Use of D-dimer testing to determine duration of anticoagulation, risk of cardiovascular events and occult cancer after a first episode of idiopathic venous thromboembolism: the extended follow-up of the PROLONG study

  • Benilde Cosmi
  • Cristina Legnani
  • Alberto Tosetto
  • Vittorio Pengo
  • Angelo Ghirarduzzi
  • Adriano Alatri
  • Domenico Prisco
  • Daniela Poli
  • Armando Tripodi
  • Gualtiero Palareti


Background The PROLONG study showed that D-dimer (D-d) testing could help tailor the duration of anticoagulation after idiopathic venous thromboembolism (VTE). In this report the initial 18 month study follow-up was extended for 1 year. Materials and Methods D-d was measured 1 month after anticoagulation withdrawal for a first episode of idiopathic VTE. Patients with a normal D-d did not resume anticoagulation, while patients with an abnormal D-d were randomized to either resume or not resume treatment. The primary outcome was the composite of recurrent VTE and major bleeding. Secondary end-points were cardiovascular events, newly diagnosed cancers and deaths. Results D-d was abnormal in 222/608 (36.5%) patients. Average follow-up was 2.55 years. Twenty-eight events occurred in the 121 patients who stopped anticoagulation (23.1%, 9.6% person-years) and five in the 101 patients who resumed anticoagulation (5.0%, 2.0% person-years, adjusted hazard ratio-HR = 3.76; P = 0.008). Recurrence rate was higher in patients with abnormal D-d who stopped anticoagulation than in patients with normal D-d (51 events in 386 patients −13.2%; 5% person-years; adjusted HR 1.70; P = 0.045). The adjusted HR ratio associated with normal D-d versus abnormal D-d in patients who resumed anticoagulation was 2.7 (P = 0.042). An abnormal D-d was associated with a non significant higher risk of cardiovascular events and newly diagnosed cancers vs normal D-d. Conclusions Patients with an abnormal D-d at 1 month after withdrawal of VKA have a significant risk of recurrence over a 2.55 year follow-up and they benefit from resuming anticoagulation.


Venous thromboembolism Recurrence D-dimer Vitamin K antagonists Cardiovascular disease Cancer 



The study was supported by the Italian Federation of Anticoagulation Clinics (FCSA) and by the Department of Angiology and Blood Coagulation of the University Hospital S. Orsola-Malpighi of Bologna (Coordinating Center), Italy. The Instrumentation Laboratory company (Milan) provided the kits for D-dimer measurement (Clearview Simplify-D dimer test). Disclosure: Drs. Palareti, Cosmi, Legnani, Pengo, Testa, and Tripodi report having been paid lecture fees by the Instrumentation Laboratory company, Milan Italy.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Benilde Cosmi
    • 1
  • Cristina Legnani
    • 1
  • Alberto Tosetto
    • 2
  • Vittorio Pengo
    • 3
  • Angelo Ghirarduzzi
    • 4
  • Adriano Alatri
    • 5
  • Domenico Prisco
    • 6
  • Daniela Poli
    • 6
  • Armando Tripodi
    • 7
  • Gualtiero Palareti
    • 1
  1. 1.Department Angiology and Blood Coagulation “Marino Golinelli”S. Orsola-Malpighi University HospitalBolognaItaly
  2. 2.Department of HematologyS. Bortolo HospitalVicenzaItaly
  3. 3.Department Clinical and Experimental Medicine, Division of Clinical CardiologyUniversity HospitalPaduaItaly
  4. 4.Department Internal Medicine I, AngiologyArcispedale Santa Maria NuovaReggio EmiliaItaly
  5. 5.Haemostasis and Thrombosis CenterGeneral HospitalCremonaItaly
  6. 6.Centro TrombosiA.O. di Careggi, Università di FirenzeFirenzeItaly
  7. 7.Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department Internal MedicineUniversity and IRCCS Maggiore HospitalMilanItaly

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