ASL PROVINCIA DI BERGAMO Corso di aggiornamento

1. ASL PROVINCIA DI BERGAMO Corso di aggiornamento La gestione del paziente in Terapia Anticoagulante Orale (TAO) TVP

2. Clinical prediction rules • Although none of the symptoms or signs of DVT is diagnostic in isolation, it has been well established that a clinical prediction rule that takes into account signs, symptoms and risk factors can be accurately applied to categorize patients as having low, moderate or high probability of DVT

4. Recommendation 1: Low-molecular-weight heparin (LMWH) rather than unfractionated heparin should be used whenever possible for the initial inpatient treatment of deep venous thrombosis (DVT). Either unfractionated eparin or LMWH is appropriate for the initial treatment of pulmonary embolism.

5. Recommendation 2: Outpatient treatment of DVT, and possibly pulmonary embolism, with LMWH is safe and cost effective for carefully selected patients and should be considered if the required support services are in place.

6. Recommendation 3: Compression stockings should be used routinely to prevent post thrombotic syndrome, beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis.

7. Recommendation 5: Anticoagulation should be maintained for 3 to 6 months for VTE secondary to transient risk factors and for more than 12 months for recurrent VTE.While the appropriate duration of anticoagulation for idiopathic or recurrent VTE is not definitively known, there is evidence of substantial benefit for extended-duration therapy.

8. Recommendation 6: LMWH is safe and efficacious for the long-term treatment of VTE in selected patients (and may be preferable for patients with cancer).

9. Antithrombotic Therapy for Venous Thromboembolic Disease American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) • For patients with DVT or PE secondary to a transient (reversible) risk factor, we recommend treatment with a VKA for 3 months over treatment for shorter periods (Grade 1A). • For patients with unprovoked DVT or PE, we recommend treatment with a VKA for at least 3 months (Grade 1A), and that all patients are then evaluated for the risks to benefits of indefinite therapy (Grade 1C). We recommend indefinite anticoagulant therapy for patients with a first unprovoked proximal DVT or PE and a low risk of bleeding when this is consistent with the patient’s preference (Grade 1A), and for most patients with a second unprovoked DVT (Grade 1A). • We recommend that the dose of VKA be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations (Grade 1A). • We recommend at least 3 months of treatment with LMWH for patients with VTE and cancer (Grade 1A), followed by treatment with LMWH or VKA as long as the cancer is active (Grade 1C). • For prevention of postthrombotic syndrome (PTS) after proximal DVT, we recommend use of an elastic compression stocking (Grade 1A). • For DVT of the upper extremity, we recommend similar treatment as for DVT of the leg (Grade 1C).

10. Situazioni nelle quali è indicato eseguire uno screening per trombofilia • età giovanile di comparsa dell’evento trombotico, arterioso o venoso (< 45 anni) • TEV idiopatica • TEV dopo stimoli di entità trascurabile • TEV ricorrente • trombosi venose in sedi non usuali • storia familiare positiva per tromboembolie venose • associazione di trombosi con perdita fetale • necrosi cutanea indotta da anticoagulanti orali • porporafulminanteneonatale

11. Test consigliabili per uno screening di trombofilia • TEMPO DI PROTROMBINA (come indice di funzionalità epatica) • aPTT • FIBRINOGENO • ANTITROMBINA III • PROTEINA C • PROTEINA S • RESISTENZA ALLA PROTEINA C ATTIVATA (se alterata ricerca della mutazione Fattore V Leiden) • MUTAZIONE G20210A DEL GENE DELLA PROTROMBINA • RICERCA DEL LUPUS ANTICOAGULANT (LAC) • ANTICORPI ANTICARDIOLIPINA (e anticorpi antibeta2 Glicoproteina I) • OMOCISTEINA (di base e dopo carico con metionina)

12. Linee guida per l’esecuzione di uno screening per trombofilia È necessario tener presente che, a differenza dei test genetici, i test funzionali per alterazioni trombofiliche risultano spesso alterati in modo aspecifico nelleseguenticondizioni: • durante la fase acuta di un evento trombotico, sia venoso che arterioso • durante la terapia anticoagulante (eparina, anticoagulanti orali) • durante malattie intercorrenti acute che possono influenzare i risultati • durantetrattamentoestro-progestinico • durante la gravidanza • in caso di presenza di epatopatie con presumibile alterazione secondaria dei test coagulativi

13. Momentifondamentalinell’interazioneospedale-territorioper la diagnosi di TVP • MMG: sospetto diagnostico e valutazione della probabilità clinica di TVP 2. MMG: invio alla struttura ospedaliera idonea secondo modalità concordate; in caso di invio non immediato valutazione dell’opportunità di iniziare terapia con EBPM a domicilio 3. OSPEDALE: accoglimento del paziente e suo inserimento nel percorso diagnostico di base predefinito 4. OSPEDALE: diagnosi di TVP o, in caso d’incertezza, predisposizione delle misure diagnostiche, predefinite, successive all’iter di base già eseguito 5. OSPEDALE: eventuale terapia per il tempo necessario per giungere alla diagnosi definitiva

14. Optimal duration of oral anticoagulant therapy after the first episode of DVT • Indefinite anticoagulation is commonly reserved for patients with permanent risk factors for thrombosis • patients with unprovoked DVT generally receive 6 months of anticoagulation • those with DVT associated with transient risk factors receive treatment for 3 months

15. Residual Thrombosis on Ultrasonography to Guide the Duration of Anticoagulation in Patients With Deep Venous ThrombosisAnn Intern Med. 2009;150:577-585. • Overall, 46 (17.2%) of 268 patients allocated to fixedduration anticoagulation and 32 (11.9%) of 270 patients allocated to flexible-duration anticoagulation developed recurrent VTE (adjusted hazard ratio [HR], 0.64 [95% CI, 0.39 to 0.99]). • For patients with unprovoked DVT, the adjusted HR was 0.61 (CI, 0.36 to 1.02) and 0.81 (CI, 0.32 to 2.06) for those with secondary DVT. • Major bleeding occurred in 2 (0.7%) patients in the fixed-duration group and 4 (1.5%) patients in the flexible-duration group (P 0.67).

16. Systematic Review: D-Dimer to Predict Recurrent Disease after Stopping Anticoagulant Therapy for Unprovoked Venous ThromboembolismAnn Intern Med. 2008;149:481-490. • In patients who have completed at least 3 months of anticoagulation for a first episode of unprovoked VTE and after approximately 2 years of follow-up, a negative D-dimer result was associated with a 3.5% annual risk for recurrent disease, whereas a positive D-dimer result was associated with an 8.9% annual risk for recurrence. These rates should inform decisions about the balance of risks and benefits of prolonging anticoagulation.