Thromb Haemost 1999; 82(04): 1222-1226
DOI: 10.1055/s-0037-1614364
Review Article
Schattauer GmbH

Long-term Clinical Follow-up in 265 Patients with Deep Venous Thrombosis Initially Treated with either Unfractionated Heparin or Dalteparin: A Retrospective Analysis

M. Holmström
1   From the Karolinska Institute at the Dept of Haematology, Huddinge University Hospital, Sweden
,
W. Åberg
1   From the Karolinska Institute at the Dept of Haematology, Huddinge University Hospital, Sweden
,
D. Lockner
1   From the Karolinska Institute at the Dept of Haematology, Huddinge University Hospital, Sweden
,
C. Paul
1   From the Karolinska Institute at the Dept of Haematology, Huddinge University Hospital, Sweden
› Author Affiliations
Further Information

Publication History

Received 24 February 1999

Accepted after resubmission 07 April 1999

Publication Date:
08 December 2017 (online)

Summary

The primary objective of this retrospective study was to describe the frequency of a post-thrombotic syndrome in 265 patients previously treated for deep venous thrombosis (DVT). The secondary objectives were to document the frequency of recurrent venous thromboembolism (VTE) and mortality, especially from malignant disease. The patients were evaluated 5-14 years after inclusion in three randomized trials comparing continuous intravenous (i. v.) infusion of unfractionated heparin (UFH) (n = 85) with a low molecular weight heparin (LMWH), dalteparin (n = 180). The median post-thrombotic score at follow-up was 2 (range 0-8). In a multiple step-wise regression analysis the post-thrombotic score was significantly higher among patients with initial proximal DVT (p = 0,0001) as compared with those who had distal DVT. A recurrent venous thromboembolic event was diagnosed in 29,4% of the patients treated with dalteparin and in 23,5% of the patients treated with UFH (ns). A secondary risk factor for venous thromboembolism and a longer duration of treatment with oral anticoagulants (OAC) were significantly associated with a lower risk for recurrent VTE, whereas malignant disease diagnosed during follow-up was associated with a higher risk. During follow-up a total of 40,7% of patients had died. No difference in total mortality or mortality from malignant disease was demonstrated between the two drugs. In conclusion, a severe post-thrombotic syndrome occured relatively infrequent. considering the long observation period. Proximal DVT was significantly associated with a more severe post-thrombotic syndrome. After 14 years follow-up, no significant differences were observed in overall mortality, mortality from malignant disease or recurrent VTE between UFH- and dalteparin-treated patients. Malignant disease was a risk factor for recurrent VTE, the presence of a secondary risk factor and a longer duration of treatment with OAC decreased the risk for recurrent VTE.

 
  • References

  • 1 Levine M, Gent M, Hirsh J, Leclerc J, Anderson D, Weitz J, Ginsberg J, Turpie AGG, Demers C, Kovacs M, Geerts M, Kassis J, Desjardins L, Cusson J, Cruickshank M, Powers P, Brien W, Haley S, Willan A. 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: 677-81.
  • 2 Koopman M M W, Prandoni P, Piovella P, Ockelford PA, Brandjes DPM, van der Meer J, Gallus A S, Simonneau G, Chesterman C, Prins MH, Bossuyt PMM, Haes H, van den Belt AGM, Sagnard L, d´Azemar P, Büller H R. 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: 682-7
  • 3 Lindmarker P, Holmström M. Use of a 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 Int Med 1996; 240 (06) 395-401
  • 4 The Columbus Investigators. Low-molecular weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997; 337: 657-62.
  • 5 Simonneau G, Sors H, Charbonnier B, Page Y, Laaban J-P, Azarian R, Laurent M, Hirsch J-L, Ferrari E, Bosson J-L. beau B from the THÉSÉÉ study group. A comparison of low-molecular weight heparin with unfractionated heparin for acute pulmonary embolism. N Engl J Med 1997; 337: 663-9s.
  • 6 Leizorovicz A, Simonneau G, Decousus A. Comparison of low molecular weight heparin and unfractioanted heparin in the treatment of DVT: A meta-analysis. BMJ 1994; 309: 299-304.
  • 7 Lensing AWA, Prins M, Davidsson BL, Hirsh J. Treatment of deep venous thrombosis with low molecular weight heaprin. Arch Int Med 1995; 155: 601-7.
  • 8 Siragusa S, Cosmi B, Piovella F, Hirsh J, Ginsberg JS. Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: Results of a meta-analysis. Am J Med 1996; 100: 269-77.
  • 9 Hull R, Raskob GE, Pineo GF, Pineo GF, Green D, Trowbridge AA, Elliott CG, Lerner RG, Hall J, Sparling T, Brettell HR, Norton J, Carter CF, George R, Merli G, Ward J, Mayo W, Rosenbloom D, Brant R. Subcutaneous low-molecular weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med 1992; 326: 975-82.
  • 10 Prandoni P, Lensing AWA, Buller HR, Carta M, Cogo A, Vigo M, Casara D, Ruol A, ten Cate JW. Comparison of subcutaneous low-molecular weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992; 339: 441-5.
  • 11 Lindmarker P, Holmström M, Granqvist S, Johnsson H, Lockner D. Comparison of once-daily subcutaneous Fragmin® with continuous intravenous unfractionated heparin in the treatment of deep vein thrombosis. Thromb Haemost 1994; 72: 186-90.
  • 12 Fiessinger JN, Lopez-Fernandez M, Gatterer E, Granqvist S, Kher A, Olsson CG, Söderberg K. Once-daily subcutaneous dalteparin a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis. Thromb Haemost 1996; 76: 195-99.
  • 13 Luonamäki K, Grankvist S, Hallert C, Jauro I, Ketola K, Kim H C, Kiviniemi H, Koskivirta H, Sörskog L, Vilkko P. A multicentre comparison of once-daily subcutaneous dalteparin (low molecular weight heparin) and continuous intravenous heparin in the treatment of deep vein thrombosis. J Int Med 1996; 240: 85-92.
  • 14 Bratt G, Tönebohm E, Granquist S, Åberg W, Lockner D. A comparison between low molecular weight heparin (KABI 2165) and standard heparin in the treatment of deep venous thrombosis. Thromb Haemost 1985; 54: 813-7.
  • 15 Bratt G, Åberg W, Johansson M, Törnebohm E, Granquist S, Lockner D. Two daily subcutaneous injections of Fragmin® compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT). Thromb Haemost 1990; 64: 506-10.
  • 16 Bratt G, Törnebohm E, Granqvist S, Åberg W, Lockner D. A comparison between low molecular weight heparin (KABI 2165) and standard heparin in the intravenous treatment of deep venous thrombosis. Thromb Haemost 1985; 54: 813-7.
  • 17 Schulman S, Rhedin A-S, Lindmarker P, Carlsson A, Lärfars G, Nicol P, Loogna E, Svensson E, Ljungberg B, Walter H, Viering S, Nordlander S, Leijd B, Jönsson K-Å, Hjorth M, Linder O, Boberg J. and the duration of anticoagulation trial study group. 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: 1661-5.
  • 18 Schulman S, Granqvist S, Holmström M, Carlsson A, Lindmarker P, Nicol P, Eklund S-G, Nordlander S, Lärfars G, Leijd B, Linder O, Loogna E. the duration of anticoagulation trial study group. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. N Engl J Med 1997; 336: 393-8.
  • 19 Kakkar VV, Lawrence D, Lindner DJ, Edwards JM, Phinney ES, Taylor LM, Porter JM. Long-term hemodynamic and clinical sequelae of lower extremity deep vein thrombosis. J Vasc Surg 1986; (04) 436-42.
  • 20 Monreal M, Martorell A, Callejas JM, Valls R, Llamazares JF, Lafoz E, Ariass A. Venographic assessment of deep vein thrombosis and risk of developing a post-thrombotic syndrome: a prospective study. J Int Med 1993; 233: 233-38.
  • 21 Franzeck UK, Schalch I, Bollinger A. On the relationship between changes in the deep veins evaluated by duplex sonography and the postthrombotic syndrome 12 years after deep vein thrombosis. Thromb Haemost 1997; 77: 1109-12.
  • 22 Bounameaux H, de Moerloose P, Sarasin FP. Optimal duration of oral anticoagulant therapy following deep vein thrombosis of lower limbs. Blood Coag Fibrinolysis 1996; 7: 507-14.
  • 23 Prandoni P, Lensing AWA, Cogo A, Cuppini S, Villalta S, Carta M, Cattelan AM, Polistena P, Bernardi E, Prins MH. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996; 125: 1-7.
  • 24 Nordström M, Lindblad B, Andersson H, Bergqvist D, Kjellström T. Deep venous thrombosis and occult malignancy: an epidemeological study. BMJ 1994; 308: 891-4.