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Il domani doloroso
della TVP
FCSA, Bologna 2014
Paolo Prandoni Università di Padova
Teatro Anatomico Università di Padova
Eventi attesi a distanza da un evento
tromboembolico venoso
• Recidiva di TEV
PTS
Eventi cardiovascolari arteriosi
Cancro
Recidiva di TEV
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Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R, Iotti M, Tormene D, Simioni P, Pagnan A
The risk of recurrent VTE after discontinuing anticoagulation in patients with acute proximal
DVT or PE
Haematologica 2007; 91: 199-205
Patients (number) 1626 Age (median, range) 66 (16,96) Gender (n., % males) 735 (45.2) Modality of clinical presentation
- DVT alone 1073 (66.0) - DVT + PE 292 (18.0) - PE alone 261 (16.0) Patients categories
- Unprovoked 864 (53.1) - Secondary to acquired risk factors 762 (46.9) Risk factors for thrombosis
- Recent trauma or surgery 553 (72.6) - Hormonal treatment, pregnancy or puerperium 109 (14.3) - Medical diseases 100 (13.1) Thrombophilic abnormalities 229/953 (24.0) Duration of oral anticoagulation
- Three months or less 540 (33.2) - Between three and six months 811 (49.9) - Between six and twelve months 196 (12.0) - Between one and two years 67 (4.1) - Between two and three years 12 (0.7)
The clinical course of 1626 patients with DVT and/or PE
The clinical course of 1626 patients with DVT and/or PE
Adjusted HR = 2.30 (95% CI, 1.82 - 2.90)
The clinical course of 1626 patients with DVT and/or PE
Prandoni, Hematologica 2007
Risk of recurrence as PE (7 prospective studies, 2554 patients)
Baglin T, J Thromb Haemost 2010
Factors associated with late recurrent VTE Baseline • Proximal DVT location
Thrombophilia
Male sex
Obesity
Elderly age
Non-0 blood group
Factors associated with late recurrent VTE Post-baseline
• Inadequacy of oral anticoagulation
• (Severe) PTS
• Persistent D-Dimer positivity
• Residual vein thrombosis
Bruinstroop E et al, J Thromb Haemost 2009
D-Dimer and Recurrent VTE
Thromb Haemost 2014 (in press)
Prandoni P, Lensing AWA, Prins MH, et al.
The impact of residual thrombosis on the long-term outcome of
patients with deep-vein thrombosis treated with conventional
anticoagulation
Semin Thromb Haemost [accepted]
Rate of RVT Recruited patients 869
RVT at 3 months after DVT 429 (49.4%)
Risk of Recurrent VTE
adjusted HR 2.03; 95% CI, 1.40 to 2.94
Palareti G, Cosmi B, Legnani C, Antonucci E, Erba N, Ghirarduzzi A, Poli D, Testa S, Tosetto A, Pengo V,
Prandoni P
Blood 2014
D-dimer to guide the duration of anticoagulation
in patients with venous thromboembolism. A
management study
Proximal DVT* 3-12 months VKA
Popliteal/femoral CUS
RVT Recanalization
D-dimer
Continuing VKA up to
a maximum of 1 year
Negative Positive
Stop VKA
Repeat DD 5 times in 3 months
Negative Positive
No VKA Resuming VKA Resuming VKA
Continuing VKA
*In patients with isolated PE proceed directly with D-dimer
Main Study Results Proportion of subjects with persistently
negative D-Dimer among eligible patients 51.2%
Annual incidence of recurrent VTE in this
patients’ group (mean f-up, 2 years) 3.0%
PTS
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Kahn SR, Shrier I, Julian JA, et al
Determinants and time course of the postthrombotic syndrome after acute
deep-venous thrombosis
Ann Intern Med 2008;149:698-707
Cumulative risk of the PTS in the study cohort
Independent predictors of the PTS
Relationship between severity of venous symptoms and signs at one month and subsequent development of the PTS
Other factors associated with increased PTS
Inadequate oral anticoagulant therapy
Obesity
CRP and other biomarkers of inflammation
Preexisting venous insufficiency
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Physiopathology of PTS
residual thrombosis valve incompetence
inflammation venous
hypertension
Prandoni P, Lensing AWA, Prins MH, et al.
The impact of residual thrombosis on the long-term outcome of
patients with deep-vein thrombosis treated with conventional
anticoagulation
Semin Thromb Haemost [accepted]
Risk of PTS
adjusted HR 2.34; 95% CI, 1.87 to 2.93
Tromboembolismo arterioso
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• Becattini et al. Eur Heart J 2005 Idiopathic PE
• Prandoni et al. J Thromb Haemost 2006 Idiopathic VTE
• Schulman et al. J Thromb Haemost 2006 All VTE
• Bova et al. Thromb Haemost 2006 Idiopathic VTE
• Young et al. J Thromb Haemost 2006 All VTE
• Sorensen et al. Lancet 2007 All VTE
• Spencer et al J Thromb Haemost 2008 Idiopathic VTE
• Klok et al Blood 2009 Idiopathic PE
• Barsoum et al Thromb Res 2014 All VTE
Is VTE predictive of arterial cardiovascular events?
yellow = yes; pale blu = no
Venous thromboembolism and subsequent hospitalization due to acute cardiovascular events – A 20 years follow-up study
Sørensen HT, Horvath-Puho E, Pedersen L, Baron
JA, Prandoni P
Lancet 2007; 370: 1773-9
Results: First year of follow-up
DVT cohort (N=25199)
DVT Controls (N=97773)
Adjusted RR
AMI or stroke 380 806 1.88 (1.66 – 2.12)
AMI 176 447 1.60 (1.35 – 1.91)
Stroke 209 371 2.19 (1.85 – 2.60)
Ischemic stroke
92 195 1.85 (1.44 – 2.37)
PE cohort (N=16925)
PE Controls (N=65793)
Adjusted RR
AMI or stroke 254 611 2.73 (2.36 – 3.16)
AMI 144 383 2.60 (2.14 – 3.14)
Stroke 113 237 2.93 (2.34 – 3.60)
Ischemic stroke
45 118 2.34 (1.66 – 3.31)
Results: Two to 20 years of follow-up
DVT cohort (N=25199)
DVT Controls (N=97773)
Adjusted RR
AMI or stroke 2388 10009 1.26 (1.20 – 1.31)
AMI 1157 5107 1.18 (1.11 – 1.26)
Stroke 1367 5504 1.31 (1.23 – 1.39)
Ischemic stroke
587 2267 1.36 (1.24 – 1.48)
PE cohort (N=16925)
PE Controls (N=65793)
Adjusted RR
AMI or stroke 1133 7559 1.31 (1.23 – 1.39)
AMI 597 3918 1.32 (1.21 – 1.43)
Stroke 608 4069 1.29 (1.18 – 1.40)
Ischemic stroke
272 1707 1.34 (1.18 – 1.52)
Prandoni P, Lensing AWA, Prins MH, et al.
The impact of residual thrombosis on the long-term outcome of
patients with deep-vein thrombosis treated with conventional
anticoagulation
Semin Thromb Haemost [accepted]
Risk of Arterial Thrombotic Events
adjusted HR 2.05; 95% CI, 1.08 to 3.88
Cancro
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Study results
Sorensen, DVT 1737 1372 1.3 (1.21-1.33)
Sorensen, PE 730 556 1.3 (1.22-1.41)
Baron 2509 784 3.2 (3.1-3.4)
Murchison 4441 3469 1.3 (1.25-11.33)
White 596 443 1.3 (1.2-1.5)
SIR = standardised incidence ratio
Cancers Observed Expected SIR
0 = 6 months after VTE
Trujillo-Santos J, Prandoni P, Rivron-Guillot K, Román P, Sánchez R, Tiberio G, Monreal M, for the RIETE Investigators
Clinical outcome in patients with venous thromboembolism
and hidden cancer
Findings from the RIETE Registry
J Thromb Haemost 2008
Variables Odds ratio (95% CI) p value
Age <60 years 60-75 years >75 years
1 (ref) 1.8 (1.2-2.7) 1.4 (0.9-2.2)
- 0.004 0.09
Anemia 1.9 (1.4-2.6) <0.001
Bilateral DVT 2.3 (1.3-4.1) 0.005
Multivariate analysis on the risk for hidden cancer
In proven deep vein thrombosis, a low positive D-Dimer* score is a strong negative
predictor for associated malignancy
Rege KP, Jones S, Day J, Hoggarth E Thromb Haemost 2004; 91: 1219-22
*Quantitative latex assay (IL D-Dimer)
Diagnoses associated with DVT at presentation
With D-Dimer > 1000 ng/ml (n=66)
With D-Dimer < 1000 ng/ml (n=66)
Prandoni P, Lensing AWA, Prins MH, et al.
The impact of residual thrombosis on the long-term outcome of
patients with deep-vein thrombosis treated with conventional
anticoagulation
Semin Thromb Haemost [accepted]
Risk of Cancer
adjusted HR 3.09; 95% CI, 1.31 to 7.28
Features RVT (No = 429)
No RVT (No = 440)
P
Age (median, range) 63 (15-91) 63 (21-89) Male gender 234 (54.5) 186 (42.3) 0.001 Family history 96 (22.4) 101 (23.0) Previous VTE 61 (14.2) 42 (9.5) 0.04 Obesity (BMI > 30) 49 (11.4) 56 (12.7) Unprovoked DVT 228 (53.1) 216 (49.1) Thrombophilia 75/295 (25.4) 79/331 (23.9) Concomitant symptomatic PE 53 (12.4) 73 (16.6) Previous arterial thrombosis 32 (7.5) 23 (5.2) Localization of DVT - common femoral only 32 (7.5) 59 (13.4) - popliteal only 174 (40.6) 265 (60.2) - both venous segments 223 (52.0) 116 (26.4) 0.001 Length of anticoagulation (mo)
5.9 + 4.7 4.6 + 3.1 0.001
Features of patients with and without RVT
Conclusioni
Una frequenza non trascurabile di pazienti
con TEV trattati con terapia convenzionale
sviluppa eventi sfavorevoli nel follow-up
Sarebbe desiderabile conoscere il destino di
pazienti trattati con i nuovi farmaci
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