Upload
anna-mcdowell
View
220
Download
0
Tags:
Embed Size (px)
Citation preview
Quali sono gli elementi predittivi di recidiva?
Gualtiero PalaretiU.O. di Angiologia e Malattie della Coagulazione
“Marino Golinelli”Policlinico S. Orsola-Malpighi
Bologna
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.
Prevalenza di recidive nel tempo
• 17,5% a 2 a
• 24,6% a 5 a
• Circa 30% a 10 a
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
L’intervallo dal primo evento
(From Keeling, Blood Review 2006, 20: 174)
Età e incidenza di TEV
0
2
4
6
8
10
12
14in
cid
enza
per
100
0/an
no
<20 20-39 40-59 60-74 >74 anni
Donne
Uomini
(EPI-GETBO Study Group, Thromb Haemost, 2000)
(McRae et al. Lancet 2006)
Tipo del primo evento
Embolia polmonareTVP prossimaleTVP distale isolata
(from Eichinger S et al, Arch Intern Med 2004; 164: 94)
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)
(from Schulman et al., NEJM 1997)
La natura del primo evento è predittiva del rischio di recidiva
(from Levine et al., Throm Haemost 1995)
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 *
La qualità del trattamento anticoagulante (specie nei primi 3 mesi)
influenza il rischio di recidiva
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)
TAO a bassa intensità (INR 1,5-1,9)o a normale intensità (INR 2,0-3,0)
LONG TERM LOW-INTENSITY WARFARIN TREATMENT (the ELATE study)
(Kearon et al., NEJM 2003)
1,90
0,60 0,96 0,93
4,9
3,6
0,00
1,00
2,00
3,00
4,00
5,00
6,00
7,00
8,00
9,00
10,00
% pt-y
rVTE Maj. Bleed Maj +min bleed
Rates of recurrent VTE and bleedinglow intensity
conventionalintensity
Trombofilia congenita e rischio di recidiva
From Baglin et al.Lancet 2003
Recurrence in subjects with/without thrombophilia(Palareti et al. Circulation 2003)
Ho et al, Arch Intern Med 2006
Risk of recurrence incommon thrombophilia
Presenza di residuo trombotico e rischio di recidiva
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)
Residual Venous Thrombosis as a Predictive Factor of Recurrent Venous Thromboembolism
Prandoni, Annals Intern Med, 2002.
0
2
4
6
8
10
12
14
16
18
N
Trombofilia Idiopatica Secondaria
58 recidive
CUS NORMTV RESIDUA
D-Dimer test to predict the risk of VTE recurrence
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)
05
101520253035404550
% of pts with abnormal D-d
on treat. 1 m. 3 m.
Cumulative probability of recurrencehazard ratio= 2.45 (1.28-4.53; p< 0.01)
(Palareti et al. T&H 2002)
(from Eichinger et al., JAMA 2003)
(from Shrivastava et al, J Thromb Haem, 2006;4:1210)
D-d carried out 1 month after OAT interruption and recurrences (Palareti et al., Circulation 2003)
0 250 500 750 10000.0
0.1
0.2
0.3
0.4
Thrombophilic alterationsand altered D-Dimer
Thrombophilic alterationsand normal D-Dimer
Hazard ratio = 8.34(95%CI: 2.72-17.43)
Days
Cum
ula
tive p
robabili
ty o
fre
curr
ence
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
Può il D-dimero essere usato per determinare il rischio individuale di
recidiva?
Lo studio prospettico, randomizzatoPROLONG
PROLONG: flow-chart of pts
627 enrolled pts in 30 Centres
Excluded3 pts no consensus5 pts had VTE before inclusion
619 pts included
392 (63.3%) = normal D-d 227 (36.7%) = abnormal D-d
yes VKA 103(2 pts excluded for LA)
randomized to
no VKA 120(2 pts excluded for LA)
No VKA 385(7 pts excluded for LA)
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)
(Palareti et al., NEJM 2006;335:1780-9)
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
The Prolong studyoutcomes 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
The Prolong study cumulative incidence of outcomes in pts with P.E.