Skip to main content
Log in

Retrospective review of d-dimer testing for venous thrombosis recurrence risk stratification: is this a useful test in the real world?

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Predicting the risk of recurrence after venous thromboembolism (VTE) remains an important clinical challenge. Post-anticoagulation cessation d-dimer has previously been shown to be associated with increased VTE recurrence in unprovoked major VTE, however this is not routinely used clinically and has not been validated in provoked VTE and isolated distal DVT (IDDVT). We aimed to retrospectively evaluate this practice in the real-world setting including examining its use in provoked VTE and IDDVT. Consecutive patients diagnosed with DVT or PE between January 2013 and December 2016 were retrospectively evaluated. Clinical features, VTE risk factors, recurrence and bleeding rates were evaluated for patients with normal and abnormal post-anticoagulation d-dimer, as well as those patients who did not undergo D-dimer testing. Patients with active malignancy, superficial vein thrombosis and inadequate follow-up were excluded. Of the 1033 patients with a diagnosis of VTE in the study period, 173 were included in the “d-dimer tested” group, and 254 in the “d-dimer un-tested” comparison group. Abnormal post-anticoagulation d-dimer was significantly associated with VTE recurrence (HR 5.96, 95% CI 2.15–14.57, p < 0.001). Abnormal d-dimer was also associated with high risk of VTE recurrence in travel-provoked VTE (67.61 events per 100 patient-years), and unprovoked IDDVT (HR 14.37, 95% CI 1.75–117.83, p = 0.013). Males with abnormal post-anticoagulation d-dimer were associated with the highest risk of VTE recurrence (HR 12.95, 95% CI 2.78–60.20, p = 0.001). Patients with unprovoked proximal DVT and/or PE who underwent d-dimer testing had a lower VTE recurrence rate compared to those who did not have d-dimer testing (HR 0.28, 95% CI 0.10–0.80, p = 0.017). We confirm the utility of post-anticoagulation cessation d-dimer testing to stratify VTE recurrence risk in the real-world setting, including potentially a role of this assay for predicting subsequent VTE in travel-provoked VTE and unprovoked IDDVT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Availability of data and material

The dataset for this research can be accessed at Wang, Julie; HO, PRAHLAD; TACEY, MARK (2020): d-dimer shared.xlsx. figshare. Dataset. https://doi.org/10.6084/m9.figshare.11743203.v1.

References

  1. Kearon C (2003) Natural history of venous thromboembolism. Circulation 107:22I–30. https://doi.org/10.1161/01.CIR.0000078464.82671.78

    Article  Google Scholar 

  2. Khan F, Rahman A, Carrier M et al (2019) Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis. BMJ 366:l4363. https://doi.org/10.1136/bmj.l4363

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lim HY, Nandurkar H, Ho P (2018) Direct oral anticoagulants and the paradigm shift in the management of venous thromboembolism. Semin Thromb Hemost 44:261–266. https://doi.org/10.1055/s-0038-1637750

    Article  PubMed  CAS  Google Scholar 

  4. Agnelli G, Büller HR, Cohen A et al (2013) Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369:799–808. https://doi.org/10.1056/NEJMoa1302507

    Article  PubMed  CAS  Google Scholar 

  5. Lip GYH, Pan X, Kamble S et al (2016) Major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin: a “real-world” observational study in the United States. Int J Clin Pract 70:752–763. https://doi.org/10.1111/ijcp.12863

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Yao X, Abraham NS, Sangaralingham LR et al (2016) Effectiveness and safety of dabigatran, rivaroxaban, and apixaban versus warfarin in nonvalvular atrial fibrillation. JAHA 5:1028–1118. https://doi.org/10.1161/JAHA.116.003725

    Article  Google Scholar 

  7. Brook R, Aswapanyawongse O, Tacey M et al (2019) Real-world direct oral anticoagulants experience in atrial fibrillation: falls risk and low dose anticoagulation are predictive of both bleeding and stroke risk. Intern Med J. https://doi.org/10.1111/imj.14640

    Article  PubMed  Google Scholar 

  8. Adam SS, Key NS, Greenberg CS (2009) D-dimer antigen: current concepts and future prospects. Blood 113:2878–2887. https://doi.org/10.1182/blood-2008-06-165845

    Article  PubMed  CAS  Google Scholar 

  9. Palareti G, Cosmi B, Legnani C et al (2006) D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 355:1780–1789. https://doi.org/10.1056/NEJMoa054444

    Article  PubMed  CAS  Google Scholar 

  10. Palareti G, Cosmi B, Legnani C et al (2014) D-dimer to guide the duration of anticoagulation in patients with venous thromboembolism: a management study. Blood 124:196–203. https://doi.org/10.1182/blood-2014-01-548065

    Article  PubMed  CAS  Google Scholar 

  11. Cosmi B, Legnani C, Tosetto A et al (2010) Usefulness of repeated D-dimer testing after stopping anticoagulation for a first episode of unprovoked venous thromboembolism: the PROLONG II prospective study. Blood 115:481–488. https://doi.org/10.1182/blood-2009-08-237354

    Article  PubMed  CAS  Google Scholar 

  12. Cosmi B, Legnani C, Cini M et al (2011) D-dimer and residual vein obstruction as risk factors for recurrence during and after anticoagulation withdrawal in patients with a first episode of provoked deep-vein thrombosis. Thromb Haemost 105:837–845. https://doi.org/10.1160/TH10-08-0559

    Article  PubMed  CAS  Google Scholar 

  13. Douketis J, Tosetto A, Marcucci M et al (2010) Patient-level meta-analysis: effect of measurement timing, threshold, and patient age on ability of D-dimer testing to assess recurrence risk after unprovoked venous thromboembolism. Ann Intern Med 153:523–531. https://doi.org/10.7326/0003-4819-153-8-201010190-00009

    Article  PubMed  Google Scholar 

  14. Weitz JI, Fredenburgh JC, Eikelboom JW (2017) A Test in Context: D-Dimer. J Am Coll Cardiol 70:2411–2420. https://doi.org/10.1016/j.jacc.2017.09.024

    Article  PubMed  CAS  Google Scholar 

  15. Tosetto A, IorioMarcucci AM et al (2012) Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). J Thromb Haemost 10:1019–1025. https://doi.org/10.1111/j.1538-7836.2012.04735.x

    Article  PubMed  CAS  Google Scholar 

  16. Rodger MA, Kahn SR, Wells PS et al (2008) Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. Can Med Assoc J 179:417–426. https://doi.org/10.1503/cmaj.080493

    Article  Google Scholar 

  17. Kearon C, Akl EA, Ornelas J et al (2016) Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 149:315–352. https://doi.org/10.1016/j.chest.2015.11.026

    Article  PubMed  Google Scholar 

  18. Genewein U, Haeberli A, Straub PW, Beer JH (1996) Rebound after cessation of oral anticoagulant therapy: the biochemical evidence. Br J Haematol 92:479–485. https://doi.org/10.1046/j.1365-2141.1996.d01-1499.x

    Article  PubMed  CAS  Google Scholar 

  19. Palareti G, Legnani C, Guazzaloca G (1994) Activation of blood coagulation after abrupt or stepwise withdrawal of oral anticoagulants-a prospective study. Thromb Haemost. https://doi.org/10.1055/s-0038-1648843

    Article  PubMed  Google Scholar 

  20. Park S-J, Chi H-S, Chun SH et al (2011) Evaluation of performance including influence by interfering substances of the Innovance D-dimer assay on the Sysmex coagulation analyzer. Ann Clin Lab Sci 41:20–24

    PubMed  CAS  Google Scholar 

  21. Iorio A, Kearon C, Filippucci E et al (2010) Risk of recurrence after a first episode of symptomatic venous thromboembolism provoked by a transient risk factor: a systematic review. Arch Intern Med 170:1710–1716. https://doi.org/10.1001/archinternmed.2010.367

    Article  PubMed  Google Scholar 

  22. Baglin T, Palmer CR, Luddington R, Baglin C (2008) Unprovoked recurrent venous thrombosis: prediction by D-dimer and clinical risk factors. J Thromb Haemost 6:577–582. https://doi.org/10.1111/j.1538-7836.2008.02889.x

    Article  PubMed  CAS  Google Scholar 

  23. Chua CC, Lim HY, Tacey M et al (2017) Retrospective evaluation of venous thromboembolism: are all transient provoking events the same? Eur J Haematol 99:18–26. https://doi.org/10.1111/ejh.12884

    Article  PubMed  Google Scholar 

  24. Watson HG, Baglin TP (2010) Guidelines on travel-related venous thrombosis. Br J Haematol 152:31–34. https://doi.org/10.1111/j.1365-2141.2010.08408.x

    Article  PubMed  Google Scholar 

  25. Hr-E MD, Mr MD (2017) Management of distal deep vein thrombosis. Thromb Res 149:48–55. https://doi.org/10.1016/j.thromres.2016.11.009

    Article  CAS  Google Scholar 

  26. Yamaki T (2016) Post-thrombotic syndrome—recent aspects of prevention, diagnosis and clinical management. Rev Vasc Med 6–7:10–19. https://doi.org/10.1016/j.rvm.2016.07.001

    Article  Google Scholar 

  27. Kearon C, Spencer FA, O'Keeffe D et al (2015) d-Dimer testing to select patients with a first unprovoked venous thromboembolism who can stop anticoagulant therapy. Ann Intern Med 162:27–14. https://doi.org/10.7326/M14-1275

    Article  PubMed  Google Scholar 

  28. Cosmi B, Legnani C, Tosetto A et al (2010) Sex, age and normal post-anticoagulation D-dimer as risk factors for recurrence after idiopathic venous thromboembolism in the Prolong study extension. J Thromb Haemost 8:1933–1942. https://doi.org/10.1111/j.1538-7836.2010.03955.x

    Article  PubMed  CAS  Google Scholar 

  29. Raskob GE, van Es N, Verhamme P et al (2018) Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 378:615–624. https://doi.org/10.1056/NEJMoa1711948

    Article  CAS  Google Scholar 

  30. Weitz JI, Lensing AWA, Prins MH et al (2017) Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med 376:1211–1222. https://doi.org/10.1056/NEJMoa1700518

    Article  PubMed  CAS  Google Scholar 

  31. Legnani C, Martinelli I, Palareti G et al (2019) D-dimer levels during and after anticoagulation withdrawal in patients with venous thromboembolism treated with non-vitamin K anticoagulants. PLoS ONE 14:e0219751–e219759. https://doi.org/10.1371/journal.pone.0219751

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Gibson C, Spyropoulos A, Cohen A et al (2017) The improvedd VTE risk score: incorporation of D-dimer into the IMPROVE score to improve venous thromboembolism risk stratification. TH Open 01:e56–e65. https://doi.org/10.1055/s-0037-1603929

    Article  Google Scholar 

  33. Spyropoulos AC, Ageno W, Albers GW et al (2018) Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness. N Engl J Med 379:1118–1127. https://doi.org/10.1056/NEJMoa1805090

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

No funding was received for this research.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed extensively to the preparation of this manuscript. PH conceived and designed the project. MT performed data analysis. JW collected and analysed data, and performed literature review.

Corresponding author

Correspondence to Julie Wang.

Ethics declarations

Conflicts of interest

All authors declare that they have no competing interest.

Ethical approval

Ethics approval was obtained from the Northern Health Office of Research & Ethics (ALR 14.2018).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, J., Tacey, M. & Ho, P. Retrospective review of d-dimer testing for venous thrombosis recurrence risk stratification: is this a useful test in the real world?. J Thromb Thrombolysis 49, 562–571 (2020). https://doi.org/10.1007/s11239-020-02101-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-020-02101-y

Keywords

Navigation