Skip to main content
Top
Published in: American Journal of Cardiovascular Drugs 1/2001

01-01-2001 | Therapy in Practice

Current Management of Acute Symptomatic Deep Vein Thrombosis

Author: Dr John A. Heit

Published in: American Journal of Cardiovascular Drugs | Issue 1/2001

Login to get access

Abstract

Venous thromboembolism is a common and potentially fatal disease. If properly used, anticoagulation therapy is effective in preventing recurrence of venous thromboembolism and in improving survival. Symptomatic patients with an objective diagnosis of acute deep vein thrombosis (DVT) or pulmonary embolism (PE) should receive immediate systemic heparin anticoagulation at dosages sufficient to rapidly prolong the activated partial thromboplastin time into the laboratory-specific therapeutic range; this range corresponds to a plasma heparin concentration of 0.2 to 0.4 IU/ml (as measured by protamine sulfate titration), or 0.3 to 0.7 anti-Xa IU/ml. An oral vitamin K antagonist (e.g. warfarin) should be started within 24 hours after starting heparin; the starting dose should be the estimated patient-specific daily dose with no loading dose. Heparin and warfarin anticoagulation should be overlapped for at least 4 to 5 days and until the international normalized ratio (INR) is within the therapeutic range (2.0 to 3.0) on 2 measurements made at least 24 hours apart.
The duration of warfarin anticoagulation should be individualized based on the respective risks of venous thromboembolism recurrence and anticoagulant-related bleeding. In general, warfarin should be continued for at least 3 months, and longer for patients with recurrent or idiopathic venous thromboembolism, malignant neoplasm, neurologic disease with extremity paresis, obesity, or laboratory evidence of a lupus anticoagulant/anticardiolipin antibody, homozygous carrier or combined heterozygous carrier for the factor V R506Q (Leiden) and prothrombin G20210A mutations, and possibly deficiency of either antithrombin, protein C, or protein S.
Low molecular weight heparin (LMWH) is effective and well tolerated as acute therapy for patients with DVT or stable PE, and does not require laboratory monitoring or dose adjustment. Outpatient LMWH therapy is also well tolerated and cost effective for most patients with DVT, and possibly for selected patients with PE.
Literature
1.
go back to reference 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: 585–93PubMedCrossRef 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: 585–93PubMedCrossRef
2.
go back to reference Heit JA, Silverstein MD, Mohr DN, et al. Predictors of survival after deep vein thrombosis and pulmonary embolism. Arch Intern Med 1999; 159: 445–53PubMedCrossRef Heit JA, Silverstein MD, Mohr DN, et al. Predictors of survival after deep vein thrombosis and pulmonary embolism. Arch Intern Med 1999; 159: 445–53PubMedCrossRef
3.
go back to reference Heit JA, Mohr DN, Silverstein MD, et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 2000; 160: 761–8PubMedCrossRef Heit JA, Mohr DN, Silverstein MD, et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med 2000; 160: 761–8PubMedCrossRef
4.
go back to reference Hyers TM, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease. Chest 1998 Nov; 114 (5 Suppl.): 561S–78SPubMedCrossRef Hyers TM, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease. Chest 1998 Nov; 114 (5 Suppl.): 561S–78SPubMedCrossRef
5.
go back to reference Brandjes CPM, Heijboer H, Buller HR, et al. Acenocoumarol and heparin compared to acenocoumarol alone in the initial treatment of proximal-vein thrombosis. N Engl J Med 1992; 327: 1485–9PubMedCrossRef Brandjes CPM, Heijboer H, Buller HR, et al. Acenocoumarol and heparin compared to acenocoumarol alone in the initial treatment of proximal-vein thrombosis. N Engl J Med 1992; 327: 1485–9PubMedCrossRef
6.
go back to reference Hellemans J, Vorlat M, Verstraete M. Survival time of prothrombin and factors VII, IX, and X after completely synthesis blocking doses of coumarin derivatives. Br J Haematol 1963; 9: 506–12PubMedCrossRef Hellemans J, Vorlat M, Verstraete M. Survival time of prothrombin and factors VII, IX, and X after completely synthesis blocking doses of coumarin derivatives. Br J Haematol 1963; 9: 506–12PubMedCrossRef
7.
go back to reference Zivelin A, Rao LVM, Rapaport SI. Mechanism of the anticoagulant effect of warfarin as evaluated in rabbits by selective depression of individual procoagulant vitamin K-dependent clotting factors. J Clin Invest 1993; 92: 2131–40PubMedCrossRef Zivelin A, Rao LVM, Rapaport SI. Mechanism of the anticoagulant effect of warfarin as evaluated in rabbits by selective depression of individual procoagulant vitamin K-dependent clotting factors. J Clin Invest 1993; 92: 2131–40PubMedCrossRef
8.
go back to reference Heit JA, Stewart ML, Owen WG. The role of plasma prothrombin activity in the acute thrombotic response to severe arterial injury. Thromb Haemost 1995; 73: 1341 Heit JA, Stewart ML, Owen WG. The role of plasma prothrombin activity in the acute thrombotic response to severe arterial injury. Thromb Haemost 1995; 73: 1341
9.
go back to reference Hull RD, Raskob GE, Brant RF, et al. Relationship between 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: 2562–8PubMedCrossRef Hull RD, Raskob GE, Brant RF, et al. Relationship between 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: 2562–8PubMedCrossRef
10.
go back to reference Hull RD, Rascob 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: 1109–14PubMedCrossRef Hull RD, Rascob 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: 1109–14PubMedCrossRef
11.
go back to reference Cruickshank MK, Levine MN, Hirsh J, et al. A standard heparin nomogram for the management of heparin therapy. Arch Intern Med 1991; 151: 333–7PubMedCrossRef Cruickshank MK, Levine MN, Hirsh J, et al. A standard heparin nomogram for the management of heparin therapy. Arch Intern Med 1991; 151: 333–7PubMedCrossRef
12.
go back to reference Raschke RA, Reilly BM, Guidry JR, et al. The weight-based dosing nomogram compared with a standard care nomogram. Ann Intern Med 1993; 119: 874–81PubMed Raschke RA, Reilly BM, Guidry JR, et al. The weight-based dosing nomogram compared with a standard care nomogram. Ann Intern Med 1993; 119: 874–81PubMed
13.
go back to reference Anand S, Ginsberg J, Kearon C, et al. The relationship between the activated partial thromboplastin time response and recurrence in patients with venous thrombosis treated with continuous intravenous heparin. Arch Intern Med 1996; 156: 1677–81PubMedCrossRef Anand S, Ginsberg J, Kearon C, et al. The relationship between the activated partial thromboplastin time response and recurrence in patients with venous thrombosis treated with continuous intravenous heparin. Arch Intern Med 1996; 156: 1677–81PubMedCrossRef
14.
go back to reference Brill-Edwards P, Ginsberg JS, Johnston M, et al. Establishing a therapeutic range of heparin therapy. Ann Intern Med 1993; 119: 104–9PubMed Brill-Edwards P, Ginsberg JS, Johnston M, et al. Establishing a therapeutic range of heparin therapy. Ann Intern Med 1993; 119: 104–9PubMed
15.
go back to reference Hirsh J, Warkentin TE, Raschke R, et al. Heparin and low-molecular-weight heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998; 114 (5 Suppl.): 489S–510SPubMedCrossRef Hirsh J, Warkentin TE, Raschke R, et al. Heparin and low-molecular-weight heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998; 114 (5 Suppl.): 489S–510SPubMedCrossRef
16.
go back to reference Young E, Prins M, Levine M, et al. Heparin binding to plasma proteins, and important mechanism for heparin resistance. Thromb Haemost 1992; 67: 639–43PubMed Young E, Prins M, Levine M, et al. Heparin binding to plasma proteins, and important mechanism for heparin resistance. Thromb Haemost 1992; 67: 639–43PubMed
17.
go back to reference Kraaigenhagen RA, in’t Anker PS, Koopman MMW, et al. High plasma concentration of Factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost 2000; 83: 5–9 Kraaigenhagen RA, in’t Anker PS, Koopman MMW, et al. High plasma concentration of Factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost 2000; 83: 5–9
18.
go back to reference Kyrle PA, Minar E, Hirschl M, et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000; 343:457–62PubMedCrossRef Kyrle PA, Minar E, Hirschl M, et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000; 343:457–62PubMedCrossRef
19.
go back to reference Levine MN, Hirsh J, Gent M, et al. Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis. Thromb Haemost 1995; 74: 606–11PubMed Levine MN, Hirsh J, Gent M, et al. Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis. Thromb Haemost 1995; 74: 606–11PubMed
20.
go back to reference Levine MN, Hirsh J, Gent M, et al. A randomized trial comparing activated thromboplastin time with heparin assay in patients with acute venous thromboembolism requiring large daily doses of heparin. Arch Intern Med 1994; 154: 49–56PubMedCrossRef Levine MN, Hirsh J, Gent M, et al. A randomized trial comparing activated thromboplastin time with heparin assay in patients with acute venous thromboembolism requiring large daily doses of heparin. Arch Intern Med 1994; 154: 49–56PubMedCrossRef
21.
go back to reference Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992; 79: 1–17PubMed Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992; 79: 1–17PubMed
23.
go back to reference Young E, Wells PS, Holloway S, et al. Ex-vivo and in-vivo evidence that low molecular weight heparins exhibit less binding to plasma proteins than unfractionated heparin. Thromb Haemost 1994; 71: 300–4PubMed Young E, Wells PS, Holloway S, et al. Ex-vivo and in-vivo evidence that low molecular weight heparins exhibit less binding to plasma proteins than unfractionated heparin. Thromb Haemost 1994; 71: 300–4PubMed
24.
go back to reference Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecular weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med 1992; 326: 975–83PubMedCrossRef Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecular weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med 1992; 326: 975–83PubMedCrossRef
25.
go back to reference Prandoni P, Lensing AW, Buller HR, et al. Comparison of subcutaneous low-molecular weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992; 339: 441–5PubMedCrossRef Prandoni P, Lensing AW, Buller HR, et al. Comparison of subcutaneous low-molecular weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992; 339: 441–5PubMedCrossRef
26.
go back to reference Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin. N Engl J Med 1995; 332: 1330–5PubMedCrossRef Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin. N Engl J Med 1995; 332: 1330–5PubMedCrossRef
27.
go back to reference Levine M, Gent M, Hirsh J, et al. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996; 334: 677–81PubMedCrossRef Levine M, Gent M, Hirsh J, et al. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996; 334: 677–81PubMedCrossRef
28.
go back to reference Koopman MMW, Prandoni P, Piovelli 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: 682–7PubMedCrossRef Koopman MMW, Prandoni P, Piovelli 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: 682–7PubMedCrossRef
29.
go back to reference Simonneau G, Sors H, Charbonnier B, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. N Engl J Med 1997; 337: 663–9PubMedCrossRef Simonneau G, Sors H, Charbonnier B, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. N Engl J Med 1997; 337: 663–9PubMedCrossRef
30.
go back to reference The Columbus Investigators. Low-molecular weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997; 337: 657–62CrossRef The Columbus Investigators. Low-molecular weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997; 337: 657–62CrossRef
31.
go back to reference 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: 1809–12PubMedCrossRef 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: 1809–12PubMedCrossRef
32.
go back to reference Brandjes DPM, Büller HR, Heijboer H, et al. Randomized trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet 1997; 349: 759–62PubMedCrossRef Brandjes DPM, Büller HR, Heijboer H, et al. Randomized trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet 1997; 349: 759–62PubMedCrossRef
33.
go back to reference Lindmarker P, Holmstrom H. Use of low molecular weight heparin (dalteparin), once daily, for the treatment of deep vein thrombosis: a feasibility and health economic study in an outpatient setting. J Intern Med 1996; 240: 395–401PubMedCrossRef Lindmarker P, Holmstrom H. Use of low molecular weight heparin (dalteparin), once daily, for the treatment of deep vein thrombosis: a feasibility and health economic study in an outpatient setting. J Intern Med 1996; 240: 395–401PubMedCrossRef
34.
go back to reference Fiessinger JN, Lopez-Fernandez M, Gatterer E, et al. Once daily subcutaneous dalteparin, a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis. Thromb Haemost 1996; 76: 195–9PubMed Fiessinger JN, Lopez-Fernandez M, Gatterer E, et al. Once daily subcutaneous dalteparin, a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis. Thromb Haemost 1996; 76: 195–9PubMed
35.
go back to reference van der Heijden JF, Prins MH, Büller, HR. For the initial treatment of venous thromboembolism: are all low-molecular-weight heparin compounds the same? Thromb Res 2000; 100: V121–30PubMedCrossRef van der Heijden JF, Prins MH, Büller, HR. For the initial treatment of venous thromboembolism: are all low-molecular-weight heparin compounds the same? Thromb Res 2000; 100: V121–30PubMedCrossRef
36.
go back to reference Gould MK, Dembitzer AD, Sanders G, 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: 789–99PubMed Gould MK, Dembitzer AD, Sanders G, 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: 789–99PubMed
37.
go back to reference Hull RD, Raskob GE, Rosenbloom D, et al. Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis. N Engl J Med 1990; 322: 1260–4PubMedCrossRef Hull RD, Raskob GE, Rosenbloom D, et al. Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis. N Engl J Med 1990; 322: 1260–4PubMedCrossRef
38.
go back to reference White RH, Zhou H, Romano PS. Length of hospital stay for treatment of deep venous thrombosis and the incidence of recurrent thromboembolism. Arch Intern Med 1998; 158: 1005–10PubMedCrossRef White RH, Zhou H, Romano PS. Length of hospital stay for treatment of deep venous thrombosis and the incidence of recurrent thromboembolism. Arch Intern Med 1998; 158: 1005–10PubMedCrossRef
39.
go back to reference Godal HC, Madsen K, Nissen-Meyer R. Thrombo-embolism in patients with total proconvertin (factor VII) deficiency: a report of two cases. Acta Med Scand 1962; 171: 325–7PubMedCrossRef Godal HC, Madsen K, Nissen-Meyer R. Thrombo-embolism in patients with total proconvertin (factor VII) deficiency: a report of two cases. Acta Med Scand 1962; 171: 325–7PubMedCrossRef
40.
go back to reference Greshwin ME, Gude JK. Deep vein thrombosis and pulmonary embolism in congenital factor VII deficiency. N Engl J Med 1973; 288: 141–2CrossRef Greshwin ME, Gude JK. Deep vein thrombosis and pulmonary embolism in congenital factor VII deficiency. N Engl J Med 1973; 288: 141–2CrossRef
41.
go back to reference Harrison L, Johnston M, Massicotte MP, et al. Comparison of 5-mg and 10-mg loading doses in initiation of warfarin therapy. Ann Intern Med 1997; 126: 133–6PubMed Harrison L, Johnston M, Massicotte MP, et al. Comparison of 5-mg and 10-mg loading doses in initiation of warfarin therapy. Ann Intern Med 1997; 126: 133–6PubMed
42.
go back to reference Schulman S, Rhedin A-S, Lindmarker P, et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med 1995; 332: 1661–5PubMedCrossRef Schulman S, Rhedin A-S, Lindmarker P, et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med 1995; 332: 1661–5PubMedCrossRef
43.
go back to reference Schulman S, Granqvist S, Holmstrom M, et al. The duration of oral anticoagulation therapy after a second episode of venous thromboembolism. N Engl J Med 1997; 336: 393–8PubMedCrossRef Schulman S, Granqvist S, Holmstrom M, et al. The duration of oral anticoagulation therapy after a second episode of venous thromboembolism. N Engl J Med 1997; 336: 393–8PubMedCrossRef
44.
go back to reference 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: 901–7PubMedCrossRef 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: 901–7PubMedCrossRef
45.
go back to reference Schulman S, Svenungsson E, Granqvist S, et al. Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Am J Med 1998; 104: 332–8PubMedCrossRef Schulman S, Svenungsson E, Granqvist S, et al. Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy. Am J Med 1998; 104: 332–8PubMedCrossRef
46.
go back to reference De Stefano V, Martinelli I, Mannucci PM, et al. The risk of recurrent deep venous thrombosis among heterozygous carriers of both factor V Leiden and the G20210A prothrombin mutation. N Engl J Med 1999; 341: 801–6PubMedCrossRef De Stefano V, Martinelli I, Mannucci PM, et al. The risk of recurrent deep venous thrombosis among heterozygous carriers of both factor V Leiden and the G20210A prothrombin mutation. N Engl J Med 1999; 341: 801–6PubMedCrossRef
47.
go back to reference De Stefano V, Finazzi G, Mannucci PM. Inherited thrombophilia: pathogenesis, clinical syndromes and management. Blood 1996; 87 (9): 3531–44PubMed De Stefano V, Finazzi G, Mannucci PM. Inherited thrombophilia: pathogenesis, clinical syndromes and management. Blood 1996; 87 (9): 3531–44PubMed
48.
go back to reference Lane DA, Mannucci PM, Bauer KA, et al. Inherited thrombophilia: part 1. Thromb Haemost 1996; 76 (5): 651–62PubMed Lane DA, Mannucci PM, Bauer KA, et al. Inherited thrombophilia: part 1. Thromb Haemost 1996; 76 (5): 651–62PubMed
49.
go back to reference Lane DA, Mannucci PM, Bauer KA, et al. Inherited thrombophilia: part 2. Thromb Haemost 1996; 76 (6): 824–34PubMed Lane DA, Mannucci PM, Bauer KA, et al. Inherited thrombophilia: part 2. Thromb Haemost 1996; 76 (6): 824–34PubMed
50.
go back to reference Lane DA, Grant PJ. Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease. Blood 2000; 95: 1517–32PubMed Lane DA, Grant PJ. Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease. Blood 2000; 95: 1517–32PubMed
Metadata
Title
Current Management of Acute Symptomatic Deep Vein Thrombosis
Author
Dr John A. Heit
Publication date
01-01-2001
Publisher
Springer International Publishing
Published in
American Journal of Cardiovascular Drugs / Issue 1/2001
Print ISSN: 1175-3277
Electronic ISSN: 1179-187X
DOI
https://doi.org/10.2165/00129784-200101010-00005

Other articles of this Issue 1/2001

American Journal of Cardiovascular Drugs 1/2001 Go to the issue

Drug Evaluation

Tenecteplase