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Age and gender specific cut-off values to improve the performance of d-dimer assays to predict the risk of venous thromboembolism recurrence

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Abstract

The Prolong study shows that continuing vitamin K antagonists (VKA) in patients with abnormal d-dimer (evaluated by a qualitative assay, Clearview Simplify d-dimer) results in a significant reduction of venous thromboembolism (VTE) recurrence. The present study retrospectively analyzes a subgroup of patients enrolled in the Prolong study with a view to calculate cut-off values for six quantitative d-dimer methods to predict the risk of VTE recurrence. We measured d-dimer levels by VIDAS d-dimer Exclusion (bioMerieux), STA Liatest d-dimer (DiagnosticaStago), HemosIL d-dimer and HemosIL d-dimer HS (Instrumentation Laboratory), Innovance d-dimer (Siemens) and AutoDimer (Trinity Biotech) in frozen plasma aliquots sampled 30 ± 10 days after VKA cessation in 390 patients enrolled in the Prolong study. During follow-up (562.7 years), 28 patients had recurrent VTE (7.2%, 5.0% person-years). Since d-dimer levels are positively correlated with age and significantly lower in men, we calculated method-specific cut-off values according to age and gender. The HRs for VTE recurrence calculated using method-specific cut-off values based on age and gender are higher than those using cut-off values indicated by the manufacturers for VTE exclusion in symptomatic outpatients. These data suggest that method-specific cut-off values calculated according to patient age and gender can be more accurate in identifying patients at a higher risk for VTE recurrence. These method-specific cut-off values are being evaluated in the ongoing prospective management multicenter DULCIS study.

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Acknowledgments

We would like to thank bioMerieux (Lyon, France), Instrumentation Laboratory (Milan, Italy), Roche Diagnostics (Monza, Italy) and Siemens (Milan, Italy) for providing all d-dimer reagents, and Stephen Jewkes for editing the English text. This study was supported by the Italian Federation of Thrombosis Centers (FCSA).

Conflict of interest

Drs. Legnani, Palareti, Cosmi, Tripodi report having received lecture fees from Instrumentation Laboratory. Drs. Legnani and Palareti report having received lecture fees also from Roche Diagnostics.

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Authors and Affiliations

  1. Department of Angiology and Blood Coagulation “Marino Golinelli”, University Hospital S.Orsola-Malpighi, Via Albertoni, 15, 40138, Bologna, Italy

    Cristina Legnani, Michela Cini, Benilde Cosmi & Gualtiero Palareti

  2. Department of Laboratory Medicine, Azienda ULSS 16 and Azienda Ospedaliera-Universitaria, Padua, Italy

    Paolo Carraro

  3. Department of Internal Medicine, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, University and IRCCS Maggiore Hospital, Milan, Italy

    Armando Tripodi

  4. Transfusion Medicine, District Hospital, Merate, Italy

    Nicoletta Erba

Authors
  1. Cristina Legnani
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  2. Michela Cini
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  3. Benilde Cosmi
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  4. Paolo Carraro
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  5. Armando Tripodi
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  6. Nicoletta Erba
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  7. Gualtiero Palareti
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Corresponding author

Correspondence to Cristina Legnani.

Additional information

On behalf of the Prolong Investigators.

Appendix

Appendix

Study sites and principal investigator (all the participating centers are affiliated in the Italian Federation of Thrombosis Centers—FCSA; number in parentheses are the number of enrolled patients):

U.O. Angiologia e Malattie della Coagulazione “Marino Golinelli”, Policlinico S.Orsola-Malpighi, Bologna—G. Palareti (143, Coordinating Center); A.O. Istituti Ospitalieri, Cremona—S. Testa (60); I° Div. di Medicina Interna—Centro Emostasi e Trombosi, Arcispedale Santa Maria Nuova, Reggio-Emilia—A. Ghirarduzzi (54); Centro Regionale Malattie Emorragiche e Trombotiche—Div. Ematologia, Ospedale S. Bortolo, Vicenza—A. Tosetto (28); Servizio di Prevenzione e Terapia della Trombosi, Ospedale “Ex Busonera”, Padova—V. Pengo (20); Sezione Trasfusionale, Ospedale San Leopoldo Mandic, Merate—N. Erba (17); Centro Sorveglianza Anticoagulati—Malattie della Coagulazione e Angiologia Medica—Div. di Med. Interna, Ospedale “S. Cuore di Gesu’“, Gallipoli—L. Ria (13); Centro Emostasi, Ospedale Regionale, Parma—C. Pattacini (13); Laboratorio Analisi—Divisione di Cardiologia, Ospedale di Bentivoglio—E. Cerè (11); Laboratorio Analisi—Ambulatorio per il Controllo della Terapia Anticoagulante Orale, Presidio Ospedaliero di Faenza—E. Bucherini (11); Laboratorio di Patologia Clinica, Presidio Ospedaliero S.Maria Incoronata dell’Olmo, Cava dei Tirreni—C. Villani (8); Centro Trombosi, A.O. di Careggi Universita’ di Firenze—D. Prisco (5); U.O. Medicina Interna, Policlinico Universitario Messina—A. Trifiletti (5); Centro per lo Studio delle Coagulopatie a Rischio Trombotico, Osp. Galliera, Genova—A. Schenone (2).

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Legnani, C., Cini, M., Cosmi, B. et al. Age and gender specific cut-off values to improve the performance of d-dimer assays to predict the risk of venous thromboembolism recurrence. Intern Emerg Med 8, 229–236 (2013). https://doi.org/10.1007/s11739-011-0608-5

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  • DOI: https://doi.org/10.1007/s11739-011-0608-5

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