La gestione del rischio tromboembolico nel paziente ortopedico S.C. Angiologia Medica - Messina

S.C. Angiologia Medica - Messina trombo embolo migrazione Circa il 50% dei pazienti con TVP prossimale degli arti inferiori presenta un’ EP asintomatica (1) Una TVP (soprattutto se asintomatica) è presente in circa l’80% dei pazienti con EP (2) + TVP EP = TEV S.C. Angiologia Medica - Messina

Patient Groups No. of Studies No. of Patients % DVT incidence IUA - International Consensus Statement 2007 Patient Groups No. of Studies No. of Patients % DVT incidence (Weighted mean) 95% CI Stroke Elective Hip Replacement Multiple Trauma Total Knee Replacement Hip Fracture Spinal Cord Injury Retropubic Prostatectomy Patients in ICU General Surgery Neurosurgery Gynecological Surgery Malignancy Myocardial Infarction Abdominal Vascular Surgery Peripheral Vascular Reconstruction Isolated Lower Limb Injuries Gynecological Surgery Benign Disease Elective Spinal Surgery General Medical Geriatric Knee Arthroscopy 9 17 4 7 15 8 3 54 5 6 2 1 395 851 536 541 805 458 335 178 4310 280 297 180 258 102 684 460 151 1026 131 832 56 51 43 47 44 35 32 25 22 19 14 12 51% to 61% 48% to 54% 39% to 47% 42% to 51% 40% to 47% 31% to 39% 27% to 37% 19% to 32% 24% to 26% 17% to 27% 17% to 26% 16% to 28% 15% to 25% 9% to 23% 15% to 20% 11% to 17% 10% to 22% 10% to 14% 5% to 15% 6% to 10% S.C. Angiologia Medica - Messina

S.C. Angiologia Medica - Messina 2012 4.3% 1.8% S.C. Angiologia Medica - Messina

PROBLEMI NELLA DIFFUSIONE DELLA PROFILASSI DEL TEV Erronea percezione/conoscenza delle dimensioni del problema Timore delle complicanze emorragiche Trombocitopenia da eparina Costi delle strategie di profilassi S.C. Angiologia Medica - Messina

S.C. Angiologia Medica - Messina PROFILASSI DEL TEV estendere la profilassi al maggior numero possibile di condizioni a rischio definire le linee generali per realizzare una profilassi efficace ma proporzionata al rischio trombotico ed emorragico con il miglior rapporto costo-beneficio favorire una valutazione del rischio tromboembolico individuale tutelare gli operatori dal punto di vista medico-legale con adozione di procedure standard S.C. Angiologia Medica - Messina

National Safety Agency . Risk Assessment S.C. Angiologia Medica - Messina

PROBLEM OF COMPLIANCE WITH VTE PROPHYLAXIS GUIDELINES IN HOSPITALS Orthopedic surgery patients Compliant 52.4% Noncompliant 47.6% Prophylaxis 7% Duration 36.8% No Prophylaxis 56.3% Non-recommended Inadequate Major take away point from this slide – those in post-acute, rehab, nursing home setting accepting these patients cannot be assured that the acute care setting has provided acceptable thromboprophylaxis. Therefore, the post-rehab setting may be the site at which thromboprophylaxis is initiated, albeit later than desirable. This study evaluated compliance with the 6th ACCP Chest Guidelines for prevention of venous thromboembolism in hospitals. They determined that for the patients with orthopedic surgery, 52% of the population received the recommended VTE prophylaxis. Of the 48% that were noncompliant, 56% of that group received no prophylaxis (26.8% of the total orthopedic surgery population). 36.8% of the noncompliant group did not receive the appropriate duration of the therapy. Of interest, the orthopedic surgery group had the highest rate of compliance with VTE prophylaxis. Other risk groups included at-risk medical conditions, general surgery, spine surgery, urologic surgery, and others. Yu HT, et al. Am J Health Syst Pharm. 2007;64(1):69-76. S.C. Angiologia Medica - Messina

mean delay to diagnosis 5.6 days Comparison of the mean delay from symptom onset to the diagnosis of DVT (n = 808) presented as a frequency distribution plot Elliott C. G. et al. Chest 2005;128:3372-3376 mean delay to diagnosis 5.6 days (upper limit of 95% confidence interval, 21 days) 21 % 5 % S.C. Angiologia Medica - Messina

mean delay to diagnosis 4.8 days Delays in the diagnosis of acute pulmonary embolism (n = 344) presented as a frequency distribution plot Elliott C. G. et al. Chest 2005;128:3372-3376 mean delay to diagnosis 4.8 days (upper limit of 95% confidence interval, 25 days) 17 % 5 % S.C. Angiologia Medica - Messina

S.C. Angiologia Medica - Messina Profilassi ideale Efficace Poco costosa Facile da somministrare e monitorare Senza complicanze e effetti collaterali S.C. Angiologia Medica - Messina

Quali sono gli obbiettivi nella profilassi del TEV ? Embolia Polmonare Fatale Embolia Polmonare non Fatale Sintomatica Asintomatica Trombosi Venosa Profonda Prossimale Distale Ricorrente Sindrome Post-Trombotica S.C. Angiologia Medica - Messina

Quali sono gli altri obbiettivi ? Evitare le complicanze del trattamento Sanguinamento Reintervento Nuovo ricovero Transfusioni Miglioramento outcomes Durata del ricovero Ripresa funzionale Costi contenuti S.C. Angiologia Medica - Messina

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S.C. Angiologia Medica - Messina 2012 I limiti delle alternative terapeutiche includono: la possibilità di un aumento di sanguinamento (che si può verificare con fondaparinux, rivaroxaban e AVK). la possibilità di una ridotta efficacia (ENF, AVK, aspirina e CPI da sola). • la carenza di dati di sicurezza a lungo termine (apixaban, dabigatran e rivaroxaban S.C. Angiologia Medica - Messina

S.C. Angiologia Medica - Messina 2012 S.C. Angiologia Medica - Messina

S.C. Angiologia Medica - Messina 2012 S.C. Angiologia Medica - Messina

S.C. Angiologia Medica - Messina 2012 S.C. Angiologia Medica - Messina

S.C. Angiologia Medica - Messina 2012 S.C. Angiologia Medica - Messina

S.C. Angiologia Medica - Messina

AAOS: Recommendations Standard Risk PE/DVT + Standard Risk Major Bleeding Aspirin LMWH Synthetic pentasaccharide Warfarin LEVEL III B Elevated Risk PE/DVT + Standard Risk Major Bleeding LMWH Synthetic pentasaccharide Warfarin LEVEL III B Standard Risk PE/DVT + Elevated Risk Major Bleeding Aspirin Warfarin None LEVEL III C Elevated Risk PE/DVT + Elevated Risk Major Bleeding Aspirin Warfarin None LEVEL III C S.C. Angiologia Medica - Messina

S.C. Angiologia Medica - Messina All Patients get Regional Anaesthesia All Patients get Pneumatic Compression Pumps High risk get LMWH Low risk get ASA, 325 bid Mandatory Duplex in first week S.C. Angiologia Medica - Messina

S.C. Angiologia Medica - Messina 2012 S.C. Angiologia Medica - Messina

E’ accettabile fare la profilassi sempre e comunque ? S.C. Angiologia Medica - Messina

S.C. Angiologia Medica - Messina 2012 S.C. Angiologia Medica - Messina

Knee Arthroscopy Recommendations Recommendations IUA - International Consensus Statement 2007 Knee Arthroscopy Recommendations Recommendations Routine prophylaxis is not recommended unless other risk factors are present (Grade C). Simple diagnostic arthroscopy LMWH starting before or after surgery (Grade B). IPC in the presence of contraindications to LMWH (Grade C) until full ambulation. Arthroscopic surgery S.C. Angiologia Medica - Messina

S.C. Angiologia Medica - Messina Injury 2006 Sep;37(9):813-7. Thromboprophylaxis following cast immobilisation for lower limb injuries. Survey of current practice in United Kingdom. Batra S, Kurup H, Gul A, Andrew JG Although the incidence of DVT in patients in plaster for lower extremity injuries is low compared to the Hip/Knee arthroplasty group, this is not insignificant. Both over and under treatment with thromboprophylaxis can have implications in terms of side effects and costs. One possible solution is to use risk stratification to identify individuals who are likely to benefit from prophylaxis. There is a substantial variation and inconsistency in practice among orthopaedic departments in United Kingdom due to a lack of clinical guidelines in this group of trauma and it remains underused even in high-risk group. S.C. Angiologia Medica - Messina

Glasziou, P. P et al. BMJ 1995;311:1356-1359 Trattare i pazienti a basso rischio è una strategia molto rischiosa perché il vantaggio che il singolo individuo può ottenere da un programma di prevenzione può essere annullato dal rischio- anche minimo -che implica lo stesso intervento preventivo. Rose G. Int. Epidemiol. 1985 rischio beneficio danno Glasziou, P. P et al. BMJ 1995;311:1356-1359 S.C. Angiologia Medica - Messina

FATTORI DI RISCHIO PER TEV ALTO GRADO GRADO INTERMEDIO BASSO GRADO 75 anni 60-75 anni 40-60 anni Pregresso TEV Familiarità per TEV Sesso maschile Pregressa TV superficiale Fumo (>15 sig/die) Viaggi (>6 ore) Trombofilia Gravidanza Gruppo non 0 Puerperio Abortività Arteriopatia periferica Chirurgia maggiore* Estroprogestinici Diabete Chirurgia ortopedica* Obesità BPCO Traumi* Insuff. Venosa Cirrosi Neoplasie MICI° TIA (in terapia) Malattie autoimmuni IRC Antipsicotici Infarto miocardico acuto* Iperomocisteinemia Scompenso (III-IV NYHA) S. mieloproliferative Ictus Scompenso (I - II NYHA) Paralisi TIA (non in terapia) * entro 3 mesi Immobilizzazione* Bronconeumopatia acuta °malattie infiammatorie croniche dell’intestino S.C. Angiologia Medica - Messina

Vascular Injury Venous Stasis Hypercoagulability Very High Risk Tourniquet Immobilization and bed rest Vascular Injury Surgical manipulation of the limb Endothelial injury Hypercoagulability Increase in thromboplastin agents Very High Risk Medium/High Risk Low/Medium Risk Core The contribution of identified risk factors to the pathogenesis of DVT have been described in terms of Virchow’s Triad, named for the pioneering anatomical work of Rudolph Virchow in 1856. Changes in the properties of the blood, changes in blood flow, and abnormalities of the vessel wall are the main contributors to DVT The specific risk factors of Virchow’s Triad in orthopedic surgery encompass — Venous stasis: immobilization, bed rest, and tourniquet use and surgical limb positioning — Vascular injury: surgical manipulation of the limb and large vessels, and endothelial injury — Hypercoagulability: increase in thromboplastin agents and reaming of the femoral canal The overall risk of developing DVT increases in direct proportion to the number of risk factors Slide #3

LEGATI ALL’INTERVENTO STRATIFICAZIONE DEL RISCHIO E PROFILASSI FATTORI CHE INFLUENZANO IL RISCHIO DI TEV SOGGETTIVI SCORE LEGATI ALL’INTERVENTO Storia di tromboembolia venosa 1,5 Chirurgia maggiore: femore, ginocchio, rachide, bacino 3,0 Età > 70 a. Frattura femore 2,0 Trombofilia congenita o acquisita Fattura vertebrale Malignità Ingessatura senza carico Età > 60 a. 1,0 Artroscopia Obesità Fratture arto superiore Pillola contraccettiva (entro 1 m) Ingessatura con carico Arteriopatia periferica/coronarica Sepsi Varici importanti 0,5 Età > 40 a. STRATIFICAZIONE DEL RISCHIO E PROFILASSI Rischio Score Profilassi Durata Basso ≤ 1 nessuna Moderato 1.5-2.5 nadroparina 0.3 ml/die 15 giorni Elevato ≥ 3 nadroparina 0.3 ml/die (< 50 kg) nadroparina 0.4 ml/die (50-70 kg) nadroparina 0.6 ml/die (> 70 kg) 45 giorni S.C. Angiologia Medica - Messina

I nuovi farmaci anti-trombotici hanno superato le ebpm ? Fibrinogeno Fibrina Trombina Protrombina Xa + Va X Tissue Factor-VIIa IXa Fondiparinux Idraparinux Hirudin Bivalirudin Argatroban Ximelagatran IX VIIIa TFPI NAPc2 FVIIai APC S.C. Angiologia Medica - Messina

Idraparinux biotinylated Initiation TF VIIa Indiretti Fondaparinux Idraparinux biotinylated X IX AT Xa IXa Propagation Protrombina II This slide shows a simplified model of the coagulation pathway. Factor Xa and thrombin are the only components of the coagulation cascade common to both the extrinsic and intrinsic coagulation pathways and thus are attractive targets for therapeutic interventions. Reference Spyropoulos AC. Expert Opin Investig Drugs 2007;16:431–40. Diretti Rivaroxaban Apixaban Edoxaban Betrixaban YM-150 Diretti Lepirudin Bivalirudin Argatroban Dabigatran TGN-167 Inactive factor Active factor Transformation IIa Trombina Catalysis Clot formation Fibrinogen Fibrin S.C. Angiologia Medica - Messina Adapted from Spyropoulos AC. Expert Opin Investig Drugs 2007;16:431–40. antitrombina