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Should patients with acute DVT limit activity?
EVIDENCE-BASED ANSWER

PROBABLY NOT. Ambulation, combined with compression of the affected extremity, appears to be safe for medically stable patients with deep venous thromboses (DVT) (strength of recommendation [SOR]: A, consistent randomized controlled trials [RCTs]). Leg compression and ambulation, compared with bed rest without compression, can effectively decrease swelling and pain (SOR: A, consistent RCTs).

Only weak data exist to suggest that early ambulation can reduce mortality (SOR: C, cohort studies with historical controls).

Evidence summary

Patients with acute DVT have traditionally been treated with immobilization and bed rest, combined with anticoagulation, for days. This approach is motivated by fear of dislodging an unstable thrombus and causing a pulmonary embolism (PE) and by the belief that inactivity relieves local pain and swelling. On the other hand, bed rest promotes stasis, an element in Virchow’s triad.

Early ambulation doesn’t raise risk of PE
We performed a structured literature review, which found 6 RCTs and 3 cohort studies that address this problem. All 6 RCTs included patients with acute DVT but without life-threatening conditions.1-6 They assessed various outcomes, including incidence of new PE, change in leg circumference, leg pain, patient well-being, and progression of DVT.

The studies consistently found that early ambulation, along with compression, is safe when compared with bed rest ( TABLE ). Although the sample size of all the RCTs was small, the RCTs showed consistent trends in favor of ambulation and compression.

A prospective cohort study of new PE in patients treated with ambulation and compression plus anticoagulation found that the incidence of PE was significantly lower than historical incidence rates in patients managed with bed rest.7

Another study using the RIETE registry, a Spanish registry of consecutively enrolled patients with objectively confirmed acute DVT or PE, found no significant difference in occurrence of new PE between immobilized and mobilized patients.8 Patients with DVT who were immobilized were generally sicker, more likely to have PaO2 <60, and more likely to have received lower doses of low-molecular-weight heparin (LMWH) compared with the group that walked (P<.005).

TABLE
Early ambulation and compression: What RCTs show

SubjectsStudy groupsResults
129 patients with DVT, treated with LMWH1 Strict immobilization for 4 days Ambulation for ≥4 h/d, along with compression for 4 days or until swelling subsidedAt 4 days: No difference in PE, leg pain, leg size, mortality At 3 months: No difference in PE, mortality
146 patients with DVT, all anticoagulated5 Hospital treatment with 5 days of bed rest Home care with early walking and compression stockingsNo difference in occurrence of new PE after 10 days
126 patients with DVT, treated with LMWH, compression6 Strict bed rest for 8 days with leg elevation Began full ambulation on day 2No difference in PE
102 patients with DVT, treated with LMWH, compression4 Bed rest for 5 days AmbulationNo differences in PE, thrombus progression, serious adverse events, or leg pain Study didn’t recruit expected number of patients Study showed a trend toward benefit from ambulation
53 patients with DVT2,7 Ambulation and use of firm, inelastic Unna boot bandages Ambulation and elastic compression stockings Strict bed rest for 9 days and no compressionNo difference in quality of life or PE
DVT-related symptoms, leg pain, and circumference improved in compression/ambulation groups No changes noted at 2 years
72 patients with DVT, treated with anticoagulation and compression3 Daily walking exercise and weekly group exercise Control groupNo difference in DVT, PE, phlebography results, or calf circumference
DVT, deep vein thrombosis; LMWH, low-molecular-weight heparin; PE, pulmonary embolism.
 

 

Does ambulation affect thrombus propagation?
A multicenter RCT showed that thrombus progression occurred more often in patients who were treated with bed rest compared with patients treated with ambulation and compression (P<.01).2

Another RCT revealed a similar trend, though the difference didn’t reach statistical significance because of small sample size.4 The clinical importance of these phlebographic studies isn’t clear.

Is it the walking, or compression, that works?
RCTs have shown that ambulation with leg compression, compared with bed rest without compression, can effectively decrease leg swelling and pain1,2,4 The difference was detectable 2 years after DVT.7

In contrast, RCTs in which both ambulating and resting patients received compression therapy showed no significant difference in leg circumference at 1 or 6 months.3 This finding suggests that the benefit on local symptoms may result from compression rather than ambulation.

Reduced mortality? Evidence is weak
Estimates of the possible effect on mortality of ambulation compared with bed rest are based on cohort studies. A cohort study in which 691 patients were kept walking with compression therapy reported a mortality rate of 0.2%.9 In another cohort, the mortality rate was also 0.2%, and all deaths occurred in patients older than 70 years.10

This rate is lower than rates reported in the historic literature, which typically are 1% among patients treated with unfractionated heparin and bed rest.9,10 A retrospective, multicenter cohort of 1647 patients treated with unfractionated heparin and bed rest in different German hospitals reported a rate of fatal PE of 2.33%.11

Data from the RIETE registry indicated that overall mortality was significantly higher in immobilized patients with a PE (3.6% vs 0.5% in mobile patients; P=.01).8 Notably, immobilized patients with a PE were more likely to be hypoxic and also tended to receive lower doses of LMWH. No differences were found in outcomes for patients with DVT.

Recommendations

The American College of Chest Physicians (ACCP) doesn’t recommend bed rest in its guidelines for treating acute venous thromboembolism, but rather ambulation as tolerated after starting anticoagulation. Patients who are not hemodynamically stable should be stabilized first.

The ACCP also recommends wearing an elastic compression stocking with a pressure of 30 to 40 mm Hg at the ankle for 2 years after an episode of DVT and a course of intermittent pneumatic compression for patients with severe edema of the leg resulting from post-thrombotic syndrome.12

A joint guideline from the American College of Physicians and the American Academy of Family Physicians doesn’t make recommendations about ambulation for therapy of DVT and PE.13

References

1. Aschwanden M, Labs KH, Engel H, et al. Acute deep vein thrombosis: early mobilization does not increase the frequency of pulmonary embolism. Thromb Haemost. 2001;85:42-46.

2. Blattler W, Partsch H. Leg compression and ambulation is better than bed rest for the treatment of acute deep venous thrombosis. Int Angiol. 2003;22:393-400.

3. Isma N, Johanssson E, Bjork A, et al. Does supervised exercise after deep venous thrombosis improve recanalization of occluded vein segments? A randomized study. J Thromb Thrombolysis. 2007;23:25-30.

4. Junger M, Diehm C, Storiko H, et al. Mobilization versus immobilization in the treatment of acute proximal deep venous thrombosis: a prospective, randomized, open, multicentre trial. Curr Med Res Opin. 2006;22:593-602.

5. Romera A, Vila R, Perez-Piqueras A, et al. Early mobilization in patients with acute deep vein thrombosis: does it increase the incidence of symptomatic pulmonary embolism? Phlebology. 2005;20:141.-

6. 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 1):127-129.

7. Partsch H, Kaulich M, Mayer W. Immediate mobilisation in acute vein thrombosis reduces post-thrombotic syndrome. Int Angiol. 2004;23:206-212.

8. Trujillo-Santos J, Perea-Milla E, Jimenez-Puente A, et al. Bed rest or ambulation in the initial treatment of patients with acute deep vein thrombosis or pulmonary embolism: findings from the RIETE registry. Chest. 2005;127:1631-1636.

9. 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;16:189-192.

10. Partsch H. Therapy of deep vein thrombosis with low molecular weight heparin, leg compression and immediate ambulation. Vasa. 2001;30:195-204.

11. Martin M. PHLECO: a multicenter study of the fate of 1647 hospital patients treated conservatively without fibrinolysis and surgery. Clin Invest. 1993;71:471-477.

12. Buller HR, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126 (suppl 3):401S-428S.

13. Snow V, Qaseem A, Barry P, et al. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007;146:204-210.

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Rola Saab, MD
James J. Stevermer, MD, MSPH
Susan Meadows, MLS
Department of Family and Community Medicine, University of Missouri, Columbia

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Rola Saab, MD
James J. Stevermer, MD, MSPH
Susan Meadows, MLS
Department of Family and Community Medicine, University of Missouri, Columbia

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James J. Stevermer, MD, MSPH
Susan Meadows, MLS
Department of Family and Community Medicine, University of Missouri, Columbia

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EVIDENCE-BASED ANSWER

PROBABLY NOT. Ambulation, combined with compression of the affected extremity, appears to be safe for medically stable patients with deep venous thromboses (DVT) (strength of recommendation [SOR]: A, consistent randomized controlled trials [RCTs]). Leg compression and ambulation, compared with bed rest without compression, can effectively decrease swelling and pain (SOR: A, consistent RCTs).

Only weak data exist to suggest that early ambulation can reduce mortality (SOR: C, cohort studies with historical controls).

Evidence summary

Patients with acute DVT have traditionally been treated with immobilization and bed rest, combined with anticoagulation, for days. This approach is motivated by fear of dislodging an unstable thrombus and causing a pulmonary embolism (PE) and by the belief that inactivity relieves local pain and swelling. On the other hand, bed rest promotes stasis, an element in Virchow’s triad.

Early ambulation doesn’t raise risk of PE
We performed a structured literature review, which found 6 RCTs and 3 cohort studies that address this problem. All 6 RCTs included patients with acute DVT but without life-threatening conditions.1-6 They assessed various outcomes, including incidence of new PE, change in leg circumference, leg pain, patient well-being, and progression of DVT.

The studies consistently found that early ambulation, along with compression, is safe when compared with bed rest ( TABLE ). Although the sample size of all the RCTs was small, the RCTs showed consistent trends in favor of ambulation and compression.

A prospective cohort study of new PE in patients treated with ambulation and compression plus anticoagulation found that the incidence of PE was significantly lower than historical incidence rates in patients managed with bed rest.7

Another study using the RIETE registry, a Spanish registry of consecutively enrolled patients with objectively confirmed acute DVT or PE, found no significant difference in occurrence of new PE between immobilized and mobilized patients.8 Patients with DVT who were immobilized were generally sicker, more likely to have PaO2 <60, and more likely to have received lower doses of low-molecular-weight heparin (LMWH) compared with the group that walked (P<.005).

TABLE
Early ambulation and compression: What RCTs show

SubjectsStudy groupsResults
129 patients with DVT, treated with LMWH1 Strict immobilization for 4 days Ambulation for ≥4 h/d, along with compression for 4 days or until swelling subsidedAt 4 days: No difference in PE, leg pain, leg size, mortality At 3 months: No difference in PE, mortality
146 patients with DVT, all anticoagulated5 Hospital treatment with 5 days of bed rest Home care with early walking and compression stockingsNo difference in occurrence of new PE after 10 days
126 patients with DVT, treated with LMWH, compression6 Strict bed rest for 8 days with leg elevation Began full ambulation on day 2No difference in PE
102 patients with DVT, treated with LMWH, compression4 Bed rest for 5 days AmbulationNo differences in PE, thrombus progression, serious adverse events, or leg pain Study didn’t recruit expected number of patients Study showed a trend toward benefit from ambulation
53 patients with DVT2,7 Ambulation and use of firm, inelastic Unna boot bandages Ambulation and elastic compression stockings Strict bed rest for 9 days and no compressionNo difference in quality of life or PE
DVT-related symptoms, leg pain, and circumference improved in compression/ambulation groups No changes noted at 2 years
72 patients with DVT, treated with anticoagulation and compression3 Daily walking exercise and weekly group exercise Control groupNo difference in DVT, PE, phlebography results, or calf circumference
DVT, deep vein thrombosis; LMWH, low-molecular-weight heparin; PE, pulmonary embolism.
 

 

Does ambulation affect thrombus propagation?
A multicenter RCT showed that thrombus progression occurred more often in patients who were treated with bed rest compared with patients treated with ambulation and compression (P<.01).2

Another RCT revealed a similar trend, though the difference didn’t reach statistical significance because of small sample size.4 The clinical importance of these phlebographic studies isn’t clear.

Is it the walking, or compression, that works?
RCTs have shown that ambulation with leg compression, compared with bed rest without compression, can effectively decrease leg swelling and pain1,2,4 The difference was detectable 2 years after DVT.7

In contrast, RCTs in which both ambulating and resting patients received compression therapy showed no significant difference in leg circumference at 1 or 6 months.3 This finding suggests that the benefit on local symptoms may result from compression rather than ambulation.

Reduced mortality? Evidence is weak
Estimates of the possible effect on mortality of ambulation compared with bed rest are based on cohort studies. A cohort study in which 691 patients were kept walking with compression therapy reported a mortality rate of 0.2%.9 In another cohort, the mortality rate was also 0.2%, and all deaths occurred in patients older than 70 years.10

This rate is lower than rates reported in the historic literature, which typically are 1% among patients treated with unfractionated heparin and bed rest.9,10 A retrospective, multicenter cohort of 1647 patients treated with unfractionated heparin and bed rest in different German hospitals reported a rate of fatal PE of 2.33%.11

Data from the RIETE registry indicated that overall mortality was significantly higher in immobilized patients with a PE (3.6% vs 0.5% in mobile patients; P=.01).8 Notably, immobilized patients with a PE were more likely to be hypoxic and also tended to receive lower doses of LMWH. No differences were found in outcomes for patients with DVT.

Recommendations

The American College of Chest Physicians (ACCP) doesn’t recommend bed rest in its guidelines for treating acute venous thromboembolism, but rather ambulation as tolerated after starting anticoagulation. Patients who are not hemodynamically stable should be stabilized first.

The ACCP also recommends wearing an elastic compression stocking with a pressure of 30 to 40 mm Hg at the ankle for 2 years after an episode of DVT and a course of intermittent pneumatic compression for patients with severe edema of the leg resulting from post-thrombotic syndrome.12

A joint guideline from the American College of Physicians and the American Academy of Family Physicians doesn’t make recommendations about ambulation for therapy of DVT and PE.13

EVIDENCE-BASED ANSWER

PROBABLY NOT. Ambulation, combined with compression of the affected extremity, appears to be safe for medically stable patients with deep venous thromboses (DVT) (strength of recommendation [SOR]: A, consistent randomized controlled trials [RCTs]). Leg compression and ambulation, compared with bed rest without compression, can effectively decrease swelling and pain (SOR: A, consistent RCTs).

Only weak data exist to suggest that early ambulation can reduce mortality (SOR: C, cohort studies with historical controls).

Evidence summary

Patients with acute DVT have traditionally been treated with immobilization and bed rest, combined with anticoagulation, for days. This approach is motivated by fear of dislodging an unstable thrombus and causing a pulmonary embolism (PE) and by the belief that inactivity relieves local pain and swelling. On the other hand, bed rest promotes stasis, an element in Virchow’s triad.

Early ambulation doesn’t raise risk of PE
We performed a structured literature review, which found 6 RCTs and 3 cohort studies that address this problem. All 6 RCTs included patients with acute DVT but without life-threatening conditions.1-6 They assessed various outcomes, including incidence of new PE, change in leg circumference, leg pain, patient well-being, and progression of DVT.

The studies consistently found that early ambulation, along with compression, is safe when compared with bed rest ( TABLE ). Although the sample size of all the RCTs was small, the RCTs showed consistent trends in favor of ambulation and compression.

A prospective cohort study of new PE in patients treated with ambulation and compression plus anticoagulation found that the incidence of PE was significantly lower than historical incidence rates in patients managed with bed rest.7

Another study using the RIETE registry, a Spanish registry of consecutively enrolled patients with objectively confirmed acute DVT or PE, found no significant difference in occurrence of new PE between immobilized and mobilized patients.8 Patients with DVT who were immobilized were generally sicker, more likely to have PaO2 <60, and more likely to have received lower doses of low-molecular-weight heparin (LMWH) compared with the group that walked (P<.005).

TABLE
Early ambulation and compression: What RCTs show

SubjectsStudy groupsResults
129 patients with DVT, treated with LMWH1 Strict immobilization for 4 days Ambulation for ≥4 h/d, along with compression for 4 days or until swelling subsidedAt 4 days: No difference in PE, leg pain, leg size, mortality At 3 months: No difference in PE, mortality
146 patients with DVT, all anticoagulated5 Hospital treatment with 5 days of bed rest Home care with early walking and compression stockingsNo difference in occurrence of new PE after 10 days
126 patients with DVT, treated with LMWH, compression6 Strict bed rest for 8 days with leg elevation Began full ambulation on day 2No difference in PE
102 patients with DVT, treated with LMWH, compression4 Bed rest for 5 days AmbulationNo differences in PE, thrombus progression, serious adverse events, or leg pain Study didn’t recruit expected number of patients Study showed a trend toward benefit from ambulation
53 patients with DVT2,7 Ambulation and use of firm, inelastic Unna boot bandages Ambulation and elastic compression stockings Strict bed rest for 9 days and no compressionNo difference in quality of life or PE
DVT-related symptoms, leg pain, and circumference improved in compression/ambulation groups No changes noted at 2 years
72 patients with DVT, treated with anticoagulation and compression3 Daily walking exercise and weekly group exercise Control groupNo difference in DVT, PE, phlebography results, or calf circumference
DVT, deep vein thrombosis; LMWH, low-molecular-weight heparin; PE, pulmonary embolism.
 

 

Does ambulation affect thrombus propagation?
A multicenter RCT showed that thrombus progression occurred more often in patients who were treated with bed rest compared with patients treated with ambulation and compression (P<.01).2

Another RCT revealed a similar trend, though the difference didn’t reach statistical significance because of small sample size.4 The clinical importance of these phlebographic studies isn’t clear.

Is it the walking, or compression, that works?
RCTs have shown that ambulation with leg compression, compared with bed rest without compression, can effectively decrease leg swelling and pain1,2,4 The difference was detectable 2 years after DVT.7

In contrast, RCTs in which both ambulating and resting patients received compression therapy showed no significant difference in leg circumference at 1 or 6 months.3 This finding suggests that the benefit on local symptoms may result from compression rather than ambulation.

Reduced mortality? Evidence is weak
Estimates of the possible effect on mortality of ambulation compared with bed rest are based on cohort studies. A cohort study in which 691 patients were kept walking with compression therapy reported a mortality rate of 0.2%.9 In another cohort, the mortality rate was also 0.2%, and all deaths occurred in patients older than 70 years.10

This rate is lower than rates reported in the historic literature, which typically are 1% among patients treated with unfractionated heparin and bed rest.9,10 A retrospective, multicenter cohort of 1647 patients treated with unfractionated heparin and bed rest in different German hospitals reported a rate of fatal PE of 2.33%.11

Data from the RIETE registry indicated that overall mortality was significantly higher in immobilized patients with a PE (3.6% vs 0.5% in mobile patients; P=.01).8 Notably, immobilized patients with a PE were more likely to be hypoxic and also tended to receive lower doses of LMWH. No differences were found in outcomes for patients with DVT.

Recommendations

The American College of Chest Physicians (ACCP) doesn’t recommend bed rest in its guidelines for treating acute venous thromboembolism, but rather ambulation as tolerated after starting anticoagulation. Patients who are not hemodynamically stable should be stabilized first.

The ACCP also recommends wearing an elastic compression stocking with a pressure of 30 to 40 mm Hg at the ankle for 2 years after an episode of DVT and a course of intermittent pneumatic compression for patients with severe edema of the leg resulting from post-thrombotic syndrome.12

A joint guideline from the American College of Physicians and the American Academy of Family Physicians doesn’t make recommendations about ambulation for therapy of DVT and PE.13

References

1. Aschwanden M, Labs KH, Engel H, et al. Acute deep vein thrombosis: early mobilization does not increase the frequency of pulmonary embolism. Thromb Haemost. 2001;85:42-46.

2. Blattler W, Partsch H. Leg compression and ambulation is better than bed rest for the treatment of acute deep venous thrombosis. Int Angiol. 2003;22:393-400.

3. Isma N, Johanssson E, Bjork A, et al. Does supervised exercise after deep venous thrombosis improve recanalization of occluded vein segments? A randomized study. J Thromb Thrombolysis. 2007;23:25-30.

4. Junger M, Diehm C, Storiko H, et al. Mobilization versus immobilization in the treatment of acute proximal deep venous thrombosis: a prospective, randomized, open, multicentre trial. Curr Med Res Opin. 2006;22:593-602.

5. Romera A, Vila R, Perez-Piqueras A, et al. Early mobilization in patients with acute deep vein thrombosis: does it increase the incidence of symptomatic pulmonary embolism? Phlebology. 2005;20:141.-

6. 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 1):127-129.

7. Partsch H, Kaulich M, Mayer W. Immediate mobilisation in acute vein thrombosis reduces post-thrombotic syndrome. Int Angiol. 2004;23:206-212.

8. Trujillo-Santos J, Perea-Milla E, Jimenez-Puente A, et al. Bed rest or ambulation in the initial treatment of patients with acute deep vein thrombosis or pulmonary embolism: findings from the RIETE registry. Chest. 2005;127:1631-1636.

9. 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;16:189-192.

10. Partsch H. Therapy of deep vein thrombosis with low molecular weight heparin, leg compression and immediate ambulation. Vasa. 2001;30:195-204.

11. Martin M. PHLECO: a multicenter study of the fate of 1647 hospital patients treated conservatively without fibrinolysis and surgery. Clin Invest. 1993;71:471-477.

12. Buller HR, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126 (suppl 3):401S-428S.

13. Snow V, Qaseem A, Barry P, et al. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007;146:204-210.

References

1. Aschwanden M, Labs KH, Engel H, et al. Acute deep vein thrombosis: early mobilization does not increase the frequency of pulmonary embolism. Thromb Haemost. 2001;85:42-46.

2. Blattler W, Partsch H. Leg compression and ambulation is better than bed rest for the treatment of acute deep venous thrombosis. Int Angiol. 2003;22:393-400.

3. Isma N, Johanssson E, Bjork A, et al. Does supervised exercise after deep venous thrombosis improve recanalization of occluded vein segments? A randomized study. J Thromb Thrombolysis. 2007;23:25-30.

4. Junger M, Diehm C, Storiko H, et al. Mobilization versus immobilization in the treatment of acute proximal deep venous thrombosis: a prospective, randomized, open, multicentre trial. Curr Med Res Opin. 2006;22:593-602.

5. Romera A, Vila R, Perez-Piqueras A, et al. Early mobilization in patients with acute deep vein thrombosis: does it increase the incidence of symptomatic pulmonary embolism? Phlebology. 2005;20:141.-

6. 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 1):127-129.

7. Partsch H, Kaulich M, Mayer W. Immediate mobilisation in acute vein thrombosis reduces post-thrombotic syndrome. Int Angiol. 2004;23:206-212.

8. Trujillo-Santos J, Perea-Milla E, Jimenez-Puente A, et al. Bed rest or ambulation in the initial treatment of patients with acute deep vein thrombosis or pulmonary embolism: findings from the RIETE registry. Chest. 2005;127:1631-1636.

9. 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;16:189-192.

10. Partsch H. Therapy of deep vein thrombosis with low molecular weight heparin, leg compression and immediate ambulation. Vasa. 2001;30:195-204.

11. Martin M. PHLECO: a multicenter study of the fate of 1647 hospital patients treated conservatively without fibrinolysis and surgery. Clin Invest. 1993;71:471-477.

12. Buller HR, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126 (suppl 3):401S-428S.

13. Snow V, Qaseem A, Barry P, et al. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007;146:204-210.

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