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Prevention of venous thromboembolism*
(PDF version)

International Consensus Statement

Guidelines compiled in accordance
with the scientific evidence

Under the auspices of the Cardiovascular Disease Educational and
Research Trust, and the International Union of Angiology.

 

Chairman of Editorial Committee: A. N. Nicolaides,
Co-editors: H.K. Breddin, J. Fareed, S. Goldhaber, S. Haas,
R. Hull, E. Kalodiki, K. Myers, M. Samama, A. Sasahara,

FACULTY:

R.S Ackchurin (Russia); C. Allegra (Italy); J. Arcelus (Spain); P. Balas (Greece); F. Becker (France); G. Belcaro (Italy); J. Bergan (USA); D. Bergqvist (Sweden); S.D. Berkowits (UK); R. Bick (USA); H. Boccalon (France); M. Boisseau (France); A. Bollinger (Switzerland); L.C. Borris (Denmark); J. Bonnar (Ireland); H.K. Breddin (Germany); M.A. Cairols (Spain); J.A. Caprini (USA); M. Catalano (Italy); D. Christopoulos (Greece); D.Clarke-Pearson (USA); D. Clement (Belgium); P. Coleridge-Smith (UK); G.A. Colditz (USA); A.J. Comerota (USA); S.S. Daskalopoulou (Greece); E. Diamantopoulos (Greece); D. Duprez (Belgium); B. Eikelboom (The Netherlands); B. Eklof (USA); B. Fagrell (Sweden); J. Fareed (USA); J. Fernandes Montequin (Cuba); J. Fernandes e Fernandes (Portugal); C. Fisher (Australia); J. Fletcher (Australia); M. Freeman (UK); S.Z Goldhaber (USA); L.J. Greenfield (USA); P. Gregg (UK); P. Gregory (UK); S. Haas (Germany); J.T. Hobbs (UK); W. Hopkinson (USA); R. Hull (Canada); E.A. Hussein (Egypt); V.V. Kakkar (UK); E. Kalodiki (Cyprus); D. Kiskinis (Greece); R. Kistner (USA); M.R. Lassen (Denmark); J. Leclerc (Canada); A. Lensing (The Netherlands); M. Lepantalo (Finland); G.D.O. Lowe (UK); M. MacGrath (Australia); A. Markel (Israel); F.H.A. Maffei (Brazil); K. Myers (Australia); A.N. Nicolaides (UK); L. Norgren (Sweden); S. Novo (Italy); G.B. Parulkar (India); H. Partsch (Austria); A. Planes (France); P. Prandoni (Italy); G. Ramaswami (India); J-B. Ricco (France); N. Rich (USA); H. Roberts (USA); P. Roderick (UK); M Samama (France); A. Sasahara (USA); J.H. Scurr (UK); R. Simkin (Argentina); S. Simonian (USA); A. Strano (Italy); M. Tsapogas (USA); A.G. Turpie (Canada); O.N. Ulutin (Turkey); M. Vandendriessche (Belgium); M. Veller (South Africa); L. Villavincencio (USA); J. Walenga (USA); Z-G. Wang (China); D. Warwick (UK).

Dedicated to the memory of Ernest Cooke

* We thank Prof. A. N. Nicolaides for the permission to reprint these guidelines.

J Vasc Br 2002;1(2):133-70

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ACKNOWLEDGEMENTS

The foundations for this International Consensus Statement were laid down by the European Consensus Statement on the Prevention of Venous Thromboembolism developed at Windsor (UK) in 1991 with support from the European Commission. The European Consensus Statement was subsequently updated by an international faculty and was forged into The International Consensus Statement by extensive evaluation of the literature and debate during the International Union of Angiology (IUA) World Congress in London in April 1995. Further work by the faculty at the IUA European Congress in Rhodes in May 1999 and by the editorial committee at subsequent meetings in the USA and UK in 2000, has ensured that the most recent major advances and the supporting evidence available have been included. We are grateful to the following companies for their educational grants towards the meetings of the faculty without which this consensus document would not have been possible: Abbott Laboratories, Advanced Technology Laboratories, Aventis, Behringwerke/Hoechst AG, Boehringer Ingelheim Ltd, Braun, Italfarmaco Spa, Kendall UK, Kendall HealthCare Inc, Knoll AG, Leo Pharmaceutical Products, Lilly Industries Ltd, Novamedix, Novartis, Novo Nordisk Pharmaceutical Ltd, N V Organon, Pentapharm, Pharmacia AB, Porton Products Ltd, Sanofi-Synthelabo, Wyeth-Ayerst Laboratories.

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DISCLAIMER

Due to the evolving nature of medicine, new research may, in due course, modify the recommendations presented in this document. At the time of publication, every attempt has been made to ensure that the information provided is up to date and accurate. It is the responsibility of the treating physician to determine the best treatment for the patient. The authors, committee members, editors, and publishers cannot be held responsible for any legal issues that may arise from the citation of this statement.

GLOSSARY

DVT: Deep vein thrombosis
FUT: Fibrinogen uptake test
GEC: Graduated elastic compression
HIT: Heparin-induced thrombocytopenia
IPC: Intermittent pneumatic compression
LMWH: Low molecular weight heparin
PE: Pulmonary embolism
Proximal DVT: DVT in popliteal or more proximal veins
VTE: Venous thromboembolism

RULES OF EVIDENCE

Prevention of VTE has been traditionally undertaken subjectively among physicians, often resulting in less than optimal strategies. In this document a systematic approach has been developed with detailed grades of recommendations, based upon cumulative evidence from the literature. Levels of evidence and grades of recommendation range from Level I and Grade A to Level III and Grade C. Level I evidence and Grade A recommendations derive from scientifically sound clinical trials in which the results are clear-cut. Level II evidence and Grade B recommendations derive from clinical studies in which the results among trials often point to inconsistencies. Level III evidence and Grade C recommendations result from poorly designed trials or from small case series.¹

Meta-analysis

Meta-analyses are included in the present document but one should be cautious about their potential abuse. Some studies are included carelessly, by failing to adequately understand substantive issues, ignoring relevant variables, being too heterogenous; or by introducing bias in interpretation.²

For example, it has been demonstrated that the outcomes of 12 large randomized controlled trials were not predicted accurately 35% of the time by meta-analyses published previously on the same topics.³

THE PROBLEM AND THE NEED FOR PREVENTION

Venous thromboembolism (VTE) due to deep vein thrombosis (DVT) or pulmonary embolism (PE) is a major international health problem. At one extreme, PE can be fatal. Often overlooked is the fact that DVT can lead to post-thrombotic venous insufficiency and ulceration which adversely impacts on the quality of life and escalates health care costs. In North America and Europe, the annual incidence is approximately 160 per 100,000 for DVT, 20 per 100,000 for symptomatic non-fatal PE, and 50 per 100,000 for fatal autopsy-detected PE.^4-8 Venous ulcers develop in at least 300 per 100,000 of the population and the proportion due to DVT is approximately 25%.^9-10 The annual cost of treating venous ulcers has been estimated to be 400 million pounds for the UK¹¹ and more than one billion dollars for the USA.¹²

Most venous thromboembolic events are not detected clinically because the diagnosis is difficult and elusive. Therefore, it is important for the medical profession to know the epidemiology and definition of high risk groups, and to be familiar with the diagnostic methodology (Tables I-VII^13-112) in order to apply appropriate prophylaxis and early treatment. Although VTE should be an appealing target for maximal preventive efforts, consensus on its prevention has been difficult to achieve because of considerable differences in attitudes toward prophylaxis, definition of high risk groups, and prophylactic methods chosen.¹⁰⁵,^113-118 The aim of this document is to provide guidelines in accordance with the available scientific evidence.

Table 1 -The frequency of all DVT in trauma, surgery and medical patients in the absence of prophylaxis (diagnosed by surveillance with objective methods: Phlebography or FUT). The listed frequency is true for the total groups of patients. The presence of additional risk factors indicated in the text is likely to increase the risk of thromboembolism for individual patients

Patient groups	Number of studies	Patients n	DVT incidence (weighted mean)	95% CI
Stroke
Czechanoswki & Heinrich 198113		41	23
Dahan et al., 198614		27	3
McCarthy et al., 197715		16	12
McCarthy & Turner 198616		161	117
Prins et al., 198917		30	15
Sandset et al., 199018		50	17
Turpie et al., 198719		25	7
Warlow et al., 197220		30	18
Total	8	380	212 (56%)	51% to 61%
Elective hip replacement
Belch et al., 198221		36	20
Bergqvist et al., 197922		71	45
Dechavanne et al., 197423		27	13
Dechavanne et al., 197524		20	8
Evarts et al., 197125		56	30
Gallus et al., 198326		47	25
Hampson et al., 197427		52	28
Harris et al., 197728		51	23
Hoek et al., 199229		99	56
Hull et al., 199030		158	77
Ishak & Morley, 198131		41	22
Kalodiki et al., 199632		14	13
Mannucci et al., 197633		51	22
Morris et al., 197434		32	16
Turpie et al., 198635		50	21
VTCSG, 197536		30	11
Welin-Berger et al., 198237		16	5
Total	17	851	435 (51%)	48% to 54%
Multiple trauma
Freeark et al., 196738		124	44
Geerts et al., 199439		349	201
Kudsk et al., 198940		28	24
Shackford et al., 199041		35	1
Total	4	536	270 (50%)	46% to 55%
Total Knee Replacement
Hull et al., 197942		29	19
Kim, 199043		244	80
Leclerc et al., 199644		57	31
Lynch et al., 198845		75	28
Stringer et al., 198946		55	31
Stulberg et al., 198447		49	41
Wilson et al., 199148		32	22
Total	7	541	252 (47%)	42% to 51%
Hip fracture
Ahlberg et al., 196849		45	16
Checketts & Bradley, 197450		26	13
Darke, 197251		66	11
Daniel et al., 197252		31	19
Galasko et al., 197653		50	23
Gallus et al., 197354		23	11
Kakkar et al., 197255		50	20
Lahnborg, 198056		69	28
Montrey et al., 198557		81	22
Morris & Mitchell, 197658		74	50
Morris & Mitchell, 197759		76	49
Myhre & Holen, 196960		55	22
Powers et al., 198961		63	29
Rogers et al., 197862		37	19
Svend-Hansen et al., 19863		65	28
Xabregas et al., 197864		25	12
Total	16	836	372 (45%)	41% to 48%
Retropubic prostatectomy
Becker et al., 197065		187	39
Coe et al., 197866		8	1
Hedlund & Blomback, 198167		28	13
Kutnowski et al., 197768		12	5
Mayo et al., 197169		41	21
Nicolaides et al., 197270		21	10
Vandendris et al., 198071		33	13
Williams, 197172		5	4
Total	8	335	106 (32%)	27% to 37%
Transurethral prostatectomy
Hedlund, 197573		101	10
Mayo et al., 197169		20	2
Nicolaides et al., 197270		29	2
Total	3	150	14 (9%)	5% to 15%
General Surgery
Clagett & Reisch, 198874
Total	54	4310	1084 (25%)	24% to 26%
Spinal cord injury
Bors et al., 195475		99	58
Brach et al., 197776		10	9
Rossi et al., 198077		18	13
Silver, 197478		32	8
Watson, 197479		234	42
Frisbie & Sasahara, 198180		17	1
Merli et al., 198881		17	8
Myllynen et al., 198582		9	9
Yelnik et al., 199183		22	12
Total	9	458	160 (35%)	31% to 39%
Neurosurgery
Skillman et al., 197884		43	11
Turpie et al., 197785		63	12
Turpie et al., 198586		68	12
Turpie et al., 198987		81	16
Zelikovski et al., 198188		20	10
Total	5	280	61 (22%)	17% to 27%
Gynaecological surgery
Malignancy
Clarke-Pearson et al., 198389		97	12
Clarke-Pearson et al., 198490		52	17
Clarke-Pearson et al., 199091		103	19
Walsh et al., 197492		45	16
Total	4	297	64 (22%)	17% to 26%
Gynaecological surgery
Benign disease
Ballard et al., 197393		55	16
Bonnar & Walsh, 197294		140	15
Taberner et al., 197895		48	11
Walsh et al., 197492		217	21
Total	4	460	63 (14%)	11% to 17%
Myocardial infarction
Emerson & Marks, 197796		41	14
Handley, 197297		24	7
Nicolaides et al., 197198		51	8
Warlow et al., 197399		64	11
Total	4	180	0 (22%)	16% to 28%
General Medical
Belch et al., 1981100		50	13
Cade, 1982101		60	16
Total	2	110	19 (17%)	10% to 24%
Geriatric (> 65 years) Dahan et al., 198614
Total	1	131	12 (9%)	5% to 15%

Table 2 - The frequency of proximal DVT in the absence of prophylaxis diagnosed by surveillance with objective methods (fibrinogen uptake test or phlebography)

Patient groups	Number of studies	Number of Patients	Incidence of DVT	95% CI
General surgery (Clagett & Reisch, 1988)74	16	1206	83(6.9%)	5.5 to 8.3%
Elective hip replacement (Imperiale & Speroff, 1994)102	25	1436	330*(23%)	20.8 to 25.2%
Total knee replacement Hull et al, 197942 Kim, 199043 Leclerc et al, 199644 Mckenna et al, 1976103 Stringer et al, 198946 Stulberg et al, 198447 Wilson et al, 199148	7	536	41(7.6%)	5.5 to 10.1%
* This number is an estimate from the percentage given in the paper.

Table 3 - Deaths caused by cardiovascular diseases in the sampled population

Patient groups	Number of studies	Number of Patients	Clinical PE	95% CI
General surgery
(Clagett & Reisch, 1988)74	32	5091	82(1.6%)	1.3 to 2.0%
Elective hip replacement
(Imperiale & Speroff, 1994)102	25	1436	57**(23%)	3.0 to 5.1%
Traumatic orthopaedic surgery (APTC,1994)104	11	494	34(6.9%)	4.8 to 9.5%
* In most of the studies using an objective method of screening for DVT, patients found to have proximal thrombosis were treated with anticoagulants; the true incidence of clinical pulmonary embolism in series without such screening and intervention is unknown. ** This number is an estimate from the percentage given in the paper.

Table 4 - The frequency of fatal pulmonary embolism without prophylaxis*

Patient groups	Number of studies	Patients n	Incidence of fatal PE	95% CI
General surgery (Clagett & Reisch, 1988)74	33	5547	48(0.87%)	0.62% to 1.1%
Elective hip replacement (Collins et al, 1988)105	12	485	8(1.65%)	0.38% to 2.7%
Fractured neck of femur (Lassen & Borris, 1994)106	23	1195	48(4.0%)	3.0% to 5.3%
* In most of the studies using an objective method of screening for DVT, patients found to have proximal thrombosis were treated with anticoagulants; the true incidence of fatal pulmonary embolism in the absence of intervention is unknown.

Table 5 - Mortality after elective hip replacement in the absence of routine pharmacological prophylaxis

Author	Number of Patients	Follow-up	Total deaths	95% CI	Fatal PE	95% CI	Anticoagulant use