Symptomatic Pulmonary Embolism and the Risk of Recurrent Venous Thromboembolism | Venous Thromboembolism | JAMA Internal Medicine | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Andersen  FA  JrWheeler  HBGoldbery  RJ  et al.  A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism: the Worcester DVT Study.  Arch Intern Med. 1991;151933- 938PubMedGoogle ScholarCrossref
Kniffin  WDBaron  JABarrett  JBirkmeyer  JDAnderson  FA  Jr The epidemiology of diagnosed pulmonary embolism and deep vein thrombosis in the elderly.  Arch Intern Med. 1994;154861- 866PubMedGoogle ScholarCrossref
Silverstein  MDHeit  JAMohr  DNPetterson  TMO'Fallon  WMMelton III  LJ Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study.  Arch Intern Med. 1998;158585- 593PubMedGoogle ScholarCrossref
Dalen  JEAlpert  JS Natural history of pulmonary embolism.  Prog Cardiovasc Dis. 1975;17259- 270PubMedGoogle ScholarCrossref
Goldhaber  SZVisani  LDe Rosa  Mfor the International Cooperative Pulmonary Embolism Registry (ICOPR), Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry.  Lancet. 1999;3531386- 1389PubMedGoogle ScholarCrossref
Goldhaber  SZ Pulmonary embolism.  N Engl J Med. 1998;33993- 110PubMedGoogle ScholarCrossref
Carson  JLKelly  MADuff  A  et al.  The clinical course of pulmonary embolism.  N Engl J Med. 1992;3261240- 1245PubMedGoogle ScholarCrossref
Van Beek  EJRKuijer  PMMBüller  HRBrandjes  DPBossuyt  PMten Cate  JW The clinical course of patients with suspected pulmonary embolism.  Arch Intern Med. 1997;1572593- 2598PubMedGoogle ScholarCrossref
Schulman  SRhedin  ASLindmarker  P  et al. 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;3321661- 1665PubMedGoogle ScholarCrossref
Kearon  CGent  MHirsh  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;340901- 907PubMedGoogle ScholarCrossref
Palareti  GLeali  NCoccheri  S  et al.  Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT): Italian Study on Complications of Oral Anticoagulant Therapy.  Lancet. 1996;348423- 428PubMedGoogle ScholarCrossref
van der Meer  FJRosendaal  FRVandenbroucke  JPBriet  E Assessment of a bleeding risk index in two cohorts of patients treated with oral anticoagulants.  Thromb Haemost. 1996;7612- 16PubMedGoogle Scholar
Levine  MNRaskob  GLandefeld  SKearon  C Hemorrhagic complications of anticoagulant treatment.  Chest. 2001;119(1, suppl)108S- 113SPubMedGoogle ScholarCrossref
Pinede  LNinet  JDuhaut  P  et al.  Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis.  Circulation. 2001;1032453- 2460PubMedGoogle ScholarCrossref
Agnelli  GPrandoni  PSantamaria  MG  et al.  Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis.  N Engl J Med. 2001;345165- 169PubMedGoogle ScholarCrossref
PIOPED Investigators, Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED).  JAMA. 1990;2632753- 2759PubMedGoogle ScholarCrossref
Bertina  RMKoeleman  BPKoster  T  et al.  Mutation in blood coagulation factor V associated with resistance to activated protein C.  Nature. 1994;36964- 67PubMedGoogle ScholarCrossref
Poort  SRRosendaal  FRReitsma  PHBertina  RM A common genetic variation in the 3′-untranslated region of the prothrombin gene.  Blood. 1996;883698- 3703PubMedGoogle Scholar
Kyrle  PAMinar  EHirschl  M  et al.  High plasma levels of factor VIII and the risk of recurrent venous thromboembolism.  N Engl J Med. 2000;343457- 462PubMedGoogle ScholarCrossref
Brandt  JTTriplett  DAAlving  BScharrer  Ifor the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH, Criteria for the diagnosis of lupus anticoagulants: an update.  Thromb Haemost. 1995;741185- 1190PubMedGoogle Scholar
Kalbfleisch  JDPrentice  RL The Statistical Analysis of Failure Time Data.  New York, NY John Wiley & Sons1980;
Kaplan  ELMeier  P Nonparametric estimation from incomplete observations.  J Am Stat Assoc. 1958;53457- 481Google ScholarCrossref
Columbus Investigators, Low-molecular-weight heparin in the treatment of patients with venous thromboembolism.  N Engl J Med. 1997;337657- 662PubMedGoogle ScholarCrossref
Douketis  JDKearon  CBates  SDuku  EKGinsberg  JS Risk of fatal pulmonary embolism in patients with treated venous thromboembolism.  JAMA. 1998;279458- 462PubMedGoogle ScholarCrossref
Murin  SRomano  PSWhite  RH Comparison of outcomes after hospitalization for deep vein thrombosis or pulmonary embolism.  Thromb Haemost. 2002;88407- 414PubMedGoogle Scholar
Eichinger  SPabinger  IStümpflen  A  et al.  The risk of recurrent venous thromboembolism in patients with and without factor V Leiden.  Thromb Haemost. 1997;77624- 628PubMedGoogle Scholar
Eichinger  SMinar  EHirschl  M  et al.  The risk of early recurrent venous thromboembolism after oral anticoagulant therapy in patients with the G20210A transition in the prothrombin gene.  Thromb Haemost. 1999;8114- 17PubMedGoogle Scholar
Moser  KMFedullo  PFLitteJohn  JKCrawford  R Frequent asymptomatic pulmonary embolism in patients with deep vein thrombosis.  JAMA. 1994;271223- 225PubMedGoogle ScholarCrossref
Prandoni  PLensing  AWACogo  A  et al.  The long-term clinical course of acute deep venous thrombosis.  Ann Intern Med. 1996;1251- 7PubMedGoogle ScholarCrossref
Prandoni  PLensing  AWPrins  MR Long-term outcomes after deep venous thrombosis of the lower extremities.  Vasc Med. 1998;357- 60Google ScholarCrossref
Original Investigation
January 12, 2004

Symptomatic Pulmonary Embolism and the Risk of Recurrent Venous Thromboembolism

Author Affiliations

From the Division of Hematology and Hemostasis, Department of Internal Medicine I (Drs Eichinger, Weltermann, Stain, Schönauer, and Kyrle), Division of Angiology, Department of Internal Medicine II (Dr Minar), and Institute of Medical Statistics (Dr Schneider), University of Vienna, Vienna, Austria; and Ludwig-Boltzmann Institute for Thrombosis Research, Vienna (Dr Kyrle). The authors have no relevant financial interest in this article.

Arch Intern Med. 2004;164(1):92-96. doi:10.1001/archinte.164.1.92

Background  In patients with a first symptomatic pulmonary embolism (PE), the risk of recurrence is unknown. We therefore investigated the risk of recurrence among patients with spontaneous symptomatic PE and among those with deep vein thrombosis (DVT) without symptoms of PE.

Methods  After discontinuation of secondary thromboprophylaxis for a first venous thromboembolism (VTE), we prospectively observed 436 patients for an average of 30 months. Patients with secondary VTE, natural inhibitor deficiencies, lupus anticoagulant, cancer, long-term antithrombotic therapy, vena cava filters, or pregnancy were excluded. The study outcome was objectively documented recurrent symptomatic VTE.

Results  Recurrent VTE was seen among 28 (17.3%) of 162 patients with symptomatic PE and among 26 (9.5%) of 274 patients with DVT without symptoms of PE. Compared with patients with DVT, the relative risk of recurrent VTE among patients with symptomatic PE was 2.2 (95% confidence interval, 1.3-3.7; P = .005). The relative risk was not affected by age, sex, presence of factor V Leiden or prothrombin G20210A, hyperhomocysteinemia, or high factor VIII levels. Compared with patients with DVT without symptoms of PE, patients with symptomatic PE had an adjusted relative risk of PE at recurrence of 4.0 (95% confidence interval, 1.3-12.3; P = .03).

Conclusion  Patients with a first symptomatic PE not only have a higher risk of recurrent VTE than those with DVT without symptoms of PE, but are also at high risk of symptomatic PE at recurrence.