Therapie der tiefen Beinvenenthrombose

H. K. Breddin

doi:10.1055/s-0037-1619513

Hämostaseologie, Table of Contents

Hamostaseologie 2001; 21(03): 111-117
DOI: 10.1055/s-0037-1619513

Original article

Schattauer GmbH

Therapie der tiefen Beinvenenthrombose

Treatment of deep venous thrombosis

H. K. Breddin

¹Internat. Institut für Thrombose- und Hämostaseforschung, Frankfurt

› Author Affiliations

Abstract

Zusammenfassung

Neben der Kompressionsbehandlung ist die Antikoagulation die wichtigste Maßnahme bei der Behandlung akuter tiefer Beinvenenthrombosen. Niedermolekulare Heparine (NMH) sind in der Behandlung der tiefen Beinvenenthrombose genauso wirksam oder etwas wirksamer als unfraktioniertes Heparin (UFH). Inzwischen haben sich die NMH in der Behandlung der tiefen Beinvenenthrombose weitgehend durchgesetzt. Diskutiert wird allerdings noch über den Wirkmechanismus, die optimale Dosis und die optimale Therapiedauer. Zunehmend häufiger werden Patienten mit tiefer Beinvenenthrombose schon nach kurzer stationärer Behandlung entlassen oder auch ausschließlich ambulant behandelt. Vorteile der NMH sind in diesen Fällen ihre bessere Bioverfügbarkeit und die deutlich einfachere Handhabung der Anwendung als s.c. Gabe. Neue Medikamente werden in Kürze verfügbar sein. Hierzu gehören besonders das Pentasaccharid und oral wirksame Thrombinhemmer wie Melagatran. Es bleibt abzuwarten, ob diese neuen Wirkstoffe die Therapie der tiefen Beinvenenthrombose weiter verbessern können. Die fibrinolytische Behand-lung der tiefen Beinvenenthrombose ist bisher mit einem erhöhten Blutungsrisiko verbunden. Neue Fibrinolytika und neue Applikationsformen könnten dieser Therapieform wieder zu einem höheren Stellenwert verhelfen.

Summary

Besides compression bandaging anticoagulation ist the most important part of treatment of acute deep venous thrombosis. Low-molecular-weight heparins (LMWH) are equally effective in the treatment of deep vein thrombosis as unfractionated heparin (UFH). Meanwhile LMWH have become the treatment of choice for acute deep venous thrombosis. The optimal dose, the optimal duration of treatment and the mechanism of action of LMWH are still under discussion. Increasingly patients with deep vein thrombosis treated with LMWH are discharged from hospital early or even primarily treated as outpatients. Advantages of LMWH are the increased bioavailability, the easier handling and the possibility of early mobilisation. New drugs will soon be available. Among those pentasaccharide and oral thrombin inhibitors as melagatran are currently studied. It remains to be seen whether these new anticoagulants may further improve the treatment of patients with deep venous thrombosis. Fibrinolytic treatment of acute deep venous thrombosis is connected with an increased bleeding risk. New fibrinolytic agents and new forms of application may increase the role of fibrinolytic treatment of deep venous thrombosis in the future.

Schlüsselwörter

Heparin - niedermolekulare Heparine - Lungenembolie - Phebographie - Rückbildung der Thrombose

Keywords

Heparin - low-molecular-weight heparins - pulmonary embolism - phebography - thrombus regression

Full Text

References

Literatur
1 Albada J, Nieuwenhuis HK, Sixma JJ. Treatment of acute venous thromboembolism with low molecular weight heparin (Fragmin). Results of a double-blind randomized study. Circulation 1989; 80: 935-40.
2 Alhenc-Gelas M, Jestin-Le Guernic C, Vitoux JF, Kher A, Aiach M, Fiessinger JN. Adjusted versus fixed doses of the low-molecular-weight heparin fragmin in the treatment of deep vein thrombosis. Thromb Haemost 1994; 71: 698-702.
3 Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial: Lancet 1960; I: 1309-12.
4 Brandjes DPM, Heijboer H, Buller HR, de Rijk M, Jagt H, ten Cate JW. Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal-vein thrombosis. NEJM 1992; 327: 1485-9.
5 Breddin HK, Hach-Wunderle V, Nakov R, Kakkar VV. Effects of a low-molecular-weight heparin on thrombus regression and recurrent thromboembolism in patients with deep-vein thrombosis. NEJM 2001; 344: 626-31.
6 Carson JL, Kelley MA, Duff A, Weg JG, Fulkderson WJ, Palevsky HI, Schwartz JS, Thompson BT, Popovich J, Hobbins TE. et al. The clinical course of pulmonary embolism. NEJM 1992; 326: 1240-5.
7 Charbonnier BA, Fiessinger JN, Banga JD, Wenzel E, d’Azemar P, Sagnard L. Comparison of a once daily with a twice daily subcutaneous nadroparin calcium regimen in the treatment of deep vein thrombosis: the FRAXODI study. Thromb Haemost 1998; 79: 897-901.
8 The COLUMBUS Investigators. Low molecular weight heparin in the treatment of patients with venous thromboembolism. NEJM 1997; 337: 657-62.
9 Dahl OE, Andreassen G, Aspelin T, Muller C, Mathiesen P, Nyhus S, Abdelnoor M, Solhaug JH, Arnesen H. Prolonged thromboprophylaxis followed hip replacement surgery. Results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin^®). Thromb Haemost 1997; 77: 26-31.
10 Dorfman GS, Cronan JJ, Tupper TB, Messersmith RN, Denny DF, Lee CH. Occult pulmonary embolism: a common occurence in patients with deep venous thrombosis. AJR 1987; 148: 263-6.
11 Doyle DJ, Turpie AG, Hirsh J, Best C, Kinch D, Levine MN, Gent M. Adjusted subcutaneous heparin or continuous intravenous heparin in patients with acute deep vein thrombosis. Ann Intern Med 1987; 107: 441-5.
12 Fiessinger JN, Lopez-Fernandez M, Gatterer E, Granqvist S, Kher A, Olsson CG, Soderberg K. Once-daily subcutaneous dalteparin, a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis. Thromb Haemost 1996; 76: 195-9.
13 Gallus AS, Jackaman J, Tilett J, Mills W, Wycherley A. Safety and efficacy of warfarin started early after submassive venous thrombosis or pulmonary embolism. Lancet II 1986; 8519: 1293-6.
14 Goldhaber SZ, Haire WD, Feildstein ML, Miller M, Toltzis R, Smith JL, Taveria da Silva AM, Come PC, Lee RT, Parker JA. Alteplase versus heparin in acute pulmonary embolism: Randomized trial assessing right ventricular function and pulmonary perfusion. Lancet 1993; 341: 507-11.
15 Goldhaber SZ, Visani L, De Rosa M. for ICOPER. Acute pulmonary embolism: Clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999; 353: 1386-9.
16 Greinacher A. Antigen generation in heparin-associated thrombocytopenia: The nonimmunologic type and the immunologic type are closely linked in their pathogenesis. Semin Thromb Haemost 1995; 21: 106-16.
17 Hach W. Phlebographie der Bein- und Beckenvenen. Konstanz: Schnetztor-Verlag; 1985
18 Hirsh J, Salzman EW, Marder VJ. Treatment of venous thromboembolism. In: Colman RW, Hirsh J, Marder VJ, Salzman EW. (eds) Hemostasis and Thrombosis. Basic principles and clinical practice. Philadelphia: Lippincott; 1994: 1346-66.
19 Hirsh J, Siragusa S, Cosmi B, Ginsberg JS. Low molecular weight heparins (LMWH) in the treatment of patients with acute venous thromboembolism. Thromb Haemost 1995; 74: 360-3.
20 Holmström MC, Granquist BS, Bratt G, Törnebohm E, Lockner D. Fragmin once or twice daily subcutaneously in the treatment of deep venous thrombosis of the leg. Thrombos Res 1992; 67: 49-55.
21 Hommes DW, Bura A, Mazzolai L, Büller HR, Cate JW ten. Subcutaneous heparin compared with continuous intravenous heparin administration in the initial treatment of deep vein thrombosis. Ann Intern Med 1992; 116: 279-84.
22 Huisman MV, Buller HR, ten Cate JW, van Royen EA, Vreeken J, Kersten MJ, Bakx B. Unexpected high prevalence of silent pulmonary embolism in patients with deep venous thrombosis. Chest 1989; 95: 498-502.
23 Hull RD, Delmore T, Genton E, Hirsh J, Gent M, Sackett D, McLoughlin D, Armstrong P. Warfarin sodium versus low dose heparin in the long-term treatment of venous thrombosis. NEJM 1979; 301: 855-8.
24 Hull RD, Hirsh J, Carter CJ, Jay RM, Dodd PE, Ockelford PA, Coates G, Gill GJ, Turpie AG, Doyle DJ, Buller HR, Raskob GE. Pulmonary angiography, ventilation lung scanning, and venography for clinically suspected pulmonary embolism with abnormal perfusion lung scan. Ann Intern Med 1983; 98: 891-9.
25 Hull RD, Raskob GE, Hirsh J, Jay RM, Leclerc JR, Geerts WH, Rosenbloom D, Sackett DL, Anderson C, Harrison L, Gent M. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal vein thrombosis. NEJM 1986; 315: 1109-14.
26 Hull RD, Raskob GE, Rosenbloom D, Panju AA, Brill-Edwards P, Ginsberg JS, Hirsh J, Martin GJ, Green D. Heparin for 5 days as compared with 10 days in the initial treatment of proximale venous thrombosis. NEJM 1990; 322: 1260-4.
27 Hull RD, Raskob GE, Pineo GF, Green D, Trowbridge AA, Elliott CG, Lerner RG, Hall J, Sparling T, Brettell HR, Norton J, Carter CJ, 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. NEJM 1992; 326: 975-82.
28 Hull RD, Raskob GE, Brant RF, Pineo GF, Elliott G, Stein PD, Got A, Valentine KA, Mah AF. Low-molecular-weight heparin vs. heparin in the treatment of patients with pulmonary embolism. American-Canadian Thrombosis Study Group. Arch Intern Med 2000; 160: 229-36.
29 Jeske WP, Walenga JM, Szatkowski E, Ero M, Herbert JM, Haas S, Bakhos M. Effect of glycoprotein IIb/IIIa antagonists on the HIT serum induced activation of platelets. Thromb Res 1997; 88: 271-81.
30 Kakkar VV, Cohen AT, Edmonson RA, Phillips MJ, Cooper DJ, Das SK, Maher KT, Sanderson RM, Ward VP, Kakkar S. Low molecular weight heparin versus standard heparin for prevention of venous thromboembolism after major abdominal surgery. Lancet 1993; 341: 259-65.
31 Kakkar VV, Boeckl O, Boneu B, Bordenave L, Brehm O A, Brücke P, Coccheri S, Cohen AT, Galland F, Haas S, Jarrige J, Koppenhagen K, LeQuerrec A, Parraguette E, Prandoni P, Roder JD, Roos M, Ruschemeyer C, Siewert JR, Vinazzer H, Wenzel E. Efficacy and safety of a low-molecular-weight heparin and standard unfractionated heparin for prophylaxis of postoperative venous thromboembolism: European Multicenter Trial. World J Surg 1997; 21: 2-9.
32 Kirchmaier CM, Wolf H, Schäfer H, Ehlers B, Breddin HK. Efficacy of a low molecular weight heparin administered intravenously or subcutaneously in comparison with intravenous unfractionated heparin in the treatment of deep venous thrombosis. Int Angiol 1998; 17: 135-45.
33 Koopman MMW, Prandoni P, Piovella F, Ockelford PA, Brandjes DPM, van der Meer J, Gallus AS, Simmoneau G, Chesterman CH, Prins MH, Bossuyt PMM, de Haes H, van den Belt AGM, Sagnard L, D’Azemar P, Büller H. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low molecular weight heparin administered at home. NEJM 1996; 334: 682-7.
34 Kruit WHJ, Boer AC de, Sing AK, Roon F van. The significance of venography in the management of patients with clinically suspected pulmonary embolism. J Intern Med 1991; 230: 333-9.
35 Kuijer PMM. Randomized comparison of LMWH versus standard heparin in the initial treatment of pulmonary embolism. Thromb Haemost 1995; 73: 974 (abstr. 288).
36 Levine M, Gent M, Hirsh J, Leclerc J, Anderson D, Weitz J, Ginsberg J, Turpie AG, Demers C, Kovacs M, Geerts W, Kassis J, Desjardins J, Cuson 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. NEJM 1996; 334: 677-81.
37 Lewis BE, Grassman ED, Wrona L, Rangel Y. Novastan registered anticoagulation during renal stent implant in a patient with heparin-induced thrombocytopenia. Blood Coagul Fibrinolysis 1997; 8: 54-8.
38 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.
39 Lopaciuk S, Meissner AJ, Filipecki S, Zawilska K, Sowier J, Ciesielski L. et al. Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial. Thromb Haemost 1992; 68: 14-8.
40 Magnani HN. Einsatz von Danaparoid (Orgaran^®) zur Antikoagulation bei kardiovaskulären Operationen. VASA 2000; 29 (Suppl. 56) D02.
41 Meyer G, Brenot F, Pacouret G, Simonneau G, Gillet Juvin K, Charbonnier B, Sors H. Subcutaneous low molecular weight heparin fragmin versus intravenous unfractionated heparin in the treatment of acute non massive pulmonary embolism: an open randomized pilot study. Thromb Haemost 1995; 74: 1432-5.
42 Partsch H, Kechavarz B, Mostbeck A, Kohn H, Lipp C. Frequency of pulmonary embolism in patients who have iliofemoral deep vein thrombosis and are treated with once- or twice-daily low molecular weight heparin. J Vasc Surg 1996; 24: 774-82.
43 Pini M, Aiello S, Manotti C, Pattacini C, Quintavalla R, Poli T, Tagliaferri A, Dettori AG. Low molecular weight heparin versus Warfarin in the prevention of recurrences after deep vein thrombosis. Thromb Haemost 1994; 72: 191-7.
44 Prandoni P, Lensing AWA, Büller 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. The Lancet 1992; 339: 441-5.
45 Rabinov K, Paulin S. Roentgendiagnosis of venous thrombosis in the leg. Arch Surg 1972; 104: 134-44.
46 Salzman EW, Deykin D, Shapiro RM, Rosenberg R. Management of heparin therapy: controlled prospective trial. NEJM 1975; 292: 1046-50.
47 Schiele F, Vuillemenot A, Kramarz P, Kieffer Y, Anguenot T, Bernard Y, Bassand JP. Use of recombinant hirudin as antithrombotic treatment in patients with heparin-induced thrombocytopenia. Am J Haematol 1995; 50: 20-5.
48 Simonneau G, Charbonnier B, Decousus H, Planchon B, Ninet J, Sie P, Silsiguen M, Combe S. Subcutaneous low-molecular weight heparin compared with continuous intravenous unfractionated heparin in the treatment of proximal deep vein thrombosis. Arch Intern Med 1993; 153: 1541-6.
49 Simonneau G, Sors H, Charbonnier B. Beau B for the THESEE Group. A comparison of low molecular weight heparin with unfractionated heparin for acute pulmonary embolism. NEJM 1997; 337: 663-9.
50 Spiro TE for the Enoxaparin Clinical Trial Group. A multicenter clinical trial comparing once or twice-daily subcutaneous enoxaparin and intravenous heparin in the treatment of acute deep vein thrombosis. Thromb Haemost 1997; (Suppl) A-1527.
51 Theiss W. Systemische Thrombolyse. In: Rieger H, Schoop W. (eds) Klinische Angiologie. Berlin, Heidelberg, New York: Springer; 1998: 984-1004.
52 Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, Kelton JG. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. NEJM 1995; 332: 1330-5.