing major surgery should be considered for
extended VTE prophylaxis [30]. The same recommendations are made by the Italian
Society of Medical Oncology (AIOM) (www.aiom.it) and the Italian Society for the
Study of Hemostasis and Thrombosis (SISET) [31].
5.5.3 Orthopedic Surgery
Major orthopedic surgery, including total hip replacement (THR), total knee
replacement (TKR), and hip fracture surgery (HFS), is associated with a very high
risk of VTE.Symptomatic DVT events occur after hospital discharge, and the risk
74
A. Falanga and V. Milesi
of VTE in this setting remains high for at least 2months after surgery, in particular
after THR [32]. The risk of VTE attributable to the surgical procedure per se is so
high that no further risk stratication based on individual risk factors is warranted
to decide the optimal thromboprophylaxis.
LMWH and low-dose UFH have been widely investigated in patients undergoing
major orthopedic surgery, and their efcacy is well documented, especially following THR and TKR. The ACCP guidelines recommend the routine use of either
LMWH, fondaparinux, new anticoagulants (apixaban, dabigatran, rivaroxaban),
low-dose UFH, low-dose warfarin, or aspirin for patients undergoing THR, TKR, or
HFS (Grade 1B) [33]. LMWH is to be given either preoperatively, that is, started
12h before surgery according to the European standard of practice, or postoperatively, that is, started 12–24h after surgery according to the North American standard. Finally, after orthopedic surgery, it is recommended to administer
thromboprophylaxis for a minimum of 10days in all patients and to extend thromboprophylaxis in the outpatient period for up to 35days. A meta-analysis of six
randomized, double-blind trials comparing extended, out-of-hospital thromboprophylaxis with LMWH versus placebo demonstrated that extended out-of-hospital
thromboprophylaxis reduces the risk of symptomatic VTE by 64% [34].
Both UFH and LMWH need subcutaneous administration, which is not always
convenient for post-discharge use. Conventional anticoagulant therapy with coumarins has some limitations due to short-term adjustment and frequent INR monitoring.
The development of new oral anticoagulant agents, i.e., the direct thrombin
inhibitor, dabigatran, and the selective FXa inhibitors, rivaroxaban and apixaban,
are approved in many countries for VTE prevention in patients undergoing hip or
knee arthroplasty. Thanks to their pharmacodynamic and pharmacokinetic prole,
DOAC can be a viable alternative to other anticoagulants: they can be administered
at xed doses, have few interactions with food and other drugs, and do not require
monitoring [35].
Large randomized controlled trials have evaluated the efcacy and safety of
DOAC for the prevention of VTE.Each of these trials used the same primary outcome measure, a composite of symptomatic or asymptomatic DVT diagnosed by
venography, nonfatal PE events, and all-cause mortality. Dabigatran was investigated for prevention of VTE in four Phase III trials, two after THR (RE-NOVATE
and RE-NOVATE II) and two after TKR (RE-MODEL and RE-MOBILIZE) [36–
39]. RE-MODEL, RE-NOVATE, and RE-NOVATE II have demonstrated non-infe-
riority versus LMWH for the primary outcome, while RE-MOBILIZE did not
demonstrate non-inferiority, although both treatments were similar for the secondary composite outcome. A meta-analysis of the data from these four trials conrmed
these ndings, showing that dabigatran versus LMWH had a similar efcacy in
preventing total VTE and all-cause mortality as well as a similar risk of major bleeding or clinically relevant bleeding [40].
Rivaroxaban was also investigated in four large Phase III trials, two after THR
(RECORD 1 and RECORD 2) and two after TKR (RECORD 3 and RECORD 4)
[41–44]. All four trials demonstrated the same efcacy of rivaroxaban compared to
LMWH for the primary outcome of total VTE and all-cause mortality. There were
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no signicant differences in the rates of major bleeding between the two treatments.
A meta-analysis of data from these four trials conrmed these ndings [40].
Apixaban was investigated in three large Phase III trials for prevention of VTE
after TKR (ADVANCE-1 and ADVANCE-2) and THR (ADVANCE-3) [45–47]. In
ADVANCE-1 despite similar efcacy, apixaban did not meet the prespecied, noninferiority goal because the event rates in the control group were much lower than
expected. Major bleeding rates were marginally lower with apixaban (0.7 vs. 1.4%
with enoxaparin). In ADVANCE-2 and ADVANCE-3, the same apixaban regimen
was as effective as LMWH in reducing total VTE plus all-cause mortality with a
similar risk of major bleeding. A meta-analysis of the data from these three trials
conrmed these ndings with a trend toward a lower risk of major bleeding and a
signicantly lower risk of clinically relevant bleeding [40].
As dabigatran, rivaroxaban, and apixaban are all partly cleared by renal elimination, their use needs to be carefully considered in patients with renal impairment,
which is rather frequent in elderly patients. European guidelines recommend that
apixaban and rivaroxaban should not be used in patients with CrCl <15mL/min,
while no dose adjustment is necessary in patients treated with rivaroxaban or apixaban who have mild (CrCl 50–80 mL/min) or moderate renal impairment (CrCl
30–49mL/min).
The guidelines note the limitations of DOAC, including the possibility of
increased bleeding, which may occur with all anticoagulants, but was clearly shown
for rivaroxaban, and the lack of long-term safety data with all medications: dabigatran, rivaroxaban, and apixaban.
Conclusions
Many conventional risk factors for VTE established in the young and middle-
aged population increase the risk of thrombosis in the elderly. Major surgery,
especially oncological or orthopedic, signicantly affects that risk. Furthermore,
the older the patients undergoing surgery, the more likely that comorbidity exists
at the time of intervention; consequently, the risk of VTE increases. Effective
VTE prophylaxis for surgical elderly patients at signicant risk of thrombosis
reduces the burden of VTE and improves outcomes. The current development of
VTE stratication models, using the increasing knowledge of the clinical and
surgical risk factors of thrombosis, is important for identifying high-risk patients,
who can most benet from thromboprophylaxis, thus reducing VTE-associated
morbidity and mortality.
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