Paolo Prandoni Università di Padova
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1 Paolo Prandoni Università di Padova Il domani doloroso della TVP FCSA, Bologna 2014 Teatro Anatomico Università di Padova
2 Eventi attesi a distanza da un evento tromboembolico venoso Recidiva di TEV PTS Eventi cardiovascolari arteriosi Cancro
3 Recidiva di TEV 6 A
4 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:
5 The clinical course of 1626 patients with DVT and/or PE 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)
6 The clinical course of 1626 patients with DVT and/or PE
7 The clinical course of 1626 patients with DVT and/or PE Adjusted HR = 2.30 (95% CI, ) Prandoni, Hematologica 2007
8 Risk of recurrence as PE (7 prospective studies, 2554 patients) Baglin T, J Thromb Haemost 2010
9 Factors associated with late recurrent VTE Baseline Proximal DVT location Thrombophilia Male sex Obesity Elderly age Non-0 blood group
10 Factors associated with late recurrent VTE Post-baseline Inadequacy of oral anticoagulation (Severe) PTS Persistent D-Dimer positivity Residual vein thrombosis
11 D-Dimer and Recurrent VTE Bruinstroop E et al, J Thromb Haemost 2009
12 Thromb Haemost 2014 (in press )
13
14 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]
15 Rate of RVT Recruited patients 869 RVT at 3 months after DVT 429 (49.4%)
16 Risk of Recurrent VTE adjusted HR 2.03; 95% CI, 1.40 to 2.94
17 D-dimer to guide the duration of anticoagulation in patients with venous thromboembolism. A management study Palareti G, Cosmi B, Legnani C, Antonucci E, Erba N, Ghirarduzzi A, Poli D, Testa S, Tosetto A, Pengo V, Prandoni P Blood 2014
18 Proximal DVT* Popliteal/femoral CUS 3-12 months VKA RVT Recanalization Continuing VKA up to a maximum of 1 year Positive D-dimer Negative Stop VKA Continuing VKA Repeat DD 5 times in 3 months *In patients with isolated PE proceed directly with D-dimer Positive Resuming VKA Negative No VKA
19 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%
20 PTS 6 A
21 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:
22 Cumulative risk of the PTS in the study cohort
23 Independent predictors of the PTS
24 Relationship between severity of venous symptoms and signs at one month and subsequent development of the PTS
25 6 A Other factors associated with increased PTS Inadequate oral anticoagulant therapy Obesity CRP and other biomarkers of inflammation Preexisting venous insufficiency
26 Physiopathology of PTS residual thrombosis valve incompetence venous hypertension inflammation
27 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]
28 Risk of PTS adjusted HR 2.34; 95% CI, 1.87 to 2.93
29 Tromboembolismo arterioso 6 A
30 Is VTE predictive of arterial cardiovascular events? 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 yellow = yes; pale blu = no
31 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:
32 Results: First year of follow-up DVT cohort (N=25199) DVT Controls (N=97773) Adjusted RR AMI or stroke ( ) AMI ( ) Stroke ( ) Ischemic stroke ( ) PE cohort (N=16925) PE Controls (N=65793) Adjusted RR AMI or stroke ( ) AMI ( ) Stroke ( ) Ischemic stroke ( )
33 Results: Two to 20 years of follow-up DVT cohort (N=25199) DVT Controls (N=97773) Adjusted RR AMI or stroke ( ) AMI ( ) Stroke ( ) Ischemic stroke ( ) PE cohort (N=16925) PE Controls (N=65793) Adjusted RR AMI or stroke ( ) AMI ( ) Stroke ( ) Ischemic stroke ( )
34 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]
35 Risk of Arterial Thrombotic Events adjusted HR 2.05; 95% CI, 1.08 to 3.88
36 Cancro 6 A
37 Study results Sorensen, DVT ( ) Sorensen, PE ( ) Baron ( ) Murchison ( ) White ( ) SIR = standardised incidence ratio Cancers Observed Expected SIR
38 0 = 6 months after VTE
39 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
40 Multivariate analysis on the risk for hidden cancer Variables Odds ratio (95% CI) p value Age <60 years years >75 years 1 (ref) 1.8 ( ) 1.4 ( ) Anemia 1.9 ( ) <0.001 Bilateral DVT 2.3 ( ) 0.005
41 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: *Quantitative latex assay (IL D-Dimer)
42 Diagnoses associated with DVT at presentation With D-Dimer > 1000 ng/ml (n=66) With D-Dimer < 1000 ng/ml (n=66)
43 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]
44 Risk of Cancer adjusted HR 3.09; 95% CI, 1.31 to 7.28
45 Features of patients with and without RVT Features RVT No RVT P (No = 429) (No = 440) Age (median, range) 63 (15-91) 63 (21-89) Male gender 234 (54.5) 186 (42.3) 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) Length of anticoagulation (mo)
46 6 A 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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