Article

Journal of Thrombosis and Thrombolysis

, 28:381

First online:

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 CosmiAffiliated withDepartment Angiology and Blood Coagulation “Marino Golinelli”, S. Orsola-Malpighi University Hospital Email author 
  • , Cristina LegnaniAffiliated withDepartment Angiology and Blood Coagulation “Marino Golinelli”, S. Orsola-Malpighi University Hospital
  • , Alberto TosettoAffiliated withDepartment of Hematology, S. Bortolo Hospital
  • , Vittorio PengoAffiliated withDepartment Clinical and Experimental Medicine, Division of Clinical Cardiology, University Hospital
  • , Angelo GhirarduzziAffiliated withDepartment Internal Medicine I, Angiology, Arcispedale Santa Maria Nuova
  • , Adriano AlatriAffiliated withHaemostasis and Thrombosis Center, General Hospital
  • , Domenico PriscoAffiliated withCentro Trombosi, A.O. di Careggi, Università di Firenze
  • , Daniela PoliAffiliated withCentro Trombosi, A.O. di Careggi, Università di Firenze
  • , Armando TripodiAffiliated withAngelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department Internal Medicine, University and IRCCS Maggiore Hospital
    • , Gualtiero PalaretiAffiliated withDepartment Angiology and Blood Coagulation “Marino Golinelli”, S. Orsola-Malpighi University Hospital

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Abstract

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.

Keywords

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