ArticlePDF Available

Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality


Abstract and Figures

Venous thromboembolism (VTE) is often asymptomatic, mis-diagnosed, and unrecognized at death, and there is a lack of routine postmortem examinations. These factors are thought to result in marked underestimates ofVTE incidence. The objective of our study was to estimate the total burden of VTE within the European Union (EU) per annum. An epidemiological model was constructed to estimate the number of community- and hospital-acquired incidents and recurrent cases (attack rate) of nonfatal VTE and VTE-related deaths, as well as incident and prevalent cases of post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (PH) occurring in the EU per annum. Individual models were developed for six EU countries. The models were populated with data from published literature and, where necessary, expert opinions. The findings were tested using probabilistic sensitivity analyses. The estimated total number of symptomaticVTE events (range based on probabilistic sensitivity analysis) per annum within the six EU countries was 465,715 (404,664-538,189) cases of deep-vein thrombosis, 295,982 (242,450-360,363) cases of pulmonary embolism (PE), and 370,012 (300,193-483,108) VTE-related deaths. Of these deaths, an estimated 27,473 (7%) were diagnosed as being antemortem; 126,145 (34%) were sudden fatal PE, and 217,394 (59%) followed undiagnosed PE. Almost three-quarters of all VTE-related deaths were from hospital-acquired VTE. VTE is a major health problem in the EU, with over one million VTE events or deaths per annum in the six countries examined. Given the availability of effective VTE prophylaxis, many of these events and deaths could have been prevented. These results have important implications for the allocation of healthcare resources.
Content may be subject to copyright.
Venous thromboembolism(VTE)inEurope
The number of VTE events andassociated morbidity andmortality
Alexander T. Cohen
,Giancarlo Agnelli
,Frederick A. Anderson
,Juan I. Arcelus
,David Bergqvist
,Josef G. Brecht
Ian A. Greer
,John A. Heit
,Julia L. Hutchinson
,Dominique Mottier
,Emmanuel Oger
Meyer-Michel Samama
fortheVTEImpact Assessment Group in Europe (VITAE)
King’sCollege Hospital,London, UK;
Division of Internal and Cardiovascular Medicine,University of Perugia, Perugia, Italy;
Center for
Outcomes Research, University of Massachusetts MedicalSchool,Worcester,MA, USA;
University of GranadaMedicalSchool and Hospital
SanJuan de Dios, Granada, Spain;
Department of Surgical Sciences, University Hospital,Uppsala, Sweden;
InForMed GmbH–Outcomes
Research andHealth Economics,Ingolstadt, Germany;
Department of Obstetrics and Gynaecology, University of Glasgow,Glasgow Royal
Infirmary, Glasgow,UK;
HematologyResearch, Mayo Clinic College of Medicine,Rochester,MN, USA;
Fourth Hurdle Consulting,London,
Centrefor SurgicalSciences, Bartsand The London-QueenMarySchool of Medicine,London, UK andThrombosis Research Institute,
Groupe d’Etude de laThrombose de BretagneOccidentale (GETBO), HôpitaldelaCavale Blanche,Brest,France;
Dieu, Départementd’HématologieBiologique,Paris,France;
Ludwig-MaximilliansUniversity Munich, Klinikum derUniversität, Abteilung
Haemostasiologe,Munich, Germany
Venous thromboembolism(VTE)isoften asymptomatic, mis-
diagnosed,andunrecognized at death,and thereisalack of rou-
tine postmortem examinations.Thesefactors arethought to re-
sult in marked underestimatesofVTE incidence.The objectiveof
our study was to estimate the total burden of VTE within the
European Union (EU)per annum.An epidemiological modelwas
constructedtoestimatethe number of community-and hospi-
tal-acquired incidents and recurrent cases(attack rate)ofnon-
fatalVTE and VTE-relateddeaths, as well as incidentand preva-
lent casesofpost-thromboticsyndrome (PTS)and chronic
thromboembolic pulmonaryhypertension (PH) occurring in the
EU perannum.Individual models were developed forsix EU
countries.Themodels were populated with datafrompublished
literatureand,where necessary, expert opinions. Thefindings
were tested using probabilistic sensitivity analyses. Theesti-
embolism, pulmonary hypertension,venous thromboembolism,
VTE prophylaxis
matedtotal number of symptomaticVTE events (range basedon
probabilistic sensitivityanalysis)per annum within thesix EU
countrieswas 465,715(404,664–538,189) casesofdeep-vein
thrombosis, 295,982 (242,450–360,363) cases of pulmonary
embolism(PE), and 370,012(300,193–483,108) VTE-related
deaths.Ofthese deaths,anestimated 27,473 (7%) were diag-
nosed as beingantemortem;126,145 (34%) were sudden fatal
PE,and 217,394 (59%) followedundiagnosedPE.Almost three-
quarters of allVTE-relateddeaths were from hospital-acquired
VTE.VTE is amajor health problem in the EU,with over one mil-
lionVTE events or deathsper annum in thesix countriesexam-
ined. Giventhe availability of effectiveVTE prophylaxis,manyof
these events and deathscouldhavebeen prevented.Thesere-
sults have important implications forthe allocationofhealthcare
ThrombHaemost 2007; 98: 756–764
Blood Coagulation, Fibrinolysis and CellularHaemostasis
Correspondence to:
Alexander T. Cohen
VascularMedicine,Department of Surgery
King’sCollege Hospital
London, SE5 9RS, UK
Te l.: +44207346 3015, Fax: +44 20 7346 3927
Received March 21, 2007
Accepted after resubmission July 25, 2007
Prepublished onlineSeptember 10,2007
Venous thromboembolism (VTE),comprising deep-vein throm-
bosis (DVT) and pulmonaryembolism(PE), is associatedwith
substantialmorbidity and mortality.Detailedestimatesofthe an-
nual number of VTE eventsare hard to obtain becauseVTE is
difficulttodiagnose.This is due to anumber of factors; VTEis
oftenclinically silent and,inmanycases,the first sign of the dis-
easeisasuddenfatal PE (1, 2). Despite modest increases in ante-
mortemdiagnosis of PE over the years,lessthan half of autopsy-
detectedPEcases are diagnosed antemortem(3). The lackof
routinely performed postmortem examinations means thatmany
©2007 Schattauer GmbH,Stuttgart
Cohen et al.Venous thromboembolisminEurope
fatalpulmonaryemboli remainunrecognized, leading to an
underestimation of their incidence. Previous analyses have
shown that, forevery caseofsymptomatic non-fatalPE, there are
2.5 cases of fatalautopsy-detectedPE(4). Only29% of patients
whosurvive an initialembolic event are diagnosed withVTE(5).
In 36% of patients diagnosedwith PE, an initialdiagnosis is
made on the date of deathorpostmortem, with PE being the
cause of death in 53% of these cases (2).Studieshavealso shown
thatasymptomatic DVTisstrongly associatedwith the develop-
ment of symptomatic VTE(6–8) and is also associated with an
increased risk of death (9).Due to these factors, modeling is the
onlyapproach to achieve annual incidencefigures and estimates
of complications.
The chronic nature of VTE and itsrecurrences and compli-
cations requires considerablehealthcare resources forits man-
agement.Additionally, morbidity and healthcare costs are in-
curred fromassociatedcomplications of VTE, such as post-
thromboticsyndrome (PTS), whichaffectsatleastone-third of
DVTpatients (10–17), and pulmonary hypertension (PH), which
occurs in 4%–5% of patients following PE (18, 19). Data from
the UK suggest that the total cost of VTE to the National Health
Service in 1993 wa235–£257 million ( e 349–e 382 million)
(20),and estimates of the combined direct and indirectcosts are
nowplaced at approximately £640 million ( e 950 million) (21).
The costs arefurther increased when long-termcomplications
such as PTS aretaken into consideration (22, 23).Therefore,itis
important for healthcare decision-makers to have reliable esti-
matesofthe total annualnumber of incident and recurrent VTE
eventsper year.
To date,the most comprehensive epidemiological datahave
beengenerated fromstudiesofspecific populations. US popu-
lation-based studies of defined geographical areas,which in-
cludedpatients with onlyincidentVTE at home or in hospital, re-
vealed aVTE incidenceof71–117 per 100,000 person-years
(24–26).One study also showedathirty-dayrateofVTE recur-
rence of 4.8% (26). In Europe, studiesinWestern France (27)
Event estimated Source of dataProbability(range) of event
Community-acquired events
Age and gender specific
Country-specific population data
Oger 2000 (27)
US CensusBureau International
Database (28)
Hospital-acquired events
At-risk populationsHES (29) and PMSI (30)databases -
Surgical risk group
DVTand PE without prophylaxis
DVTand PE with prophylaxis
Geerts et al. 2004 (31)
Derived from Geerts et al. 2004 (31)
Medicalrisk group
DVTwith and without prophylaxis
PE with and without prophylaxis
Geerts et al. 2001 (32)
Derived from Geerts et al. 2001 (32)
Mild/moderate PTSinpatientwith DVT
Severe PTSinpatientwith DVT(new)
Derived from
Prandoni et al. 1996 (10)
Prandoni et al. 1996 (10)
0.147 (0.074–0.221) first year,
0.01 (0.005–0.015) in following years
0.026 (0.013–0.039) first year,
0.017 (0.009–0.026) in following years
PH Pengoetal. 2004(18) 0.31 (0.16–0.47) first year,
0.38 (0.19–0.57) in following years
Symptomatic and diagnosed
Death from DVT
Medical DVTthat has developed
into PE
Geerts et al. 2004 (31);
Piovellaetal. 2005(35)
Osteretal. 1987(33)
Osteretal. 1987(33)
0.10 (0.05–0.15)
0.006 (0.003–0.009)
0.115 (0.058–0.173)
Symptomatic and diagnosed
Death from undiagnosed PE
Death from diagnosedPE
Oster et al. 1987 (33)
Oster et al. 1987 (33)
Oster et al. 1987 (33)
Oster et al. 1987 (33)
0.29 (0.15–0.44)
0.11 (0.06–0.17)
0.30 (0.15–0.45)
0.08 (0.04–0.12)
PE recurrence
Prandoni et al. 1996 (10);
Heit et al. 2000(34)
Prandoni et al. 1996 (10);
Heit et al. 2000(34)
0.104 (0.052– 0.156) first year,
0.02 (0.01–0.03) in following years
0.025 (0.013–0.038) first year,
0.005 (0.003–0.008) in following years
DVT, deep-veinthrombosis; HES, HospitalEpisodesStatistics; PE, pulmonaryembolism; PH,pulmonary hypertension; PMSI, Le Programme de Médicalisation
des Systèmesd’Information; PTS, post-thrombotic syndrome.
and Sweden (5), thatincludedboth incident and recurrent VTE
events, reported an overallVTE incidenceof160–180 per
100,000 person-years. Although these studies have contributed
considerablytoour understanding of the epidemiologyofVTE,
theyunderestimate the total burden of the diseaseonthe health-
care system because theydonot include undiagnosedormis-
diagnosedclinical VTEevents or unrecognizedVTE-related
In view of the potential impact of VTE to public health and
the lackofcomprehensive estimatesonthe number of sympto-
matic VTE eventsand associated morbidityand mortality in Eu-
rope,theVTE ImpactAssessment Group in Europe (VITAE) de-
signed amodified incidence-basedmodel to estimate the total
annualnumber of non-fatalincident and recurrent VTE events,
associatedcomplications (PTS and PH), and VTE-related deaths
in six countries within the European Union (EU).
Data searches
An extensive search of nationaldatabases wasperformed look-
ing at publishedpapersand grey literature. Thesearch wascon-
ductedusing MEDLINE and EMBASE databasesbetween 1994
to date.Seventy-five original papers were identifiedthat de-
scribed newepidemiologicalresearch.Onlythose giving infor-
mation about the prevalenceand incidenceinEurope in defined
geographical populations were used in the model. Keysearch
termswere “venous thromboembolism”,“deep-vein thrombo-
sis”, and “pulmonaryembolism”.These terms were crossed with
the terms“epidemiology”,“prevalence”, “incidence”, “risk fac-
tors”,and “naturalhistory”.
Amodel wasdeveloped to estimate the number of country-spe-
cific,non-fatalsymptomatic VTE eventsand VTE-related
deaths in aone-year period. Eventsestimatedincludedincident
and recurrent cases of non-fatalVTE, and incident and existing
cases of PTS, PH,and VTE-related death. The base year fores-
timating eventswas 2004.
The core model structure, methodologies, and assumptions
were validatedbyanadvisoryboardconsisting of VTE experts
from across Europe and the USA. Individual models were devel-
opedfor six EU countries: France, Germany,Italy,Spain,
Sweden, and the UK. Whereverpossible, the parameter esti-
mates for models were derivedfrom datainthe published litera-
ture (Table 1) (10, 18, 27–35). Where data on model parameters
were unavailable, the advisoryboardprovided an expertopinion
on the plausible ranges for sensitivity analyses. Published data
were used as asourcefor all event rates,for the at-risk hospital
population, and for the probabilities of events. Estimatesofpro-
phylaxisrates fromexperts in the individual countries were only
used when publisheddatawere notavailable. Wheretherewere
anydifferences, or disagreements arose,experts were asked to
reach aconsensus.
The model estimated the number of community-acquired
VTE eventsand hospital-acquiredVTE events. Hospital-ac-
quired eventswere definedasevents that occurredfollowing ex-
posure to hospital-related risk factors, surgical procedures,or
admission to amedical ward,and whichoccurred within ahospi-
tal setting or in the community within a90-dayperiod of admis-
sion to hospital. Eventsnot meeting these criteria were classified
as community-acquired. Thegeneral modelstructureapplies to
both community- and hospital-acquiredevents (Fig. 1).
Estimation of the numberofcommunity-acquired
Community-acquired eventsfor each of the six EU countries
were estimatedonthe basis of alarge French epidemiological
study (the Groupe d'Etude de la Thrombose de Bretagne Occi-
dentale [EPI-GETBO] study) (27) with age-and gender-specific
incidencerates appliedtocountry-specific population data.The
authorsofthe EPI-GETBO study (27) re-analyzedtheir study
and provided additional data.Theyseparated the eventsthat took
placeinthe community occurring within threemonths of hospi-
Figure1:General model
structurefor estimating
the number of country-
specific,non-fatal sympto-
bolism (VTE) events and
VTE-related deaths in a
one-year period. *Treated
and pulmonaryembolism (PE)
(for thepurpose of themodel,
we assume all diagnosedVTE is
treated). PH, pulmonaryhy-
pertension;PTS, post-throm-
Cohen et al.Venous thromboembolisminEurope
talization (16%ofthese events). As in the VITAEstudy these
would not constituteacommunity-acquired event.The re-analy-
sis of the EPI-GETBO study (27) also allowedthe calculation of
age-adjusted numbersofevents for community-acquiredVTE.
Estimation of the numberofhospital-acquiredevents
Patients were includedinthe hospital-acquiredevents model if
theywere deemed to be at risk of developingVTE (the at-risk
population), and met the aforementioned criteria. At-risk popu-
lations were estimatedonthe basis of patient numbersderived
from the HospitalEpisodes Statistics (HES) database (29) in the
UK and Le Programme de Médicalisation desSystèmes d’Infor-
mation (PMSI) database(30) in France (Table 2).All HESand
PMSI diagnostic and procedurecodes relating to disease groups
were carefully reviewed and thosedeemed to put apatient at risk
of VTEaccording to currentAmerican CollegeofChest Phys-
icians (ACCP) consensus guideline definitions (31) were in-
cluded. At-risk patients from both public and private sectors
were included. Thehospital at-risk population wasthen divided
into categoriesaccording to eithertype of surgery(moderate,
high,and highest risk of VTE),ormedical diagnosis on admis-
sion (myocardialinfarction, stroke, and other medicaldiagnoses
associatedwith VTErisk, e.g.heartfailure, respiratoryfailure,
infectious and inflammatorydiseases)(36). Cancer patients
were notseparatelyincludedinorder to avoid double counting
with cancerleading to surgery.This is because coding does not
specify whether an admission for cancer leads to operation or
whether an operation, suchascolectomy, is for abenign or ma-
lignant condition. We also did not include hematological cancers
suchasleukemia,and other cancers not known to be associated
with VTE (e.g. skin cancers).Hence we took aconservative ap-
proach.Inaddition, patients whowere in hospitalfor daypro-
cedures and minor surgery were excluded. Diagnoses requiring
therapywith anticoagulants were alsoexcluded.
The at-risk populations for the UK and France were based on
the HES(29) and PMSI (30) data,respectively. These databases
are robust and readilyaccessible sources of patient-leveldata.
Equivalent databaseswere eithernot available, or the method of
data collection wasinconsistent with HES and PMSI for the
other countries. Forthese countries (Germany, Italy, Spain,and
Sweden), aweightedaverage of the UK and French datawas
used to derive patient numbers. Foreach at-risk group, the age-
adjustednumber ofVTE eventswas calculated on the basis of the
weighteddataand this wasapplied to age-specific breakdowns
of the relevant countrypopulations.
Hospital-acquired eventswere estimatedbyapplying spe-
cific risk frequenciesfor developingVTE to the surgical and
medical at-risk populations, according to whether or notthey
were receiving VTE prophylaxis. Theprobability of developing
VTE withand without prophylaxis (Table 3) (31–33, 37) was
combined with estimatesofcurrent prophylaxis use (Table 4) in
ordertocalculatethe number of incident clinicalVTE eventsin
each at-risk group. Prophylaxis use wasestimatedbased on pub-
lisheddatawherever possible and,ifotherwise, on expertcon-
Estimation of the numberofrecurrentVTE events
In order to fully capturethe number of VTE eventsexpected in a
givenyear,weestimatedthe number of recurrent clinicallyevi-
dent eventsalongside incident cases of clinical VTE.Themajor-
ity of cases of recurrence occurwithin the first year of the index
France Germany ItalySpain Sweden UK
Generalpopulation 60,424,000 82,425,000 58,058,000 40,281,000 8,986,000 60,271,000
At-risk population
Moderate risk
High risk
Highest risk
Myocardial infarction*
Other medical
Cardiac, respiratory, and inflammatorydiseases and severe infections. *Themajorityofpatientswith myocardial infarction receiveanticoagulant therapyand
Table2:At-risk hospital
population estimates
or based on the Hospital
EpisodesStatistics (29)
and Le Programme de
Médicalisation desSystèm-
es d’Information (30) data-
ProbabilityofVTE event
Without prophylaxisWithprophylaxis
At-risk population
Moderate risk
High risk
Highest risk
Other medical
0.025 (0.27)
0.057 (0.067)
0.017 (0.047)
*Objectivelyverifiedbyvenography(i.e.all deep-veinthrombosis [DVT] events –both symptomatic
and asymptomatic).
In order to calculate mortality,the frequency of pulmonary embolism (PE) for
surgical patients was inflated from the probability of diagnosedclinical PE to the probability of all PE
(i.e.toinclude undiagnosedclinical PE) (37). Formedical patients, the PE frequency was calculated
by applying the Oster algorithm (33) to DVTfrequencies.
Cardiac, respiratory, and inflammatory
diseases andsevereinfections.
Figures based on clinical trials and inflatedfromthe probability of
diagnosedclinical PE to the probability of all PE.
Table3:Probability of venous thromboembolism (VTE)events
extracted or derived from Geerts et al.2001 (32) and 2004
Cohen et al.Venous thromboembolisminEurope
event;however,the cumulative frequencycontinues to increase
as timefrom the indexevent elapses (34).Total recurrent events
expected in agiven year therefore comprised recurrences of inci-
dent cases occurring in thatyear plus recurrences fromincident
eventsoccurring in previous years.Inorder to incorporatethis
into the model, we assumedaconstant incidenceofindexVTE
over the previous five years and applied1-to5-year recurrence
rates to these data (Table 5) (10,18, 34).
Estimation of the numbers of PTS and PH events
Asimilarapproach wastaken to estimate the expected number of
PTS cases. Totalcases expected in agiven year therefore com-
prised PTS related to incident cases of VTE occurring in that
year plus PTSrelated to incident cases of VTEoccurring in the
previous five years (10).However,given thatPTS is achronic
disease, thereisalso an underlying levelofdiseaseexisting in
anygiven year thatisequivalent to the sum of cases developedin
previous years.Inthe model, PTS wasfurther separated into
mild/moderate disease and severe disease. This distinction was
made becausediseaseseverity drives resource use. We assumed
thatonce apatient haseithersevere or mild/moderatePTS,they
willremaininthis state (23).Inreality,itislikelythat patients
will pass from one state to anotheroverthe course of the disease.
The expected number of PH cases wasestimatedbased on
publishedincidence rates (18).SimilartoPTS,expected cases of
PH in anygiven year comprisedPHrelated to incident cases of
VTEoccurring in thatyear plus PH related to incident cases of
PE occurring in the previous twoyears.Rates of chronic PH ex-
pected to result in surgicalintervention were appliedtothe esti-
mate of incident cases of PE in ordertoestimate the total number
of PH cases in agiven year.
Estimation of the numberofVTE-relateddeaths
Estimates of the number of VTE-related deaths included esti-
matesofsudden death, death following diagnosedand treated
disease, and death following undiagnosed, untreateddisease.
Thenumber of deaths from recurrent cases wasalso estimated.
Thenumber of VTE-related deaths wasestimatedfrom
numbers of treated VTEevents on the basis of an algorithm de-
velopedbyOster et al.(33). Asimplifiedversion of the algo-
rithm is shown in Figure 2(31, 33, 35). The keyparameters de-
fined by the algorithm are rates of diagnosed DVT, likelihoodof
progression from undiagnosedDVT (symptomaticand asympto-
matic) to PE, and rates of death from diagnosed and undiagnosed
VTE (symptomatic). Forthe purpose of the analysis, we as-
sumedthat diagnosed VTE wassynonymous with treatedVTE.
We thenapplied the algorithm to the numbersoftreated DVTand
PE eventsinorder to estimate the number of deaths related to
diagnosedVTE in each of the sixEUcountries. This allowedus
to estimate the number of expected deaths from cases of VTE
that arenot diagnosedaswellasexpected deaths from cases that
arediagnosed. In order to assess whether the algorithm wasap-
plicable and reflectedcurrent understanding of VTE, it wasre-
viewed by the advisoryboard. On the basis of this review, one
parameter wasadjusted. The likelihood of all DVT(initially
asymptomatic and symptomatic) being detected and treated was
adjustedfrom 16%, based on areport by Oster et al. (33), to 10%
on thebasis of morerecent data(31, 35), whichsuggestedthat
the original estimate overstatesthe current likelihood of clinical
presentation and diagnosis.
Probabilistic sensitivityanalyses
Probabilistic sensitivity analyses (PSAs) were conducted to as-
sess the impactofuncertaintyonthe model results. One-way
At-riskpopulation France Germany Spain ItalySwedenUK
Moderate risk
High risk
Highest risk
Myocardial infarction
Other medical*
*Cardiac, respiratory, and inflammatorydiseases and severe infections.
Table4:Probability (base-
line estimate)ofvenous
thromboembolism pro-
phylaxis use in theat-risk
population estimated from
publisheddata and clini-
cian estimates, 2004.
Recurrent event/outcome Year 1Year 2Year 3Year 4Year 5Cumulative
Deep-veinthrombosis 0.104 0.030 0.017 0.017 0.017 0.185
Pulmonaryembolism 0.025 0.007 0.004 0.004 0.004 0.044
Mild/moderate PTS 0.147 0.038 0.001 0.001 0.001 0.188
Severe PTS0.026 0.0170.017 0.0170.017 0.094
Pulmonaryhypertension0.014 0.003- --0.017
PTS, post-thrombotic syndrome.
Table5:Probability of re-
currence of venous throm-
boembolism (10, 34) and
associated outcomes (10,
18) in theat-risk popu-
Cohen et al.Venous thromboembolisminEurope
sion of the Osteretal. (33)
algorithm showing poten-
tial outcomes of hospital-
acquired venous throm-
boembolism. *The likelihood
of adiagnosisofdeep-vein
thrombosis (DVT) wasad-
justed from 16% as reported
by Oster et al. (33) to 10% on
(31, 35) estimatingthe current
likelihood of diagnosis. PE, pul-
monaryembolism; P=Probabil-
sensitivity analyses were conducted according to the methodolo-
gy of Sullivanetal. (38)with allinputs varied by ±50%. All pa-
rametersthat had an impact >1%onthe overalloutput of the
model were includedasinputs in PSAs. The distribution of the
at-risk population and rates of VTE prophylaxis use were in-
cluded apriori in the PSAs. Distribution and ranges of modelin-
puts were definedaccording to availableinformation and recom-
mendedbestpractice as follows:clinicianestimateswere used
forrates of VTEprophylaxis use;ACCP-specified ranges (31,
32)were used forthe rates of VTE with and without prophylax-
is; published data were used for recurrence rates (34)and PTS
rates (10);and methodology as outlined by Sullivanetal. (38)
wasusedfor the at-risk population, rates of death, and the prob-
ability of symptomatic/diagnosedDVT and PE.
To estimate the number of VTEevents occurring per annum
across the whole of the EU,the country-specific outputs from the
six EU countries modeled were summedand then inflatedbythe
ratio of population size in the six included countries (310.4 mil-
lion) to the population sizeinall 25 member-state countries
(454.4 million).
To tal numberofnon-fatalVTE events and associated
In total, the modelestimatedthat 761,697 non-fatalVTE events
(465,715cases of DVTand 295,982 cases of PE) and 399,808 as-
sociated complications (395,673 patients with PTS and 4,135
with PH) occurredacross the six EU countries in 2004(Table6).
Event,n(95% CI) Community-acquired Hospital-acquired To tal
Non-fatalVTE event
VTE-related deaths
Untreated VTE
Associated outcome
Post-thrombotic syndrome
*Modeledcountries were France,Germany, Italy, Spain,Sweden, and theUK.
Including deep-veinthrombosis- and pulmonary embolism-related deaths.
Including all post-thrombotic syndrome (newcases plus those underlying from previous years). CI,confidence interval.
Table6:Total non-fatal ve-
nous thromboembolism
deaths, and associated
outcomes across allsix
European Union countries
modeled* in 2004.
Cohen et al.Venous thromboembolisminEurope
Hospital-acquired eventsrepresent 63%ofall cases of VTEplus
Basedonatotal population estimate of 310.4 million inhab-
itants and the number of non-fatalVTE eventsacross the six EU
countries includedinour model, the estimated DVTattack rate
(incidence of first lifetime and recurrent DVT) was148 per
100,000 person-years (65 per 100,000 for community-acquired
DVT, and 83 per 100,000for hospital-acquiredDVT). Similarly,
the estimatedPEattack ratewas 95 per 100,000person-years
(28per 100,000for community-acquiredPE, and 67 per 100,000
for hospital-acquired PE).
To tal numberofVTE-relateddeaths
The total estimated number of VTE-related deaths for 2004
across the sixEUcountries was370,012 (Table 6). Of these,7%
(26,473)were expected to have resultedfrom diagnosed (and
presumably treated) VTE, 34%(126,145) from sudden fatalPE,
and 59% (217,394)from PE-related deaths followingundiag-
nosed (untreated) VTE. Deaths that occurredasaconsequence
of hospital-acquiredVTE comprised 71% of the total number of
VTE-related deaths in the sixEUcountries.
Sensitivity analyses
The results of the sensitivityanalyses arereported as 95%con-
fidenceintervals in Table6.
This study describes the extent of the health burden attributedto
VTE in theEUinterms of the totalnumber of incident and recur-
rent non-fatal DVTand PE clinicalevents, and VTE-related
deaths per year in six EU countries.Our estimates indicate that
VTE is amajor public-health probleminthese six countries, with
apredicted totalnumber of just under half amillion DVTevents
and almost athird of amillion PE eventsper annum.Fur-
thermore,athird of amillion deaths occurper year duetosudden
PE or following undiagnosedand untreatedVTE. Giventhe
availability of effectiveVTE prophylaxis(31), manyofthese
eventsand deaths could be prevented –particularlythose that are
The estimated total number ofVTE events(DVTand PE: 148
per 100,000 and 95 per 100,000, respectively)inthe EU is higher
than that reported for US communities (24–26),but is close to
that reported in the EPI-GETBO study (27) in WesternFrance
(124per 100,000and 60 per 100,000, respectively). Onlythe
community data from the EPI-GETBO study (27) were used in
our analysis; the EPI-GETBO hospitaldatawas not. Many of the
other differencesbetween estimatescan be accounted forbythe
fact thatthe Worcester,MA(24) and Olmsted County, MN (25)
studiesexcludedrecurrentevents, whereas the EPI-GETBO
study (27)and our study included both incident and recurrent
events; recurrentevents accountedfor 25% of eventsinthe EPI-
GETBO study (27) and 19% of eventsinthis study.Our model
conservativelyassessedthe contribution of asymptomatic hospi-
tal eventstosymptomatic events(10% insteadof16% conver-
sion rate).Inaddition, acomparison of the number of VTE
eventspredicted by our model with data from the above epidemi-
ological studies(24–27) is complicated by the fact thatthe latter
onlycollectedsymptomatic, diagnosedVTE events, while our
modelalso accounted forundiagnosed eventsleading to VTE
mortality.The number of deaths in the 25 member states of the
EU has beenreported to be 4,432,177 perannum (40).Based on
apopulation of 454.4 million, this givesanannual death rate of
approximately 1%. The total number of deaths occurring in
France, Germany,Italy,Spain, Sweden, and the UK has beenre-
ported to be 2,982,816 perannum (40).Our model estimates that
370,012 (300,193–483,108) (12%)deaths per annum in these six
EU countries are duetoVTE, withthe proportion varying from
10%inthe UK to 14% in Italy.While this figure mayatfirst
seem high,itisconsistent with data from community- and hospi-
tal-based postmortem examination studies, whichhaveshown
that approximately 10% of deaths in hospitals aredue to PE
(41–43).Furthermore,ofthe estimated 370,012 (300, 193–483,
108)VTE-related deaths predicted per annum, 93% were aresult
of either sudden fatalPEorundiagnosed, untreatedVTE. This
means that only7%ofdeaths followeddiagnosedand treated
VTE, and would have beenrecognized as VTE-related by the
treating physician. Treating physicians maynot be aware that
VTE is responsiblefor more than 14 times as manydeaths as
thoserecognized as being VTE-related,reflecting the poor
awarenessthat manyphysicians have of the potentiallyfatal out-
comes of VTEand the importanceofproviding at-risk patients
with VTEprophylaxis. In addition, at least25% of VTE-related
deaths were estimatedtobe“sudden” and,therefore onlypre-
ventable with appropriate prophylaxis as currentlyrecom-
mended(4, 31).
The cost of treating VTE and related morbidityissubstantial.
Our data have important implications regarding VTE prophylax-
is in both the surgical and medical settings. While some formof
prophylaxis is giventomost major-surgerypatients, studieshave
shown thatthe type, duration, and intensityofprophylaxis are
frequentlyinappropriate, usuallyleading to inadequate prophy-
laxis (44). Furthermore, the use of recommendedprophylaxis in
medical patients, asizeable proportion of whom will develop
VTEifleft unprotected,has been reportedtobesuboptimal (45,
Estimatesofthe number of VTE eventsacross the EU,based
on extrapolation from the six modeledcountries, were 684,019
DVTevents, 434,723 PE events, and 610,138PTS eventsper
annum.The number of VTE-related deaths wasestimatedat
543,454 across the EU per annum, whichismore than double the
number of combined deaths due to AIDS (5,860),breast cancer
(86,831), prostate cancer (63,636), and transport accidents
(53,599)(40). This figure of 543,454 deaths is similar to that cal-
culated from the most complete postmortem examination data
setknown, whichestimatesaround 514,000deaths fromPEin
the EU (42). These datagiveastrong indication of the burden of
VTE in the EU,but further researchiswarrantedtoestimate this
numbermore accurately.However,these figuresleave no doubt
that thereisanurgent need forhealthcare policy-makers across
the EU to review their nationalguidelines and hospital protocols
with respecttothe accepted international guidelines for VTE
prophylaxis and to ensurethat theyare consistently implemented
Cohen et al.Venous thromboembolisminEurope
Our approach for estimating thenumber of VTE eventsand re-
latedmorbidity and mortality has some limitations.These types
of modeling exercisesare widelyusedinmanyclinical areas to
estimate the diseaseburdenwhereotherepidemiologicalmeth-
odshavefailedtocapturethe complete picture or arenot feas-
ible. External validity hasbeen testedfor the mortality data as
previouslypresented. Some country-specific data were unavail-
able.Wherethis wasthe case, data were extrapolatedfrom the
UK and France. Forsurgicalpatients, the frequencies of PE were
availablefrom observationalstudies(31) and these were used;
however, for non-surgical patients, onlyclinical trialdata(see
Table3)were available, hence we used the Oster algorithm (33)
to calculate the frequencyofPE. Usingthis modified algorithm
rather than clinicaltrial dataresultedinmore conservativeout-
comes(16% conversion rate would have resultedinmore
events). Also, as there are no current dataavailableregarding
howmanyVTE eventsare symptomatic butundiagnosed, we
used the Oster algorithm (33) to calculate this as it is still the best
availablemethod. Although the Osteralgorithm wasoriginally
used for the assessment of surgicalpatients, its inputs comefrom
studiesexamining all VTE, henceitwas suitable forour model.
Rates of VTE prophylaxis use arenot currentlyavailableinthe
literaturefor all settings. We therefore used the most appropriate
prophylaxis rates based on publishedfigures and the opinions of
experts in each country. Our calculations followedcurrent con-
vention and classified eventsoccurring up to 90 days post-hospi-
taldischargeasbeing hospital acquired (34);this led to most
eventsbeing related to hospitalization. Theseevents were ex-
cluded fromcommunity-acquired total event rates in orderto
avoid double-counting. The classification method did not there-
foreaffect overallnumbers. Finally, even with the uncertainty re-
vealed in the PSA, the estimatesofthe number of eventsare high.
Additional research is needed to refinethe inputs to the model
reported here, and to assess the impact of increasing prophylax-
is use in medicaland surgicalat-risk populations.
VTE is apreventable disease and effective prophylaxis is widely
available(4, 31), butimplementation remains suboptimal
(44–46). Giventhe current mortality rate associated with VTE
and its enormous burden in the EU in termsoflong-term morbid-
ity and costofpatient management, there is aclear opportunity
for physicians and policy-makers to have alarge, positive impact
on public health by making implementation of appropriate pro-
phylaxis use ahigherpriority (47). Strategiesfor improving the
uptakeofthe evidence-based guidelinesfor the use of thrombo-
prophylaxis should be reviewedand implemented.
TheVITAE study wasfunded by sanofi-aventis. Themodel structure and
underlying data were approvedbyanindependent expertboard. Editorial
assistance wasprovided by sanofi-aventis.
1. SteinPD, HenryJW. Prevalence of acute pulmon-
aryembolismamong patients in ageneralhospital and
at autopsy. Chest 1995;108: 978–981.
2. Heit JA,Silverstein MD,Mohr DN et al. Predictors
of survivalafter deepvein thrombosisand pulmonary
embolism: apopulation-based,cohort study.Arch In-
tern Med 1999;159: 445–453.
3. Pineda LA,Hathwar VS,Grant BJ.Clinical suspi-
cion of fatalpulmonary embolism. Chest2001;120:
4. NicolaidesAN,BreddinHK, Fareed J, et al. Preven-
tionofvenousthromboembolism. International Con-
sensus Statement. Guidelines compiled in accordance
withthe scientific evidence. IntAngiol 2001; 20: 1–37.
5. Nordstrom M, Lindblad B, Bergqvist D, et al. A
prospective study of theincidenceofdeep-vein throm-
bosis within adefined urban population. JInternMed
1992; 232:155–160.
6. Hull RD, Pineo GF,Stein PD,etalExtended out-of-
hospital low-molecular-weight heparin prophylaxis
against deepvenous thrombosisinpatients afterelec-
tive hip arthroplasty: asystematic review.Ann Intern
Med 2001;135: 858–869.
7. Mismetti P, LaporteS,DarmonJY, et al. Meta-
analysisoflow molecular weight heparin in thepreven-
tionofvenousthromboembolismingeneralsurgery. Br
JSurg2001;88: 913–930.
8. DouketisJD, EikelboomJW, QuinlanDJ, et al.
Short-durationprophylaxisagainst venousthrom-
boembolismaftertotal hip or kneereplacement: a
meta-analysisofprospectivestudies investigating
symptomatic outcomes. Arch Intern Med 2002;162:
9. Vaitkus PT,LeizoroviczA, CohenAT, et al. Mortal-
ity rates and risk factors forasymptomatic deepvein
thrombosisinmedical patients. Thromb Haemost
2005; 93: 76–79.
10. Prandoni P, Lensing AW,CogoA,etal. The long-
term clinical courseofacute deepvenous thrombosis.
AnnInternMed 1996; 125:1–7.
11. McColl MD, EllisonJ,Greer IA,etal. Prevalence
of thepost-thrombotic syndromeinyoungwomen with
previous venousthromboembolism. BrJHaematol
2000; 108:272–274.
12. Mohr DN,Silverstein MD,Heit JA,etal. The ve-
nousstasissyndrome afterdeep venousthrombosis or
pulmonary embolism: apopulation-based study.Mayo
Clin Proc 2000;75: 1249–1256.
13. AsbeutahAM, RihaAZ, CameronJD, et al. Five-
year outcome study of deepvein thrombosisinthe
lowerlimbs. JVascSurg2004;40: 1184–1189.
14. Bova C, Rossi V, Ricchio R, etal. Incidenceofpost-
thrombotic syndromeinpatients withprevious pul-
monaryembolism. Aretrospectivecohort study.
ThrombHaemost2004;92: 993–996.
15. GabrielF,Labios M,PortolesO,etal. Incidenceof
post-thrombotic syndromeand its associationwith
various risk factors in acohort of Spanish patients after
one year of follow-up followingacute deepvenous
thrombosis. ThrombHaemost2004;92: 328–336.
16. Roumen-Klappe EM,den HeijerM,Janssen MC,
et al. The post-thrombotic syndrome: incidence and
prognostic valueofnon-invasive venousexaminations
in asix-year follow-up study.Thromb Haemost2005;
94: 825–830.
17. Wille-Jorgensen P, Jorgensen LN,CrawfordM.
Asymptomatic postoperative deepvein thrombosisand
thedevelopment of postthrombotic syndrome. Asys-
tematic review and meta-analysis. ThrombHaemost
2005; 93: 236–241.
18. Pengo V, Lensing AW,Prins MH, et al.Incidenceof
chronic thromboembolic pulmonary hypertensionafter
pulmonaryembolism. NEnglJMed 2004;350:
19. Ribeiro A, Lindmarker P, Johnsson H, et al. Pul-
monaryembolism: one-year follow-up withechoc-
ardiographydopplerand five-year survivalanalysis.
Circulation 1999;99: 1325–1330.
20. GriffinJ.Deep vein thrombosisand pulmonaryem-
bolism. London: Office of HealthEconomics 1996;
21. HouseofCommonsHealthCommittee. The pre-
vention of venousthromboembolisminhospitalised
patients. Second reportofSession2004–05.Available
February27, 2007.
22. BergqvistD,JendtegS,Johansen L, et al. Costof
long-term complications of deepvenous thrombosisof
thelower extremities: an analysisofadefined patient
populationinSweden.Ann Intern Med 1997;126:
23. CapriniJA, Botteman MF, Stephens JM,etal.
Economicburden of long-term complications of deep
vein thrombosisafter totalhip replacement surgeryin
theUnited States.Value Health2003;6:59–74.
24. Anderson JrFA, Wheeler HB,GoldbergRJ, et al. A
population-based perspective of thehospital incidence
and case-fatality rates of deepvein thrombosisand pul-
monaryembolism.The Worcester DVTStudy.Arch In-
tern Med 1991;151: 933–938.
25. SilversteinMD, Heit JA,Mohr DN,etal. Trendsin
theincidenceofdeepvein thrombosisand pulmonary
embolism: a25-year population-based study.Arch In-
tern Med 1998;158: 585–593.
Cohen et al.VenousthromboembolisminEurope
26. Spencer FA,Emery C, Lessard D, et al.The Wor-
cester Venous Thromboembolismstudy: apopulation-
based study of theclinical epidemiology of venous
thromboembolism. JGen InternMed 2006; 21:
27. Oger E. Incidence of venous thromboembolism: a
community-based studyinWesternFrance.EPI-
GETBO Study Group. Groupe d'Etude de la Throm-
bose de Bretagne Occidentale.ThrombHaemost 2000;
83: 657–660.
28. US Census Bureau. International Data Base (IDB).
html. Accessed February27, 2007.
29. Department of Health.Hospital Episode Statistics
(HES) data 2004–05. Availableat:
sodeStatistics/fs/en.Accessed February27, 2007.
30. AgenceTechnique de l’Informationsur l’Hospitali-
sation. Programme de dicalisationdes systèmes
d'information(PMSI)2004. Availableat: http://www. Accessed February27, 2007.
31. Geerts WH,Pineo GF,HeitJA, et al.Preventionof
venous thromboembolism: theSeventhACCP Confer-
ence on Antithrombotic and Thrombolytic Therapy.
Chest 2004;126 (3 Suppl): 338S–400S.
32. Geerts WH,HeitJA, ClagettGP, et al.Preventionof
venous thromboembolism. Chest 2001; 119(1 Suppl):
33. OsterG,Tuden RL,Colditz GA. Acost-effective-
ness analysis of prophylaxisagainst deep-veinthrom-
bosis in majororthopedicsurgery. JAmMed Assoc
1987;257: 203–208.
34. Heit JA,Mohr DN,Silverstein MD,etal. Predictors
of recurrence after deep vein thrombosisand pulmon-
aryembolism: apopulation-based cohortstudy.Arch
InternMed 2000; 160: 761–768.
35. Piovella F, Anderson Jr FA,etal; for theIMPROVE
Investigators.Rates of clinically apparent venous
thromboembolismand deathresultingfrom pulmonary
embolismamong unselected hospitalized acutelyill
medical patientsversus rates predicted from clinical
studies. Blood (ASH Annual Meeting Abstracts)2005;
106: Abstract1620.
36. Cohen AT,Alikhan R. Prophylaxisofvenous
thromboembolisminmedical patients. CurrOpinPulm
Med 2001;7:332–337.
37. DalenJE, Alpert JS. Natural historyofpulmonary
embolism. ProgCardiovasc Dis 1975; 17: 259–270.
38. SullivanSD, Davidson BL,Kahn SR, et al.Acost-
effectiveness analysis of fondaparinux sodium com-
pared with enoxaparin sodium as prophylaxisagainst
venous thromboembolism: use in patientsundergoing
majororthopaedicsurgery. Pharmacoeconomics2004;
22: 605–620.
39. Kucher N, KooS,Quiroz R, et al.Electronic alerts
to prevent venous thromboembolismamong hospital-
ized patients. NEngl JMed 2005; 352: 969–977.
40. Eurostat.Eurostatstatisticsonhealth and safety
2001. Availableat:
alth&scrollto=0. Accessed February27, 2007.
41. Cohen AT,Edmondson RA,PhillipsMJ, et al.The
changing pattern of venous thromboembolic disease.
Haemostasis1996; 26: 65–71.
42. LindbladB,Sternby NH, Bergqvist D. Incidence of
venous thromboembolismverifiedbynecropsyover30
years.BMJ 1991;302: 709–711.
43. Sandler DA,Martin JF.Autopsy provenpulmonary
embolisminhospital patients: are we detectingenough
deep vein thrombosis? JRSoc Med 1989; 82: 203–205.
44. ArnoldDM, Kahn SR, Shrier I. Missed opportun-
itiesfor preventionofvenous thromboembolism: an
evaluationofthe use of thromboprophylaxis guide-
lines. Chest 2001; 120: 1964–1971.
45. Ageno W, SquizzatoA,Ambrosini F, et al.Throm-
bosis prophylaxisinmedical patients: aretrospective
review of clinical practice patterns. Haematologica
2002; 87: 746–750.
46. RashidST, Thursz MR,Razvi NA,etal. Venous
thromboprophylaxis in UK medical inpatients. JRSoc
Med 2005; 98: 507–512.
47. ShojaniaKG, Duncan BW,McDonaldKM, et al.
Makinghealth care safer: acritical analysis of patient
safetypractices. Evidence report/technologyassess-
ment:number 43. Availableat:
clinic/ptsafety/.Accessed February27, 2007.
Cohen et al.VenousthromboembolisminEurope
... According to an epidemiological study from 6 European countries, more than 317,000 deaths were associated with pulmonary embolism in 2004 [15]. Of these, 34% presented with fatal pulmonary embolism; 59% of the deaths were caused by pulmonary embolism that had not been diagnosed during lifetime. ...
... Of these, 34% presented with fatal pulmonary embolism; 59% of the deaths were caused by pulmonary embolism that had not been diagnosed during lifetime. The average mortality rate from pulmonary embolism is given as 11% (40,000 deaths/year in Germany), but is significantly higher in patients in shock (40-50%) or in patients requiring resuscitation (70-80%) [15]. ...
Shock is a life threatening pathological condition characterized by inadequate tissue oxygen supply. Four different subgroups of shock have been proposed according to the mechanism causing the shock. Of these, obstructive shock is characterized by reduction in cardiac output due to noncardiac diseases. The most recognized causes include pulmonary embolism, tension pneumothorax, pericardial tamponade and aortic dissection. Since obstructive shock typically cannot be stabilized unless cause for shock is resolved, diagnosis of the underlying disease is eminent. In this review, we therefore focus on diagnosis of obstructive shock and suggest a structured approach in three steps including clinical examination, ultrasound examination using the rapid ultrasound in shock (RUSH) protocol and radiological imaging if needed.
... Blood clot-mediated blockage of the pulmonary artery resulting in obstruction of pulmonary circulation and hemodynamic collapse is termed as acute pulmonary embolism (APE) (Cohen et al., 2007;Geerts et al., 2008;Lang et al., 2013). Due to the paucity of symptoms and the absence of an appropriate diagnosis, the exact epidemiological details of APE are unknown. ...
Full-text available
Acute pulmonary embolism (APE) is a debilitating condition with high incidence and mortality rates. APE is widely treated with the serine protease urokinase or urokinase-type plasminogen activator (uPA) that functions by resolving blood clots via catalyzing the conversion of plasminogen to plasmin. Treatment with recombinant uPA has been shown to increase endogenous expression of uPA and its cognate receptor, uPAR; however, the mechanisms for this induction are not known. Using an in vitro hypoxia/reoxygenation model in bronchial epithelial BEAS-2B cells, we show that induction of hypoxia/reoxygenation induces apoptosis and increases secretion of tumor necrosis factor–alpha, brain natriuretic peptide, and fractalkine, which are attenuated when treated with exogenous uPA. Induction of hypoxia/reoxygenation resulted in decreased expression of uPAR on cell surface without any significant changes in its messenger RNA expression, highlighting post-transcriptional regulatory mechanisms. Determination of uPAR protein half-life using cycloheximide showed treatment with uPA significantly increased its half-life (209.6 ± 0.2 min from 48.2 ± 2.3 min). Hypoxia/reoxygenation promoted the degradation of uPAR. Inhibition of proteasome-mediated degradation using MG-132 and lactacystin revealed that uPAR was actively degraded when hypoxia/reoxygenation was induced and that it was reversed when treated with exogenous uPA. Determination of the proteolytic activity of 20S proteasome showed a global increase in ubiquitin–proteasome activation without an increase in proteasome content in cells subjected to hypoxia/reoxygenation. Our results cumulatively reveal that uPAR is actively degraded following hypoxia/reoxygenation, and the degradation was significantly weakened by exogenous uPA treatment. Given the importance of the uPA/uPAR axis in a multitude of pathophysiological contexts, these findings provide important yet undefined mechanistic insights.
... PE presents a wide range of hemodynamic effects, from asymptomatic and undiagnosed disease to life-threatening emergencies. It is the third most frequent cause of death in hospitalized patients and a major cause of morbidity and mortality, with a total annual effect of 62 to 112 cases per 100,000 inhabitants [3]. Prognosis may worsen in PE patients, during intrahospital treatment, by experiencing hemorrhagic complications, which are mainly attributed to anticoagulant therapy [4]. ...
Full-text available
Background: The prevalence of anticoagulant therapy-associated hemorrhagic complications in hospitalized patients with pulmonary embolism (PE) has been scarcely investigated. Aim: To evaluate the prevalence of hemorrhages in hospitalized PE patients. Methods: The Information System "ASKLIPIOS™ HOSPITAL" implemented in the Respiratory Medicine Department, University of Thessaly, was used to collect demographic, clinical and outcome data from January 2013 to April 2021. Results: 326 patients were included. Males outnumbered females. The population's mean age was 68.7 ± 17.0 years. The majority received low molecular weight heparin (LMWH). Only 5% received direct oral anticoagulants. 15% of the population were complicated with hemorrhage, of whom 18.4% experienced a major event. Major hemorrhages were fewer than minor (29.8% vs. 70.2%, p = 0.001). Nadroparin related to 83.3% of the major events. Hematuria was the most common hemorrhagic event. 22% of patients with major events received a transfusion, and 11% were admitted to intensive care unit (ICU). The events lasted for 3 ± 2 days. No death was recorded. Conclusions: 1/5 of the patients hospitalized for PE complicated with hemorrhage without a fatal outcome. The hemorrhages were mainly minor and lasted for 3 ± 2 days. Among LMWHs, nadroparin was related to a higher percentage of hemorrhages.
... VTE is a leading cause of mortality and morbidity. In Europe, there are nearly 760,000 VTE cases per year [1] In France alone, the number of VTE cases per year is around 120,000 [2]. Moreover, VTE occurred in 1% of hospital stays in 2010-2011 in France [3]. ...
Full-text available
Introduction: The direct oral anticoagulant (DOAC) apixaban has shown to have non-inferior efficacy and better safety than vitamin K antagonists (VKAs) in patients with venous thromboembolism (VTE). We determined whether healthcare resource use (HCRU) and direct all-cause medical and non-medical costs in patients with VTE in France differed between VKAs and apixaban. Methods: A retrospective cohort study was conducted using French national health data from January 2013-June 2018 for anticoagulant-naïve adults hospitalized with VTE. All-cause costs and HCRU per patient per month (PPPM) were compared between apixaban and VKA cohorts created by 1:1 propensity score matching. Two-part models with bootstrapping were used to calculate marginal effects for costs and HCRU. Results: The matched VKA and apixaban cohorts each comprised 7503 patients. Compared to VKAs, patients prescribed apixaban had significantly lower (P < 0.0001) mean all-cause costs PPPM for outpatient visits (€438.54 vs. €455.58), overall laboratory tests (€21.26 vs. €83.73), and hospitalizations (€249.48 vs. €343.82), but significantly higher (P < 0.0001) mean all-cause costs PPPM for overall drugs (€97.06 vs. €69.56) and medical procedures (€42.12 vs. €35.50). Mean total all-cause direct medical costs (€687.93 vs. €798.70) and total all-cause direct medical and non-medical costs (€771.60 vs. €883.66) were significantly lower (P < 0.0001) for apixaban. Mean HCRU PPPM showed similar trends. Subgroup analyses showed that, among patients with recurrent VTE, patients prescribed apixaban had significantly lower (P < 0.0001) all-cause costs PPPM for total medical costs (€17.26 vs. €18.12) and total all-cause direct medical and non-medical costs (€18.37 vs. €19.20) than patients prescribed VKAs. Similarly, among patients with bleeding, patients prescribed apixaban had significantly lower (P < 0.0001) all-cause costs PPPM for total medical costs (€15.34 vs. €32.61) and total all-cause direct medical and non-medical costs (€16.23 vs. €34.63) than patients prescribed VKAs. Conclusion: Compared to VKAs, apixaban may be cost-saving in the treatment of patients hospitalized for acute VTE.
... Pulmonary thromboembolism (PTE) and deep vein thrombosis (DVT) are part of the spectrum of venous thromboembolism. The annual incidence of PTE is 100-200 cases/100,000 population, (1,2) and the overall 30-day mortality rate ranges from 6.7% to 11.0%, (3)(4)(5) reaching 30.0% in the absence of treatment. (6) Autopsy-based studies suggest that these figures are underestimated. ...
Full-text available
Objective: To determine the prevalence of alternative diagnoses based on chest CT angiography (CTA) in patients with suspected pulmonary thromboembolism (PTE) who tested negative for PTE, as well as whether those alternative diagnoses had been considered prior to the CTA. Methods: This was a cross-sectional, retrospective study involving 191 adult patients undergoing CTA for suspected PTE between September of 2009 and May of 2012. Chest X-rays and CTAs were reviewed to determine whether the findings suggested an alternative diagnosis in the cases not diagnosed as PTE. Data on symptoms, risk factors, comorbidities, length of hospital stay, and mortality were collected. Results: On the basis of the CTA findings, PTE was diagnosed in 47 cases (24.6%). Among the 144 patients not diagnosed with PTE via CTA, the findings were abnormal in 120 (83.3%). Such findings were consistent with an alternative diagnosis that explained the symptoms in 75 patients (39.3%). Among those 75 cases, there were only 39 (20.4%) in which the same alterations had not been previously detected on chest X-rays. The most common alternative diagnosis, made solely on the basis of the CTA findings, was pneumonia (identified in 20 cases). Symptoms, risk factors, comorbidities, and the in-hospital mortality rate did not differ significantly between the patients with and without PTE. However, the median hospital stay was significantly longer in the patients with PTE than in those without (18.0 and 9.5 days, respectively; p = 0.001). Conclusions: Our results indicate that chest CTA is useful in cases of suspected PTE, because it can confirm the diagnosis and reveal findings consistent with an alternative diagnosis in a significant number of patients.
Full-text available
Background: Venous thromboembolism (VTE) is a common and lethal disease. Assessing the risk factors will help to modify exposures. Aim: This study, assessed VTE risk factors in hospitalized patients at the University of Nigeria Teaching Hospital, Enugu. Patients and Methods: This was an observational, case-control study. Three hundred and fifty (350) patients were recruited for the study: This comprised 150 medical patients, 140 surgical patients and a population of 60 healthy control group. Subjects were evaluated once using the Caprini risk assessment model (RAM). Results: Over 50% of all hospitalized patients, were at risk for VTE. Surgical patients were at a higher risk than medical patients. Hemoglobin concentration was associated with the risk of VTE in surgical patients, while d-dimer was associated with VTE risk in medical patients. Conclusion: This study shows a high prevalence of VTE risk factors among hospitalized patients at the University of Nigeria Teaching Hospital.
Background The prognostic role of serial electrocardiographic modifications in patients with acute pulmonary embolism (PE) have been poorly investigated. We evaluate the electrocardiographic changes in PE patients during their hospitalization and the prognostic role of such ECG modifications in respect to 30-day mortality in patients enrolled in the Italian Pulmonary Embolism Registry (IPER). Methods Subjects enrolled into the IPER (September 2006–August 2010) were stratified according to their hemodynamic status, as high- (hemodynamically unstable) and non-high-risk (hemodynamically stable) patients. ECG features were analysed at three fixed time points: at presentation, on day 3 and at discharge. Results Overall, 687 patients (286 males, mean age 69.0 ± 15.5 years) were included in the study. Among these, 71 (10.3 %) were at high-risk. In these patients, multivariate analysis revealed that the persistence of right ventricular strain (RVS) after three days from hospitalization was a predictor of 30-day mortality [HRa: 2.78 (95 % CI: 1.05–7.31, p = 0.003)]. Moreover, the persistence of right bundle branch block (RBBB) [HRa: 2. 48 (95 % CI: 1.03–5.09, p = 0.002)], negative T waves in V1-V4 (NTWs) [HRa: 1.63 (95 % CI: 1.04–2.55), p < 0.0001] and qR complex in lead V1 [HRa: HR: 5.44, (95 % CI: 3.22–9.44, p < 0.0001)] were associated with an increased risk of 30-day mortality. When RBBB, NTWs and qR complex in V1 lead were present concomitantly, the 30-day risk of death resulted significantly higher [HR: 12.5 (95 % CI: 3.39–46.4,) p < 0.0001]. Conclusions Persistence of RBBB, NTWs, and qR pattern in V1 lead at day 3 of hospitalization are independent prognostic factors of death within 30 days in high-risk acute PE patients. The prognostic power of any single ECG abnormality is lower compared to the combination of the three ECG variables.
Venous thromboembolism (VTE) occurs frequently and represents a serious threat to patient health. However, its effects on mental health have not been studied sufficiently. The objective of this study was to investigate whether VTE alters the patients’ mental state. We gathered questionnaire data on 100 patients (59 men, 41 women; age ranging from 24 to 85 years) concerning psychological symptoms and body image. Our results show that after a VTE, patients develop psychological symptoms, some of which persist for more than 2 years. Examples of those symptoms include depression, intrusion, and increased scrutiny of the body. Intrusion (flashbacks, nightmares, and other traumatic sensations of reliving the thrombotic event) affected 69% of patients and may lead to social isolation, occasionally including loss of employment. Depression affected more than 50% of patients. Productivity typically decreases, and body functionality and feeling of health changed in 34–76% of patients. However, anxiety, disordered impulse control, and maladjustment were less frequent (40% or less), and patients’ emotional attitude to their bodies (liking their bodies or being angry with their bodies, feelings of shame and attractiveness) tended not to change over time. Nevertheless, we feel it may be advisable to identify patients with relevant psychological changes after VTE by means of a short evidence-based questionnaire and to offer them psychological treatment in order to improve management and quality of life of these patients. The goal is, therefore, to develop diagnostic and therapeutic recommendations.
Full-text available
The incidence of venous thromboembolism has not been well described, and there are no studies of long-term trends in the incidence of venous thromboembolism. To estimate the incidence of deep vein thrombosis and pulmonary embolism and to describe trends in incidence. We performed a retrospective review of the complete medical records from a population-based inception cohort of 2218 patients who resided within Olmsted County, Minnesota, and had an incident deep vein thrombosis or pulmonary embolism during the 25-year period from 1966 through 1990. The overall average age- and sex-adjusted annual incidence of venous thromboembolism was 117 per 100000 (deep vein thrombosis, 48 per 100000; pulmonary embolism, 69 per 100000), with higher age-adjusted rates among males than females (130 vs 110 per 100000, respectively). The incidence of venous thromboembolism rose markedly with increasing age for both sexes, with pulmonary embolism accounting for most of the increase. The incidence of pulmonary embolism was approximately 45% lower during the last 15 years of the study for both sexes and all age strata, while the incidence of deep vein thrombosis remained constant for males across all age strata, decreased for females younger than 55 years, and increased for women older than 60 years. Venous thromboembolism is a major national health problem, especially among the elderly. While the incidence of pulmonary embolism has decreased over time, the incidence of deep vein thrombosis remains unchanged for men and is increasing for older women. These findings emphasize the need for more accurate identification of patients at risk for venous thromboembolism, as well as a safe and effective prophylaxis.
Full-text available
To determine the incidence of venous thromboembolism in all necropsy reports over 30 years. Study of all necropsies in one hospital in 1987 and longitudinal analysis of results of necropsy in 1957, 1964, 1975, and 1987. Departments of general surgery, infectious diseases, internal medicine, oncology, and orthopaedics in a Swedish general hospital. Number of cases of venous thromboembolism. About a third of all necropsies showed venous thromboembolism. In 1987, 260 of 347 necropsies showing venous thromboembolism found pulmonary embolism, of which 93 were classified as fatal, 90 as contributory, and 77 as incidental. Only 21 contributory or fatal postoperative pulmonary emboli were seen. In only 106 of 260 patients with pulmonary embolism did routine necropsy not show the source of embolism. Calf veins were not routinely examined. Deep venous thrombosis was seen in 239 patients in 1987. The incidence of venous thromboembolism in the four years studied was remarkably stable except in the department of orthopaedics, where the proportion fell from 60.7% in 1975 to 32.2% in 1987 (p less than 0.05), although there were only a few patients. The overall incidence of venous thromboembolism has not changed over 30 years. During this period the proportion of the population aged over 65 has doubled, and this may have masked the beneficial effects of prophylaxis and early mobilisation. Prevalences corrected for age are needed.
We prospectively assessed the implementation of venous thromboembolism (VTE) prophylaxis guidelines and the impact of grand round presentation of the data in changing clinical practice. Two NHS teaching hospitals were studied for 24 months from January 2003. Patients were risk stratified according to the THRIFT (thromboembolic risk factor) consensus group guidelines and compared with the recommendations of the THRIFT and ACCP (American College of Chest Physicians) consensus groups. Six months following presentation of the initial results, a further analysis was made to assess changes in clinical practice. 1128 patients were assessed of whom 1062 satisfied the inclusion criteria for thromboprophylaxis. 89% of all patients were stratified as having high or moderate risk of developing VTE. Of these only 28% were prescribed some form of thromboprophylaxis–-4% received the THRIFT-recommended and 22% received the ACCP-recommended thromboprophylaxis. The vast majority (72%) received no thromboprophylaxis at all. Reassessment, following data presentation at grand rounds, showed a significant increase to 31% in patients receiving THRIFT (P<0.0001) and ACCP (P=0.002) recommended thromboprophylaxis. However, the proportion of patients receiving no form of prophylaxis barely changed (72% to 69%: P=0.59). We found a gross underutilization of thromboprophylaxis in hospitalized medical patients. A simple grand-round presentation of the data and recommended guidelines to clinicians significantly increased the proportion of patients receiving recommended thromboprophylaxis but did not increase the overall proportion of patients receiving it. We therefore conclude that a single presentation of guidelines is not enough to achieve the desired levels. Such presentations may only serve to make DVT (deep venous thromboembolism) aware clinicians prescribe prophylaxis more accurately.
This article discusses the prevention of venous thromboembolism (VTE) and is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggestions imply that individual patient values may lead to different choices (for a full discussion of the grading, see the “Grades of Recommendation” chapter by Guyatt et al). Among the key recommendations in this chapter are the following: we recommend that every hospital develop a formal strategy that addresses the prevention of VTE (Grade 1A). We recommend against the use of aspirin alone as thromboprophylaxis for any patient group (Grade 1A), and we recommend that mechanical methods of thromboprophylaxis be used primarily for patients at high bleeding risk (Grade 1A) or possibly as an adjunct to anticoagulant thromboprophylaxis (Grade 2A). For patients undergoing major general surgery, we recommend thromboprophylaxis with a low-molecular-weight heparin (LMWH), low-dose unfractionated heparin (LDUH), or fondaparinux (each Grade 1A). We recommend routine thromboprophylaxis for all patients undergoing major gynecologic surgery or major, open urologic procedures (Grade 1A for both groups), with LMWH, LDUH, fondaparinux, or intermittent pneumatic compression (IPC). For patients undergoing elective hip or knee arthroplasty, we recommend one of the following three anticoagulant agents: LMWH, fondaparinux, or a vitamin K antagonist (VKA); international normalized ratio (INR) target, 2.5; range, 2.0 to 3.0 (each Grade 1A). For patients undergoing hip fracture surgery (HFS), we recommend the routine use of fondaparinux (Grade 1A), LMWH (Grade 1B), a VKA (target INR, 2.5; range, 2.0 to 3.0) [Grade 1B], or LDUH (Grade 1B). We recommend that patients undergoing hip or knee arthroplasty or HFS receive thromboprophylaxis for a minimum of 10 days (Grade 1A); for hip arthroplasty and HFS, we recommend continuing thromboprophylaxis > 10 days and up to 35 days (Grade 1A). We recommend that all major trauma and all spinal cord injury (SCI) patients receive thromboprophylaxis (Grade 1A). In patients admitted to hospital with an acute medical illness, we recommend thromboprophylaxis with LMWH, LDUH, or fondaparinux (each Grade 1A). We recommend that, on admission to the ICU, all patients be assessed for their risk of VTE, and that most receive thromboprophylaxis (Grade 1A).
Objectives To identify and characterize cases of potentially preventable venous thromboembolism (VTE): cases for which thromboprophylaxis was indicated, according to the American College of Chest Physicians (ACCP) consensus guidelines for VTE prevention, yet was administered inadequately. Design A historical cohort study to examine all cases of deep vein thrombosis and pulmonary embolism from 1996 to 1997 at a large teaching hospital. Of these, we determined the proportion that was potentially preventable. We examined the reasons for inadequacy of prophylaxis and the setting in which preventable VTE occurred. Results Of 253 objectively diagnosed cases of VTE in 245 patients, 44 cases (17.4%) were considered potentially preventable. This represented two thirds of all VTE cases for which thromboprophylaxis had been indicated (n = 65). Of preventable cases, the most frequent reason for inadequacy of prophylaxis was omission of prophylaxis (47.7%), followed by inadequate duration of prophylaxis (22.7%), and by incorrect type of prophylaxis (20.5%). Surgical and medical indications for thromboprophylaxis that were common among preventable cases included nonorthopedic surgery, admission to hospital for pneumonia, and stroke with lower limb paralysis. Underlying risk factors for VTE that were common among preventable cases included recent immobility, active cancer, and obesity. Conclusions One of six cases of all VTE and two of three cases of VTE for which thromboprophylaxis had been indicated could potentially have been prevented had physicians followed the recommended ACCP guidelines. Inadequacy of prophylaxis was most often caused by omission of prophylaxis. Missed opportunities for prevention occurred most commonly in the settings of nonorthopedic surgery, pneumonia, and stroke.
The authors hypothesized that use of a computer alert program to alert physicians regarding hospitalized patients at high risk for VTE might reduce the frequency of DVT by increasing the frequency of prophylaxis. A computer program was developed linked to a patient database to identify hospitalized patients at risk for VTE. The patients were randomly assigned to an intervention group in which the treating physician was made aware of the patient’s risk of VTE (n = 1255) or to a control group in which no such alert was issued (n = 1251). Physicians receiving the alert for VTE prophylaxis were required to acknowledge the alert and could then order or withhold prophylaxis according to clinical judgment. Prophylaxis included graduated compression stockings, pneumatic compression boots, unfractionated heparin, warfarin, or low-molecular-weight heparin. Clinically diagnosed, objectively confirmed VTE (DVT or pulmonary embolism) at 90 days was the primary end point.