Clinical and Applied

Thrombosis/Hemostasis
Identification of Patient Venous 17(6) 590-599
ª The Author(s) 2011
Reprints and permission:
Thromboembolism Risk Across sagepub.com/journalsPermissions.nav
DOI: 10.1177/1076029611404217
the Continuum of Care http://cath.sagepub.com

Joseph A. Caprini, MD, MS, FACS, RVT1,2

Abstract
Venous thromboembolism (VTE) complications are the leading cause of preventable in-hospital mortality and morbidity in the
United States. Initiatives by the National Quality Forum, the Joint Commission, and the Surgical Care Improvement Project aim
to improve the prevention of VTE and emphasize the need to recognize the risk of the condition in hospitalized patients. In clinical
practice, individual risk assessment using a validated scoring system provides patients with the best care in the prevention of VTE.
This is accomplished by a weighted scoring of risk factors, selection of the most appropriate prevention strategy for patients at
risk, and regular risk review across the continuum of care. All hospitals should have a local, written, care pathway which assesses
inpatient risk of VTE as early as possible upon admission and identifies members of the health care team responsible for applying
risk assessment. Venous thromboembolism risk should be regularly reassessed for any changes in the level of risk, with extended
out-of-hospital prophylaxis considered for patients with continued risk factors, such as prolonged immobility or illness, treated at
home, or in a long-term care facility. Finally, a mandatory alert system requiring the clinician to address the issue of prophylaxis
before any orders are carried out by the nursing staff is one way to protect all hospitalized patients.

Keywords
anticoagulants, deep venous thrombosis, factor Xa inhibitors, thrombosis prophylaxis, low-molecular-weight heparins, pulmonary
embolism

Introduction performance measures aimed at reducing complications in

Venous thromboembolism (VTE), comprising deep vein
thrombosis (DVT) and pulmonary embolism (PE), is a leading
cause of preventable in-hospital mortality and morbidity in the
United States.1 Fatal PE is frequently the first sign of VTE and
accounts for up to 10% of all hospital deaths.2,3 Prevention of
VTE has been identified by the Agency for Healthcare
Research and Quality (AHRQ) as the most important strategy
for improving the safety of hospitalized patients.4 Despite
the existence of evidence-based consensus guidelines on the
prevention of VTE, including recommendations from the
American College of Chest Physicians (ACCP),1 many patients
remain at unnecessary risk of VTE during hospitalization.5
These considerations are consistent with The National Quality
Forum (NQF) standards, which call for all patients to be eval-
uated for VTE risk upon hospital admission and periodically
thereafter, with appropriate VTE prophylaxis prescribed if nec-
essary.6 The NQF in collaboration with The Joint Commission
has recently drafted an extended set of seven hospital-focused
performance measures.6,7 These measures provide a venue to
assess the implementation of safe-practice guidelines which
target assessment, prophylaxis, and care management.6,7
A similar initiative was launched earlier for surgical patients, the
Surgical Care Improvement Project (SCIP), with VTE-related
surgical patients.8 These initiatives emphasize the need to
recognize the risk of VTE in hospitalized patients and act upon
it accordingly. Adherence to, and reporting of, SCIP and NQF/
Joint Commission VTE performance measures is increasingly
becoming mandatory, linked to pay-for-performance measures
and other reimbursement schemes.
This review discusses the importance of VTE risk assessment
early after hospital admission, with emphasis on the continua-
tion of prophylaxis and risk monitoring across the continuum
of care.
The Disease Burden of DVT/PE
Anderson et al reported that 31% of all patients (both medical
and surgical patients) hospitalized in the United States each
year (>12 million patients) are at risk of VTE and meet current
1
Division of Vascular Surgery, NorthShore University HealthSystem,
Evanston, IL, USA
2
The University of Chicago Pritzker School of Medicine, Chicago, IL, USA
Corresponding Author:
Joseph A. Caprini, 28 Coventry Road, Northfield, IL 60093, USA
Email: jcaprini2@aol.com
Caprini 591

Table 1. Venous Thromboembolism (VTE) Risk Factors in Hospita- questionnaires compared with those who did not develop PTS,
lized Surgical and Medical Patients According to Relative Strength and less improvement in QoL over time.15
Kucher et al18,a Anderson and Spencer19,b
Venous Thromboembolism Risk Factors
High-risk factor (score 3) Strong risk factor (odds ratio >10)
 Cancer  Major orthopedic surgery Several independent risk factors for VTE have been identi-
 Hypercoagulability  Major general surgery fied.10 Venous thromboembolism risk factors in hospitalized
 Prior VTE  Major trauma surgical and medical patients are listed in Table 1 and grouped
 Spinal cord injury according to their relative weight.18,19 Hospitalization per se
Intermediate risk factor (score 2) Moderate risk factor (odds
ratio 2-9) has been shown to be an independent risk factor for the devel-
 Major surgery  Acute respiratory failure opment of VTE.10 Prolonged venous stasis due to bed rest and
 Arthroscopic knee surgery immobilization, and acuteness and severity of medical illness,
 Cancer or surgery are likely factors contributing to the overall
 Central venous lines increased risk associated with hospital confinement.10
 Chemotherapy Predisposing or patient-related risk factors that affect the
 Congestive heart failure incidence of VTE among inpatients include increasing age,
 Hormone-replacement
therapy
obesity, cancer, previous VTE, varicose veins, thrombophilia,
 Hypercoagulability oral contraceptives, and hormone replacement.20 A study by
 Oral contraceptives Borow and Goldson reports that age >60 years and length of
 Paralytic stroke surgery are factors significantly increasing the risk of VTE.21
 Pregnancy–postpartum Venous thromboembolism is an important complication of
 Prior VTE malignancy22 and the second most common cause of death
Minor risk factor (score 1) Weak risk factor (odds ratio <2) among the patients with cancer.23 In addition to cancer, major
 Advanced age  Advanced age
 Bed rest  Bed rest
surgical procedures, chemotherapy, and central venous cathe-
 Hormone-replacement  Immobility due to sitting ters contribute to the cancer patients with systemic thromboem-
therapy (eg, prolonged car or air bolic risk.10,24 Individual patients are often exposed to multiple
 Obesity travel) risk factors that are cumulative to the overall risk.19,22,25
 Oral contraceptives  Laparoscopic surgery
 Obesity
 Pregnancy–antepartum Individual VTE Risk Assessment
 Varicose veins
One approach to identify patients at VTE risk is a group-
a
Risk score model as used in a prospective study on electronic alerts to specific routine approach, as detailed in the 2008 ACCP recom-
improve VTE prevention. An increased risk of VTE was defined as a cumulative mendations for thromboprophylaxis of hospitalized patients.1
risk score of 4.
b
Review summarizing the strength of the evidence regarding specific risk fac-
These guidelines stratify surgical patients into group-specific
tors for VTE. categories of risk (Table 2); risk levels are less well defined for
medical patients.1 In the most recent update, the guidelines
criteria for VTE prophylaxis.9,10 Venous thromboembolism state in a section (1.4.5) on application of evidence to individ-
has been traditionally regarded primarily as a complication ual patients: ‘‘Decisions about prescribing thromboprophylaxis
occurring after surgery. However, a postmortem study into for the individual patient are best made by combining knowl-
in-hospital deaths revealed that up to three quarters of fatal edge of the literature (including the recommendations provided
PE events and approximately two thirds of symptomatic VTE herein) with clinical judgment, the latter based on specific
episodes occur in medical inpatients.2 knowledge about each patient’s risk factors for VTE.’’1
Pulmonary embolism and DVT are among the top 10 most This section seems to contradict an earlier section (1.3) on
common hospital adverse events.11 In addition to the risk of risk stratification where a group-specific approach for routine
fatal PE, VTE is associated with long-term health complications, thromboprophylaxis for all patients who belong to each of the
including recurrent VTE, postthrombotic syndrome (PTS), and major target groups is supported, rather than individual throm-
chronic pulmonary hypertension.12-16 A long-term clinical study boprophylaxis prescribing.1 The use of clinical judgment sug-
reported that 30% of patients with VTE experienced a recurrent gested by the former statement is an important concept
event after 8 years.12 Postthrombotic syndrome, encompassing because many of the patients seen in clinical practice do not
limb pain, swelling, and ulcers, is an important long-term compli- match inclusion criteria of clinical trials and the clinical trial
cation of VTE occurring in 15% to 50% of patients within 8 years data may not apply.
of an initial VTE episode.12-14,17 In a quality-of-life (QoL) study Each patient has a unique set of thrombotic risk factors
carried out during a 2-year period after a diagnosis of DVT in 387 which may not ‘‘fit’’ neatly into a preset level of risk.5,26
patients, 47% of patients developed PTS. Development of PTS Therefore, both the strength of the patient’s risk factors and the
was the principal determinant of health-related QoL after VTE cumulative weight of these risk factors must be taken into
(P < .0001). Patients with PTS had lower scores on QoL account when assessing the overall VTE risk. Accurate VTE
592 Clinical and Applied Thrombosis/Hemostasis 17(6)

Table 2. Recommended Prophylaxis Options1

Risk Level Type of Patient Recommended VTE Prophylaxis

Medical patients
Low to moderate risk General medical patients No specific prophylaxis
High risk Acutely ill medical patients admitted to hospital with LMWH, LDUH, or fondaparinux; optimal use of GCS
congestive heart failure or severe respiratory disease or or IPC when anticoagulant thromboprophylaxis is
confined to bed with additional risk factors (cancer, prior contraindicated
VTE, sepsis, acute neurological disease, or inflammatory
bowel disease)
Surgical patients
Low risk Minor surgery in mobile patients with no additional risk No specific prophylaxis; early and aggressive
factors mobilization
Moderate risk Most general, open gynecological, or urological surgery LMWH at recommended dose, LDUH 2 or 3 times
patients (major procedure for benign disease) daily, or fondaparinux
High risk Orthopedic patients undergoing hip or knee arthroplasty or LMWH at recommended dose, fondaparinux, and
hip fracture surgery, major trauma patients, and spinal oral vitamin K antagonist (INR 2-3)
cord injury
High-risk general surgery; major surgery for cancer LMWH at recommended dose, LDUH 3 times daily,
or fondaparinux
In patients with multiple risk factors considered to be at high Combine pharmacological (LMWH, LDUH 3 times
risk daily, or fondaparinux) with mechanical thrombo-
prophylaxis (IPC, GCS)
Abbreviations: GCS, graduated compression stockings; INR, international normalized ratio; IPC, intermittent pneumatic compression; LDUH, low-dose unfrac-
tionated heparin; LMWH, low-molecular-weight heparin; VTE, venous thromboembolism.

risk assessment for individual patient is important for selecting
patients who benefit from prophylaxis.5 Due to the unique
VTE risk profile of each patient, individual risk assessment
should be carried out as early as possible using a clinically
validated, hospital-approved risk-assessment model18,27-34
(RAM; Figure 1). Advantages of individual risk assessment
include individual risk-factor profiles with tailored prophylaxis
measures.28,29
The case study described in Table 3 exemplifies the case of
individual versus group prophylaxis; according to patient
groups identified to be at risk in the ACCP guidelines, this
patient would not have been considered to be at risk of
VTE due to the nature of her injury and the surgical procedure.
However, individual risk calculation identified her to be at high
risk of VTE.35
Risk of VTE cannot, however, be viewed in isolation, and
the concomitant risk factors for bleeding must also be taken
into account when considering the appropriateness of thrombo-
prophylaxis. Recently, Decousus and colleagues utilized a
multivariate analysis to identify and score factors associated
with bleeding risk in medical patients (Table 4). The authors
also created an online resource where bleeding risk can be
assessed (available at: http://www.outcomes-umassmed.org/
IMPROVE/bleeding_risk_score.cfm).36
In summary, certain broad groups of patients should be
considered for VTE prophylaxis. Although data suggest that for
large heterogeneous patients groups, such as medical patients,
the absolute benefits of VTE prophylaxis may be small,1 indi-
vidualized risk assessment offers a possible route for the opti-
mization of patient care. Through the identification of those
patients not at risk of VTE, those patients at risk of bleeding,
and those patients at very high risk of VTE, individualized risk
assessment allows the tailoring of appropriate patient-specific
prophylactic regimens. Such targeted prophylaxis may result
in an increase in the absolute benefits to patients, although
large-scale studies would be required to confirm this. In addition
to RAMs and consensus recommendations from the literature, a
decision concerning any patient is best made by applied clinical
judgment and extrapolation from limited clinical data in some
patient groups.
Venous Thromboembolism Prophylaxis
The current recommended VTE prophylaxis options for surgi-
cal and medical patients are listed in Table 2. Methods used to
establish a diagnosis of DVT include D-dimer assay, duplex
ultrasound, magnetic resonance imaging, and/or contrast veno-
graphy. Venography is the most accurate method for detecting
thrombi and is the gold standard objective assessment method
used in clinical trials of VTE prophylaxis.1 Recent studies have
validated the importance of asymptomatic venographically
detected DVT.37,38 A study of 1738 acutely ill medical inpati-
ents demonstrated a significant higher mortality rate at 90 days
among patients with proximal asymptomatic DVT (13.75%)
than patients with no VTE (1.92%; hazard ratio [HR], 7.63;
95% confidence interval [CI], 3.8%-15.3%; P < .0001). Distal
asymptomatic DVT was not associated with an increased
90-day mortality rate (3.39%; HR, 1.36; 95% CI, 0.41%-4.45%).3
Several further studies have shown that reductions in
asymptomatic VTE events with thromboprophylaxis parallel
a similar reduction in symptomatic VTE.39-42 A meta-analysis
by Eikelboom et al, of 3999 patients analyzed from 9 studies
demonstrated that in patients undergoing hip or knee replacement
surgery, extended-duration prophylaxis for 30 to 42 days
Caprini 593

Figure 1. Example of a risk-assessment model.

594 Clinical and Applied Thrombosis/Hemostasis 17(6)

Table 3. Case Study

VTE Risk

Treating Physician Following a

Group VTE Risk Strategy Individual Risk Approach

Patient (actual patient)

Woman, aged 46 years No Yes, >40 years (1)
Injury
Rupture of Achilles tendon No Yes, leg trauma (1)
Surgical procedure
Surgical repair No Yes, surgery (2)
Patient characteristics
15-Year history of inflammatory bowel disease, No Yes, inflammatory bowel disease (1)
receiving intravenous infliximab every 6 weeks
On estrogen (birth control pills) No Yes, on estrogen (1)
Leg plaster cast, on crutches No Yes, the cast inactivates the calf muscle pump (1)
Yes, reduced mobility (1)
Is the patient at risk of VTE? No Yes, at least 7 risk factors and a score of 8 put her at
very high risk
VTE prophylaxis? No Should receive VTE prophylaxis until the cast is
removed and the patient is ambulating normally
Patient outcome The patient died of PE, 3 weeks Prophylaxis can reduce the risk of postoperative fatal
after her injury PE by 80%35
Abbreviations: PE, pulmonary embolism; VTE, venous thromboembolism.

Table 4. Bleeding Risk Factors in Medical Patients According to
Relative Strength36
Bleeding Risk Factors
Moderate renal failure GFR 30 to 59 vs 60 mL/min per m2
Male vs female
Age 40 to 84 vs <40 years
Current cancer
Rheumatic disease
Central venous catheter
Intensive care unit/coronary care unit
Severe renal failure GFR < 30 vs 60 mL/min per m2
Hepatic failure (international normalized ratio >1.5)
Age  85 vs < 40 years
Platelet count < 50  109 cells/L
Bleeding in 3 months before admission
Active gastroduodenal ulcer
Abbreviation: GFR, glomerular filtration rate.
significantly reduced the risk of symptomatic VTE versus
placebo or untreated control (1.3% vs 3.3%; odds ratio [OR],
0.38; 95% CI, 0.24%-0.61%).40 This reduction in symptomatic
VTE paralleled a reduction in asymptomatic, venographically
detected DVT (9.6% vs 19.6%; OR, 0.48; 95% CI, 0.36%-
0.63%). Extended-duration prophylaxis versus control was not
associated with an increase in major bleeding (0.1% vs 0.3%;
OR, 0.62; 95% CI, 0.22%-1.75%) but did increase the rate of
minor bleeding (3.7% vs 2.5%; OR, 1.45; 95% CI, 1.08%-
2.26%).40 These studies highlight the importance of risk-
appropriate, evidence-based prophylaxis to reduce the number
of asymptomatic VTE events in high-risk patients and to
reduce the risk of these events becoming symptomatic.
No randomized controlled trials have been performed for
patients such as the one presented in the case study (Table 3).
However, Kakkar showed that prophylaxis cuts the risk of
Points fatal PE by 80% compared with no prophylaxis in
1 surgical patients (0.098% [2 of 2045] vs 0.771% [16 of
1 2076]; P < .005). Wound hematomas occurred more frequently
1.5 with prophylaxis (7.7% [158 of 2045] vs 5.6% [117 of 2076];
2 P < .01).35 Collins et al reaffirmed these results in 16 000
2 patients from 70 medical centers collected in the decade that
2 followed the original multicenter trial, reporting a reduction
2.5
of 64% + 15% (P < .0001) in fatal PE but with increased bleed-
2.5
2.5 ing.43 A more recent study reported that anticoagulant prophy-
3.5 laxis was also associated with a significant reduction in fatal
4 PE in medical patients (relative risk [RR], 0.38; 95% CI,
4 0.21%-0.69%), with a nonsignificant increase in major bleed-
4.5 ing (RR, 1.32; 95% CI, 0.73%-2.37%).44 Logic and experience
should guide the physician in appropriately using preventive
measures in those patients for whom clear guidance is lacking,
but who were individually identified to be at risk of VTE.
The Care Pathway in VTE Prevention
At Admission
All hospitals should have a local, written, care pathway based
on clinical guidelines, which assesses inpatient risk of VTE at
admission and which allows the treating physician to decide on
the most appropriate management. Indeed, the current ACCP
guidelines include ‘‘that every hospital develop a formal strat-
egy that addresses the prevention of VTE,’’ as a key recommen-
dation.1 In order to improve the quality of care and early
identification of patients at VTE risk, a multidisciplinary team
or steering committee should be established in every hospital.
Caprini
Figure 2. Clinically proven venous thromboembolism rates at 30 days:
incidence rate by risk level and cumulative risk score.32 Reprinted with
permission.
It is important to identify members of the health care team,
such as nurses, pharmacists, VTE specialists, and treating
physicians, who could be responsible for applying RAMs.
Nurses could play a greater role in VTE risk assessment, timely
diagnosis, appropriate prophylaxis, patient education, and
psychological support. Successful nurse involvement, such as
a nurse-managed VTE care pathway, would heighten clinical
surveillance on individual patients.45,46 The skills of nurses
should be utilized to a greater extent. However, at the present
time, they are required to assess the patient for fall risk, psycho-
social risk, ulcer risk, and others. Some feel these nurses may
experience ‘‘assessment fatigue’’ and should not be asked to
add yet another assessment to their long list. However, it is well
known that VTE is the number one preventable cause of
in-hospital mortality,1 and this should be considered when
setting assessment priorities for nurses. The importance of
pharmacists in the care pathway has recently been underlined
in a systematic review by Mahan and Spyropoulos.47
Five pharmacy-driven interventions aimed at improving VTE
prophylaxis were reviewed and demonstrated substantial
improvements in patient care. It should be noted, however, that
although pharmacy-driven, all 5 interventions were multidisci-
plinary in nature. The importance of an integrated multidisci-
plinary approach to the care pathway cannot be overstated. In
addition, further education across all professional groups
regarding risk assessment and administration of appropriate
prophylaxis would improve the coordination of patient care
through the continuum.
One helpful technique would be to involve patients in their
own care. This can be accomplished by asking each patient to
complete a simple form listing most of the common risk
factors. This can be done on admission or earlier in the physi-
cian’s waiting room. The completed form can be given to the
admitting physician, nurse, or physician assistant who can then
complete the risk-assessment form.
Active multifaceted systems aimed at reducing VTE risk
have the greatest effect. The systematic review by Mahan
and Spyropoulos advocates both human- and computer-based
595
active alert systems.47 The use of a computer-prescribing alert
system linked to altered care procedures significantly increases
the use of prophylaxis by physicians.18,48 Computer alert systems
can also reduce the incidence of VTE. In one series by 41% during
a 90-day study period (4.9% vs 8.2%; P ¼ .001), with no differ-
ence in major (1.5% vs 1.5%; P ¼ .87) or minor bleeding compli-
cations (6.5% vs 7.0%; P ¼ .43) or mortality (22.5% vs 22.3%;
P ¼ .74).18 Computerized decision-support software linked to
patient VTE risk assessment can be highly successful in increas-
ing appropriate prophylaxis.49 However, in a study of 866 patients
at high risk of VTE who were not receiving thromboprophylaxis,
a majority of physicians (62.3%) did not order VTE prophylaxis,
despite receiving an electronic alert. These results suggest that
electronic alerts alone may be insufficient.50
There are other ways to ensure early VTE risk assessment of
patients upon admission to hospital. Mahan and Spyropoulos
stress the potential utility of RAMs in identifying specific
at-risk populations to allow targeted use of prophylaxis.47
Caprini et al proposed a RAM, comprising a simple, hospital-
wide, and self-contained scoring sheet for risk stratification of
both surgical and medical patients based on clearly defined
clinical settings and the presence of specified risk factors (Fig-
ure 1). Partial validation has been carried out in medical
patients and in patients screened in the American Venous
Forum screening program.29,51 Recently, formal validation of
this tool was published in a study by Bahl et al of 8216 surgical
patients from the University of Michigan. The risk score corre-
lated with the 30-day incidence of clinically evident and
imaging-proven VTE. This retrospective VTE risk scoring
method based on the Caprini RAM has shown that the rate of
acquired VTE within 30 days appears to accelerate for patients
identified as having the highest cumulative risk score, whereby
patients with a score of 9þ have a VTE incidence rate of 6.5%
(Figure 2).32 Further data validating the Caprini RAM, in a var-
ied cohort of 1126 cosmetic and reconstructive surgery
patients, has recently been published by the Venous Throm-
boembolism Prevention Study (VTEPS) Network. Importantly,
as well as confirming the increasing VTE risk with increasing
Caprini score, this study showed that individuals with a score of
>7 experienced 50% of their VTE events at 15 to 60 days post-
surgery. Thus, the use of this RAM offers an opportunity to
identify high-risk patients who may benefit from extended
duration prophylaxis.52 Validation of the previously mentioned
electronic alert-based RAM developed by Kucher et al revealed
a similar correlation between risk score and VTE rate. How-
ever, this model showed a lesser sensitivity for low-risk
patients, likely due to incorporating less risk factors than the
Caprini/Bahl model.47 A further predictive and evidence-
based VTE risk score, specifically designed for medical
patients and based on a large multicenter study of 15 156
patients, derived a weighted scoring system from the hazard
ratios of 7 independent VTE risk factors. These risk factors are
previous VTE (assigned 3 points), thrombophilia (2 points),
lower limb paralysis (2 points), current cancer (2 points),
immobilization 7 days (1 point), ICU/CCU stay (1 point), and
age >60 years (1 point).53,54
596
A valuable source of information recently provided by the
AHRQ is a guide for the practitioner on important steps in the
quality improvement process, including the creation or adapta-
tion of protocols that standardize VTE risk assessment
embedded in patient care (http://www.ahrq.gov/qual/vtguide/).
During Hospital Stay
Venous thromboembolism risk should be regularly reassessed
during a patient’s stay in hospital for any change in the level
of risk. Potentially, additional VTE risk factors may arise as
a result of hospitalization, for example, prolonged immobility
or sepsis. A decrease in VTE risk during hospitalization
is less likely to occur. Individual risk assessment is important
in determining the timing of onset, intensity, and duration of
prophylaxis, as well as the choice of prophylaxis method.
Continued Care After Hospital Discharge
Continued outpatient prophylaxis is of particular importance,
given the continued VTE risk in the outpatient setting and the
trend for reduced duration of hospital stays.19,55-57 Data from
the Registro Informatizado de la Enfermedad TromboEmbólica
(RIETE) registry illustrate that more than half (55%) of symp-
tomatic, postoperative VTE events occur over 15 days after
surgery. Overall, 77% of the 3500 DVT patients entered into
the database developed their VTE events following hospital
discharge and 53% of these events occurred after prophylaxis
was stopped.55 The Million Women Study reveals that increased
risk of VTE subsequent to surgery can, in fact, persist for a dura-
tion of 12 weeks.57 This was a prospective cohort study involv-
ing 947 454 women followed for 6 years. Surgery was carried
out in 239 614 patients with 5419 VTE events, including
270 VTE-related deaths. Compared with not having surgery,
women were 70 times more likely to be admitted with VTE in
the first 6 weeks after an inpatient operation and 10 times more
likely after a day case operation. The risks were lower, but still
substantially increased, 7 to 12 weeks after surgery.57
In medical patients, the increased VTE risk is similarly
prolonged; in a study of 158 325 medical discharges, the med-
ian time for developing VTE was 74 days.56 These data along
with the Bahl et al32 and Panucci33,52 data illustrate another
important feature of the scoring system, namely the significant
incidence of VTE events at 30 and 60 days in those with high
scores. Repeat risk assessment as part of the discharge planning
process may, therefore, be useful in identifying patients who
will remain at risk of VTE postdischarge; in particular, to deter-
mine which patients would benefit the most from long-term
prophylaxis and guide the decision on the duration of prophylaxis
that individual patients should receive.
Standard recommended duration of prophylaxis in major
orthopedic surgery, for example, is a minimum of 10 days,1
which effectively means that most patients should receive out-
patient prophylaxis as the average hospital stay is approxi-
mately 4 days.19
Clinical and Applied Thrombosis/Hemostasis 17(6)
Further extended prophylaxis for up to 35 days is
recommended after total hip replacement, total knee replace-
ment, or hip fracture surgery.1 Ample clinical evidence is
available that extended prophylaxis with either a low-
molecular-weight heparin (enoxaparin or dalteparin) or fonda-
parinux can prevent late-occurring VTE complications after
several major surgical procedures, including major orthopedic
surgery and abdominal surgery (Table 5).40-42,58,59 The
Extended Prophylaxis for Venous ThromboEmbolism in
Acutely Ill Medical Patients With Prolonged Immobilization
(EXCLAIM) study provided clinical evidence that the use of
extended prophylaxis with enoxaparin also reduced VTE
more than it increased major bleeding events in certain
groups of acutely ill medical patients, namely those with level
1 immobility, those aged >75 years, and women.60 Two trials,
A Phase 3 Randomized, Double-Blind, Parallel-group,
Multi-center Study of the Safety and Efficacy of Apixaban for
Prophylaxis of Venous Thromboembolism in Acutely Ill
Medical Subjects During and Following Hospitalization
(ADOPT) and Multicenter, Randomized, Parallel Group
Efficacy and Safety Study for the Prevention of Venous
Thromboembolism in Hospitalized Medically Ill Patients
Comparing Rivaroxaban With Enoxaparin (MAGELLAN),
are investigating extended duration prophylaxis with new
oral anticoagulants.61 The trials will investigate the efficacy
of extended duration prophylaxis with apixaban and rivaroxaban
in medical patients, for 30 and 35 days, respectively, in com-
parison to enoxaparin during hospitalization (6-14 days) and
placebo after hospital discharge. Data from these trials may
offer additional information as to the benefits of extended
prophylaxis in medical patients. Further studies will be
needed to identify subgroups of high-risk medical patients for
whom there is a cost-effective clinical benefit of extended
thromboprophylaxis.
For many patients, outpatient prophylaxis is advised due to
short hospital stay or prolonged prophylaxis.62 There is a need
for hospital protocols that allow for appropriate transition
of care. The transition between acute and long-term care is
an important opportunity to reduce the incidence of VTE.63
The NQF recommends that provision be made for guideline-
directed therapy that addresses care setting transitions.6 Risk
factors for VTE during transition of patients, such as the
elderly, through subacute care settings or rehabilitation centers
have not been clearly defined, except for major surgical proce-
dures and stroke.1,26,64 Nursing-home residents who develop
VTE are 4.6 times (95% CI, 1.65%-13.06%; P ¼ .004) more
likely to have returned from hospital compared with
nursing-home residents who do not develop DVT. They are
also more likely to require assistance with mobility-related
activities, such as personal hygiene (OR, 3.35; 95%
CI, 1.26%-8.94%; P ¼ .02), toileting (OR, 4.00; 95%
CI, 1.37%-11.70%; P ¼ .01), or wheelchair use (OR, 2.69;
95% CI, 1.26%-5.74%; P ¼ .01).63 There is an urgent need
to define the risk factors and assess the benefit of extended-
duration prophylaxis in this growing population of patients
hospitalized in long-term care or rehabilitation centers.
Caprini 597

Table 5. Clinical Evidence for the Use of Extended-Duration Prophylaxis in Surgical Patients

VTE Major Bleeding

Extended Extended
Study Patient Group Extended Regimen Duration Comparator OR (95% CI) Duration Comparator OR (95% CI)

Meta-analysis40 THR or TKR LMWH or UFH for 1.3%a 3.3%a 0.38 (0.24-0.61) 0.1% 0.3% 0.62
(N ¼ 3999) 30-42 days (0.22-1.75)
versus
6-17 days
Systematic THR LMWH for 27-35 1.4%a 4.2%a 0.36 (0.20-0.67) 0% 0.1% NA
review41 days versus
(N ¼ 1953) 6-14 days
RCT42 HFS Fondaparinux 0.3%a 2.7%a P ¼ .02 2.4% 0.6% P ¼ .06
(N ¼ 656) 2.5 mg/kg
daily for
19-23 days
versus
6-8 days
RCT58 Surgery for Enoxaparin 4.8%b 12.0%b 0.60 (0.10-0.82) 1.2% 0.4% P ¼ .62
(N ¼ 332) abdominal or 40 mg daily
pelvic cancer for 25-31 days
versus
6-10 days
RCT59 Abdominal Subcutaneous 7.3%b 16.3%b 0.55 (0.15-0.76) 0.5% 1.8% NA
(N ¼ 343) surgery dalteparin
5000 IU daily for
28 days versus
7 days

Abbreviations: CI, confidence interval; HFS, hip fracture surgery; LMWH, low-molecular-weight heparin; NA, not available; OR, odds ratio; RCT, randomized
controlled trial; THR, total hip replacement; TKR, total knee replacement; UFH, unfractionated heparin; VTE, venous thromboembolism.
a
Symptomatic VTE.
b
Asymptomatic and symptomatic VTE.

Conclusions Declaration of Conflicting Interests

Assessment of individual patient’s VTE risk is vital for the The author has no current consulting agreements but has been a
consultant in the past for Sanofi, GSK, Covidian, and Pfizer.
selection of appropriate, evidence-based thromboprophylaxis.
Venous thromboembolism risk assessment should occur as Funding
early as possible after patients are admitted to hospital and
The author(s) received no financial support for the research and/or
involve a multidisciplinary team. The use of a validated risk-
authorship of this article.
assessment tool featuring risk factors tied to the development
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