1. DEFINING THE DURATION OF ANTICOAGULATION

2. HOW LONG TO TREAT A DVT?

3. WHAT DO THE ACCP GUIDELINES SAY?

4. Duration of Long-term Anticoagulant Therapy In patients with a proximal DVT of the leg provoked by surgery, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period (Grade 1B), (ii) treatment of a longer time-limited period (eg, 6 or 12 months) (Grade 1B), or (iii) extended therapy (Grade 1B regardless of bleeding risk).

5. Duration of Long-term Anticoagulant Therapy In patients with a proximal DVT of the leg provoked by a nonsurgical transient risk factor, we recommend treatment with anticoagulation for 3 months over (i) treatment of a shorter period (Grade 1B), (ii) treatment of a longer time-limited period (eg, 6 or 12 months) (Grade 1B), and (iii) extended therapy if there is a high bleeding risk (Grade 1B). We suggest treatment with anticoagulation for 3 months over extended therapy if there is a low or moderate bleeding risk (Grade 2B).

6. Duration of Long-term Anticoagulant Therapy In patients with an isolated distal DVT of the leg provoked by surgery or by a nonsurgical transient risk factor (see remark), we suggest treatment with anticoagulation for 3 months over treatment of a shorter period (Grade 2C) and recommend treatment with anticoagulation for 3 months over treatment of a longer time-limited period (eg, 6 or 12 months) (Grade 1B) or extended therapy (Grade 1B regardless of bleeding risk).

7. Duration of Long-term Anticoagulant Therapy In patients with an unprovoked DVT of the leg (isolated distal [see remark] or proximal), we recommend treatment with anticoagulation for at least 3 months over treatment of a shorter duration (Grade 1B). After 3 months of treatment, patients with unprovoked DVT of the leg should be evaluated for the risk-benefit ratio of extended therapy.

8. Duration of Long-term Anticoagulant Therapy In patients with a first VTE that is an unprovoked proximal DVT of the leg and who have a low or moderate bleeding risk, we suggest extended anticoagulant therapy over 3 months of therapy (Grade 2B).

9. Duration of Long-term Anticoagulant Therapy In patients with a first VTE that is an unprovoked proximal DVT of the leg and who have a high bleeding risk, we recommend 3 months of anticoagulant therapy over extended therapy (Grade 1B).

10. Duration of Long-term Anticoagulant Therapy In patients with a first VTE that is an unprovoked isolated distal DVT of the leg (see remark), we suggest 3 months of anticoagulant therapy over extended therapy in those with a low or moderate bleeding risk (Grade 2B) and recommend 3 months of anticoagulant treatment in those with a high bleeding risk (Grade 1B).

11. Duration of Long-term Anticoagulant Therapy In patients with a second unprovoked VTE, we recommend extended anticoagulant therapy over 3 months of therapy in those who have a low bleeding risk (Grade 1B), and we suggest extended anticoagulant therapy in those with a moderate bleeding risk (Grade 2B).

12. Duration of Long-term Anticoagulant Therapy In patients with a second unprovoked VTE who have a high bleeding risk, we suggest 3 months of anticoagulant therapy over extended therapy (Grade 2B).

13. Duration of Long-term Anticoagulant Therapy In patients with DVT of the leg and active cancer, if the risk of bleeding is not high, we recommend extended anticoagulant therapy over 3 months of therapy (Grade 1B), and if there is a high bleeding risk, we suggest extended anticoagulant therapy (Grade 2B). Remarks (3.1.3, 3.1.4, 3.1.4.3): Duration of treatment of patients with isolated distal DVT refers to patients in whom a decision has been made to treat with anticoagulant therapy; however, it is anticipated that not all patients who are diagnosed with isolated distal DVT will be given anticoagulants (see section 2.3). In all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (eg, annually).

14. What Factors Do You Consider? Gender Age Precipitating events/factors Inherited or acquired thrombophilias Site of primary event Residual thrombosis on ultrasound Elevated D-dimers

15. DULCIS (D-DIMER AND ULTRASOUND I COMBINATION ITALIAN STUDY)

16. Flow chart of the DULCIS study. Palareti G et al. Blood 2014;124:196-203 ©2014 by American Society of Hematology

17. Prevalence of first-time-ever D-dimer result above the predefined cutoff levels in the investigated study population at the serial measurement days after VKA withdrawal. Palareti G et al. Blood 2014;124:196-203 ©2014 by American Society of Hematology

18. Kaplan-Meier cumulative event rates for the primary efficacy outcome in patients with persistently negative D-dimer results in whom anticoagulation was definitively stopped (dotted line) and in those with positive D-dimer results who refused to resume antic... Palareti G et al. Blood 2014;124:196-203 ©2014 by American Society of Hematology

19. OTHER STUDIES

20. Meta-analysis – Annualized risk of recurrence 8.8 per 100 pt years with + D-Dimer 3.7 per 100 pt years with - D-Dimer – Age and timing of testing no significant difference Douketis J et al. Annals 2010. 153: 523-531

21. WHAT DID THE PROLONG AND PROLONG II TRIALS SHOW?

22. The flow chart of the study from T0 to T30. Cosmi B et al. Blood 2010;115:481-488 ©2010 by American Society of Hematology

23. Frequency of conversion from D-dimer (D-d) normal to abnormal from the third month (T90) to the 13th month (T390). Cosmi B et al. Blood 2010;115:481-488 ©2010 by American Society of Hematology

24. Cumulative incidence and hazard ratios (HRs) of main outcomes according to D-d time course from the third month (T90) to the 13th month (T390). Cosmi B et al. Blood 2010;115:481-488 ©2010 by American Society of Hematology

25. ANNALS 2015: PROSPECTIVE MANAGEMENT STUDY

26. D-Dimer Testing to Select Patients With a First Unprovoked Venous Thromboembolism Who Can Stop Anticoagulant Therapy: A Cohort Studyd-Dimer Testing to Select Patients With VTE Who Can Stop Anticoagulant Therapy Ann Intern Med. 2015;162(1):27-34. doi:10.7326/M14-1275 Copyright © American College of Physicians. All rights reserved.American College of Physicians

27. D-Dimer Testing to Select Patients With a First Unprovoked Venous Thromboembolism Who Can Stop Anticoagulant Therapy: A Cohort Studyd-Dimer Testing to Select Patients With VTE Who Can Stop Anticoagulant Therapy Ann Intern Med. 2015;162(1):27-34. doi:10.7326/M14-1275 Copyright © American College of Physicians. All rights reserved.American College of Physicians

28. D-Dimer Testing to Select Patients With a First Unprovoked Venous Thromboembolism Who Can Stop Anticoagulant Therapy: A Cohort Study d-Dimer Testing to Select Patients With VTE Who Can Stop Anticoagulant Therapy Ann Intern Med. 2015;162(1):27-34. doi:10.7326/M14-1275 Copyright © American College of Physicians. All rights reserved.American College of Physicians

29. Idiopathic Thrombosis – Men 16%/ year with + D-Dimer 8% / year with – D-Dimer – Women 10%/ year with + D-Dimer 5% / year with – D-Dimer – Women with estrogen-associated clots <1% / year with + D-Dimer 0% / year with – D-Dimer

30. HOW DO YOU INCORPORATE DUCLIS INTO PRACTICE?

31. DUCLIS If – D-Dimer – 25/528 with event (4.7%) or 3 per 100 patient year – Age >70 years vs. younger  8.9% vs. 2.1% – Event circumstances Idiopathic vs. secondary  6.1% vs. 1.3% If + D-Dimers – 15/109 with event (13.8%) or 8.8 per 100 patient year – NO difference based on age or event circumstances