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Quali sono gli elementi predittivi di recidiva?

Quali sono gli elementi predittivi di recidiva?. Gualtiero Palareti U.O. di Angiologia e Malattie della Coagulazione “Marino Golinelli” Policlinico S. Orsola-Malpighi Bologna. Recurrence after DVT and PE. A population based cohort study.

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Quali sono gli elementi predittivi di recidiva?

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  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. 106.470 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. 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)

  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. Circulation 2003)

  23. Ho et al, Arch Intern Med 2006Risk 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., 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 m58.1% “ 1 y69.3% “ 2 y73.8% “ 3 y • 58 recurrences41 in pts with RVT17 in pts without RVT • Cox proportional hazard model: 2.9 (95%CI 1.6-5.2; p=0.001)

  26. Residual Venous Thrombosis as a Predictive Factor of Recurrent Venous ThromboembolismPrandoni, 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. after this was stopped (Palareti et al., T&H 2002)

  29. Cumulative probability of recurrencehazard ratio= 2.45 (1.28-4.53; 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 withidiopathic events according to combination of D-dimerand 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, randomizzatoPROLONG

  35. 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 227 (36.7%) = abnormal D-d 392 (63.3%) = normal 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)

  36. Outcomes 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 Prolong: outcomes in 608 pts(during 864.8 y follow up) (Palareti et al., NEJM 2006)

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

  38. The Prolong studyresults 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 = 321.0 y

  39. The Prolong studyoutcomes in patients with P.E. # = major bleeding

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

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