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Am Fam Physician. 2002;66(3):475-477

Questions Addressed

  • What are the effects of treatments for proximal deep venous thrombosis?

  • What are the effects of treatments for isolated calf vein thrombosis?

  • What are the effects of treatments for pulmonary embolism?

  • What are the effects of computerized decision support on oral anticoagulation management?

Trade-off of benefits and harms
Oral anticoagulants in people with deep venous thrombosis
Unfractionated and low-molecular-weight heparin in people with deep venous thrombosis
Warfarin plus heparin in people with isolated calf vein thrombosis
Unfractionated and low-molecular-weight heparin in people with pulmonary embolism
Oral anticoagulants in people with pulmonary embolism
Unknown effectiveness
Computerized decision support in oral anticoagulation
To be covered in future updates of Clinical Evidence
Thrombolysis for pulmonary embolism
Compression stockings for deep venous thrombosis
Oral antithrombotic agents (such as glycoprotein IIb/IIIa antagonists)
Inferior vena cava filters
Aspirin
Thromboembolism in pregnancy
DefinitionVenous thromboembolism is any thromboembolic event occurring within the venous system, including deep venous thrombosis and pulmonary embolism. Deep venous thrombosis is a radiologically confirmed partial or total thrombotic occlusion of the deep venous system of the legs sufficient to produce symptoms of pain or swelling. Proximal deep venous thrombosis affects the veins above the knee (popliteal, superficial femoral, common femoral, and iliac veins). Isolated calf vein thrombosis is confined to the deep veins of the calf and does not affect the veins above the knee. Pulmonary embolism is radiologically confirmed partial or total thromboembolic occlusion of pulmonary arteries, sufficient to cause symptoms of breathlessness, chest pain, or both. Post-thrombotic syndrome is edema, ulceration, and impaired viability of the subcutaneous tissues of the leg occurring after deep venous thrombosis. Recurrence refers to symptomatic deterioration caused by a further (radiologically confirmed) thrombosis, after a previously confirmed thromboembolic event, where there had been an initial, partial, or total symptomatic improvement. Extension refers to a radiologically confirmed new, constant, symptomatic intraluminal filling defect extending from an existing thrombosis.
Incidence/PrevalenceWe found no reliable study of the incidence/prevalence of deep venous thrombosis or pulmonary embolism in the United Kingdom. A prospective Scandinavian study found an annual incidence of 1.6 to 1.8 per 1,000 people in the general population.1,2 One postmortem study estimated that 600,000 people develop pulmonary embolism each year in the United States, of whom 60,000 die as a result.3
Etiology/Risk FactorsRisk factors for deep venous thrombosis include immobility, surgery (particularly orthopedic), malignancy, smoking, pregnancy, older age, and inherited or acquired prothrombotic clotting disorders.4 Evidence for these factors is mainly observational. The oral contraceptive pill is associated with death caused by venous thromboembolism (absolute risk increase with any combined oral contraception: 1 to 3 per million women per year).5 The principal cause of pulmonary embolism is a deep venous thrombosis.4
PrognosisThe annual recurrence rate of symptomatic calf vein thrombosis in people without recent surgery is more than 25 percent.6,7 Proximal extension develops in 40 to 50 percent of people with symptomatic calf vein thrombosis.8 Proximal deep venous thrombosis may cause fatal or nonfatal pulmonary embolism, recurrent venous thrombosis, and the post-thrombotic syndrome. One observational study published in 1946 found 20 percent mortality from pulmonary emboli in people in the hospital with untreated deep venous thrombosis.9 One non-systematic review of observational studies found that, in people after recent surgery who have an asymptomatic calf vein deep venous thrombosis, the rate of fatal pulmonary embolism was 13 to 15 percent.10 The incidence of other complications without treatment is not known. The risk of recurrent venous thrombosis and complications is increased by thrombotic risk factors.11
Clinical AimsTo reduce acute symptoms of deep venous thrombosis and to prevent morbidity and mortality associated with thrombus extension, the post-thrombotic syndrome, and pulmonary embolization; to reduce recurrence; and to minimize any adverse effects of treatment.
Clinical OutcomesRates of symptomatic recurrence, post-thrombotic syndrome, symptomatic pulmonary embolism, and death. Proxy outcomes include radiologic evidence of clot extension or pulmonary embolism.
Evidence-Based Medicine Findings
SEARCH DATE: CLINICAL EVIDENCE UPDATE SEARCH AND APPRAISAL JULY 2001

Proximal Deep Venous Thrombosis

Warfarin versus placebo: We found no randomized controlled trials (RCTs). Combined warfarin plus intravenous unfractionated heparin versus warfarin alone for initial treatment: One RCT found reduced recurrence of proximal deep venous thrombosis. Longer versus shorter duration of anticoagulation: Systematic reviews have found significantly fewer deep venous thrombosis recurrences with longer anticoagulation. One nonsystematic review found limited evidence of significantly increased major hemorrhage, but another nonsystematic review found no significant increase. Low-molecular-weight heparin versus unfractionated heparin: Systematic reviews have found no significant difference in recurrence of thromboembolism but significantly decreased major hemorrhage. Long-term low-molecular-weight heparin versus oral anticoagulation: Systematic reviews and subsequent RCTs have found no significant difference in recurrent thromboembolism, major hemorrhage, or mortality. Heparin treatment at home versus in the hospital: One systematic review has found limited evidence of no significant difference in recurrence of thromboembolism.

Calf Vein Deep Venous Thrombosis

One RCT found that, in isolated calf vein thrombosis, warfarin plus intravenous unfractionated heparin versus heparin alone (International Normalized Ratio [INR] of 2.5 to 4.2) reduced rates of proximal extension. One unblinded RCT found no significant difference between shorter versus longer courses of anticoagulation in recurrent thromboembolism.

Pulmonary Embolism

We found no direct evidence in people with pulmonary embolism about the optimum intensity and duration of anticoagulation. Evidence for intensity and duration of treatment has been extrapolated from studies in people with proximal deep venous thrombosis and any venous thromboembolism. One small RCT found that heparin plus warfarin versus no anticoagulation significantly reduced mortality in people with pulmonary embolism. Two RCTs found no significant difference between low-molecular-weight heparin versus unfractionated heparin in mortality or new episodes of thromboembolism in people with pulmonary embolism.

Computerized Decision Support

We found no RCTs of computerized decision support versus usual management of oral anticoagulation that used clinically important outcomes (major hemorrhage or death). One systematic review and two subsequent RCTs have found that computerized decision support in oral anticoagulation improves time spent in the target INR range. Another subsequent RCT found no significant difference between computerized decision support and standard manual support in the time spent in the target INR range. A subsequent RCT of initiation of warfarin found no significant difference between computerized decision support versus usual care in the time taken to reach therapeutic levels of anticoagulation. Most RCTs were small and brief.

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