Treatment of the Patient with Deep Vein Thrombosis

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Applied Evidence

Treatment of the Patient with Deep Vein Thrombosis

J Fam Pract. 2001 February;50(2):249-256

References

1. Anderson FA, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case fatality rates of deep vein thrombosis and pulmonary embolism: the Worcester DVT study. Arch Intern Med 1991;151:933-38.

2. Silverstein MD, Heit JA, Mohr DN, et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998;158:585-93.

3. Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary embolism: a statement for healthcare professionals: Council on Thrombosis (in consultation with the Council on Cardiovascular Radiology), American Heart Association. Circulation 1996;93:2212-45.

4. Hull RD, Raskob GE, Hirsh J, et al. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal vein thrombosis. N Engl J Med 1986;315:1109-14.

5. Hull RD, Raskob GE, Brant RF, et al. Relation between the time to achieve the lower limit of the APTT therapeutic range and recurrent venous thromboembolism during heparin treatment for deep vein thrombosis. Arch Intern Med 1997;157:2562-68.

6. Raschke RA, Reilly BM, Guidry JR, et al. The weight-based heparin dosing nomogram compared with a “standard care” nomogram. Ann Intern Med 1993;119:874-81.

7. Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997;337:688-98.

8. Gould MK, Dembitzer AD, Doyle RL, et al. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis: a meta-analysis of randomized, controlled trials. Ann Intern Med 1999;130:800-09.

9. Dolovich LR, Ginsberg JS, Douketis JD, et al. A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism. Arch Intern Med 2000;160:181-88.

10. Koopman MMW, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med 1996;334:682-87.

11. Wells PS, Kovacs MJ, Bormanis J, et al. Expanding eligibility for outpatient treatment of deep venous thrombosis and pulmonary embolism with low-molecular-weight heparin: a comparison of patient self-injection with homecare injection. Arch Intern Med 1998;158:1809-11.

12. Harrison L, McGinnis J, Crowther M, et al. Assessment of outpatient treatment of deep-vein thrombosis with low-molecular-weight heparin. Arch Intern Med 1998;158:2001-03.

13. Gould MK, Dembitzer AD, Sanders GD, et al. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis: a cost-effectiveness analysis. Ann Intern Med 1999;130:789-99.

14. Hyers TM. Antithrombotic therapy for venous thromboembolic disease. Chest 1998;114 (suppl):561S-78S.

15. Institute for Clinical Systems Improvement. Health care guideline: deep vein thrombosis. Bloomington, Minn: Institute for Clinical Systems Improvement; 1999.

16. Decousus H, Leizorovicz A, Parent F, et al. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep vein thrombosis. N Engl J Med 1998;338:409-15.

17. Partsch H, Kechavarz B, Kohn H, et al. The effect of mobilisation of patients during treatment of thromboembolic disorders with low-molecular-weight heparin. Int Angiol 1997;16:189-92.

18. Schellong SM, Schwarz T, Kropp J, et al. Bed rest in deep vein thrombosis and the incidence of scintigraphic pulmonary embolism. Thromb Haemost 1999;82 (suppl):127-29.

19. Crowther MA, Ginsberg JB, Kearon C, et al. A randomized trial comparing 5-mg and 10-mg loading doses. Arch Intern Med 1999;159:46-48.

20. Schulman S, Rhedin AS, Lindmarker P, et al. A comparison of six weeks with 6 months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med 1995;332:1661-65.

21. Kearon C, Gent M, Hirsh J, et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999;340:901-07.

22. Hutten BA, Prins MH. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism (Cochrane review). In: The Cochrane library Issue 4. Oxford, England: Update Software; 2000.

23. Brandjes DPM, Buller HR, Heijboer H, et al. Randomized trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet 1997;349:759-62.

24. Cornuz J, Pearson SD, Creager MA, et al. Importance of findings on the initial evaluation for cancer in patients with symptomatic idiopathic deep vein thrombosis. Ann Intern Med 1996;125:785-93.

25. Prandoni P, Lensing AWA, Buller HR, et al. Deep-vein thrombosis and the incidence of subsequent symptomatic cancer. N Engl J Med 1992;327:1128-33.

Several studies have demonstrated the efficacy and safety of administering LMWH at home. One study of 400 patients with DVT compared home therapy with LMWH with inpatient UH and failed to demonstrate any significant difference in risk of recurrent thromboembolism or major bleeding (LOE=1b).¹⁰ Additionally, no difference in these clinical outcomes was found in another prospective study comparing patient self-injection with injection by home care nurse (LOE=2b).¹¹ Patients are both capable and willing to participate in this treatment regimen; 91% were pleased with home therapy, and 70% felt comfortable with self-injection of LMWH (LOE=2c).¹²

A cost-effectiveness analysis published in 1999 studied the economic viability of universal treatment of acute DVT with LMWH. The cost of initial care was higher in hospitalized patients receiving LMWH, but this was partly offset by the reduced costs for early complications. Treatment with LMWH increased the quality-adjusted life expectancy by approximately 0.02 years. The incremental cost-effectiveness of inpatient LMWH treatment was $7820 per additional quality-adjusted life-year. Sensitivity analysis demonstrated that LMWH was cost saving when at least 8% of the patients were treated at home or if late complications were assumed to occur 25% less frequently in patients receiving LMWH. It was concluded that LMWH is highly cost-effective and is the preferred treatment for DVT (LOE=1b).¹³

Because using LMWH to treat outpatients with DVT has the potential to reduce health care costs, several organizations have published recommendations or guidelines suggesting an outpatient alternative for uncomplicated DVT.^3,14,15 It is generally agreed that patients with an uncomplicated DVT, good cardiopulmonary reserve, no excessive bleeding risk, and normal renal function can safely be treated with LMWH at home. Those with the comorbidities or the possible contraindications to anticoagulation noted in Table 2 should typically be hospitalized for initial management. Also, the home therapy patient will require education on the correct dosage and administration of LMWH, recognition of adverse events, and available resources to address problems or questions during the treatment course. Although there is limited evidence to support these specific recommendations, current expert opinion favors a conservative approach in the selection of patients for home treatment of DVT (LOE=5).

Whether patients are treated in the hospital or at home, LMWH should be considered the primary standard treatment for DVT. The relative safety, tolerability, efficacy, and cost-effectiveness of LMWH make it the obvious and preferred therapeutic alternative.

Vena Caval Filter Placement

Placement of an inferior vena caval filter is reserved for patients with a contraindication to anticoagulation, a serious complication of anticoagulation, or recurrent thromboembolism despite adequate anticoagulation. To date there have been no randomized or cohort studies directly comparing inferior vena caval interruption with standard anticoagulation therapy. However, a recent clinical trial of vena caval filter placement in 400 anticoagulated patients revealed a significant decrease in pulmonary embolism assessed at day 12 of therapy (ARR=3.7%; NNT=27) but a significant increase in the rate of recurrent symptomatic DVT over the next 2 years (absolute risk increase [ARI]=9.2%; number needed to harm [NNH]=11; LOE=1b).¹⁶ The available evidence does not support the use of vena caval filters in the management of the patient with an initial and uncomplicated DVT.

Activity

Patients with acute DVT have traditionally been confined to bed rest for a period of 3 to 7 days, yet there is no evidence that this practice improves clinical outcomes. A study of 638 patients with DVT who were allowed to ambulate with compression stockings demonstrated a low incidence of pulmonary emboli documented by ventilation-perfusion scan when compared with that in the literature (LOE=4).¹⁷ A more recent randomized trial of 126 patients with acute proximal vein thrombosis compared 8 days of strict bed rest with early mobilization; there was no statistically significant difference in the incidence of scintigraphically detectable pulmonary embolism (LOE=1b).¹⁸ These studies do not currently support the previous recommendation of bed rest for the acute treatment of DVT.

Extended Therapy

After the initial evaluation, stabilization, and treatment of a patient with DVT, a plan is needed to minimize the risk of recurrent thromboembolism and chronic postphlebitic complications. Although unsupported by specific evidence, most recommendations include the discontinuation and avoidance of any exogenous estrogen therapy. Oral anticoagulation with warfarin decreases the incidence of recurrent thromboembolic events, while the extended use of compression stockings decreases the development of the postphlebitic syndrome.

Oral Anticoagulation with Warfarin

For a patient presenting with a first DVT, oral anticoagulation with warfarin should be initiated on the first day of treatment, after heparin loading is complete. Adequacy of therapy is monitored by measurement of the INR, a standardization of the plasma thromboplastin ratio now used to correct for the variance between laboratories resulting from the use of different thromboplastin reagents. The antithrombotic effect of warfarin is best established after 3 to 5 days; it is for this reason that heparin is overlapped with warfarin during the first several days of therapy. The algorithm in Table 3 has been shown to improve the success of achieving a stable and therapeutic INR by day 5 of therapy with less initial risk of hemorrhagic complication (LOE=1b).¹⁹ The heparin may be discontinued when the INR is within the therapeutic range of 2.0 to 3.0 for patients with DVT (LOE=5).¹⁴