CARDIOVASCULAR DISEASES

Health Evidence Bulletins - Wales (logo)
Team Leader: Dr David Fone

Date of completion: 30.9.98

10: Deep vein thrombosis

This bulletin is a supplement to, not a substitute for, professional skills and experience. Users are advised to consult the supporting evidence for a consideration of all the implications of a recommendation.

The Statements The Evidence
10.1 Preventive therapy
10.1a. Prophylactic antiplatelet therapy for one to three weeks in high risk surgical and medical patients is associated with a 39% odds reduction of venous thrombosis (SD 5%), p<0.000; benefit 90/1000 patients treated and a 64% odds reduction of pulmonary embolism (SD 10%), p<0.000; benefit 17/1000 patients treated. There is limited evidence that the effects of antiplatelet therapy on pulmonary embolism are additive to heparin. Antiplatelet therapy is associated with a small increase in non-fatal haemorrhagic complications (0.7% vs. 0.4%, one-sided p=0.04)i.
(Health gain notation - 1 "beneficial")
i. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy-III: Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. British Medical Journal 1994;308:235-46.
http://www.bmj.com/cgi/content/full/308/6923/235
In: Database of Reviews of Effectiveness. The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 5181 patients in 53 DVT trials and 9446 patients in 62 PE trials)
10.1b. There is evidence that low molecular weight heparins are at least as effective as standard heparin in prevention of deep vein thrombosis (DVT) and pulmonary embolus (PE) in perioperative patientsi-iii.
(Health gain notation - 1 "beneficial")
i. Nurmohamed MT, Rosendaal FR, Buller HR, et al. Low molecular weight heparin versus standard heparin in general and orthopaedic surgery: a meta analysis. Lancet 1992;340:152-56
(Type I evidence - systematic review and meta-analysis of 6878 patients in 17 general surgery trials and 1294 patients in 6 orthopaedic surgery trials )
ii. Leyvraz PF, Bachmann F, Hoek J, et al. Prevention of deep vein thrombosis after hip replacement: randomised comparison between unfractionated heparin and low molecular weight heparin. British Medical Journal 1991;303:543-48
(Type II evidence - randomised controlled trial of 349 patients)
iii. Leizorovicz A, Haugh MC, Chapius FR, et al. Low molecular weight heparin in the prevention of perioperative thrombosis. British Medical Journal 1992;305:913-20
(Type I evidence - systematic review and meta-analysis of 2045 patients in 16 randomised controlled trials)
10.1c. There is evidence that graduated compression stockings prevent post-operative DVT after moderate risk (non-orthopaedic) surgery (odds ratio 0.28; 95% CI: 0.23, 0.42; p<0.0001)i.
(Health gain notation - 1 "beneficial")
i. Wells PS, Lensing AW, Hirsh J. Graduated compression stockings in the prevention of postoperative venous thromboembolism: a meta-analysis. Archives of Internal Medicine 1994;154: 67-72
(Type I evidence - systematic review and meta-analysis of 1842 patients in 12 randomised controlled trials)

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10.1d. All hospital patients who are at moderate or high risk of venous thromboembolism should receive specific prophylaxisi,ii. Evidence-based guidelines for the prophylaxis of venous thromboembolism are currently being updatedi and due for publication in 1999.
(Health gain notation - 1 "beneficial")
i. Scottish Intercollegiate Guidelines Network (SIGN). Prophylaxis of Venous Thromboembolism. Edinburgh, Royal College of Physicians, 1995
(Type V evidence - expert opinion)
ii. Thromboembolic Risk Factors (THRIFT) Consensus Group. Risk of and prophylaxis for venous thromboembolism in hospital patients. British Medical Journal 1992;305:567-74
(Type V evidence - expert opinion)
10.1e. Thrombocytopenia occurs in about 3% to 4% of patients given prophylactic heparin. The Committee on Safety of Medicines recommends that the platelet count is monitored in patients receiving heparin for more than five days, and that heparin is stopped immediately if thrombocytopenia occursi.
(Health gain notation - 3 "trade-off between beneficial and adverse effects")
i. Scottish Intercollegiate Guidelines Network (SIGN). Prophylaxis of Venous Thromboembolism. Edinburgh: Royal College of Physicians, 1995
(Type V evidence - expert opinion)
10.2 Diagnostic imaging
10.2a. Non-invasive venous ultrasonography is now the investigation of first choice in patients with suspected DVTi. Compression venous ultrasonography of the common femoral vein and the popliteal vein to the level of the trifurcation of the calf veins repeated at one week is an effective diagnostic investigation; after six months follow-up, the cumulative incidence of DVT or PE was 0.7% in patients with two normal scansii. Venography should be reserved for patients with a high clinical probability of disease and a negative non-invasive test resulti. Evidence-based recommendations for the non-invasive diagnosis of DVT have been publishediii.
(Health gain notation - 1 "beneficial")
Caveat: Compression venous ultrasonography findingsii may not be generalisable to patients with previous DVT or pregnancy excluded from the study.
i. Wheeler HB, Hirsh J, Welss P, Anderson FA. Diagnostic tests for deep vein thrombosis. Archives of Internal Medicine 1994; 54: 921-28
(Type IV evidence - narrative review of test characteristics of non-randomised studies and case series in patients with suspected thromboembolism)
ii. Cogo A, Lensing AWA, Koopman MMW, et al. Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study. British Medical Journal 1998;316:17-20
(Type IV evidence - case series of 1702 patients with clinically suspected DVT of common femoral vein in the groin and popliteal vein to the trifurcation of the calf veins, followed-up for six months after compression ultrasonography)
iii. Kearon C, Julian JA, Newman TE, Ginsberg JS, for the McMaster Diagnostic Imaging Practice Guidelines Initiative. Non-invasive diagnosis of deep venous thrombosis. Annals of Internal Medicine 1998;128:663-77
(Type I evidence - systematic review)
10.2b. The clinical utility of D-dimer testing, for the diagnostic evaluation of DVT has not been proveni.
(Health gain notation - 4 "unknown")
Caveat: Methodological problems in the primary studies, including wide variability in assay performance, heterogeneity among subjects and lack of criterion standard for diagnosis, results in a wide range of sensitivities and specificities for the test. Further research is required before D-dimer testing is used as a diagnostic test for venous thromboembolism - the development of a highly specific test for the exclusion of DVT will have important clinical benefits.
i. Becker D, Philbrick J, Bachhuber T, Humphries J. D-dimer testing and acute venous thromboembolism. Archives of Internal Medicine 1996;156:939-46
(Type II evidence - systematic review of 29 studies and 4205 patients)

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10.3 Drug therapy
10.3a. Thrombophilia should be considered in patients aged less than 40 years presenting with venous thromboembolism, recurrent venous thrombosis, venous thrombosis in an unusual site or with a family historyi.
(Health gain notation - 1 "beneficial")
i. Anon. Management of patients with thrombophilia. Drug & Therapeutics Bulletin 1995;33(1):6-8
(Type V evidence - expert opinion)
10.3b. Low molecular weight heparin (LMW) preparations are as effective and safer than adjusted doses of standard heparin for the treatment of venous thromboembolism. Odds ratio of recurrent venous thromboembolism for LMW heparin compared to adjusted dose standard heparin 0.75; 95% CI: 0.55, 1.01; for major haemorrhage during treatment 0.55; 95% CI: 0.34, 0.89; and mortality at long-term follow-up 0.74; 95% CI: 0.57, 0.98i.
(Health gain notation - 1 "beneficial")
Caveat: Since the majority of patients had DVT, further trials of the efficacy and safety of LMW heparins in pulmonary embolism are required, together with trials comparing different brands of LMW heparini.

 

i. van den Belt AGM, Prins MH, Lensing AW, et al. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Review [Updated 14 January 1998]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 4354 patients (75% DVT and 25% PE) in 13 trials)

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10.3c. A Cochrane Review to compare the effectiveness and safety of different duration of initial treatment with standard and LMW heparin is due for publication in 1999i.
(Health gain notation - 4 "unknown")
i. Castro AA, Clark OAC, Atallah AN, Burihan E. Duration of initial heparin treatment for deep-vein thrombosis. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review)
10.3d. Six months of secondary prophylaxis of deep vein thrombosis (DVT) or pulmonary embolus (PE) with oral anticoagulants following initial heparin therapy results in a lower recurrence rate over two years than treatment for six weeks, odds ratio 2.1; 95% CI: 1.4, 3.1i.
(Health gain notation - 1 "beneficial")
i. Schulman S, Rhedin A, Lindmarker P et al, for the Duration of Anticoagulation Trial Study Group. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. New England Journal of Medicine 1995;332:1661-65
(Type II evidence - randomised controlled trial of 897 patients, 790 with DVT and 107 with PE with two year follow-up)
10.3e. Prophylactic oral anticoagulation for four years following a second episode of venous thromboembolism is associated with a lower rate of recurrence than treatment for six months: relative risk of recurrence in six month group 8.0; 95% CI: 2.5, 25.9, NNT 6 (4, 10), with no significant differences in the risk of major haemorrhage or mortality between the two groupsi.
(Health gain notation - 1 "beneficial")
i. Schulman S, Granqvist S, Holmstrom M et al, for the Duration of Anticoagulation Trial Study Group. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. New England Journal of Medicine 1997;336:393-98
(Type II evidence - randomised controlled trial of 227 patients, over 95% with DVT, with four year follow-up)
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Health Evidence Bulletins: Wales, Duthie Library, UWCM, Cardiff CF14 4XN. e-mail: weightmanal@cardiff.ac.uk