Risk of recurrent venous thromboembolism and major hemorrhage in cancer-associated incidental pulmonary embolism among treated and untreated patients: a pooled analysis of 926 patients

J Thromb Haemost. 2016 Jan;14(1):105-13. doi: 10.1111/jth.13172. Epub 2016 Jan 11.


ESSENTIALS: We performed a pooled analysis of 926 patients with cancer-associated incidental pulmonary embolism (IPE). Vitamin K antagonists (VKA) are associated with a higher risk of major hemorrhage. Recurrence risk is comparable after subsegmental and more proximally localized IPE. Our results support low molecular weight heparins over VKA and similar management of subsegmental IPE.

Background: Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on computed tomography scanning not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management.

Methods: Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major hemorrhage, and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization, and management were performed.

Results: In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major hemorrhage and mortality were 5.8% (95% confidence interval [CI] 3.7-8.3%), 4.7% (95% CI 3.0-6.8%), and 37% (95% CI 28-47%). VTE recurrence risk was comparable under low molecular weight heparins (LMWH) and vitamin K antagonists (VKAs) (6.2% vs. 6.4%; hazard ratio [HR] 0.9; 95% CI 0.3-3.1), while 12% in untreated patients (HR 2.6; 95% CI 0.91-7.3). Risk of major hemorrhage was higher under VKAs than under LMWH (13% vs. 3.9%; HR 3.9; 95% CI 1.6-10). VTE recurrence risk was comparable in patients with an subsegmental IPE and those with a more proximally localized IPE (HR 1.1; 95% CI 0.50-2.4).

Conclusion: These results support the current recommendation to anticoagulate cancer-associated IPE with LMWH and argue against different management of subsegmental IPE.

Keywords: hemorrhage; incidental finding; prognosis; pulmonary embolism; venous thromboembolism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use
  • Cohort Studies
  • Data Interpretation, Statistical
  • Female
  • Follow-Up Studies
  • Hemorrhage / complications*
  • Hemorrhage / diagnosis
  • Hemorrhage / prevention & control
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Neoplasms / complications*
  • Pulmonary Embolism / complications*
  • Pulmonary Embolism / diagnosis
  • Recurrence
  • Registries
  • Risk Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Venous Thromboembolism / complications*
  • Venous Thromboembolism / diagnosis
  • Vitamin K / antagonists & inhibitors
  • Young Adult


  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Vitamin K