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Semin Vasc Med 2001; 01(1): 027-038
DOI: 10.1055/s-2001-14539
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Natural History of Venous Thromboembolism

Clive Kearon
  • McMaster Clinic, Henderson General Hospital, Hamilton, Ontario, Canada
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Publication History

Publication Date:
31 December 2001 (online)

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ABSTRACT

Most deep vein thromboses (DVTs) start in the calf; however, thrombi that remain confined to the calf rarely cause leg symptoms or are associated with symptomatic pulmonary embolism (PE). The probability that calf DVT will extend to involve the proximal veins, and subsequently cause PE, increases with the severity of the initiating prothrombotic stimulus and if this stimulus persists. Although acute venous thromboembolism (VTE) usually presents with either leg or pulmonary symptoms, most patients have thrombosis at both sites at the time of diagnosis. Treated proximal DVTs resolve slowly, and half of patients still have detectable thrombi after a year. About 10% of patients with symptomatic DVT develop severe postthrombotic syndrome within 5 years. This is more likely to occur if there has been an ipsilateral recurrent DVT. About 10% of PEs are rapidly fatal. Of PEs that are diagnosed before death, about 50% are associated right ventricular dysfunction, a finding that is associated with a high short-term mortality. There is about 50% resolution of PE after 1 month of treatment, and perfusion eventually returns to normal in two thirds of patients. After a course of treatment, the risk of recurrent thrombosis is higher in patients without a reversible risk factor and in those with certain biochemical abnormalities, including antiphospholipid antibodies, hyperhomocysteinemia, and homozygous factor V Leiden.

KEYWORD

Natural history - venous thrombosis - deep vein thrombosis - pulmonary embolism

REFERENCES

  • 1 Nicolaides A N, Kakkar V V, Field E S, Renney J TG. The origin of deep vein thrombosis: a venographic study.  Br J Radiol . 1971;  44 653-663
    PubMedGoogle Scholar
  • 2 Kakkar V V, Howe C T, Flanc C, Clarke M B. Natural history of postoperative deep-vein thrombosis.  Lancet . 1969;  2 230-232
    Google Scholar
  • 3 Cogo A, Lensing A WA, Prandoni P, Hirsh J. Distribution of thrombosis in patients with symptomatic deep-vein thrombosis: implications for simplifying the diagnostic process with compression ultrasound.  Arch Intern Med . 1993;  153 2777-2780
    Google Scholar
  • 4 Moser K M, LeMoine J R. Is embolic risk conditioned by location of deep venous thrombosis?.  Ann Intern Med . 1981;  94 439-444
    PubMedGoogle Scholar
  • 5 McIntyre K M, Sasahara A A. Determinants of right ventricular function and hemodynamics after pulmonary embolism.  Chest . 1974;  65 534-543
    CrossrefPubMedGoogle Scholar
  • 6 Alpert J S, Smith R, Carlson J, Ockene I S, Dexter L, Dalen J E. Mortality in patients treated for pulmonary embolism.  JAMA . 1976;  236 1477-1480
    CrossrefPubMedGoogle Scholar
  • 7 Flanc C, Kakkar V V, Clarke M B. The detection of venous thrombosis of the legs using 125-I fibrinogen.  Br J Surg . 1968;  55 742-747
    PubMedGoogle Scholar
  • 8 Maynard M J, Sculco T P, Ghelman B. Progression and regression of deep vein thrombosis after total knee arthroplasty.  Clin Orthop Related Res . 1991;  273 125-130
    PubMedGoogle Scholar
  • 9 Pellegrini V D, Langhans M J, Totterman S, Marder V J, Francis C W. Embolic complications of calf thrombosis following total hip arthroplasty.  J Arthroplasty . 1993;  8 449-457
    PubMedGoogle Scholar
  • 10 Kakkar V V, Corrigan T P, Fossard D P. Prevention of fatal postoperative pulmonary embolism by low doses of heparin. An international multicentre trial.  Lancet . 1975;  II 45-51
    PubMedGoogle Scholar
  • 11 Dahl O E, Andreassen G, Aspelin T. Prolonged thromboprophylaxis following hip replacement surgery-results of a double-blind, prospective, randomized, placebo-controlled study with dalteparin (Fragmin).  Thromb Haemost . 1997;  77 26-31
    PubMedGoogle Scholar
  • 12 Planes A, Vochelle N, Darmon J Y, Fagola M, Bellaud M, Huet Y. Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo.  Lancet . 1996;  348 224-228
    CrossrefPubMedGoogle Scholar
  • 13 Cerrato D, Ariano C, Fiacchino F. Deep vein thrombosis and low-dose heparin prophylaxis in neurosurgical patients.  J Neurosurg . 1978;  49 378-381
    CrossrefPubMedGoogle Scholar
  • 14 Heatley R V, Hughes L E, Morgan A. Preoperative or postoperative deep vein thrombosis.  Lancet . 1976;  1 437-439
    PubMedGoogle Scholar
  • 15 Cruickshank M K, Levine M N, Hirsh J. An evaluation of impedance plethysmography and 125I-fibrinogen leg scanning in patients following hip surgery.  Thromb Haemost . 1989;  62 830-834
    PubMedGoogle Scholar
  • 16 Eriksson B I, Wille-Jorgensen P, Kalebo P. A comparison of recombinant hirudin with a low-molecular weight heparin to prevent thromboembolic complications after total hip replacement.  N Engl J Med . 1997;  337 1329-1335
    CrossrefPubMedGoogle Scholar
  • 17 Bounameaux H, Huber O, Khabiri E, Schneider P-A, Didier D, Rohnet A. Unexpectedly high rate of phlebographic deep venous thrombosis following elective general abdominal surgery among patients given prophylaxis with low-molecular-weight heparin.  Arch Surg . 1993;  128 326-328
    PubMedGoogle Scholar
  • 18 Agnelli G, Cosmi B, Radicchia S. Features of thrombi and diagnostic accuracy of impedance plethysmography in symptomatic and asymptomatic deep vein thrombosis.  Thromb Haemost . 1993;  70 266-269
    PubMedGoogle Scholar
  • 19 Geerts W H, Heit J A, Clagett G P. Prevention of venous thromboembolism.  Chest . 2001;  132S-175S (132S-175S)
    PubMedGoogle Scholar
  • 20 Robinson K S, Anderson D R, Gross M. Ultrasonographic screening before hospital discharge for deep venous thrombosis after arthroplasty: the Post-Arthoplasty Screening Study. A randomized, controlled trial.  Ann Intern Med . 1997;  127 439-445
    PubMedGoogle Scholar
  • 21 Leclerc J R, Gent M, Hirsh J, Geerts W, Ginsberg J S. The incidence of symptomatic venous thromboembolism during and after prophylaxis with enoxaparin.  Arch Intern Med . 1998;  158 873-878
    CrossrefPubMedGoogle Scholar
  • 22 Colwell Jr C W, Collis D K, Paulson R, et al. Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty.  J Bone J Surg . 1999;  81-A 932-940
    PubMedGoogle Scholar
  • 23 Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial.  Lancet. 2000;  355(9212) 1295-1302
    CrossrefPubMedGoogle Scholar
  • 24 Karon C, Julian J A, Newman T E, Ginsberg J S. for the McMaster Diagnostic Imaging Practice Guidelines Initiative.  Non-invasive diagnosis of deep vein thrombosis  Ann Intern Med . 1998;  128 663-677
    Google Scholar
  • 25 Lagerstedt C I, Olsson C G, Fagher B O, Oqvist B W, Albrechtsson U. Need for long-term anticoagulant treatment in symptomatic calf-vein thrombosis.  Lancet . 1985;  515-518
    PubMedGoogle Scholar
  • 26 Heijboer H, Buller H R, Lensing A WA, Turpie A GG, Colly L P, ten Cate J W. A comparison of real-time compression ultrasonography with impedance plethysmography for the diagnosis of deep-vein thrombosis in symptomatic outpatients.  N Engl J Med . 1993;  329 1365-1369
    Google Scholar
  • 27 Hull R, Hirsh J, Sackett D L, Powers P, Turpie A GG, Walker I. Combined use of leg scanning and impedance plethysmography in suspected venous thrombosis. An alternative to venography.  N Engl J Med . 1977;  296 1497-1500
    CrossrefPubMedGoogle Scholar
  • 28 Hull R, Hirsh J, Sackett D L. Replacement of venography in suspected venous thrombosis by impedence plethysmography and 125I-fibrinogen leg scanning.  Ann Intern Med . 1981;  94 12-15
    CrossrefPubMedGoogle Scholar
  • 29 Doyle D J, Turpie A GG, Hirsh J. Adjusted subcutaneous heparin or continuous intravenous heparin in patients with acute deep vein thrombosis.  Ann Intern Med . 1987;  107 441-445
    PubMedGoogle Scholar
  • 30 Moser K M, Fedullo P F, LittleJohn J K, Crawford R. Frequent asymptomatic pulmonary embolism in patients with deep venous thrombosis.  JAMA . 1994;  27 223-225
    PubMedGoogle Scholar
  • 31 Nielsen H K, Husted S E, Krusell L R, Fasting H, Hansen P C, Hansen H H. Silent pulmonary embolism in patients with deep venous thrombosis. Incidence and fate in a randomized, controlled trial of anticoagulation versus no anticoagulation.  J Intern Med . 1994;  235 457-461
    CrossrefPubMedGoogle Scholar
  • 32 Huisman M V, Buller H R, ten Cate J. Unexpected high prevalence of silent pulmonary embolism in patients with deep venous thrombosis.  Chest . 1989;  95 498-502
    CrossrefPubMedGoogle Scholar
  • 33 Dorfman G S, Cronan J J, Tupper T B, Messersmith R N, Denny D F, Lee C H. Occult pulmonary embolism: a common occurrence in deep venous thrombosis.  AJR . 1987;  148 263-266
    PubMedGoogle Scholar
  • 34 Hull R D, Hirsh J, Carter C J. Diagnostic value of ventilation-perfusion lung scanning in patients with suspected pulmonary embolism.  Chest . 1985;  88 819-828
    PubMedGoogle Scholar
  • 35 The PIOPED investigators. Value of the ventilation perfusion scan in acute pulmonary embolism.  JAMA . 1990;  263 2753-2759
    Google Scholar
  • 36 Hull R, Delmore T, Genton E. Warfarin sodium versus low-dose heparin in the long-term treatment of venous thrombosis.  N Engl J Med . 1979;  301 855-858
    CrossrefPubMedGoogle Scholar
  • 37 Nielsen H K, Husted S E, Krusell L R. Anticoagulant therapy in deep venous thrombosis. A randomized controlled study.  Thromb Res . 1994;  73 215-226
    CrossrefPubMedGoogle Scholar
  • 38 Barritt D W, Jordan S C. Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial.  Lancet . 1960;  1 1309-1312
    PubMedGoogle Scholar
  • 39 Coon W W, Willis P W. Recurrence of venous thromboembolism.  Surgery . 1973;  73 823-827
    PubMedGoogle Scholar
  • 40 Prandoni P, Lensing A WA, Cogo A. The long-term clinical course of acute deep venous thrombosis.  Ann Intern Med . 1996;  125 1-7
    CrossrefPubMedGoogle Scholar
  • 41 Research Committee of the British Thoracic Society. Optimum duration of anticoagulation for deep-vein thrombosis and pulmonary embolism.  Lancet . 1992;  340 873-876
    PubMedGoogle Scholar
  • 42 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 deep vein thrombosis.  Thromb Haemost . 1995;  74 606-611
    PubMedGoogle Scholar
  • 43 Schulman S, Rhedin A-S, Lindmarker P. 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 1661-1665
    CrossrefPubMedGoogle Scholar
  • 44 Kearon C, Gent M, Hirsh J. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism.  N Engl J Med . 1999;  340 901-907
    PubMedGoogle Scholar
  • 45 Pini M, Aiello S, Manotti C. Low molecular weight heparin versus warfarin the prevention of recurrence after deep vein thrombosis.  Thromb Haemost . 1994;  72 191-197
    PubMedGoogle Scholar
  • 46 Kalodiki E, Domjan J, Nicolaides A N. V/Q defects and deep venous thrombosis following total hip replacement.  Clin Radiol . 1995;  50 400-403
    PubMedGoogle Scholar
  • 47 Philbrick J T, Becker D M. Calf deep venous thrombosis: A wolf in sheep's clothing?.  Arch Intern Med . 1988;  148 2131-2138
    CrossrefPubMedGoogle Scholar
  • 48 Stein P D, Henry J W. Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy.  Chest . 1995;  108 978-981
    CrossrefPubMedGoogle Scholar
  • 49 Bell W R, Simon T L. Current status of pulmonary embolic disease: pathophysiology, diagnosis, prevention, and treatment.  Am Heart J . 1982;  103 239-261
    CrossrefPubMedGoogle Scholar
  • 50 Morganthaler T I, Ryu J H. Clinical characterisitics of fatal pulmonary embolism in a referral hospital.  Mayo Clin Proc . 1995;  70 417-424
    CrossrefPubMedGoogle Scholar
  • 51 Bergqvist D, Lindblad B. A 30 year survey of pulmonary embolism verified at autopsy: an analysis of 1274 surgical patients.  Br J Surg . 1985;  72 105-108
    PubMedGoogle Scholar
  • 52 Rasmussen M S, Wille-Jorgensen P, Jorgensen L N. Postoperative fatal pulmonary embolism in a general surgical department.  Am J Surg . 1995;  169 214-216
    CrossrefPubMedGoogle Scholar
  • 53 Stein P D, Henry J W, Relyea B. Untreated patients with pulmonary embolism: outcome, clinical, and laboratory assessment.  Chest . 1995;  107 931-935
    PubMedGoogle Scholar
  • 54 Sevitt S, Gallagher N G. Prevention of venous thrombosis and pulmonary embolism in injured patients.  Lancet . 1959;  ii 981-989
    PubMedGoogle Scholar
  • 55 Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin.  N Engl J Med . 1988;  318 1162-1173
    CrossrefPubMedGoogle Scholar
  • 56 Clagett G P, Reisch J S. Prevention of venous thromboembolism in general surgical patients. Results of meta-analysis.  Ann Surg . 1988;  208 227-240
    CrossrefPubMedGoogle Scholar
  • 57 Douketis J D, Kearon C, Bates S, Duku E K, Ginsberg J S. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism.  JAMA . 1998;  279 458-462
    CrossrefPubMedGoogle Scholar
  • 58 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;  100 269-277
    CrossrefPubMedGoogle Scholar
  • 59 Hutten B A, Prins M, Gent M, Ginsberg J, Tijssen J, Buller H. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis.  J Clin Oncol . 2000;  18 3078-3083
    PubMedGoogle Scholar
  • 60 Palareti G, Legnani C, Lee A. A comparison of the safety and efficacy of oral anticoagulation for the treatment of venous thromboembolic disease in patients with or without malignancy.  Thromb Haemost . 2000;  84 805-810
    Article in Thieme ConnectPubMedGoogle Scholar
  • 61 Holmstrom M, Lindmarker P, Granqvist S, Johnsson H, Lockner D. A 6-month venographic follow-up in 164 patients with acute deep vein thrombosis.  Thromb Haemost . 1997;  78 803-807
    PubMedGoogle Scholar
  • 62 Heijboer H, Jongbloets L MM, Buller H R, Lensing A WA, ten Cate W J. Clinical utility of real-time compression ultrasonography for diagnostic management of patients with recurrent venous thrombosis.  Acta Radiologica . 1992;  33 297-300
    CrossrefPubMedGoogle Scholar
  • 63 Prandoni P, Cogo A, Bernardi E. A simple ultrasound approach for detection of recurrent proximal vein thrombosis.  Circulation . 1993;  88 1730-1735
    CrossrefPubMedGoogle Scholar
  • 64 Jay R, Hull R, Carter C. Outcome of abnormal impedance plethysmography results in patients with proximal-vein thrombosis: frequency of return to normal.  Thromb Res . 1984;  36 259-263
    CrossrefPubMedGoogle Scholar
  • 65 Huisman M V, Buller H R, ten Cate W J. Utility of impedance plethysmography in the diagnosis of recurrent deep-vein thrombosis.  Arch Intern Med . 1988;  148 681-519
    PubMedGoogle Scholar
  • 66 Hirsh J, Lensing A. Thrombolytic therapy for deep vein thrombosis.  Int Angiol . 1996;  5 S22-S25
    PubMedGoogle Scholar
  • 67 Elliot M S, Immelman E J, Jeffery P. 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
    CrossrefPubMedGoogle Scholar
  • 68 Turpie A GG, Levine M N, Hirsh J. Tissue plasminogen activator (rt-PA) vs heparin in deep vein thrombosis.  Chest . 1990;  97 172S-175S
    PubMedGoogle Scholar
  • 69 Schweizer J, Kirch W, Koch R. Short- and long-term results after thrombolytic treatment of deep venous thrombosis.  Am Coll Cardiol . 2000;  36 1336-1343
    PubMedGoogle Scholar
  • 70 Negus D. The post-thrombotic syndrome.  Ann R Coll Surg Engl . 1970;  47 92-105
    PubMedGoogle Scholar
  • 71 Johansson L, Nylander G, Hedner U, Nilsson I M. Comparison of streptokinase with heparin: late results in the treatment of deep venous thrombosis.  Acta Med Scand . 1979;  206 93-98
    PubMedGoogle Scholar
  • 72 Kakkar V V, Lawrence D. Hemodynamic and clinical assessment after therapy for acute deep vein thrombosis.  Am J Surg . 1985;  150 54-63
    PubMedGoogle Scholar
  • 73 Lindner D J, Edwards J M, Phinney E S, Taylor L M, Porter J M. Long-term hemodynamic and clinical sequelae of lower extremity deep vein thrombosis.  J Vasc Surg . 1986;  4 436-442
    CrossrefPubMedGoogle Scholar
  • 74 McEnroe C S, O'Donnell T F, Mackey W C. Correlation of clinical findings with venous hemodynamics in 386 patients with chronic venous insufficiency.  Am J Surg . 1988;  156 148-152
    PubMedGoogle Scholar
  • 75 Ginsberg J S, Shin A, Turpie A GG, Hirsh J. Detection of previous proximal venous thrombosis with Doppler ultrasonography and photoplethysmography.  Arch Intern Med . 1989;  149 2255-2261
    CrossrefPubMedGoogle Scholar
  • 76 Strandness D E, Langlois Y, Cramer C, Randlett A, Thiele B L. Long-term sequelae of acute venous thormbosis.  JAMA . 1983;  250 1289-1292
    CrossrefPubMedGoogle Scholar
  • 77 Heldal M, Seem E, Sandset P M, Abildgaard U. Deep vein thrombosis: a 7-year follow-up study.  J Intern Med . 1993;  234 71-75
    PubMedGoogle Scholar
  • 78 Biguzzi E, Mozzi E, Alatri A, Taioli E, Moia M, Mannucci P M. The post-thrombotic syndrome in young women: retrospective evaluation of prognostic factors.  Thromb Haemost . 1998;  80 575-577
    PubMedGoogle Scholar
  • 79 Ginsberg J S, Turkstra F, Buller H R, MacKinnon B, Magier D, Hirsh J. Postthrombotic syndrome after hip or knee arthroplasty: a cross-sectional study.  Arch Intern Med . 2000;  160 669-672
    CrossrefPubMedGoogle Scholar
  • 80 Lindhagen A, Bergqvist D, Hallbook T, Efsing H O. Venous function five to eight years after clinically suspected deep venous thrombosis.  Acta Med Scand . 1985;  217 389-395
    PubMedGoogle Scholar
  • 81 Kahn S R, Solymoss S, Lamping D L, Abenhaim L. Long-term outcomes after deep vein thrombosis: postphlebitic syndrome and quality of life.  J Gen Intern Med . 2000;  15 425-429
    CrossrefPubMedGoogle Scholar
  • 82 Prandoni P, Lensing A W, Prins M H, Bagatella P, Scudeller A, Girolami A. Which is the outcome of the post-thrombotic syndrome?.  <~>[published erratum appears in Thromb Haemost 1999 Nov;82:XII]. Thromb Haemost . 1999;  82 1358
    PubMedGoogle Scholar
  • 83 Brandjes D PM, Büller H R, Heijboer H. Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis.  Lancet . 1997;  349 759-762
    CrossrefPubMedGoogle Scholar
  • 84 Cockett F B, Lea Thomas M, Negus D. Iliac vein compression. Its relation to iliofemoral thrombosis and the post-thrombotic syndrome.  Br Med J . 1967;  2 14-19
    PubMedGoogle Scholar
  • 85 Cockett F B, Lea Thomas M. The illiac compression syndrome.  Br J Surg . 1965;  52 816-821
    CrossrefPubMedGoogle Scholar
  • 86 Qvarfordt P, Eklof B, Ohlin P, Plate G, Saltin B. Intramuscular pressure, blood flow, and skeletal muscle metabolism in patients with venous claudication.  Surgery . 1984;  95 191-195
    PubMedGoogle Scholar
  • 87 Christenson J T, Al-Hassan H K, Shawa N J. Subcutaneous and intramuscular pressures in the post-phlebitic limb.  Scand J Clin Lab Invest . 1986;  46 137-141
    PubMedGoogle Scholar
  • 88 Barnett H G, Clifford J R, Llewellyn R C. Safety of mini-dose heparin administration for neurosurgical patients.  J Neurosurg . 1977;  47 27-30
    CrossrefPubMedGoogle Scholar
  • 89 Grifoni S, Olivotto I, Cecchini P. Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction.  Circulation . 2000;  101 2817-2822
    CrossrefPubMedGoogle Scholar
  • 90 Jerjes-Sanchez C, Ramirez-Rivera A, de Lourdes Garcia M. Streprokinase and heparin versus heparin alone in massive pulmonary embolism: a randomized controlled trial.  J Thromb Thrombolys . 1995;  2 227-229
    CrossrefPubMedGoogle Scholar
  • 91 Goldhaber S Z. Pulmonary embolism.  N Engl J Med . 1998;  339 93-104
    CrossrefPubMedGoogle Scholar
  • 92 Dalen J E, Alpert J S, Hirsh J. Thrombolytic therapy for pulmonary embolism. Is it effective?.  <~>Is it safe? <~>When is it indicated? Arch Intern Med . 1997;  157 2550-2556
    PubMedGoogle Scholar
  • 93 Goldhaber S Z, Haire W D, Feldstein M L. Aleptase versus heparin in acute pulmonary embolism: randomized trial assessing right-ventricular function and pulmonary perfusion.  Lancet . 1993;  341 507-511
    CrossrefPubMedGoogle Scholar
  • 94 Ribeiro A, Lindmarker P, Juhlin-Dannfelt A, Johnsson H, Jorfeldt L. Echocardiography Doppler in pulmonary embolism: right ventricular dysfunction as a predictor of mortality rate.  Am Heart J . 1997;  134 479-487
    CrossrefPubMedGoogle Scholar
  • 95 Goldhaber S Z, Visni L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER).  Lancet . 1999;  353 1386-1389
    CrossrefPubMedGoogle Scholar
  • 96 Verstraete M, Hellemans J, Vermylen C, Vorlat M. On the concept of slowly and rapidly acting coumarin drugs.  Acta Haemat . 1963;  30 181-189
    PubMedGoogle Scholar
  • 97 Miller R L, Das S, Anandarangam T. Association between right ventricular function and perfusion abnormalities in hemodynamically stable patients with acute pulmonary embolism.  Chest . 1998;  113 665-670
    CrossrefPubMedGoogle Scholar
  • 98 Carson J L, Kelley M A, Duff A. The clinical course of pulmonary embolism.  N Engl J Med . 1992;  326 1240-1245
    CrossrefPubMedGoogle Scholar
  • 99 van Beek J R E, Kuijer P MM, Buller H R, Brandjes D PM, Bossuyt P MM, ten Cate W J. The clinical course of patients with suspected pulmonay embolism.  Arch Intern Med . 1997;  157 2593-2598
    CrossrefPubMedGoogle Scholar
  • 100 Ribeiro A, Lindmarker P, Johnsson H, Juhlin-Dannfelt A, Jorfeldt L. Pulmonary embolism. One year follow-up with echocardiography doppler and five-year survival analysis.  Circulation . 1999;  99 1325-1330
    CrossrefPubMedGoogle Scholar
  • 101 Wicki J, Perrier A, Perneger T V, Bounameaux H, Junod A F. Predicting adverse outcome in patients with acute pulmonary embolism: a risk score.  Thromb Haemost . 2000;  84 548-552
    Article in Thieme ConnectPubMedGoogle Scholar
  • 102 Heit J A, Silverstein M D, Mohr D N, Petterson T M, O'Fallon W M, Melton III J L. Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based, cohort study.  Arch Intern Med . 1999;  159 445-453
    CrossrefPubMedGoogle Scholar
  • 103 McIntyre K M, Sasahara A A. The hemodynamic response to pulmonary embolism in patients without prior cardiopulmonary disease.  Am J Cardiol . 1971;  28 288-294
    CrossrefPubMedGoogle Scholar
  • 104 Dalen J E, Banas J S, Brooks H L, Evans G L, Paraskos J A, Dexter L. Resolution rate of acute pulmonary embolism in man.  N Engl J Med . 1969;  280 1194-1199
    PubMedGoogle Scholar
  • 105 Rosenberg R D, Aird W C. Vascular-bed-specific hemostasis and hypercoagulable states.  N Engl J Med . 1999;  340 1555-1564
    CrossrefPubMedGoogle Scholar
  • 106 Blackmon J R, Sautter R D, Wagner H N. Urokinase pulmonary embolism trial: phase I results.  JAMA . 1970;  214 2163-2172
    CrossrefPubMedGoogle Scholar
  • 107 Levine M, Hirsh J, Weitz J. A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism.  Chest . 1990;  98 1473-1479
    CrossrefPubMedGoogle Scholar
  • 108 PIOPED Investigators. Tissue plasminogen activator for the treatment of acute pulmonary embolism.  Chest . 1990;  97 528-533
    PubMedGoogle Scholar
  • 109 Dalla-Volta S, Palla A. PAIMS 2-alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism: Plasminogen Activator Italian Multicenter Study 2.  J Am Coll Cardiol . 1992;  20 520-526
    CrossrefPubMedGoogle Scholar
  • 110 Paraskos J A, Adelstein S J, Smith R E. Late prognosis of acute pulmonary embolism.  N Engl J Med . 1973;  289 55-58
    PubMedGoogle Scholar
  • 111 Hall R JC, Sutton G C, Kerr I H. Long-term prognosis of treated acute massive pulmonary embolism.  Br Heart J . 1977;  39 1128-1134
    PubMedGoogle Scholar
  • 112 Riedel M, Stanek V, Widimsky J. Long term follow-up of patients with pulmonary thromboembolism: late prognosis and evolution of hemodynamic and respiratory data.  Chest . 1982;  81 151-158
    CrossrefPubMedGoogle Scholar
  • 113 Moser K M, Auger W R, Fedullo P F. Chronic major-vessel thromboembolic pulmonary hypertension.  Circulation . 1990;  81 1735-1743
    CrossrefPubMedGoogle Scholar
  • 114 Couturaud F, Kearon C. Long-term treatment for venous thromboembolism.  Curr Opin Hematol . 2000;  7 302-308
    CrossrefPubMedGoogle Scholar
  • 115 Brown M, Glassenberg M. Mortality factors in patients with acute stroke.  JAMA . 1973;  224 1493
    CrossrefPubMedGoogle Scholar
  • 116 Schulman S. The effect of the duration of anticoagulation and other risk factors on the recurrence of venous thromboembolisms. Duration of Anticoagulation Study Group.  Wien Med Wochenschr . 1999;  149 66-69
    PubMedGoogle Scholar
  • 117 Kearon C, Crowther M, Hirsh J. Management of patients with hereditary hypercoagulable disorders.  Annu Rev Med . 2000;  51 169-185
    CrossrefPubMedGoogle Scholar
  • 118 Lindmarker P, Schulman S, Sten-Linder M, Wiman B, Egberg N, Johnsson H. The risk of recurrent venous thromboembolism in carriers and non-carriers of the G1691A Allele in the coagulation factor V gene and the G20210A Allele in the prothrombin gene.  Thromb Haemost . 1999;  81 684-689
    Article in Thieme ConnectPubMedGoogle Scholar
  • 119 Eichinger S, Stumpflen A, Hirschl M. Hyperhomocysteinemia is a risk factor of recurrent venous thromboembolism.  Thromb Haemost . 1998;  80 566-569
    PubMedGoogle Scholar
  • 120 Kryle P, Minar E, Hirschl M. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism.  N Engl J Med . 2000;  343 457-462
    CrossrefPubMedGoogle Scholar
  • 121 Ridker P M, Miletich J P, Stampfer M J, Goldhaber S Z, Lindpaintner K, Hennekens C H. Factor V Leiden and risks of recurrent idiopathic venous thromboembolism.  Circulation . 1995;  92 2800-2802
    CrossrefPubMedGoogle Scholar
  • 122 Simioni P, Prandoni P, Lensing A WA. The risk of recurrent venous thromboembolism in patients with an Arg506→Gln mutation in the gene for factor V (factor V Leiden).  N Engl J Med . 1997;  336 399-403
    CrossrefPubMedGoogle Scholar
  • 123 Eichinger S, Minar E, Hirschl M. The risk of early recurrent venous thromboembolism after oral anticoagulant therapy in patients with the G20210A transition in the prothrombin gene.  Thromb Haemost . 1999;  81 14-17
    PubMedGoogle Scholar
  • 124 Eichinger S, Pabinger I, Stumpflen A. The risk of recurrent venous thromboembolism in patients with and without Factor V Leiden.  Thromb Haemost . 1997;  77 624-628
    PubMedGoogle Scholar
  • 125 Schulman S, Granqvist S, Holmström M. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism.  N Engl J Med . 1997;  336 393-398
    CrossrefPubMedGoogle Scholar
  • 126 Schulman S. Optimal duration of oral anticoagulant therapy in venous thromboembolism.  Thromb Haemost . 1997;  78 693-698
    PubMedGoogle Scholar
  • 127 Lindmarker P, Schulman S. The risk of ipsilateral versus contralateral recurrent deep vein thrombosis in the leg. The DURAC Trial Study Group.  J Intern Med . 2000;  247 601-606
    PubMedGoogle Scholar
  • 128 Turkstra F, Karemaker R, Kuijer P MM, Prins M H, Buller H R. Is the prevalence of the factor V Leiden mutation in patients with pulmonary embolism and deep vein thrombosis really different?.  Thromb Haemost . 1999;  81 345-348
    PubMedGoogle Scholar
  • 129 Margaglione M, Brancaccio V, De Lucia D. Inherited thrombophilic risk factors and venous thromboembolism: distinct role in peripheral deep venous thrombosis and pulmonary embolism.  Chest . 2000;  118 1405-1411
    CrossrefPubMedGoogle Scholar
  • 130 Flordal P A, Bergqvist D, Ljungstrom K G, Torngren S. Clinical relevance of the fibrinogen uptake test in patients having general abdominal surgery-relation to major thromboembolism and mortality.  Thromb Res . 1995;  80 491-497
    CrossrefPubMedGoogle Scholar
  • 131 White R H, Romano P S, Zhou H, Rodrigo J, Bargar W. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty.  Arch Intern Med . 1998;  158 1525-1531
    CrossrefPubMedGoogle Scholar
  • 132 Cogo A, Bernardi E, Prandoni P. Acquired risk factors for deep-vein thrombosis in symptomatic outpatients.  Arch Intern Med . 1994;  154 164-167
    CrossrefPubMedGoogle Scholar
  • 133 Hull R D, Hirsh J, Carter C J. Pulmonary angiography, ventilation lung scanning, and venography for clinically suspected pulmonary embolism with abnormal perfusion lung scan.  Ann Intern Med . 1983;  98 891-899
    CrossrefPubMedGoogle Scholar
  • 134 Kruit W HJ, de Boer C A, Sing A K, van Roon F. The significance of venography in the management of patients with clinically suspected pulmonary embolism.  J Intern Med . 1991;  230 333-339
    PubMedGoogle Scholar
  • 135 Kearon C, Ginsberg J S, Hirsh J. The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism.  Ann Intern Med . 1998;  129 1044-1049
    Google Scholar
  • 136 Hull R D, Raskob G E, Coates G, Panju A A, Gill G J. A new noninvasive management strategy for patients with suspected pulmonary embolism.  Arch Intern Med . 1989;  149 2549-2555
    CrossrefPubMedGoogle Scholar
  • 137 Pinede L, Duhaut P, Cucherat M, Ninet J, Pasquier J, Boissel J P. Comparison of long versus short duration of anticoagulant therapy after a first episode of venous thromboembolism: a meta-analysis of randomized, controlled trials.  J Intern Med . 2000;  247 553-562
    CrossrefPubMedGoogle Scholar
  • 138 Schulman S, Svenungsson E, Granqvist S. Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy.  Am J Med . 1998;  104 332-338
    CrossrefPubMedGoogle Scholar
  • 139 Prandoni P, Simioni P, Girolami A. Antiphospholipid antibodies, recurrent thromboembolism, and intensity of warfarin anticoagulation.  Thromb Haemost . 1996;  75 859
    PubMedGoogle Scholar
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