Aktuelle Aspekte zu Diagnostik und Therapie der tiefen Venenthrombose aus internistischer Sicht

Zusammenfassung

Die tiefe Venenthrombose stellt eine häufige Erkrankung dar, deren klinische Diagnose aufgrund der unspezifischen Symptomatik oft unsicher ist. Die diagnostische Methode der Wahl ist heute die Kompressions- oder Duplexsonographie. Bei unsicheren Befunden ist eine Phlebographie indiziert. Im Rahmen der Ursachenklärung spielen die verschiedenen Thrombophilien, bei älteren Patienten auch die Tumorsuche, eine wichtige Rolle. Die klassische Behandlung besteht aus der therapeutischen Antikoagulation mit Heparin, die möglichst rasch eingeleitet werden muss, sowie der anschließenden Sekundärprophylaxe. Niedermolekulare Heparine stellen heute die Therapie der Wahl in der Initialphase dar, sie bieten den Vorteil der einfacheren und sichereren Anwendung sowie die Möglichkeit zur früheren Mobilisierung und ambulanten Therapie. Im Rahmen der Sekundärprophylaxe kommen orale Antikoagulanzien zum Einsatz, bei Kontraindikationen ist auch hier der Einsatz von niedermolekularen Heparinen möglich. Die Dauer ist dabei vor allem von Lokalisation und Ausdehnung der Thrombose sowie von begleitenden Risikofaktoren abhängig und muss individuell festgelegt werden. Eine wichtige Rolle bei der Verhinderung postthrombotischer Syndrome spielt die Kompressionsbehandlung. Durch die Entwicklung neuer antithrombotischer Wirkstoffe wie Pentasaccharide oder orale Thrombininhibitoren ergeben sich neue Perspektiven in der Prophylaxe und Therapie thromboembolischer Erkrankungen.

Abstract

Deep vein thrombosis is a common disease, but clinical diagnosis is often unreliable due to unspecific symptoms. Today, compression or duplex ultrasonography is the diagnostic method of choice in most patients. Venography should be performed in case of uncertain ultrasound test results. Predisposing factors for venous thromboembolism like thrombophilias or malignant disease should be examined. By initial treatment with heparin a therapeutic range should be reached as soon as possible. Low molecular weight heparins are the initial treatment of choice, they are at least as effective and safe as unfractionated heparin. Due to the advantage of simplicity of administration, they have the potential for ambulant treatment. Initial heparin therapy is usually followed by long-term treatment with oral anticoagulants, in case of contraindications use of low molecular weight heparins is also possible. The optimal duration depends on localization of thrombosis and concomitant risk factors, and should be individualized. Compression therapy should be performed to reduce the incidence of postthrombotic syndrome. Development of new antithrombotic agents like pentasaccharides or oral thrombin inhibitors has raised new possibilities in prophylaxis and treatment of venous thromboembolism.

Schlüsselwörter

Tiefe Venenthrombose - Diagnostik - Therapie - Antikoagulation - NMH - Thrombophilie

Key words

Deep vein thrombosis - diagnosis - treatment - anticoagulation - LMWH - thrombophilia

Literatur

• 1 Bauersachs R M, Lindhoff-Last E, Wolff U, Ehrly A M. Aktuelles Management der tiefen Venenthrombose.  Med Welt. 1998;  49 194-214
• 2 Beek v an, Büller H R, Tencate J. Epidemiology of venous thromboembolism. In: Tooke JE, Lowe GDO (edts) Vascular medicine 1996: 472-488
• 3 Lindblad B, Tengborn L, Bergqvist D. Deep vein thrombosis of the axillary-subclavian veins: epidemiologic data, effects of different types of treatment and late sequelae.  Eur J Vasc Surg. 1988;  2 161-165
• 4 Martin M, Brors G. Vena-subclavia Thrombose: Epidemiologische Daten der PHLEKO-Studie.  VASA. 1995;  24 120-125
• 5 Hach W, Hach-Wunderle V. Phlebographie der Bein- und Beckenvenen. Konstanz: Schnetztor 1996: 155
• 6 Koper I K, Vogt J, Sybrecht G W. Erkrankungen des Lungenkreislaufs. Lungenembolie. In: Classen M, Diehl V, Kochsieck K (Hrsg) Innere Medizin 1991: 1154
• 7 Mostbeck A, Partsch H, Köhn H, König B. Lungenembolie bei Bein-/Beckenvenenthrombose: Ergebnisse einer prospektiven Studie.  Wien Klin Wschr. 1980;  92 464-471
• 8 Alpert J S, Dalen J E. Epidemiology and natural history of venous thromboembolism.  Prog Cardiovasc Dis. 1994;  36 417-422
• 9 Partsch H, Oburger K, Mostbeck A, König B, Kühn H. Frequency of pulmonary embolism in ambulant patients with pelvic vein thrombosis: A prospective study.  J Vasc. Surg1992;  16 715-722
• 10 Odenthal H J, Josephs W, Lenga P, Wiechmann H W. Lungenembolie.  Intern Prax. 1991;  31 661
• 11 Eichlisberger R, Widmer M T, Frauchiger B, Widmer L K, Jäger K. Zur Häufigkeit des postthrombotischen Syndroms.  Wien Med Wschr. 1994;  144 192-195
• 12 Strandness D E, Langlois Y, Cramer M, Randlett A, Thiele B L. Long-term sequelae of acute venous thrombosis.  JAMA. 1983;  250 1289-1292
• 13 Biland L, Zemp E, Widmer L K. Zur Epidemiologie der venösen Thromboembolie.  Internist. 1987;  28 285-290
• 14 Franzeck U K, Schalch I, Jäger K, Grimm J, Schnieder E, Bollinger A. Prospective 12-year follow-up study of clinical and hemodynamic sequelae after deep vein thrombosis (Zurich study).  Circulation. 1996;  93 74-79
• 15 Franzeck U K, 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 1109-1112
• 16 Kakkar V V, Lawrence D. Hemodynamic and clinical assessment after therapy for acute deep vein thrombosis.  Am J Surg. 1985;  150 (Suppl) 54-63
• 17 Partsch H. Diagnose und Therapie der tiefen Venenthrombose.  VASA. 1996;  46 (Suppl) 1-53
• 18 Prandoni P, Lensing A W, Cogo A. et al . The long-term clinical course of acute deep venous thrombosis.  Ann Intern Med. 1996;  125 1-7
• 19 Diehm C, Stammler F, Amendt K. Die tiefe Venenthrombose. Diagnostik und Therapie.  Dt Ärztebl. 1997;  94 A301-311
• 20 Fries R, Böhm M. Tiefe Beinvenenthrombose. Diagnostik und Therapie.  Dtsch Med Wochenschr. 2003;  128 994-1002
• 21 Bauer K A. The thrombophilias: well-defined risk factors with uncertain therapeutic implications.  Ann Intern Med. 2001;  135 367-373
• 22 Seligsohn U, Lubetzky A. Genetic susceptibility to venous thrombosis.  N Engl J Med. 2001;  344 1222-1231
• 23 Andree C H. Zur Entstehung der Virchow'schen Triade.  Ann Univ Sarav Med. 1990;  26 45-52
• 24 Goldhaber S Z, Savage D D. et al . Risc factors for pulmonary embolism. The Framingham study.  Am J Med. 1983;  74 1023-1028
• 25 Coon W W, Willis P W, Keller J B. Venous thromboembolism and other venous diseases in the Tecumseh community health study.  Circulation. 1973;  48 839-846
• 26 World Health Organisation . World Health Organisation collaborative study of cardiovascular disease and steroid hormone contraception. Venous thromboembolic disease and combined oral contraceptives: results of international multicentre case-control study.  Lancet. 1995;  346 1575-1578
• 27 Briet E, van der Meer F J, Rosendaal F R, Houwing Duistermaat J J, van Houwelingen H C. The family history and inherited thrombophilia.  Br J Haematol. 1994;  87 348-352
• 28 Ludwig M. Venenerkrankungen. In: Angiologie in Klinik und Praxis.  Stuttgart: Thieme,. 1998;  1 137-227
• 29 Rieger H, Theis W. Tiefe Bein- und Becken-Venenthrombose. In: Rieger H, Schoop W (Hrsg) Klinische Angiologie. Berlin: Springer 1998: 1037-1073
• 30 Gaffney P J, Joe F. The lysis of crosslinked human fibrin by plasmin yields initially a single molecular complex, D-Dimer-E.  Thromb Res. 1979;  15 673-687
• 31 Gaffney P J, Edgell T, Creighton K empsford. et al . Fibrin degradation product (FnDP) test: analysis of standardization issues and target antigens in plasma.  Br J Haematol. 1995;  90 187-194
• 32 Wells P S, Brill-Edwards P, Stevens P. et al . A novel and rapid whole-blood assay for D-Dimer in patients with clinically suspected deep vein thrombosis.  Circulation. 1995;  91 2184-2187
• 33 Bounameaux H, de Moerloose P, Perrier A, Reber G. Plasma measurement of D-Dimer as diagnostic aid in suspected venous thromboembolism: an overview.  Thromb Haemost. 1994;  71 1-6
• 34 Perrier A, Desmarais S, Miron M J. et al . Non-invasive diagnosis of venous thromboembolism in outpatients.  Lancet. 1999;  353 190-195
• 35 Leitlinien der Deutschen Gesellschaft für Angiologie . AWMF-Leitlinien-Register Nr. 065/002. Diagnostik und Therapie der Venenthrombose und Lungenembolie.  VASA. 2002;  31 (Suppl 60) 1-19
• 36 Dietrich C F, Bauersachs R M. Sonographische Thrombosediagnostik.  Dtsch Med Wochenschr. 2002;  127 567-572
• 37 Kearon C, Julian J A, Newman T E, Ginsberg J S. Noninvasive diagnosis of deep venous thrombosis. McMaster Diagnostic Imaging Ppractice Guidelines Initiative.  Ann Intern Med. 1998;  128 663-677
• 38 Schonhofer B, Bundschuh H D, Wolf K, Grehn S. Color-coded duplex ultrasonography compared to phlebography in deep leg and pelvic vein thrombosis.  Med Klin. 1992;  87 172-178
• 39 Rabinov K, Paulin S. Roentgen diagnosis of venous thrombosis in the leg.  Arch Surg. 172;  104 134-144
• 40 Fraser J D, Anderson D R. Deep venous thrombosis: recent advances and optimal investigation with US.  Radiology. 1999;  211 9-24
• 41 Poort S, Rosendaal F, Reitsma P, Bertina R. A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis.  Blood. 1996;  88 3670-3698
• 42 Sorensen H T, Mellemkjaer L, Steffensen F H, Olsen J H, Nielsen G L. The risk of a diagnosis of cancer after primary deep vein thrombosis or pulmonary embolism.  N Engl J Med. 1998;  338 1169-1173
• 43 Monreal M, Prandoni P. Venous thromboembolism as first manifestation of cancer.  Semin Thromb Hemost. 1999;  25 1313-1336
• 44 Hull R D. Anticoagulant treatment.  Inter Angio. 1995;  14 32-43
• 45 Hull R D, Raskob G E, 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 1109-1114
• 46 Barritt D W, Jordan S C. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trail.  Lancet. 1960;  I 1309-1312
• 47 Leizorovicz A, Simonneau G, Decousus H, Boissel J P. Comparison of efficacy and safety of low molecular weight heparins and unfractionated heparin in initial treatment of deep venous thrombosis: a meta-analysis.  BMJ. 1994;  309 299-304
• 48 Lensing A W, Prins M H, Davidson B L, Hirsh J. Treatment of deep venous thrombosis with low-molecular-weight heparins. A meta-analysis.  Arch Intern Med. 1995;  155 601-607
• 49 Siragusa S, Cosmi B, Piovella F, Hirsh J, Ginsberg J S. 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;  100 267-269
• 50 Albada J, Nieuwenhuis H K, Sixna J J. Treatment of acute deep venous thromboembolism with low molecular weight heparin (Fragmin). Results of a double-blind randomized trail.  Circulation. 1989;  80 935-940
• 51 Hull R D, Raskob G E, Pineo G F. et al . Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis.  N Engl J Med. 1992;  326 975-982
• 52 Pandroni P. the Collaborative European Multicentre Study . A randomized trail of subcutaneous low molecular weight heparin (CY216) compared with intravenous unfractionated heparin in the treatment of deep-vein thrombosis.  Thromb Haemost. 1991;  65 251-256
• 53 Dolovich L R, Ginsberg J S, Douketis J D. et al . A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism: examining some unanswered questions regarding location of treatment, product type and dosing frequency.  Arch Intern Med. 2000;  160 181-188
• 54 Breddin H K, Hach-Wunderle V, Nakov R, Kakkar V V. Effects of a low-molecular-weight heparin on thrombus regression and recurrent thromboembolism in patients with deep-vein thrombosis.  N Engl J Med. 2001;  344 626-631
• 55 Couturaud F, Julian J A, Kearon C. Low molecular weight heparin administered once versus twice daily in patients with venous thromboembolism: a meta-analysis.  Thromb Haemost. 2001;  86 980-984
• 56 Fiessinger J N, Charbonnier B A, Sixma J J. et al . Comparison of a once daily with a twice daily subcutaneous nadroparin calcium regimen in the treatment of deep vein thrombosis.  Thromb Haemost. 1997;  Suppl 388
• 57 Bendetowicz A V, Beguin S, Caplain H, Hemker H C. Pharmacokinetics and pharmacodynamics of a low molecular weight heparin (enoxaparin) after subcutaneous injection, comparison with unfractionated heparin - a three way cross over study in human volunteers.  Thromb Haemost. 1994;  71 305-313
• 58 Warkentin T E, Levine M N, Hirsh J. et al . Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin.  N Engl J Med. 1995;  332 1330-1335
• 59 Schellong S M, Schwarz T. Differenzialtherapie der tiefen Beinvenenthrombose.  Internist. 2002;  43 36-46
• 60 Anonymous . International Committee for Standardization in Haematology, International Committee on Thrombosis and Haemostasis: ICSH/ICTH recommendations for reporting prothrombin time in oral anticoagulant control.  Thromb Haemost. 1985;  53 155-156
• 61 Hirsh J. Substandard monitoring of warfarin in North America. Time for change.  Arch Intern Med. 1992;  152 257-258
• 62 Levine M N, Hirsh J, Gent M. Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal vein thrombosis.  Thromb Haemost. 1995;  74 606-611
• 63 Research Committee of the British Thoracic Society . Optimum duration of anticoagulation for deep-vein thrombosis and pulmonary embolism.  Lancet. 1992;  340 873-876
• 64 Schulman S. the Duration of Anticoagulation Trial Study Group . A comparison of six weeks with six months of oral anticoagulation therapy after a first episode of venous thromboembolism.  N Engl J Med. 1995;  332 1661-1665
• 65 Agnelli G, Prandoni R, Santamaria M G. et al . Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trail Investigators.  J Engl J Med. 2001;  345 165-169
• 66 Prins M H, Hutten B A, Koopman M MW. et al . Long-term treatment of venous thromboembolic disease.  Thromb Haemost. 1999;  82 892-898
• 67 Hirsh J. The optimal duration of anticoagulant therapy for venous thrombosis.  N Engl J Med. 1995;  332 1710-1711
• 68 Lopaciuk S, Bielska-Falda H, Noszczyk W. et al . Low molecular weight heparin versus acenocoumarol in the secondary prophylaxis of deep vein thrombosis.  Thromb Haemost. 1999;  81 26-31
• 69 Gonzalez-Fajardo J A, Arreba E, Castrodeza J. et al . Venographic comparison of subcutaneous low-molecular weight heparin with oral anticoagulant therapy in the long-term treatment of deep venous thrombosis.  J Vasc Surg. 1999;  30 283-292
• 70 Veiga F, Escriba A, Maluenda M P. et al . Low molecular weight heparin (enoxaparin) versus oral anticoagulation therapy (acenocoumarol) in the long-term treatment of venous thrombosis in the elderly: a randomized trial.  Thromb Haemost. 2000;  84 559-564
• 71 Farner B, Eichler P, Kroll H. et al . A comparison of danaparoid and lepirudin in heparin-induced thrombocytopenia.  Thromb Haemost. 2001;  85 950-957
• 72 Eriksson B I, Ekman S, Kälebo P. et al . Prevention of deep-vein thrombosis after total hip replacement: direct thrombin inhibition with recombinant hirudin, CGP 39393.  Lancet. 1996;  347 635-639
• 73 Eriksson B I, Wille-Jorgensen P, Kälebo P. et al . A comparison of recombinant hirudin with a low-molecular weight heparin to prevent thromboembolic complications after total hip replacement.  N Engl J Med. 1991;  337 1329-1335
• 74 Partsch H. Therapy of deep vein thrombosis with low molecular weight heparin, leg compression and immediate ambulation.  VASA. 2001;  30 195-204
• 75 Ehringer H, Minar E. Die Therapie der akuten Becken-Beinvenenthrombose.  Internist. 1987;  28 317
• 76 Koopman M M, Prandoni P, Piovella 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;  334 682-687
• 77 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;  334 677-681
• 78 Aschwanden M, Labs K H, Engel H. et al . Acute deep vein thrombosis: early mobilization does not increase the frequency of pulmonary embolism.  Thromb Haemost. 2001;  85 42-46
• 79 Schellong S M, Schwarz T, Kropp J. et al . Bed rest in deep vein thrombosis and the incidence of scintigraphic pulmonary embolism.  Thromb Haemost. 1999;  82 127-129
• 80 Wells P S, Kovacs M J, Forgie M A. et al . Expanded eligibility for outpatient treatment of deep venous thrombosis and pulmonary embolism with low molecular weight heparin: A comparison of patient self-injection to home care injection.  Arch Intern Med. 1998;  158 1809-1812
• 81 Schwarz T, Schmidt B, Hohlein U. et al . Eligibility for home treatment of deep vein thrombosis: prospective study.  BMJ. 2001;  322 1212-1213
• 82 Brandjes D PM, Büller H R, Heijboer H. et al . Randomized trial of the effect of compression stockings in patients with symptomatic proximal-vein thrombosis.  Lancet. 1997;  349 759-762
• 83 Plate G, Einarsson E. Ohlin P et al. Thrombectomy with temporary arterio-venous fistula in acute iliofemoral thrombosis.  J Vasc Surg. 1984;  1 867-876
• 84 Weidmann B, Jansen W, Franzen B. et al . Lysetherapie bei tiefen Beinvenenthrombosen.  Med Klin. 1999;  94 140-149
• 85 Arnesen H, Høiseth A, Ly B. Streptokinase or heparin in the treatment of deep vein thrombosis: Follow-up results of a prospective study.  Thromb Haemost. 1982;  211 65-68
• 86 Elliot M S, Immelman E J, Jeffrey P. et al . A comparative randomized trial of heparin versus streptokinase in the treatment of acute proximal venous thrombosis: an interim report of a prospective trial.  Br J Surg. 1979;  66 838-843
• 87 Wells P S, Forster A. Thrombolysis in deep vein thrombosis; is there still an indication?.  Thromb Haemost. 2001;  86 499-505
• 88 Martin M. PHLEKO-/PHLEFI-Studien.  VASA. 1997;  26 (Suppl. 49) 5-39
• 89 O'Meara J J, McNutt R A, Evans A T, Moore S W, Downs S M. A decision analysis of streptokinase plus heparin as compared with heparin alone for deep vein thrombosis.  N Engl J Med. 1994;  330 1864-1969
• 90 Eichlisberger R, Frauchiger B, Widmer M T, Widmer L K, Jäger K. Spätfolgen der tiefen Beinvenenthrombose: ein 13-Jahre-Follow-up von 223 Patienten.  VASA. 1994;  23 234-243
• 91 Ockert D, Schellong S, Bergert H. et al . Therapie der tiefen Beinvenenthrombose.  Wann ist eine chirurgische Therapie indiziert? Zentralbl Chir. 1999;  124 7-11
• 92 Weber H, Loeprecht H. Venöse Thrombektomie. Indikation, Technik, Ergebnisse.  Langenbecks Arch Chir. 1988;  Suppl 2 169-175
• 93 Decousus H, Leizorovicz A, Parent F. et al . A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis.  N Engl J Med. 1998;  338 409-415
• 94 Herbert J M, Petitou M, Lormeau J C. et al . SR 90107A/Org 31540, a Novel Anti-Factor Xa Antithrombotic Agent.  Cardiovasc Drug Rev. 1997;  15 1-26
• 95 Andersson L O, Barrowcliffe T W, Holmer E, Johnson E A, Sims G EC. Anticoagulant properties of heparin fractionated by affinity chromatography on matrix-bound antithrombin III and by gel filtration.  Thromb Res. 1976;  9 575-583
• 96 Verstraete M. Pharmacotherapeutic aspects of unfractionated and low molecular weight heparins.  Drug. 1990;  40 498-530
• 97 Turpie A GG, Gallus A S, Hoek J A. A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement.  N Engl J Med. 2001;  344 619-625
• 98 Lassen M R, Bauer K A, Eriksson B I, Turpie A GG. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomized double-blind comparison.  Lancet. 2002;  359 1715-1720
• 99 Turpie A GG, Bauer K A, Eriksson B I, Lassen M R. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomized double-blind comparison.  Lancet. 2002;  359 1721-1726
• 100 Bauer K A, Eriksson B I, Lassen M R, Turpie A GG. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery.  N Engl J Med. 2001;  345 1305-1310
• 101 Eriksson B I, Bauer K A, Lassen M R, Turpie A GG. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery.  N Engl J Med. 2001;  345 1298-1304
• 102 Gustafsson D, Nyström J E, Carlsson S. et al . The Direct Thrombin Inhibitor Melagatran and Its Oral Prodrug H 376/95: Intestinal Absorption Properties, Biochemical and Pharmacodynamic Effects.  Thromb Res. 2001;  101 171-181
• 103 Heit J A, Colwell C W, Francis C W. et al . Comparison of the Oral Direct Thrombin Inhibitor Ximelagatran With Enoxaparin as Prophylaxis Against Venous Thromboembolism After Total Knee Replacement.  Arch Intern Med. 2001;  161 2215-2221
• 104 Eriksson B I, Lindbratt S, Kälebo P. et al . METHRO II: dose-response study of the novel oral, direct thrombin inhibitor, H376/95, and ist subcutaneous formulation melagatran, compared with dalteparin as thromboembolic prophylaxis after total hip or total knee replacement.  Haemostasis. 2000;  30 (suppl 1) 20-21