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2013 19: 357 originally published online 22 April 2013CLIN APPL THROMB HEMOSTRussell D. Hull, Tazmin Merali, Allan Mills, Abigail L. Stevenson and Jane Liang

Influence of Risk FactorsVenous Thromboembolism in Elderly High-Risk Medical Patients: Time Course of Events and

  

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Original Article

Venous Thromboembolism in ElderlyHigh-Risk Medical Patients: Time Courseof Events and Influence of Risk Factors

Russell D. Hull, MBBS, MSc1, Tazmin Merali, BPharm, MBA2,Allan Mills, PharmD3, Abigail L. Stevenson, DPhil4, andJane Liang, MSc1

AbstractVenous thromboembolism (VTE) causes significant morbidity and mortality in hospitalized medical populations; however, medicalpatients do not currently receive thromboprophylaxis beyond their hospital stay. We reviewed the real-life occurrence of VTE-related care for 100 days post-hospitalization in Calgary, Canada. Using medical visit records with a unique patient identifier num-ber applied throughout the city’s hospitals, 989 high-risk patients were selected for review. Almost three-quarters of the elderlypatients received appropriate prophylaxis while in hospital, and only 2% received prophylaxis on discharge. Over the 100-dayfollow-up, 21% of the patients presented with clinically suspected VTE, of which 3.8% had confirmed VTE. Patients with multiplerisk factors (�3) had the highest frequency of confirmed VTE (�6.1%). This study suggests that the actual rate of VTE-relatedfollow-up care in patients post-hospitalization is high in the first 100 days, particularly among those who have multiple risk factors,warranting consideration of extended thromboprophylaxis in this population.

Keywordsvenous thromboembolism, thrombosis prophylaxis, anticoagulants, deep venous thrombosis, pulmonary embolism, thrombosis

Introduction

Hospitalized medical patients are at high risk of venous throm-

boembolism (VTE), with approximately one-quarter of all

VTE events occurring in this nonsurgical population.1 A

prospective cohort study suggested a symptomatic, clinically

evident VTE rate of 11% for hospitalized high-risk medical

patients not receiving prophylaxis,2 and there is strong evi-

dence that thromboprophylaxis in this population results in

fewer VTE events and reduced mortality.1 As such, the

American College of Chest Physicians recommends pharmaco-

logical prophylaxis for acutely ill hospitalized medical patients

at increased risk of thrombosis, but does not recommend

extending the duration of therapy beyond the period of immo-

bilization or hospital stay.1 The American College of Physi-

cians (ACP) also recommends prophylaxis with heparin (or

related drug) for medical patients, unless the assessed risk of

bleeding outweighs the benefits of thromboprophylaxis.3 Risk

factors for VTE in hospitalized medical patients include

increasing age (especially >70 years), previous VTE, known

thrombophilia, immobilization for �3 days, hormonal medica-

tions, and history of comorbid illness (eg, cancer, heart failure,

and respiratory failure).1 Further research is needed to validate

the risk factors for VTE, as prophylaxis may harm patients who

are at low risk of VTE but at high risk of bleeding; yet, its

underuse may result in avoidable mortality and morbidity.1

Much of the current evidence focuses on VTE risk of

medical patients during hospitalization, with some evidence

to suggest the risk extends beyond hospital stay. The

EXCLAIM trial examined extended-duration thromboprophy-

laxis with enoxaparin in hospitalized medical patients, which

determined a 90-day VTE incidence of 4.4% in medical

patients not receiving postdischarge prophylaxis.4 Similarly,

the MEDENOX trial suggested that VTE risk in medical

patients extends for up to 3 months, with 8 VTE events (includ-

ing 4 fatal pulmonary embolisms) occurring between days 15

and 110 after discharge.5 However, both these studies were ran-

domized clinical trials that used routine diagnostic screening in

addition to clinical events to calculate the rates of VTE and had

strict exclusion criteria for their study populations, which

1 Department of Medicine, Thrombosis Research Unit, University of Calgary,

Canada2 Drug Intelligence Inc, Toronto, Ontario, Canada3 Trillium Health Centre, University of Toronto, Ontario, Canada4 Watermeadow Medical, Macclesfield, United Kingdom

Corresponding Author:

Russell D. Hull, Department of Medicine, Thrombosis Research Unit, University

of Calgary, Foothills Medical Center, 1403 29 Street NW, Calgary, Alberta,

Canada.

Email: rdhull@ucalgary.ca

Clinical and AppliedThrombosis/Hemostasis19(4) 357-362ª The Author(s) 2013Reprints and permission:sagepub.com/journalsPermissions.navDOI: 10.1177/1076029613481105cath.sagepub.com

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excluded risk factors for bleeding. In comparison, few ‘‘real-

life’’ studies have been performed which identified sympto-

matic, clinically evident VTE events in populations not

screened for risk factors for bleeding; an example is the

IMPROVE observational study, which showed that 45% of the

VTE events occurred after discharge in medical patients.6 Such

‘‘real-life data’’ regarding the timing of VTE events in high-

risk medical patients after leaving hospital are lacking, and the

relationship between risk factors and VTE in this population

has not been fully examined. Furthermore, data are lacking

on rates of VTE in high-risk subgroups of patients, such as

those with cancer. Previous retrospective cohort database stud-

ies have estimated the incidence of VTE in hospitalized

patients with cancer to be between 0.6% and 5.4%, but there are

few data on rates in discharged patients.7,8 Our objective was to

document the time course of symptomatic VTE events in high-

risk elderly medical patients over 100 days postdischarge and

to correlate the frequency of risk factors for the likelihood of

VTE development. A subgroup analysis of these medical

patients with cancer was also performed. These data recorded

in everyday clinical practice may help to clarify the VTE risk

of ‘‘real-world’’ medical patients and to determine the appro-

priateness of long-term VTE prophylaxis in high-risk elderly

medical patients, including those with cancer, as well as to

establish strategies regarding the frequency of clinical surveil-

lance postdischarge in these populations.

Methods

Study Design

Data from the charts of high-risk elderly medical patients

hospitalized in the Calgary region and discharged between Jan-

uary 1, 2008 and February 28, 2008 were collected using case

records and screened for eligibility. All identified patients were

followed for any subsequent medical attention related to VTE.

All hospitals in the region use a unique patient identifier num-

ber, enabling the tracking of subsequent patient visits to the

emergency room, inpatient admissions, or outpatient visits

occurring anywhere in the region’s acute care system. Data

were collected on patient’s risk factors, thromboprophylaxis

received in hospital or at discharge, and VTE-related events for

up to 100 days postdischarge. Statistical methods used were as

follows: Wilson procedure without correction for continuity

was applied to calculate the proportion of patients with VTE

symptoms and confirmed events, including 95% confidence

intervals. Chi-square tests of association were used for asses-

sing the association between the number of risk factors and the

rates of VTE. Further details of methods can be found in the

protocol in the Online Supplementary Information.

Inclusion and Exclusion Criteria

High-risk elderly medical patients were defined as aged >60

years and having at least one of the following risk factors:

history of malignancy, respiratory illness, neurological illness,

inflammatory bowel disease, previous VTE, acute infection, or

heart failure. Medical patients with cancer were defined as

those aged >60 years with a cancer diagnosis at hospital admis-

sion, had a planned cancer surgery, were receiving cancer/pal-

liative treatment or whose cancer treatment was not specified;

patients with a remote history of cancer were excluded.

Records were excluded if the patient was originally admitted

for VTE, or to rule out VTE, receiving chronic anticoagulation,

experiencing an acute coronary syndrome, had a hospital stay

� 3 days, was a surgical or orthopedic patient, or was pregnant.

Outcome Measures

Outcomes included any medical attention for VTE symptoms

up to 100 days postdischarge, including emergency room

admissions, outpatient visits, or readmissions. The patients

were classed as confirmed VTE if they were subsequently

confirmed by diagnostic testing.

Results

Study Population: High-risk Elderly Medical Patients

Of the 1134 hospital discharges in the review period, 989

(87%) were identified as consecutive high-risk elderly medical

patients that met eligibility criteria and were selected for

Table 1. Rate and Time Course of VTE Events: All High-Risk Elderly Medical Patients Compared With Elderly Medical Patients With Cancer.a

All high-risk acute medicalpatients (n ¼ 989)

Acute medical patientswith cancer (n ¼ 358)

% Female 55% (543) 51% (181)Mean age/median age, years 79/79 79/78Age range, years 62–107 64–101Clinically suspected VTE requiring medical care and objective testing 21.0% [18.5–23.7] (208) 22.9% [18.7–27.6] (82)VTE event confirmed by diagnostic testing 3.8% [2.7–5.2] (38) 4.7% [2.8–7.5] (17)Negative/inconclusive diagnostic test for VTE 17.2% [14.9–19.7] (170) 18.2% [14.3–22.5] (65)Mean time to VTE event (days + SE [95% CI]) 33.5 + 5.1 [23.1–43.9] 38.2Median time to VTE event (days) 23 28

Abbreviations: CI, confidence interval; SD, standard error; VTE, venous thromboembolism.a Data are % [95% CI], (n) unless otherwise stated. In the subpopulation of high-risk elderly medical patients receiving inhospital prophylaxis, the frequency ofconfirmed VTE was 4.2% (31 of 733). Statistical analysis of the mean time to VTE event in the cancer subgroup was not performed.

358 Clinical and Applied Thrombosis/Hemostasis 19(4)

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follow-up as the high-risk group. Baseline demographics are

shown in Table 1. This population included all cases with risk

factors, but ruled out those where a complicating factor may

cloud the causation of VTE (eg, currently has/suspected of

having VTE, surgical cases, and acute coronary syndromes).

Data extracted from patient charts determined the incidence

of medical risk factors for the study population and VTE

prophylaxis prescribed (Figure 1A and B).

Symptomatic VTE Rates and Time Course Postdischarge:High-Risk Elderly Medical Patients

Rates of VTE and length of time from discharge to first

confirmed VTE event for the high-risk group are shown in

Table 1. The cumulative event rate over time determined that

80% of the confirmed VTE events occurred within 57 days

after discharge (Figure 2).

Correlation of VTE Rates with Risk Factors: High-riskElderly Medical Patients

Next, we analyzed the association between patients’ number of

risk factors and their rates of VTE post-discharge (Figure 3).

Patients with a greater number of risk factors were more likely

to seek medical attention for VTE symptoms than those with

fewer risk factors; patients with �3 risk factors had signifi-

cantly more VTE events than those with �2 risk factors

(3.2% absolute difference, P ¼ .015). A further increase in risk

was observed in patients with� 4 risk factors (5.8% difference,

50

A

B

45

40

35

30

25

20

15

10

5

0

Prevalence of prevailing medical risk factors (n=989)

Pat

ient

s (%

)

Malignancy

46

Respiratory illness

44

Neurological ill

ness

15

Inflammatory

bowel disease

6

Previous h

istory

of VTE

4

Acute infection

17

Heart failure

9

Eligible hospitalized medical patients:989

Did not receiveprophylaxis inhospital: 256 (26%)

Did not receiveprophylaxis ondischarge: 969 (98%)

Received prophylaxis in hospital:733 (74%)

Unfractionated heparin: 281 (28%)LMWH: 281 (28%)

Mechanical: 40 (4%)Combination: 131 (13%)

Received prophylaxis ondischarge: 20 (2%)

Figure 1. High-risk elderly medical patients study population: prevailing medical risk factors (A) and VTE prophylaxis received (B). LMWH,low-molecular-weight heparin; VTE, venous thromboembolism.

Hull et al 359

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P ¼ 0.011 vs �2 risk factors), but this was not statistically

significant when compared to patients with �3 risk factors.

Subpopulation Analysis: VTE Rates and Time Course inPatients With Acute Cancer

Of the 1134 hospital discharges in the review period, 358

(32%) patients met the criteria for inclusion as medical patients

with cancer in the subpopulation analysis. In all, 73% (261 of

358) of the subgroup received mechanical or pharmacological

prophylaxis in hospital, whereas only 2% of all the patients

received anticoagulation prophylaxis after discharge. The

results of the subpopulation analysis of patients with cancer are

shown in Table 1.

Interpretation

We selected the records of high-risk elderly medical patients,

including a subset of elderly medical patients with cancer,

discharged from hospital in Calgary during a 2-month period

in 2008 and followed them for 100 days for subsequent VTE

events. Almost three-quarters of the patients in both the groups

received appropriate prophylaxis while in hospital and only 2%received prophylaxis on discharge, in keeping with current

ACP guidelines not to prescribe prophylaxis on discharge.3

Throughout the entire follow-up, a considerable proportion of

the study population presented with clinically suspected VTE,

requiring medical care and objective testing (21% of the entire

study population and 23% for the cancer subgroup), resulting in

rates of confirmed VTE diagnoses of 4% for the entire study

population and 5% in the cancer subgroup. The cumulative

event rate over time revealed that the majority of these cases

occurred just over 1 month after discharge (mean time to VTE

event: 34/38 days in the high-risk/cancer subgroup). In the sub-

group population with cancer, it was noted that 23% sought out

medical attention for VTE symptoms, with 5% having a con-

firmed VTE diagnosis. Furthermore, this population followed

the same pattern of VTE event rates with a mean time to VTE

of 38 days. As expected, patients with a greater number of risk

factors had a higher prevalence of VTE: 6% of hospitalized

medical patients with �3 risk factors developed symptomatic

VTE confirmed by diagnostic testing, which increased to

8.7% for those with �4 risk factors. Only 2.9% of the patients

with �2 risk factors developed VTE.

The age criterion of >60 years was chosen due to the signif-

icantly increased rates of VTE in older patients compared with

younger patients,9 which ensured enough events would occur

to achieve statistical significance. The high-risk criteria chosen

for this study are supported by risk factors identified in the

EXCLAIM study, where patients >75 years were identified

as a key group to target for prophylaxis, being at a greater risk

of VTE than bleeding.4 As such, the majority of the discharged

population were classified as high risk in our study, but this

may not reflect the demographics of all centers or those of other

countries. Also, this study had a high proportion of patients

with malignancy (46%) when compared to a previous analysis

(9%),10probably due to 1 of the 3 hospitals chosen being a

major cancer treatment center. Notably, the rate of high-risk

elderly medical patients seeking out medical attention for VTE

symptoms in our real-life review (21%) was higher than rates

observed in clinical studies; in MEDENOX, only 17% of the

patients in the placebo group experienced VTE up to 110 days

after discharge.5 Despite inhospital prophylaxis, our real-life

study showed dramatically higher symptomatic VTE rates

postdischarge than the LIFENOX study: only 0.7% in the

placebo group.11 This result was not unexpected, since routine

screening for thrombosis is often performed in clinical trials,

but not in everyday clinical practice, so it is thought sympto-

matic VTE rates are underestimated in clinical trials compared

to real-life settings; screening and/or treating for asymptomatic

VTE in clinical trials reduces the potential for these thrombi to

progress and become symptomatic.1 Also, LIFENOX studied a

40

35

30

25

20

15

10

5

00 10 20 30

Interquartilerange

40 50 60 70 80 90 100Days (post-discharge)

Cum

ulat

ive

num

ber o

f VTE

eve

nts

Figure 2. Cumulative event rate over time: high-risk elderly medicalpatients. VTE, venous thromboembolism.

20181614121086420

≤2Pat

ient

s w

ith a

con

firm

ed V

TE e

vent

(%)

2.9

Number of risk factors

p=0.015

≥3

p=0.01

p=NS

6.1

≥4

8.7

Figure 3. Influence of risk factors on rates of VTE. Data are the per-centage of patients with confirmed VTE, according to the presence ofrisk factors for VTE. Error bars represent 95% CIs. CI, confidenceinterval; VTE, venous thromboembolism.

360 Clinical and Applied Thrombosis/Hemostasis 19(4)

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patient population discharged with elastic stockings, which is

unrepresentative of Canadian practices.11 In our study, 4% of

the high-risk elderly medical patients had a VTE confirmed

by diagnostic testing in the postdischarge follow-up period, a

total of 38 events. This is consistent with EXCLAIM, which

reported a VTE incidence of 4.4% in a 90-day period in

medical patients not receiving postdischarge prophylaxis.4 Our

100-day follow-up was chosen to ensure the plateau in the time

course of VTE events was captured in order to identify an

optimal time to consider prophylaxis; indeed our design was

successful, identifying the plateau of events, with the number

of events reducing after day 50. Previous clinical trials studying

postdischarge VTE rates in medical patients have shorter

follow-ups (ADOPT: 30 days)12; our study suggests these

follow-up periods are not long enough for a complete evalua-

tion of the benefits of prolonged prophylaxis.

As expected, patients with a greater number of risk factors

had a higher prevalence of VTE events than those with fewer

risk factors. This correlation is in agreement with risk assess-

ment models of similar at-risk groups, both in hospitalized

patients2 and in those post-discharge.6 However, are the rates

of VTE in a high-risk older population sufficient to outweigh

the risks of bleeding? Our data, showing a VTE risk of over

6% in patients with � 3 risk factors, increasing to 9% in those

with �4, suggests targeting prophylaxis to these high-risk

subgroups has a more favorable risk-benefit profile than

observed in the overall medical populations examined in

previous studies, such as EXCLAIM, ADOPT, and MAGEL-

LAN.4,12,13 Patients with �2 risk factors had a lower rate of

VTE (2.9%). Our results need to be balanced with the outcomes

of EXCLAIM, which while not supporting a general need

for extended thromboprophylaxis in a hospitalized medical

population, identified high-risk subgroups where the benefit

did outweigh the risks.4 Prolonged use of enoxaparin prevented

6 fewer symptomatic VTE cases per 1000 patients but at a cost

of 5 more major bleeding events per 1000; however, the bene-

fits of additional prophylaxis outweighed the risks of bleeding

in high-risk subgroups: women, patients >75 years and those

without bathroom privileges.4 Our real-life study shows that

a subset of high-risk patients >60 years may also benefit from

extended use of thromboprophylaxis. In particular, patients >60

years with cancer may benefit, since approximately 1 in 20

patients experienced a confirmed VTE event in our review

post-discharge. Our data support the use of clinical risk factors

at hospital admission to predict VTE risk in medical patients

and suggest that the short courses of prophylaxis currently

prescribed predischarge may not adequately provide coverage

for those at highest risk.

Strengths and Limitations

Traditionally, chart review data are seen as weak due to their

many limitations; however, our study design has unique

strengths, making it a more robust study. The Calgary region

has a single, integrated information system used across acute

care sites, so tracking of all subsequent visits was possible

using the unique Calgary patient identifier. Also, the location

is geographically isolated, minimizing the likelihood of

patients seeking medical attention elsewhere, maximizing the

chances of patient follow-up. However, there are inherent lim-

itations of chart reviews; unlike clinical trials, our review was

an uncontrolled, epidemiological study carried out in everyday

clinical practice, not designed to measure efficacy or safety. As

safety outcomes were not measured, a comprehensive risk-

benefit analysis was not possible. Also, as our study relied on

data accuracy in the patients’ charts, incomplete

documentation may be a limitation. Our study relied on the

patient to seek out medical attention for VTE symptoms to

determine event rates, so patients not seeking attention, who

died or went to alternative care providers would not be

captured. Finally, the prophylaxis practices and the patient

population in the Calgary region may not be representative

of, or be applicable to, other centers and/or countries.

Conclusion

Our study suggests that in a real-life setting, cumulative risk

factors (including cancer) result in an increased risk of VTE

events post-discharge in a hospitalized medical population. A

mean prevalence of 4% confirmed VTE (increasing to 6% and

9% in patients with �3 or �4 risk factors, respectively) was

recorded, with patients continuing to seek medical attention for

VTE symptoms up to 100 days postdischarge, with 34 days

being the mean time to first event. Evidence-based guidelines

do not currently support extended prophylaxis for medical

patients,1 yet our data show that the risk extends well beyond

a typical hospital stay. The 4% VTE rate was greater than

expected for a real-life study and may change the perception

of a low benefit-to-risk ratio of prophylaxis upon discharge.

Coupled with the results of the EXCLAIM study, the VTE rates

observed here may suggest that prolonged VTE prophylaxis

may be of benefit in high-risk medical populations, such as

older patients. These data also highlight the problem of early

discharge before adequate prophylaxis can be administered.14

However, such extended prophylaxis would increase the cost

of therapy and may increase the bleeding risk of certain

patients. Indeed, recent trials have failed to show an increased

benefit-to-risk ratio of novel oral anticoagulants over

traditional subcutaneous (sc) thromboprophylaxis; the MAGEL-

LAN study determined an increased bleeding profile of oral

rivaroxaban compared with sc enoxaparin,13 whereas the

ADOPT study found increased bleeding and no superior efficacy

with oral apixaban compared with sc enoxaparin.12 Therefore, a

patient’s individual benefit-risk assessment must always be

taken into account1 when considering prophylaxis. Further,

large-scale clinical trials and real-life studies are warranted to

confirm the relative risks and benefits of extended thrombo-

prophylaxis in high-risk elderly medical patients postdischarge.

Authors’ Note

This study was presented orally at the annual meeting of the American

Society for Hematology (ASH) in Orlando, FL, December 2010.

Hull et al 361

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Authors’ Contribution

R.D. Hull had the original idea for the study, provided guidance and

input into all drafts, and is the guarantor of the study. J. Liang

performed the statistical analyses and reviewed and approved all

drafts. A.L. Stevenson interpreted data, wrote the first draft, and

approved the final draft. T. Merali developed the study protocol,

supervised data collection, data management, analysis, and reviewed

all drafts. A. Mills provided clinical assistance in reviewing the

results, provided input into the drafts, and reviewed all drafts.

Declaration of Conflicting Interests

The author(s) declared a potential conflict of interest as follows: R.D.

Hull has received grants/research support from Bayer Pharmaceuticals

Corp, LEO Pharma Inc, and Sanofi-Aventis; been a consultant for

Bayer Pharmaceuticals Corp, LEO Pharma Inc, Pfizer Inc, GlaxoS-

mithKline, and Wyeth Pharmaceuticals; and sat on advisory boards for

Bayer Pharmaceuticals Corp, Pfizer Inc, and Sanofi-Aventis. A. Ste-

venson is an employee of Watermeadow Medical, which received

payment from the Medical Continuing Education Fund, University

of Calgary for work on this manuscript. Editorial assistance was

provided by Watermeadow Medical. T. Merali is an employee of Drug

Intelligence, which received payment from the Thrombosis Research

Group, University of Calgary for work on this study. J. Liang and A.

Mills have no conflicts of interest to declare.

Funding

The author(s) disclosed receipt of the following financial support for

the research and/or publication of this article: This work was funded

by Sanofi-Aventis, Canada.

References

1. Kahn SR, Lim W, Dunn AS, et al; American College of Chest

Physicians. Prevention of VTE in nonsurgical patients: antithrom-

botic therapy and prevention of thrombosis. 9th ed. American

College of Chest Physicians Evidence-Based Clinical Practice

Guidelines. Chest. 2012;141(suppl 2):e195S-e226S.

2. Barbar S, Noventa F, Rossetto V, et al. A risk assessment model

for the identification of hospitalized medical patients at risk for

venous thromboembolism: the padua prediction score. J Thromb

Haemost. 2010;#8(11):2450-2457.

3. Qaseem A, Chou R, Humphrey LL, Starkey M, Shekelle P.

Venous thromboembolism prophylaxis in hospitalized patients:

a clinical practice guideline from the American college of physi-

cians. Ann Intern Med. 2011;155(9):625-632.

4. Hull RD, Schellong SM, Tapson VF, et al. Extended-duration

venous thromboembolism prophylaxis in acutely ill medical

patients with recently reduced mobility: a randomized trial. Ann

Intern Med. 2010;153(1):8-18.

5. Samama MM, Cohen AT, Darmon JY, et al. A comparison of

enoxaparin with placebo for the prevention of venous throm-

boembolism in acutely ill medical patients. N Engl J Med.

1999;341(11):793-800.

6. Spyropoulos AC, Anderson FA Jr, Fitzgerald G, et al. Predictive

and associative models to identify hospitalized medical patients at

risk for VTE. Chest. 2011;140(3):706-714.

7. Levitan N, Dowlati A, Remick SC, et al. Rates of initial and

recurrent thromboembolic disease among patients with malig-

nancy vs. those without malignancy. Risk analysis using Medi-

care claims data. Medicine. 1999;78(5):285-291.

8. Khorana AA, Francis CW, Culakova E, Fisher RI, Kuderer NM,

Lyman GH. Thromboembolism in hospitalized neutropenic

cancer patients. J Clin Oncol. 2006;24(3):484-490.

9. Stein PD, Hull RD, Kayali F, Ghali WA, Alshab AK, Olson

RE. Venous thromboembolism according to age: the impact

of an aging population. Arch Intern Med. 2004;164(20):

2260-2265.

10. Kahn SR, Panju A, Geerts W, et al. Multicenter evaluation of

the use of venous thromboembolism prophylaxis in acutely ill

medical patients in Canada. Thromb Res. 2007;119(2):

145-155.

11. Kakkar AK, Cimminiello C, Goldhaber SZ, Parakh R, Wang C,

Bergmann JF. Low-molecular-weight heparin and mortality in

acutely ill medical patients. N Engl J Med 2011;365(26):

2463-2472.

12. Goldhaber SZ, Leizorovicz A, Kakkar AK, et al. Apixaban vs.

enoxaparin for thromboprophylaxis in medically ill patients.

N Engl J Med. 2011;365(23):2167-2177.

13. Cohen AT, Spiro T, Buller H, et al; On behalf of the MAGELLAN

Steering Committee and Investigators. Rivaroxaban compared

with enoxaparin for the prevention of venous thromboembolism

in acutely ill medical patients. Paper presented at: American Col-

lege of Cardiology 60th Annual Scientific Session; April 2–5,

2011. Presentation number: 3015-6.

14. Stein PD, Hull RD, Matta F, Yaekoub AY. Early discharge of

patients with venous thromboembolism: implications regarding

therapy. Clin Appl Thromb Hemost. 2010;16(2):141-145.

362 Clinical and Applied Thrombosis/Hemostasis 19(4)

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