Quali sono gli elementi predittivi di recidiva?

1
Quali sono gli elementi predittivi di recidiva?

• Gualtiero Palareti
• U.O. di Angiologia e Malattie della
  CoagulazioneMarino GolinelliPoliclinico 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
Lintervallo 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. TH 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 lt1.5 during the first 90 days of OAT course
5th quintile continuous line 1st-4th quintiles
dashed line HR 2.77 (95CI 1.758.40)
(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 lt 2.0 mm o lt 3.0 mm in 2 visits
• CUS normal in38.8 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 (95CI
  1.6-5.2 p0.001)

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., TH 2002)
29
Cumulative probability of recurrencehazard
ratio 2.45 (1.28-4.53 plt 0.01) (Palareti et
al. TH 2002)
   
30
(from Eichinger et al., JAMA 2003)
31
(from Shrivastava et al, J Thromb Haem,
200641210)
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., TH 200594969)
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
(No Transcript)
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
227 (36.7) abnormal D-d
392 (63.3) normal D-d
randomized to
yes VKA 103(2 pts excluded for LA)
no VKA 120(2 pts excluded for LA)
No VKA 385(7 pts excluded for LA)
37
Prolong outcomes in 608 pts(during 864.8 y
follow up)
(Palareti et al., NEJM 2006)
38
(Palareti et al., NEJM 20063351780-9)
39
The Prolong studyresults in the subgroup of pts
with P.E.

• 227 patients 105 males 67 y (19-84)
• Isolated PE n 118
• PEDVT n 109
• Total follow-up period 321.0 y

40
The Prolong studyoutcomes in patients with P.E.
Normal-Dd N144 Abnormal-Dd No VKA N47 Abnormal-Dd VKA N36
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.