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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