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Anemo 2015-31-Ferrari-La prevenzione tromboembolica in chirurgia protesica maggiore
- 1. Un pericolo nascostoUn pericolo nascosto Dott. M.C. FerrariDott. M.C. Ferrari Responsabile Servizio Medicina Interna HospitalistResponsabile Servizio Medicina Interna Hospitalist OrthocenterOrthocenter Il Tromboembolismo venoso inIl Tromboembolismo venoso in chirurgia ortopedica maggiorechirurgia ortopedica maggiore
- 2. Fattori di rischio del TEV:Fattori di rischio del TEV: numerosi e frequentinumerosi e frequenti Deficit di Proteina C (1) Deficit di Proteina S (1) Deficit di Antitrombina (1) Resistenza alla proteina C attivata (1) Protrombina G20210A (1) Elevata concentrazione di Fattore VIII (1) Iperomocisteinemia (1) Terapia estroprogestinica Età (1) Fumo di sigaretta Chirurgia (1) Trauma (2) Neoplasie (1) IMA (3,4) Infezione acuta (3,4) Insufficienza cardiaca acuta (2) Insufficienza respiratoria acuta (3,4) Sindrome antifosfolipidica (1) Stroke (2) Insufficienza cardiaca congestizia (2) Ipertensione (5) Disordini mieloproliferativi (1) Sindrome nefrosica (2) Malattie intestinali infiammatorie (2) Obesità (2) Vene varicose (2) Immobilità (1) Viaggi a lunga distanza (6) Gravidanza e puerperio (1) Trombosi venosa pregressa (1) 1. Rosendaal FR. Semin Hematol. 1997;34(3):171–187 2. Clagett GP, et al. Chest. 1998;114(5) (Suppl):531–560S 3. Fraisse F, et al. Am J Respir Crit Care Med. 2000;161(4) part 1:1109–1114 4. Samama MM, et al. N Engl J Med. 1999;341(11):793–800
- 3. TEV:TEV: un’ampia popolazione a rischioun’ampia popolazione a rischio Prevalenza del rischio di TEV in pazienti ospedalizzati: percentuale di pazienti con almeno 3 fattori di rischio % pazienti con almeno 3 fattori di rischio 0 10 20 30 40 50 60 70 80 Medicina Interna Chirurgia maggiore Chirurgia addominale Chirurgia vascolare Neurochirurgia Chirurgia urologica Cardiochirurgia 1.Anderson FA, et al. Arch Intern Med. 1992;152(8):1660–1664
- 4. Tromboembolismo Venoso (TEV)Tromboembolismo Venoso (TEV) Una patologia silenziosaUna patologia silenziosa • 50% di TVP sintomatica evolve in EP asintomatica1 • 10-20% delle morti improvvise è causato da una EP asintomatica2 • Il TEV è asintomatico in circa il 70 % dei casi3 , ma può mettere in pericolo la vita o evolvere in patologie croniche • L’EP è sottostimata4,5 perchè: – spesso non è riconosciuta prima del decesso – origina da una TVP asintomatica – spesso compare dopo la dimissione ospedaliera 1 Kelley MA et al 1994 Clinics in Chest Medicine 15(3):549-60 2 Heit JA Semin Thromb Hemost 2002; 28 suppl 2: 3-14 3 Hirsh J Circulation 1996;93(12):2212-45 4 Dahl OE Curr Opin Pulm Med 2002;8:394-397 5 Huber O et al.Arch Surg 1992;127:310-3.
- 5. (Lindblad, 1991b) Sandler, 1989 Incidenza di TEV fra le autopsie di un singolo ospedale Tromboembolismo VenosoTromboembolismo Venoso 0 5 10 15 20 25 30 35 40 TEV EP EP fatali 1.Lindbald B, et al. BMJ 1991;302:709-11 2. Dahl OE ,Curr Opin Pulm Med 2002 8:394-7 %diriscontriautoptici 26% 35% 9.4%
- 6. Un problema misconosciuto: Fino al 2 % dei pazienti muore per embolia polmonare (EP) nonostante la profilassi antitrombotica 1. Geerts WH, et al. Chest 2001;119 (Suppl):132S–75S. 2Hirsh J Circulation 1996;93:2212-45 Il Tromboembolismo venoso inIl Tromboembolismo venoso in chirurgia ortopedica maggiorechirurgia ortopedica maggiore
- 7. TEV: una stretta correlazioneTEV: una stretta correlazione tra TVP ed EPtra TVP ed EP 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) Migrazione Trombosi Embolizzazione
- 8. • I pazienti sottoposti a tale chirurgia hanno il rischio più alto di sviluppare TEV1 fino ad almeno un mese dopo l’intervento2 • Dopo chirurgia ortopedica maggiore, fino a 2 pazienti su 100 possono sviluppare un’ EP fatale2 nonostante venga attuata una profilassi tromboembolica 1. Geerts WH, et al. Chest 2001;119 (Suppl):132S–75S. 2Hirsh J Circulation 1996;93:2212-45 Embolia Polmonare FataleEmbolia Polmonare Fatale Dopo Chirurgia ortopedica Maggiore
- 9. 14,80 1,00 1,50 2,20 1,00 1,30 Frattura d'anca Protesi d'anca Protesi di ginocchio Mortalità EP fatale 1Frostick SP. Haemost 2000;30(Suppl 2):84-7. Incidenzadimortalitàa6mesi%EP fatale nonostante la profilassi antitrombotica Il Tromboembolismo venoso inIl Tromboembolismo venoso in chirurgia ortopedica maggiorechirurgia ortopedica maggiore
- 10. N=1907 N=1907 1,50 1,10 0,80 1,30 0 0,2 0,4 0,6 0,8 1 1,2 1,4 1,6 Frattura d'anca Protesi d'anca Protesi di ginocchio TOTALI N=386 N=3954 Dahl OE, XVIII ISTH,July 2001,Paris FRANCE ,Abstract P 22 57 Il Tromboembolismo venoso inIl Tromboembolismo venoso in chirurgia ortopedica maggiorechirurgia ortopedica maggiore EP non fatale nonostante la profilassi antitrombotica
- 11. Il TEV in Chirurgia OrtopedicaIl TEV in Chirurgia Ortopedica maggiore:maggiore: frequente nonostante la profilassifrequente nonostante la profilassi 1. Geerts WH, et al. Chest 2001;119 Suppl 1:132–75S 4. Leyvraz PF, et al. BMJ 1991;303:543–8 2. Freedman KB et al. J Bone Joint Surg Am 2000;82:929–38 5. Fragmin® US package insert. April 2001 3. Lovenox® US package insert. April 2001 0 5 10 15 20 25 30 35 Eparina a basse dosi Warfarin1 Enoxaparina 2 40 mg o.d. Enoxaparina3 30 mg b.i.d. Nadroparina 4 38 then 57 IU/kg/d Dalteparina 5 5,000 IU o.d. %di TVP %di sanguinamenti maggiori o.d. = onc-ea-day b.i.d. =bis in die %di pazienti con TEV in protesi d’anca
- 12. 93 72 82 67 30 48 0 10 20 30 40 50 60 70 80 90 100 Kruit et al, 1991 Simonneau 1997 Girard et al, 1999 Tutte le TVP TVP asintomatiche Pazienti con EP confermata %deipazienti 1 Girard P et al Chest 1999; 116(4):903-8 2 Hull et al,AIM 1983;98:891-9 3 Kruit et al,J Intern Med 1991;230:333-9 4 Simonneau et al,NEJM 1997;337:663-9 L’embolia polmonare è causata da unaL’embolia polmonare è causata da una TVP asintomatica nel 50% circa deiTVP asintomatica nel 50% circa dei pazientipazienti
- 13. 0 10 20 30 40 50 60 EP sintomatica TVP sintomatica 3485 pazienti operati di protesi d’anca o ginocchio (1989–1998) che avevano ricevuto 10gg. di EBPM NumerodiEP Dahl OE, XVIII ISTH,July 2001,Paris FRANCE ,Abstract P 22 57 Dahl OE Acta Orthop Scand 2000;71:47-50 L’EP è provocata da una TVP asintomatica 6 50 Il Tromboembolismo venoso inIl Tromboembolismo venoso in chirurgia ortopedica maggiorechirurgia ortopedica maggiore
- 14. Il Tromboembolismo venoso inIl Tromboembolismo venoso in chirurgia ortopedica maggiorechirurgia ortopedica maggiore 0,0% 0,2% 0,4% 0,6% 0,8% 1,0% 1,2% 1,4% 1,6% 1,8% 2,0% NO TVP TVP distale TVP prossimale Haas, SB, et al. JBJS 1992;74:799-802.*1257Pazienti sottoposti a protesi di ginocchio e profilassi con ASA EP sintomatica: uguale rischio sia con TVP distale che prossimale*
- 15. La TVP compare dopo la dimissioneLa TVP compare dopo la dimissione ospedalieraospedaliera Insorgenza (media) di TVP dopo chirurgia 3485 pazienti operati di protesi d’anca e di ginocchio (1989–1998) I pazienti di chirurgia maggiore ricevevano 10 giorni di profilassi con EBPM Dahl OE, et al. Acta Orthop Scand 2000;71:47–50. 27 16 36 0 5 10 15 20 25 30 35 40 Protesi d’anca Protesi di ginocchio Frattura d’anca Giornatepost-operatorie Durata media della profilassi
- 16. White RH, et al. Arch Intern Med1998;158:1525–31. Il Tromboembolismo venoso in chirurgia ortopedica maggiore Il TEV compare dopo la dimissione ospedaliera Protesi d’anca - Incidenza di TEV dopo la dimissione: 76% Protesi di ginocchio - Incidenza di TEV dopo la dimissione : 47% Ginocchi o Anca2,8 2,1 45.000 pazienti
- 17. Dahl OE, et al. Thromb Haemost 2001;86:[Abstract]. Il Tromboembolismo venoso inIl Tromboembolismo venoso in chirurgia ortopedica maggiorechirurgia ortopedica maggiore Il TEV compare dopo la dimissione ospedaliera
- 18. TEV: un grande problemaTEV: un grande problema Riepilogo • Il TEV è una patologia frequente – circa 2.2 milioni di procedure di chirurgia ortopedica maggiore/anno mettono i pazienti a rischio • Il TEV è una patologia silente – l’80% di tutte le TVP è asintomatico – Il 50% delle EP è causato da una TVP asintomatica • Il TEV è una patologia pericolosa – L’ EP è la terza malattia cardiovascolare più comune – Fino al10% delle morti in ospedale è causato dall’EP – L’1-2% di EP fatali dopo chirurgia ortopedica maggiore avviene nonostante sia stata attuata regolare profilassi 1 1. Popovic JR. 1999. National Hospital Discharge Survey. Vital Health Stat 2001;13:151
- 19. • 1-2 % dei pazienti dopo chirurgia ortopedica maggiore può morire per EP entro 1 mese dalla dimissione ospedaliera1,2 • L’EP origina soprattutto da una TVP asintomatica durante il periodo di ospedalizzazione • Il rischio di evolvere in EP è simile nelle TVP prossimali e distali 3 • La profilassi fino al 2001 sembrava essere insufficiente a prevenire tale silente patologia 4 1 Hirsh J 1996 Circulation 93(12):2212-45 2 Gray HW Sem Nucl Med 2002; 32(3): 159-72 3. Haas SB et al.JBJS 1992;74:799-802 4.Hansson PO, Arch Int Med1997; 157:1665-70 Il TEV in chirurgia ortopedica maggioreIl TEV in chirurgia ortopedica maggiore ConclusioniConclusioni
- 20. Tromboembolismo Venoso: CONCLUSIONITromboembolismo Venoso: CONCLUSIONI • Le conseguenze fatali del TEV devono essere prevenute1 • Esistono delle evidenze per cui gli attuali farmaci utilizzati per la profilassi antitrombotica sono insufficienti • Un bilancio ottimale tra efficacia e sicurezza d’uso deve essere sempre ricercato2 La sfida è stata quindi di riuscire a trovare un farmaco antitrombotico più potente e ugualmente sicuro3 1 Geerts GH CHEST 2001;119:132S-175S 2 Hirsh J CHEST 2001;119:1S-2S 3 Dahl OE Curr Opin Pulm Med 2002;8:394-97
- 21. I farmaci utilizzati nel trattamentoI farmaci utilizzati nel trattamento del TEV agiscono a livelli differentidel TEV agiscono a livelli differenti nella cascata coagulativanella cascata coagulativa Inibito dall’eparina Inibito dagli antagonisti della vitamina K Meccanismi coagulantiXa Anticoagulante endogenoATIII Legenda Via intrinseca Via estrinseca Coagulo T M TF Ca2+ Xa TFPI PCa PC PS X II IX XI XII XIIa FibrinaFibrinogeno Xa Va FL Ca2+ IIa VII ATIII XIa VIIa VIIIa Ca2+ FL IXa TF: fattore tissutale FL: fosfolipidi TFPI: inibitore della via del fattore tissutale PS: proteina S PC: proteina C PCa: proteina C attivata TM: trombomodulina ATIII: antitrombina III 1.Rosenberg RD, Aird WC. N Engl J Med. 1999;340:1555–1564 2.Hirsh J, et al. Chest. 1995;108(Suppl):258–275S 3.Samama CM et al. Thromb Haemost. July 2001. ISTH Abstract 4.Hirsh J, Fuster V. Circulation. 1994;89:1469–1480 5.Hirsh J, Fuster V. Circulation. 1994;89:1449–1468
- 22. TEV: i nuovi farmaci che agisconoTEV: i nuovi farmaci che agiscono sulla coagulazione,sulla coagulazione, la ricerca della selettivitàla ricerca della selettività TFPI = Inibitori della via del Fattore Tissutale NAPc2 = Proteina Nematode Anticoagulante C2 APC = Proteina C attivata AT III = Antitrombina III • Inibitori della trombina irudina, bivalirudina, argatroban, melagatran, dabigatran • Inibitori del fattore IXa Inibitori IXa, anticorpi IXa • Attivatori della proteina C APC, trombomodulina • Inibitori del fattore Xa fondaparinux, rivaroxaban, apixaban Cascata coagulativa Ultimi sviluppi della ricerca Inibitori della via del Fattore Tissutale TFPI, NAPc2 Inizio Generazione di trombina Attività della trombina TF/VIIa IIa II Xa IXa IXX VIIIa Va 1.Weitz J, Hirsh J. Chest. 2001;119:95–107S
- 23. Fattore Xa:Fattore Xa: un ruolo centraleun ruolo centrale nella cascata coagulativa (1)nella cascata coagulativa (1) Via estrinsecaVia intrinseca 1 50 Xa X II FibrinaFibrinogeno Coagulo Xa Va FL Ca2+ IIa VIIIa Ca2+ FL IXa L’inibizione di una molecola di fattore Xa può inibire la generazione di 50 molecole di trombina (2) 1.Rosenberg RD, Aird WC. N Engl J Med. 1999;340:1555–1564 2.Wessler S, Yin ET. Thrombos Diath Haemorrh. 1974;32:71–78
- 24. Fattore Xa:Fattore Xa: un ruolo centrale nella formazioneun ruolo centrale nella formazione e crescita del tromboe crescita del trombo Il fattore Xa favorisce la genesi del trombo stimolandone la formazione nella fase fluida Inoltre, stimola l’amplificazione del trombo facilitandone la crescita sulla superficie del coagulo Generazione di trombina Fase fluida AMPLIFICAZIONE ATTIVAZIONE Xa Fibrinogeno Fibrina Xa Va IIa VIIIa 1.Petitou M, Herbert JM. Pour la Science. 2000;274:2–8 2.Rosenberg RD, Aird WC. N Engl J Med. 1999;340:1555–1564
- 25. • I costi ospedalieri diretti del TEV sono sovrapponibili a quelli di un IMA o di uno stroke (1,2) • Ulteriori costi sanitari a lungo termine della TVP: 75% del costo iniziale (3) COSTO ECONOMICO DEL TEVCOSTO ECONOMICO DEL TEV Costo medio per ogni ricovero negli USA ($) EP(1) TVP(1) IMA(2) Stroke(2) 12.595 9.337 9.643 6.367 0 5000 100002500 7500 12500 1. Bick RL. Clin Appl Thromb Hemost. 1999;5(1):2–9 2. Medicare & DRG. 1996 3. Bergqvist D, et al. Ann Intern Med. 1997;126:454–457
- 31. CONFRONTO FRA I NAO vsCONFRONTO FRA I NAO vs ENOXAPARINAENOXAPARINA 9.643 6.367 RivaroxabanRivaroxaban ApixabanApixaban DabigatranDabigatran THR Record 1 ⬆ Advance 3 ⬆ Re-novate 1 ↔ THR Record 2 ⬆ Re-novate 2 ↔ TKR Record 3 ⬆ Advance 2 ⬆ Re-model ↔ TKR Record 4 ⬆ Advance 1⬇ Re-mobilize ⬇ END POINTS: TEV, MORTALITA’ E COMPLICANZE
- 32. CONFRONTO FRA I NAO E EBPMCONFRONTO FRA I NAO E EBPM • Dabigatran: 110 mg 1-4 h dopo l’intervento, poi 220 mg ogni 24 h • Apixaban: 2.5 mg ogni 12 h iniziando 12-24 dopo l’intervento • Rivaroxaban: 10 mg 6-10 h dopo l’intervento, poi ogni 24 h • Enoxaparina-Nadroparina: s.c., peso-dipendenti, cominciare 12 ore prima dell’intervento (sanguinamento in sede operatoria e/o spinale?), trombocitopenia • Fondaparinux: 2.5 mg s.c. 6-10 h dopo l’intervento e poi ogni 24 h
- 33. Da circa 4 anni utilizziamo esclusivamente i NAO (circa 5000 pazienti ad oggi). In preferenza utilizziamo Rivaroxaban (XARELTO): 1. Superiore in efficacia rispetto alle EBPM 2. Non lascia scoperto il paziente troppo a lungo dopo l’intervento (vedi Apixaban-ELIQUIS), e non è troppo precoce (vedi Dabigatran-PRADAXA) 3. Non induce piastrinopenia 4. Monodose giornaliera orale 5. Utilizzabile vista la sua emivita anche in caso di cateteri peridurali rimuovibili con sicurezza 6. Nessun sanguinamento imprevisto o maggiore; scarsissimi effetti collaterali che abbiano indotto alla sospensione del farmaco QUINDI SICURO, MANEGGEVOLE ED EFFICACE NOSTRA ESPERIENZA IN HUMANITASNOSTRA ESPERIENZA IN HUMANITAS 9.643
- 34. • Inibitore orale e diretto del Fattore Xa • Inattiva il FXa libero e legato a fibrina e al complesso protrombinico • Nessun effetto sull’aggregazione e sull’emostasi piastrinica, quindi non induce piastrinopenia • Scarsa variabilità di risposta intra ed interindividuale • Biodisponibilità prevedibile, senza necessità di aggiustamento posologico sulla base del peso del paziente • Scarsa interazione con cibo e altri farmaci • Metabolismo: EPATICO: 66% degradazione metabolica (CYP3A4 and others); 33% eliminato per via fecale come farmaco inattivato. RENE: 33% eliminazione diretta(P-gp and others) come farmaco attivo non metabolizzato; 33% eliminato come farmaco inattivato RIVAROXABANRIVAROXABAN
- 35. 9.643 6.367
Editor's Notes
- Market research has shown that orthopaedic surgeons underestimate Venous Thromboembilism (VTE) in their practice. Specifically in major orthopaedic surgery of the lower limbs. The following slides will describe the reasons of this and bring the discussion why they should use from the very beginning potent thromboprophylaxis
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- Despite overwhelming epidemiological evidence concerning its high incidence and risks, VTE remains an underestimated problem among doctors. Part of the problem stems from the silent nature of the disease. Approximately 80% of all DVTs are silent, and very few fatal and non-fatal PE events are suspected prior to their occurrence. Of those VTE events that prove fatal, only 20% are suspected prior to death. In certain conditions where diagnosis of DVT is difficult, such as major orthopedic surgery, only 12% of patients present with clinical DVT prior to onset of PE. The disease is often silent so these incidences probably represent an underestimate.
- Former slide figures more in detail.
- The prevalence of VTE (Deep Venous Thrombosis / Pulmonary Embolism) among 994 autopsies performed in 1293 who died in a single hospital (Malmo, General Hospital, Lund University, Malmo, Sweden) was as high as 35 %. (Lindbald, BMJ 1991;302:709-11) PE was the direct cause of death in the 9,4% of the cases, showing that about one patient out of ten died due to a complication of the venous thrombotic process. The presence of PE was identified in 26% of all autopsies ; 8 % had only DVT without PE, reflecting how frequently and rapidly DVT leads to PE . It is of note that the PE rate is even underreported since only 15% of hospitals perform autopsies and some autopsies overlook pulmonary embolism ( Dahl OE, Curr Opin Pulm Med 2002 8:394-97)
- The ACCP guidelines (Chest 2001) assess the risk of developing VTE in patients undergoing major orthopaedic surgery at the highest level. Despite currently recommended prophylaxis up to 2 in 100 patients may die from pulmonary embolism. Currently more than two million people in the US and Europe undergo major orthopaedic surgery (hip replacement, knee replacement, hip fracture surgery) each year, a rate which is increasing at about 4% per year. Whilst a large proportion of this increase is due to a rise in the number of patients with hip fracture, related to an aging population, and the burden of osteoporosis in the elderly, still patients undergoing elective surgery are experiencing clinical VTE and fatal events. VTE however has been shown to be a preventable disease that should be prevented to save lives and reduce VTE linked morbidity and expenses.
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- The ACCP guidelines (Chest 2001) assess the risk of developing VTE in patients undergoing major orthopaedic surgery at the highest level. Up to 2 in 100 patients may die from pulmonary embolism. Currently more than two million people in the US and Europe undergo major orthopaedic surgery (hip replacement, knee replacement, hip fracture surgery) each year, a rate which is increasing at about 4% per year. Much of this increase is due to a raising number of patients with hip fracture, due to an ageing population and the burden of osteoporosis in the elderly. VTE is a preventable disease that should be prevented to save life and reduce VTE linked morbidity.
- A recent randomised study by Frostick et al[ Haemostasis 2000;30 (Suppl 2):84-7] compared mortality rates in 887 patients from one single large hospital undergoing lower limb arthroplasty, hip and knee replacement, of which 358 had a proximal femur fracture. Patients received in-hospital thromboprophylaxis with the low molecular weight heparin (LMWH), dalteparin or unfractionated heparin (UFH) for 8 2 days and were followed for 6 months after discharge. Post-mortem examination was carried out on all of the patients who died during follow-up. A mortality rate of 14.8% (53/358) was recorded in the femoral fracture group. This compared with rates of 1% and 1.5% respectively in total hip replacement (THR) and total knee replacement (TKR) patients. The incidence of fatal PE in the hip fracture group was 2.2% (8/358), all of which occurred after thromboprophylaxis had ceased. In the other two elective surgery groups almost 100% of the deaths were due to PE. These interesting data show that such a situation could be found in some current hospitals
- The incidence of clinical pulmonary embolism in patients undergoing major orthopedic surgery goes up to 1.3% as shown in an abstract from Dahl O. presented at XVIII ISTH in Paris 2001. The files of more than 3400 patients from 1989 up to 1998 having undergone MOS surgery were retrospectively reviewed; PE occurring within 6 months of the operation was retained for the analysis. Respectively 1.50%, 1,10% and 0.80% of patients undergoing hip fracture, total hip replacement and total knee replacement surgery developed PE despite prophylaxis with LMWH was given at least until discharge, (either enoxaparin 40 mg SC qD or dalteparin 5000 IU SC qD.) .
- Girard and colleagues have recently looked at the prevalence of DVT in patients hospitalized with confirmed pulmonary embolism PE either by lung scan or by angiography (Chest 1999 ;116:903-7) In this study, 82% of the patients with confirmed PE had venographic signs of DVT and 48% of the patients had asymptomatic DVT and 34% had clinical signs of DVT. These figures match with data from other papers (Kruit and Simonneau) .In average about 50% of patients with confirmed PE also had a concomitant asymptomatic DVT. This demonstrates the silent evolution of a thrombotic process that leads to potentially fatal complications (fatal pulmonary embolism). This is the same in MOS (next slide)
- Pulmonary embolism (PE) , the most serious consequence of the venous thrombotic process has been shown to originate from asymptomatic DVT in a paper assessing this in more than 3400 patients undergoing knee or hip surgery under LMWH prophylaxis. (Dahl OE,XVIII ISTH, 2001) While 50 patients had confirmed PE , only 6 presented with symptomatic Deep Venous Thrombosis (DVT) , demonstrating that in the majority of the cases no clinical signs precede PE. These data strongly suggest that 88% of these PEs were associated with asymptomatic (venographic) DVT. There is no need to wait for these signs for starting prophylaxis, which must happen as soon as possible after surgical closure.
- Referring to the natural history of the venous thrombotic process , Haas and colleagues (JBJS 1992;74:799-802) have shown in more than 1200 patients undergoing Total Knee Replacement (TKR) with prophylaxis that whatever the location of Deep Venous Thrombosis (DVT), the risk level of symptomatic pulmonary embolism (PE) is similar. Of the 1257 patients who had had THR surgery , 759, (60,4 %) were found to have thrombosis; 655 (52,1 %) distal DVT and 104 (8,3 %) proximal DVT. In those patients with no venographic signs of DVT, 0.2% developed PE versus 1.7% in those with distal signs (p 0.034) and 1.9% in those with signs of proximal DVT. Patients with distal or proximal DVT were found to have similar rates of positive lung scans and symptomatic pulmonary embolism.
- In a retrospective work, Dahl OE et al have shown that most of the MOS patients get short term thromboprophylaxis.However, considering the incidence of DVT, it appears that the first signs are seen on average 27 days after surgery for THR, 16 days post surgery for TKR and up to 36 days for hip fracture. So, once patients have left hospital. As VTE is a silent and ongoing process, close follow up and extended prophylaxis are needed to prevent a face of the disease that can be fatal, pulmonary embolism.
- White and al. reviewed from a hospital discharge data base the incidence of DVT or PE within three months of surgery in 45.000 patients having undergone THR or TKR. Cumulative incidence of VTE was respectively 2,8% and 2,1% after THR and TKR. The diagnosis of VTE was made after discharge in 76% and 47% for THR and TKR respectively. The mean length of stay was 74 days. 95% of these patients were given in-hospital thromboprophylaxis, either subcutaneous heparin, warfarin, or a combination of these. 32% of the patients were given thromboprophylaxis after discharge with warfarin with an average duration of 4 weeks. These findings suggest that to further reduce VTE more potent thromboprophylaxis is needed.
- As previously said, PE can be a complication that occurs after discharge. In this study looking at non fatal PE rate in THR and hip fracture surgery patients, risks of developing non fatal PE are highest during about 40 days within surgical closure. However, discharge occurs on average 9-10 days post surgery. The figure shows that VTE risk still persists after discharge. To improve this situation a potent antithrombotic agent that dramatically decreases the risk of developing DVT at the very beginning and impacts the further evolution to PE should be used . Such an agent is available.
- Venous thromboembolism is a condition which in the coming years will grow due to aging of the population and an increased number of MOS procedures. The ACCP guidelines (Chest, 2001) assess the risk of VTE in major orthopedic surgery at the highest level The natural history of the disease shows that serious events such as pulmonary embolism are the consequence of a silent and sly process. It all starts with asymptomatic deep vein thrombosis that further moves to proximal before ending in PE, symptomatic in less than 50% of the cases. PE explains one fifth of the sudden death in hospitalized patients. Current guidelines for VTE prophylaxis in MOS recommend the use of LMWH and /or mechanical devices such as foot pomps for instance. Though these measures are rather safe, it appears that still up to 2% of patients may die from a preventable disease. Which situation is unacceptable and requires new measures like more potent prophylaxis
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- Though guidelines are followed by care providers to prevent VTE in several clinical conditions, the measures taken ,being either pharmacological or mechanical, appear insufficient. Increasing incidence of VTE in an aging population require that new techniques or more potent but safe antithrombotic drugs are used to prevent . This constitute a challenge for the next decade. For those patients at the highest risk, like patients undergoing major orthopedic surgery, newly approved drugs have proven to meet this requirement.
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)
- VTE is a common disease: about 2 million patients world-wide suffer from this disorder.Venous thromboembolism (VTE) is a major health problem and one of the most common disorders of the circulatory system, with an incidence that exceeds 1 per 1000 [ two thirds of these VTE events are deep-vein thrombosis (DVT) and one third pulmonary embolism (PE)]. In the USA between 300,000 to 600,000 patients are hospitalised each year for a thromboembolic event. In Europe, some 700,000 patients will develop VTE each year. However, this is not a condition confined to Western countries. An emerging body of evidence from various Asian countries has demonstrated an incidence of the disease in hospitalised patients that is comparable to Western countries, providing support for the conclusion that VTE is a global health problem . Of patients suffering a VTE event, 30% die within 30 days and one out of five suffer death due to pulmonary embolism (Heit JA Semin Thromb Haemost 2002;28-Suppl 2:3-14.) Moreover, VTE is the third most common cardiovascular disease after ischemic heart disease and stroke, and is the cause of significant morbidity and mortality (Giundini C et al;Chest 1995:3S-9S)