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Original Research: VENOUS THROMBOEMBOLISM |

The Natural Course of Hemodynamically Stable Pulmonary Embolism*: Clinical Outcome and Risk Factors in a Large Prospective Cohort Study

Mathilde Nijkeuter, MD; Maaike Söhne, MD; Lidwine W. Tick, MD; Pieter Willem Kamphuisen, MD; Mark H. H. Kramer, MD; Laurens Laterveer, MD; Anja A. van Houten, MD; Marieke J. H. A. Kruip, MD; Frank W. G. Leebeek, MD; Harry R. Büller, MD; Menno V. Huisman, MD
Author and Funding Information

Affiliations: *From the Vascular Unit, Department of Internal Medicine-Endocrinology (Drs. Nijkeuter and Huisman), Leiden University Medical Center, Leiden; Department of Vascular Medicine (Drs. Söhne and Büller), Academic Medical Center, Amsterdam; Department of Internal Medicine (Drs. Tick and Kramer), Meander Medical Center, Amersfoort; Department of General Internal Medicine (Dr. Kamphuisen), St. Radboud University Medical Center, Nijmegen; Department of Internal Medicine (Dr. Laterveer), Diakonessen Hospital, Meppel; Department of Internal Medicine (Dr. van Houten), Medical Center Rijnmond Zuid, Rotterdam; and Department of Hematology (Drs. Kruip and Leebeek), Erasmus University Medical Center, Rotterdam, the Netherlands.,  On behalf of the Christopher Study Investigators. A list is given in the Appendix.

Correspondence to: Mathilde Nijkeuter, MD, Department of General Internal Medicine and Endocrinology, Post zone C4-R 70, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, the Netherlands; e-mail: M.Nijkeuter@lumc.nl



Chest. 2007;131(2):517-523. doi:10.1378/chest.05-2799
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Background: Pulmonary embolism (PE) is a potentially fatal disease with risks of recurrent venous thrombotic events (venous thromboembolism [VTE]) and major bleeding from anticoagulant therapy. Identifying risk factors for recurrent VTE, bleeding, and mortality may guide clinical decision making.

Objective: To evaluate the incidence of recurrent VTE, hemorrhagic complications, and mortality in patients with PE, and to identify risk factors and the time course of these events.

Design: We evaluated consecutive patients with PE derived from a prospective management study, who were followed for 3 months, treated with anticoagulants, and underwent objective diagnostic testing for suspected recurrent VTE or bleeding.

Results: Of 673 patients with complete follow-up, 20 patients (3.0%; 95% confidence interval [CI], 1.8 to 4.6%) had recurrent VTE. Eleven of 14 patients with recurrent PE had a fatal PE (79%; 95% CI, 49 to 95%), occurring mostly in the first week after diagnosis of initial PE. In 23 patients (3.4%; 95% CI, 2.2 to 5.1%), a hemorrhagic complication occurred, 10 of which were major bleeds (1.5%; 95% CI, 0.7 to 2.7%), and 2 were fatal (0.3%; 95% CI, 0.04 to 1.1%). During the 3-month follow-up, 55 patients died (8.2%; 95% CI, 6.2 to 10.5%). Risk factors for recurrent VTE were immobilization for > 3 days and being an inpatient; having COPD or malignancies were risk factors for bleeding. Higher age, immobilization, malignancy, and being an inpatient were risk factors for mortality.

Conclusions: Recurrent VTE occurred in a small percentage of patients treated for an acute PE, and the majority of recurrent PEs were fatal. Immobilization, hospitalization, age, COPD, and malignancies were risk factors for recurrent VTE, bleeding, and mortality. Close monitoring may be indicated in these patients, precluding them from out-of-hospital start of treatment.

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