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Deep venous thrombosis recommendations
Vol. XXIV No. 3
JOURNAL OF VASCULAR NURSING www.jvascnurs.net
PAGE 91
Research Column Deep venous thrombosis recommendations Wendy L. Marr, RN, BSN, CCNC
The American College of Chest Physicians (ACCP) first published the Antithrombotic and Thrombolytic Therapy Evidence-Based Guidelines in 1986. Since this time the number of antithrombotic agents has vastly increased, the rigor of evaluations of drugs has improved, and the ACCP grading system has been refined. This column will review these new guidelines, as they are most pertinent to nursing, using more recent studies and reviews to fill in the gap between the publication of the ACCP guidelines and what is happening today. See Table 1 for a summary of all the abbreviations used in this column. Table 2 provides a summary of the recommendations for the duration of vitamin K antagonist (VKA) therapy.
SUMMARY OF THE RECOMMENDATIONS AND THEIR GRADING
Initial treatment of deep venous thrombosis and pulmonary embolism For deep venous thrombosis (DVT) and pulmonary embolism (PE), short-term treatment with low-molecular-weight heparin (LMWH), intravenous unfractionated heparin (UFH), or subcutaneous UFH is recommended and should be continued for 5 days for acute DVT or PE until the VKA is therapeutic (international normalized ratio [INR] 2.0-3.0).1 It is recommended that initial outpatient treatment consist of subcutaneous LMWH with no monitoring of antifactor Xa.2-10 Inpatient treatment is acceptable if necessary. In the presence of renal failure, intravenous UFH should be used because LMWH is cleared renally and not by dialysis.
Thrombolytics The ACCP recommends against the routine use of systemic thrombolytics for initial treatment of DVT and PE, but there are circumstances in which use of these agents and mechanical and surgical intervention should be considered. Address reprint requests to J Vasc Nurs 2006;24:91-93.
Inferior vena cava filters Inferior vena cava filters should not be used routinely in addition to anticoagulants. However, an inferior vena cava filter is recommended for use in patients with a contraindication for anticoagulant treatment or with recurrent venous thromboembolism (VTE) despite adequate anticoagulation. It is of note that the benefit of filters can be outweighed by the risk of recurrent VTE associated with them. It is recommended that anticoagulation therapy be restarted as soon as possible after inferior vena cava placement to prevent VTE reoccurrence. At the time of publication, the new temporary filters were still in trial, and therefore recommendations for their use could not be made by the ACCP. However, there is promise with the inclusion of these in the armamentarium of VTE treatment and prophylaxis for the future.
Ambulation It is recommended that ambulation should be as tolerated without restriction once anticoagulation therapy is initiated. According to Aldrich and Hunt’s2 recent review of the current evidence, it is reasonable for the patient to ambulate early in the presence of VTE providing adequate anticoagulation and adequate cardiopulmonary reserves are present. In addition, the use of compression stockings is acceptable.
Long-term treatment of lower extremity deep venous thrombosis (data can be extrapolated for pulmonary embolism) The ACCP recommends the continued monitoring of VKA levels using the prothrombin time and its reporting as the INR. They also recommend against low-intensity therapy (INR 1.51.9) and high-intensity therapy (INR 3.0-4.0), and to use standard or conventional therapy (INR 2.0-3.0). It has been shown that use of low-intensity therapy does not increase the efficacy of anticoagulation or decrease the overall risk of bleeding. In addition, the use of standard therapy does increase the efficacy without increasing the risk of bleeding. Furthermore, the use of high-intensity therapy does not provide improved antithrombotic protection and is associated with an increased risk of clinically significant bleeding.
1062-0303/2006/$32.00 Copyright © 2006 by the Society for Vascular Nursing, Inc.
Postthrombotic syndrome
doi:10.1016/j.jvn.2006.06.013
It is recommended to use elastic compression stockings with 30 to 40 mm pressure during the first year after the first DVT.
PAGE 92
JOURNAL OF VASCULAR NURSING www.jvascnurs.net
SEPTEMBER 2006
TABLE 1 GRADING SYSTEM ACCP 7TH CONFERENCE ON ANTITHROMBOTIC AND THROMBOLYTIC THERAPY Grade Grade Grade Grade Grade Grade
1; certainty that benefits do or do not outweigh risks, burden and costs. Strong recommendations. 2; less certainty of the magnitude of the benefits and risks, burden and costs and thus their relative impact. A; consistent results from RCTs. C⫹; observational studies with very strong effects or secure generalizations from RCTs. B; inconsistent results from RCTs. C; observational studies.
Postthrombotic syndrome is found in patients with previous DVT and is characterized by a cluster of symptoms including pain, heaviness, skin discoloration, swelling, and, in late stages, ulcerations. Postthrombotic syndrome has an incidence of 20% to 50% in patients with a documented previous DVT.
Treatment of upper-extremity deep venous thrombosis UFH or LMWH is the recommended initial treatment. Long-term therapy is recommended with VKA (INR range 2.0-3.0). There is a lack of clinical trial data supporting the treatment of upper-extremity DVT; however, at this time, the recommendations for treatment include the same interventions as for lower-extremity DVT.
DISCUSSION Although this is a brief overview of some of the recommendations by the ACCP with support from others,2,3,5,6,8,9 I hope it answers some of the pressing questions we have as vascular nurses. In addition, reoccurrence of VTE and the future of thrombolytic therapy are two areas worth more attention. The risk of recurrence is a significant factor in treating VTE and is highly relative to the nature of the original occurrence. When a major risk factor that is reversible is identified as the sole source and treated, the risk is relatively low. However, for those with an unprovoked VTE (idiopathic) or the presence of irreversible risk factors (unresolved cancer, prothrombotic states or precursors, previous episodes of VTE), the relative risk of recurrence will be high. The ACCP made their recommendations ascribing a rela-
TABLE 2 DURATION OF TREATMENT
Category First episode of DVT secondary to a transient (reversible) risk factor* First episode of DVT and concurrent cancer First episode idiopathic DVT**
Duration of treatment with VKA (INR 2-3) These are recommendations unless stated as suggestions (less certainty) 3 months 3-6 months (with LMWH) Indefinite (with VKA) or until cancer resolved 6-12 months Indefinite (suggests)
First episode DVT associated with a prothrombotic genotype or a marker of an increased risk of recurrent VTE⫹⫹
12 months Indefinite (suggests)
Recurrent DVT (two or more episodes of VTE)
Indefinite (suggests)
Strength of evidence 1A 1A 1C 1A 2A
1C⫹ 2C 2A
*Transient risk factors include surgery, immobility, trauma, hospitalization. **Occurring in the absence of a known identifiable risk factor. ⫹⫹This subgroup includes those with a deficiency of antithrombin III, protein C or S, presence of a prothrombotic gene mutation (prothrombin 20210 or Factor V Leiden), antiphospholipid antibodies, homocysteinemia or increased Factor III levels.
Vol. XXIV No. 3
JOURNAL OF VASCULAR NURSING www.jvascnurs.net
TABLE 3 LEGEND OF TERMS VTE DVT PE UFH LMWH VKA RCT tPA
Venous Thromboembolism Deep Venous Obstruction Pulmonary Embolism Unfractionated Heparin (given intravenously or subcutaneously) Low Molecular Weight Heparin (fractionated) Vitamin K antagonist (i.e. Coumadin) Random Controlled Trial (level 1 evidence) Tissue Plasminogen Activase (thrombolytic, commonly replacing Urokinase and Streptokinase in most centers)
tively high value to preventing reoccurrence in most cases and a relatively low value to cost and bleeding. The identification of those at ongoing risk of recurrence and the measuring of that risk are the all-important focus. In determining the risk of cessation of therapy and the need for ongoing therapy, it is recommended that periodic evaluations of the patient and the current evidence be performed to ensure safe and efficacious treatment. In looking ahead, although LMWH, UFH, and VKAs are the gold standards of VTE therapy today, they are associated with risks and can be cumbersome for patients. There are new agents on the horizon that offer hope of safer and easier use. New oral antithrombotic agents (ximelagatran and dabigatran) are direct thrombin inhibitors. Ximelagatran has been through two major clinical trials and has been shown to be equally safe and efficacious for use as more conventional treatment modalities. The main unanswered question with this agent is the unexplained increase in liver function tests, which have not been shown to be significant or nonsignificant. Other agents include indirect inhibitors such as synthetic pentasaccharides (fondaparinux and idraparinux) that are given subcutaneously. Fondaparinux has been shown in recent trials to be as efficacious and safe as UFH for the initial treatment of PE and as LMWH for the initial treatment of DVT. This new agent can now be used safely in the initial treatment of VTE. Fondaparinux is given daily, and idraparinux has an extended half-life and is given weekly. However, it is still early to say whether this longer-acting agent will replace VKAs in long-term therapy. The
PAGE 93
pentasaccharides do not produce an antibody response and therefore do not cause heparin-induced thrombocytopenia. However, there is no known antidote to these agents, and uncontrolled bleeding is managed by administering procoagulants and discontinuation of the agent. Neither the direct thrombin inhibitors nor the pentasaccharides require any laboratory test monitoring, adding significantly to their ease of use and no doubt increased effect through improved adherence by patients. Buller and colleagues’ recent article3 identifies this present phase in the evolution of antithrombotic therapies as having started with the introduction of LMWH (1990s) and see its conclusion with the final results and entrenchment of use of the present agents by 2010, thus moving the evolution of these therapies another step ahead (Table III).
REFERENCES 1. Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3);204s-33s. 2. Aldrich D, Hunt DP. When can the patient with deep vein thrombosis begin to ambulate? Phys Ther 2004;84(3);268-73. 3. Buller HR, Sohne M, Middledorp S. Treatment of venous thromboembolism. J Thromb Haemost 2005;3(8);1554-60. 4. Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3);401s-28s. 5. Crowther M, McCourt K. Venous thromboembolism: a guide to prevention and treatment. Nurse Pract 2005;30(8); 26-9, 32-4, 39-43. 6. Federman DG, Brescia GR, Moriarty JP, Haskell SG, Krishnamurthy R, Kirsner RS. Update in thrombosis: answers to perplexing questions. Cleve Clin J Med 2005;72(10);907-15. 7. Hirsh J, Raschke R. Heparin and low-molecular weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3);188s–203. 8. Kearon C. Long-term management of patients after venous thromboembolism. Circulation 2004;110(9 Suppl 1);I10-8. 9. Nutescu EA. Emerging options in the treatment of venous thromboembolism. Am J Health Syst Pharm 2004;61(23 Suppl 7);s12–s7. 10. Weitz JI, Hirsh J, Samama MM. New anticoagulant drugs: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3);265s-86s.
JOURNAL OF VASCULAR NURSING www.jvascnurs.net
PAGE 91
Research Column Deep venous thrombosis recommendations Wendy L. Marr, RN, BSN, CCNC
The American College of Chest Physicians (ACCP) first published the Antithrombotic and Thrombolytic Therapy Evidence-Based Guidelines in 1986. Since this time the number of antithrombotic agents has vastly increased, the rigor of evaluations of drugs has improved, and the ACCP grading system has been refined. This column will review these new guidelines, as they are most pertinent to nursing, using more recent studies and reviews to fill in the gap between the publication of the ACCP guidelines and what is happening today. See Table 1 for a summary of all the abbreviations used in this column. Table 2 provides a summary of the recommendations for the duration of vitamin K antagonist (VKA) therapy.
SUMMARY OF THE RECOMMENDATIONS AND THEIR GRADING
Initial treatment of deep venous thrombosis and pulmonary embolism For deep venous thrombosis (DVT) and pulmonary embolism (PE), short-term treatment with low-molecular-weight heparin (LMWH), intravenous unfractionated heparin (UFH), or subcutaneous UFH is recommended and should be continued for 5 days for acute DVT or PE until the VKA is therapeutic (international normalized ratio [INR] 2.0-3.0).1 It is recommended that initial outpatient treatment consist of subcutaneous LMWH with no monitoring of antifactor Xa.2-10 Inpatient treatment is acceptable if necessary. In the presence of renal failure, intravenous UFH should be used because LMWH is cleared renally and not by dialysis.
Thrombolytics The ACCP recommends against the routine use of systemic thrombolytics for initial treatment of DVT and PE, but there are circumstances in which use of these agents and mechanical and surgical intervention should be considered. Address reprint requests to J Vasc Nurs 2006;24:91-93.
Inferior vena cava filters Inferior vena cava filters should not be used routinely in addition to anticoagulants. However, an inferior vena cava filter is recommended for use in patients with a contraindication for anticoagulant treatment or with recurrent venous thromboembolism (VTE) despite adequate anticoagulation. It is of note that the benefit of filters can be outweighed by the risk of recurrent VTE associated with them. It is recommended that anticoagulation therapy be restarted as soon as possible after inferior vena cava placement to prevent VTE reoccurrence. At the time of publication, the new temporary filters were still in trial, and therefore recommendations for their use could not be made by the ACCP. However, there is promise with the inclusion of these in the armamentarium of VTE treatment and prophylaxis for the future.
Ambulation It is recommended that ambulation should be as tolerated without restriction once anticoagulation therapy is initiated. According to Aldrich and Hunt’s2 recent review of the current evidence, it is reasonable for the patient to ambulate early in the presence of VTE providing adequate anticoagulation and adequate cardiopulmonary reserves are present. In addition, the use of compression stockings is acceptable.
Long-term treatment of lower extremity deep venous thrombosis (data can be extrapolated for pulmonary embolism) The ACCP recommends the continued monitoring of VKA levels using the prothrombin time and its reporting as the INR. They also recommend against low-intensity therapy (INR 1.51.9) and high-intensity therapy (INR 3.0-4.0), and to use standard or conventional therapy (INR 2.0-3.0). It has been shown that use of low-intensity therapy does not increase the efficacy of anticoagulation or decrease the overall risk of bleeding. In addition, the use of standard therapy does increase the efficacy without increasing the risk of bleeding. Furthermore, the use of high-intensity therapy does not provide improved antithrombotic protection and is associated with an increased risk of clinically significant bleeding.
1062-0303/2006/$32.00 Copyright © 2006 by the Society for Vascular Nursing, Inc.
Postthrombotic syndrome
doi:10.1016/j.jvn.2006.06.013
It is recommended to use elastic compression stockings with 30 to 40 mm pressure during the first year after the first DVT.
PAGE 92
JOURNAL OF VASCULAR NURSING www.jvascnurs.net
SEPTEMBER 2006
TABLE 1 GRADING SYSTEM ACCP 7TH CONFERENCE ON ANTITHROMBOTIC AND THROMBOLYTIC THERAPY Grade Grade Grade Grade Grade Grade
1; certainty that benefits do or do not outweigh risks, burden and costs. Strong recommendations. 2; less certainty of the magnitude of the benefits and risks, burden and costs and thus their relative impact. A; consistent results from RCTs. C⫹; observational studies with very strong effects or secure generalizations from RCTs. B; inconsistent results from RCTs. C; observational studies.
Postthrombotic syndrome is found in patients with previous DVT and is characterized by a cluster of symptoms including pain, heaviness, skin discoloration, swelling, and, in late stages, ulcerations. Postthrombotic syndrome has an incidence of 20% to 50% in patients with a documented previous DVT.
Treatment of upper-extremity deep venous thrombosis UFH or LMWH is the recommended initial treatment. Long-term therapy is recommended with VKA (INR range 2.0-3.0). There is a lack of clinical trial data supporting the treatment of upper-extremity DVT; however, at this time, the recommendations for treatment include the same interventions as for lower-extremity DVT.
DISCUSSION Although this is a brief overview of some of the recommendations by the ACCP with support from others,2,3,5,6,8,9 I hope it answers some of the pressing questions we have as vascular nurses. In addition, reoccurrence of VTE and the future of thrombolytic therapy are two areas worth more attention. The risk of recurrence is a significant factor in treating VTE and is highly relative to the nature of the original occurrence. When a major risk factor that is reversible is identified as the sole source and treated, the risk is relatively low. However, for those with an unprovoked VTE (idiopathic) or the presence of irreversible risk factors (unresolved cancer, prothrombotic states or precursors, previous episodes of VTE), the relative risk of recurrence will be high. The ACCP made their recommendations ascribing a rela-
TABLE 2 DURATION OF TREATMENT
Category First episode of DVT secondary to a transient (reversible) risk factor* First episode of DVT and concurrent cancer First episode idiopathic DVT**
Duration of treatment with VKA (INR 2-3) These are recommendations unless stated as suggestions (less certainty) 3 months 3-6 months (with LMWH) Indefinite (with VKA) or until cancer resolved 6-12 months Indefinite (suggests)
First episode DVT associated with a prothrombotic genotype or a marker of an increased risk of recurrent VTE⫹⫹
12 months Indefinite (suggests)
Recurrent DVT (two or more episodes of VTE)
Indefinite (suggests)
Strength of evidence 1A 1A 1C 1A 2A
1C⫹ 2C 2A
*Transient risk factors include surgery, immobility, trauma, hospitalization. **Occurring in the absence of a known identifiable risk factor. ⫹⫹This subgroup includes those with a deficiency of antithrombin III, protein C or S, presence of a prothrombotic gene mutation (prothrombin 20210 or Factor V Leiden), antiphospholipid antibodies, homocysteinemia or increased Factor III levels.
Vol. XXIV No. 3
JOURNAL OF VASCULAR NURSING www.jvascnurs.net
TABLE 3 LEGEND OF TERMS VTE DVT PE UFH LMWH VKA RCT tPA
Venous Thromboembolism Deep Venous Obstruction Pulmonary Embolism Unfractionated Heparin (given intravenously or subcutaneously) Low Molecular Weight Heparin (fractionated) Vitamin K antagonist (i.e. Coumadin) Random Controlled Trial (level 1 evidence) Tissue Plasminogen Activase (thrombolytic, commonly replacing Urokinase and Streptokinase in most centers)
tively high value to preventing reoccurrence in most cases and a relatively low value to cost and bleeding. The identification of those at ongoing risk of recurrence and the measuring of that risk are the all-important focus. In determining the risk of cessation of therapy and the need for ongoing therapy, it is recommended that periodic evaluations of the patient and the current evidence be performed to ensure safe and efficacious treatment. In looking ahead, although LMWH, UFH, and VKAs are the gold standards of VTE therapy today, they are associated with risks and can be cumbersome for patients. There are new agents on the horizon that offer hope of safer and easier use. New oral antithrombotic agents (ximelagatran and dabigatran) are direct thrombin inhibitors. Ximelagatran has been through two major clinical trials and has been shown to be equally safe and efficacious for use as more conventional treatment modalities. The main unanswered question with this agent is the unexplained increase in liver function tests, which have not been shown to be significant or nonsignificant. Other agents include indirect inhibitors such as synthetic pentasaccharides (fondaparinux and idraparinux) that are given subcutaneously. Fondaparinux has been shown in recent trials to be as efficacious and safe as UFH for the initial treatment of PE and as LMWH for the initial treatment of DVT. This new agent can now be used safely in the initial treatment of VTE. Fondaparinux is given daily, and idraparinux has an extended half-life and is given weekly. However, it is still early to say whether this longer-acting agent will replace VKAs in long-term therapy. The
PAGE 93
pentasaccharides do not produce an antibody response and therefore do not cause heparin-induced thrombocytopenia. However, there is no known antidote to these agents, and uncontrolled bleeding is managed by administering procoagulants and discontinuation of the agent. Neither the direct thrombin inhibitors nor the pentasaccharides require any laboratory test monitoring, adding significantly to their ease of use and no doubt increased effect through improved adherence by patients. Buller and colleagues’ recent article3 identifies this present phase in the evolution of antithrombotic therapies as having started with the introduction of LMWH (1990s) and see its conclusion with the final results and entrenchment of use of the present agents by 2010, thus moving the evolution of these therapies another step ahead (Table III).
REFERENCES 1. Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3);204s-33s. 2. Aldrich D, Hunt DP. When can the patient with deep vein thrombosis begin to ambulate? Phys Ther 2004;84(3);268-73. 3. Buller HR, Sohne M, Middledorp S. Treatment of venous thromboembolism. J Thromb Haemost 2005;3(8);1554-60. 4. Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3);401s-28s. 5. Crowther M, McCourt K. Venous thromboembolism: a guide to prevention and treatment. Nurse Pract 2005;30(8); 26-9, 32-4, 39-43. 6. Federman DG, Brescia GR, Moriarty JP, Haskell SG, Krishnamurthy R, Kirsner RS. Update in thrombosis: answers to perplexing questions. Cleve Clin J Med 2005;72(10);907-15. 7. Hirsh J, Raschke R. Heparin and low-molecular weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3);188s–203. 8. Kearon C. Long-term management of patients after venous thromboembolism. Circulation 2004;110(9 Suppl 1);I10-8. 9. Nutescu EA. Emerging options in the treatment of venous thromboembolism. Am J Health Syst Pharm 2004;61(23 Suppl 7);s12–s7. 10. Weitz JI, Hirsh J, Samama MM. New anticoagulant drugs: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3);265s-86s.