1. Quali sono gli elementi predittivi di recidiva?
Gualtiero Palareti
U.O. di Angiologia e Malattie della Coagulazione “Marino Golinelli” Policlinico S. Orsola-Malpighi
Bologna

2. Recurrence after DVT and PE. A population based cohort study.
Olmsted County, Minnesota, Missouri inhabitants
Heit JA et al. Arch Intern Med 2000.

3. Prevalenza di recidive nel tempo
17,5% a 2 a
24,6% a 5 a
Circa 30% a 10 a

4. Tipologia dei fattori di rischio di recidiva
Intervallo dal primo evento
Età e sesso
Tipo del 1° evento (presentazione come TVP o EP, TVP prox o dist)
Natura del 1° evento (idiopatico, secondario a causa rimuovibile o non)
Adeguata terapia del 1° evento
Patologia associata (cancro, pat. flogistica, ecc)
Trombofilia (congenita, acquisita)
Familiarità
Persistenza residuo trombotico
D-dimeri
Altro

5. L’intervallo dal primo evento

6. (From Keeling, Blood Review 2006, 20: 174)

7. Età e incidenza di TEV
(EPI-GETBO Study Group, Thromb Haemost, 2000)

8. (McRae et al. Lancet 2006)

9. Tipo del primo evento Embolia polmonare TVP prossimale
TVP distale isolata

10. (from Eichinger S et al, Arch Intern Med 2004; 164: 94)

11. 3 or 6 m. OAT after a first episode of proxymal DVT/PE 6 or 12 w
3 or 6 m. OAT after a first episode of proxymal DVT/PE 6 or 12 w. OAT after isolated calf DVT (DOTAVK; Pinede et al., Circulation 2001)

12. (from Schulman et al., NEJM 1997)

13. La natura del primo evento è predittiva del rischio di recidiva

14. (from Levine et al., Throm Haemost 1995)

15. VTE recurrences during follow-up (Palareti et al. T&H 2002)
Type of index VTE
Rate % pts
% pt-y
Idiopathic
10.8
6.9
Permanent risk factor
34 **
24.7 ***
Transient risk factor
4.3 *
2.6 *

16. La qualità del trattamento anticoagulante (specie nei primi 3 mesi) influenza il rischio di recidiva

17. Cumulative incidence of recurrence during follow-up according to the % of time spent at INR values <1.5 during the first 90 days of OAT course
5th quintile = continuous line
1st-4th quintiles = dashed line
HR = 2.77 (95%CI 1.75–8.40)
(Palareti et al., J Thromb Haemost 2005)

18. TAO a bassa intensità (INR 1,5-1,9) o a normale intensità (INR 2,0-3,0)

19. LONG TERM LOW-INTENSITY WARFARIN TREATMENT (the ELATE study) (Kearon et al., NEJM 2003)

20. Trombofilia congenita e rischio di recidiva

21. From Baglin et al. Lancet 2003

22. Recurrence in subjects with/without thrombophilia (Palareti et al
Recurrence in subjects with/without thrombophilia (Palareti et al. Circulation 2003)

23. Ho et al, Arch Intern Med 2006 Risk of recurrence in
common thrombophilia

24. Presenza di residuo trombotico e rischio di recidiva

25. Residual vein thrombosis (RVT) and risk of recurrences (Prandoni et al
Residual vein thrombosis (RVT) and risk of recurrences (Prandoni et al., Ann Intern Med 2002)
CUS normal if ø < 2.0 mm o < 3.0 mm in 2 visits
CUS normal in: 38.8% at 6 m 58.1% “ 1 y 69.3% “ 2 y 73.8% “ 3 y
58 recurrences 41 in pts with RVT 17 in pts without RVT
Cox proportional hazard model: (95%CI ; p=0.001)

26. Residual Venous Thrombosis as a Predictive Factor of Recurrent Venous Thromboembolism Prandoni, Annals Intern Med, 2002.
RR = 2,4

27. D-Dimer test to predict the risk of VTE recurrence

28. Rate of abnormal D-d results in pts on AVK treatment, 1 m. and 3 m
Rate of abnormal D-d results in pts on AVK treatment, 1 m. and 3 m. after this was stopped (Palareti et al., T&H 2002)

29. Cumulative probability of recurrence hazard ratio= 2. 45 (1. 28-4
Cumulative probability of recurrence hazard ratio= 2.45 ( ; p< 0.01) (Palareti et al. T&H 2002)

30. (from Eichinger et al., JAMA 2003)

31. (from Shrivastava et al, J Thromb Haem, 2006;4:1210)

32. D-d carried out 1 month after OAT interruption and recurrences (Palareti et al., Circulation 2003)

33. Cumulative recurrence in pts with idiopathic events according to combination of D-dimer and RVO (Cosmi et al., T&H 2005;94:969)
A= normal D-dimer without RVO
B= RVO and normal D-dimer
C= abnormal D-dimer without RVO
D= abnormal D-dimer and RVO

34. Può il D-dimero essere usato per determinare il rischio individuale di recidiva? Lo studio prospettico, randomizzato PROLONG

36. PROLONG: flow-chart of pts
627 enrolled pts in 30 Centres
Excluded
3 pts no consensus
5 pts had VTE before inclusion
619 pts included
392 (63.3%) = normal D-d
227 (36.7%) = abnormal D-d
randomized to
yes VKA 103 (2 pts excluded for LA)
No VKA 385 (7 pts excluded for LA)
no VKA 120 (2 pts excluded for LA)

37. Prolong: outcomes in 608 pts (during 864.8 y follow up)
Normal- Dd
n 385
Abnormal-
Dd No VKA
n 120
Abnormal
-Dd+VKA
No. 103
n/n total
n/100 person-yr
6.2%
4.4
15.0%
10.9
2.9%
2.0
(Palareti et al., NEJM 2006)

38. (Palareti et al., NEJM 2006;335:1780-9)

39. The Prolong study results in the subgroup of pts with P.E.
227 patients [105 males; 67 y (19-84)]
Isolated PE n = 118
PE+DVT n = 109
Total follow-up period = y

40. The Prolong study outcomes in patients with P.E.
Normal-Dd
N=144
Abnormal-Dd No VKA
N=47
Abnormal-Dd VKA
N=36
No. (%) of VTE recurrence
5 (3.5%)
8 (17.0%)
1 (2.8%)#
No./100 patient/yr
2.4
12.3
1.9
# = major bleeding

41. The Prolong study cumulative incidence of outcomes in pts with P.E.