Interruzione della terapia an/coagulante/an/aggregante per procedure invasive

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1 Interruzione della terapia an/coagulante/an/aggregante per procedure invasive Giorgia Saccullo Ematologia con trapianto Policlinico Universitario di Palermo

2 1. L en2tà del rischio trombo2co/emorragico 2. Gli approcci a=uali 3. Le procedure a basso rischio 4. La bridging therapy 5. Le linee guida ACCP/FCSA

3 Sensi2vity analysis on the annual risk of stroke and periprocedural risk of hemorrhage Periprocedural Probability of hemorrhage A Hold warfarin Annual risk of stroke per 100 pt/yrs without antithrombotic therapy B C Dose Reduction Continue warfarin Gerson LB et al, Am J Med 2004

4 Percentuale di trombosi e sua riduzione in terapia an2coagulante Indicazioni % di trombosi senza terapia Riduzione del rischio in terapia TEV acuto 1 mese TEV acuto 2 e 3 mese TEV recidivante FA non valvolare FA non valvolare con embolismo Valvole meccaniche 8 75 Trombosi arteriosa acuta (1 mese) 15 66

5 Il rischio peri operatorio standard Pre operatorio Intra operatorio Post operatorio Rischio emorragico * - +* Rischio trombo2co * + ++* *Secondo la procedura chirurgica

6 Il rischio peri operatorio nei pazien2 an2coagula2 Pre operatorio Intra operatorio Post operatorio Rischio emorragico ** ** Rischio trombo2co - +* ** ** * Secondo la patologia di base **Secondo la patologia di base e/o la procedura chirurgica

7 Fa=ori di scelta per un approccio idoneo: Rischio di trombosi Valutazione del rischio di tromboembolie (TE) mentre la TAO è sospesa: Indicazioni per la TAO Fa=ori di rischio associa2 Conseguenze della TE 7. Prandoni P et al. Thromb Haemost. 2002;88(3): Fedullo PF, Tapson VF. N Engl J Med. 2003; 349:

8 Classificazione del rischio tromboembolico Rischio TE Elevato Indicazioni TAO Protesi mitralica Protesi aor2ca non recente o associata a FA TEV < 3 mesi Basso FA senza storia di stroke o altri fa=ori di rischio Protesi valvolare aor2ca a doppio disco FA > 3 mesi Ansell et al. Chest 2004

9 Classificazione del rischio tromboembolico Rischio TE Elevato Moderato Indicazioni TAO Protesi mitralica, aor2ca non recente o associata a pregresso stroke FA + stroke o TIA o valvulopa2a mitralica TEV recente o associato a neoplasia, APA, cardiopa2a e pneumopa2a cronica Protesi aor2ca o FA e > 2 fa=ori di rischio per stroke TEV < 6 mesi Basso Protesi aor2ca o FA e < 2 fa=ori di rischio per stroke TEV > 6 mesi DoukeXs et al. Thromb Res. 2003

10 Conseguenze del tromboembolismo (TE) Pazien/ con TE arterioso Pazien/ con TEV ricorrente Mortatlità 20% 6% Danno permanente 60% 5%

11 Fa=ori di scelta per un approccio idoneo: Rischio di emorragia Rischio di emorragie: Terapia an2coagulante Tipo di intervento Conseguenze delle emorragie

12 Fa=ori di rischio emorragico Rischio emorragico basso pre operatoriamente ma elevato durante e dopo la chirurgia maggiore (2po e sede dell intervento) TAO: INR >1,5; dopo sospensione occorrono 3 5 giorni per o=enere un INR < 1,5. Eparina: aumento del rischio di emorragie post operatorie: 3% (Kearon C. NEJM, 1997)

13 Conseguenze delle emorragie Emorragie post chirurgiche maggiori: 3%, spesso senza conseguenze Fatali nel 3% degli even2

14 Classificazione del rischio emorragico Rischio Elevato Chirurgia o procedure invasive Neurologica, vescicale, vascolare maggiore; Prostatectmia, bypass AoC, biopsie a cielo coperto; olipectomie Moderato Addominale, toracica, ortopedica maggiore; Inserzione di pacemaker Basso Catara=a; cucolecistectomia laparoscopica; ernioplas2ca; Angiografia coronarica; avulsione dentaria DoukeXs et al. 2003

15 1. L en2tà del rischio trombo2co/emorragico 2. Gli approcci a=uali 3. Le procedure a basso rischio 4. La bridging therapy 5. Le linee guida ACCP/FCSA

16 Opzioni terapeu2che: 1. Con2nuazione della TAO 2. Sospensione temporanea della TAO 3. Sospensione temporanea della TAO e sos2tuzione con eparina ( bridging therapy ) quando INR < intervallo terapeu2co

17 Problema2che con gli an2coagulan2 La sospensione della warfarina richiede diversi giorni per o=enere un INR < 1.5 (ritenuto sicuro per le manovre interven2s2che) Alla ripresa, sono necessari diversi giorni per ripris2nare un INR terapeu2co Di fa=o, la ges2one perioperatoria con la sola warfarina non è ohmale

18 Problema2che con gli an2coagulan2 Pochi studi prospehci e controlla2 con un numero significa2vo di pazien2 Studi disponibili: Retrospehvi, Numero limitato di pazien2, Indicazioni a TAO diverse, Procedure ed interven2 diversi. Poche informazioni sull efficacia e sicurezza delle diverse modalità terapeu2che

19 Non vi è consenso nel tra=amento perioperatorio. Le opzioni terapeu2che sono classicamente: Non sospendere il tra=amento con AVK. La sua sospensione temporanea con eventuale sos2tuzione con eparina a dosi terapeu2che ( bridging therapy ) quando l INR è inferiore all intervallo terapeu2co. L American College of Cardiology e l American Heart Associa2on (ACC/AHA) e l American College of Chest Physicians (ACPP) suggeriscono la bridging therapy nella maggior parte dei pazien2 mentre altri autori applicano la terapia eparinica solo nei pazien2 con un rischio TE molto elevato (*, **, ***). Mentre vi è chiara evidenza che l eparina non frazionata (ENF) ed a basso peso molecolare (EBPM) siano efficaci nella prevenzione del TE venoso, controverso è il loro effe=o nella prevenzione del TE arterioso (^). Le scelte terapeu2che sono in genere condivise nei pazien2 ad elevato rischio di TE, controverse sono quelle per i pazien2 con rischio moderato e basso. * Kearon C. Management of an2coagula2on before and aner elec2ve surgery. Hematology 2003: (ASH 2003 Ed. book). **Ansell JE, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists. Seventh ACCP conference on an2thrombo2c and thromboly2c therapy. Chest 2004, 126:204S 233S. ***Bonow RO, Carabello B, de Leon AC jr, et al. ACC/AHA guidelines for the management of pa2ents with valvular heart disease: execu2ve summary. A report of the American College of Cardiology/American Task Force on Prac2ce Guidelines (Commi=ee on Management of pa2ents with Valvular Heart Disease) Circula2on 1998,98: ^5. Kearon C, Hirsh J. Management of an2coagula2on before and aner elec2ve surgery. N Engl J Med 1997, 336:

20 1. La dimensione del problema 2. L en2tà del rischio trombo2co/emorragico 3. Gli approcci a=uali 4. Le procedure a basso rischio 5. La bridging therapy 6. Le linee guida ACCP/FCSA

21 Problema2che con gli an2coagulan Interven</procedure per i quali non è necessario sospendere il traaamento con AVK Chirurgia cutanea Catara=a con anestesia topica (da preferire) Artrocentesi e iniezioni intessu2 molli e ar2colari Punture e cateterismi di vene ed arterie superficiali Puntura sternale e biopsia osteomidollare Procedure cardiologiche Eco transesofageo Procedure odontoiatriche semplici Avulsioni dentarie e altre procedure

22 1. La dimensione del problema 2. L en2tà del rischio trombo2co/emorragico 3. Gli approcci a=uali 4. Le procedure a basso rischio 5. La bridging therapy 6. Le linee guida ACCP/FCSA

23 Execu/ve Summary: An/thrombo/cTherapy and Preven/on of Thrombosis, 9 th ed: American College of Chest Physicians. Evidence Based Clinical Prac/ce Guidelines Chest 2012;141;7S 47S DOI /chest.1412S In pa/ents who require temporary interrup/on of a VKA before surgery, we recommend stopping VKAs approximately 5 days before surgery instead of stopping VKAs a shorter /me before surgery (Grade 1C) 2.2. In pa/ents who require temporary interrup/on of a VKA before surgery, we recommend resuming VKAs approximately 12 to 24 h auer surgery (evening of or next morning) and when there is adequate hemostasis instead of later resump/on of VKAs (Grade 2C) In pa/ents with a mechanical heart valve, atrial fibrilla/on, or VTE at high risk for thromboembolism, we suggest bridging an/coagula/on instead of no bridging during interrup<on of VKA therapy (Grade 2C). In pa/ents with a mechanical heart valve, atrial fibrilla/on, or VTE at low risk for thromboembolism, we suggest no bridging instead of bridging an/coagula/on during interrup/on of VKA therapy (Grade 2C).

24 FEDERAZIONE CENTRI PER LA DIAGNOSI DELLA TROMBOSI E LA SORVEGLIANZA DELLE TERAPIE ANTITROMBOTICHE FCSA TERAPIA ANTICOAGULANTE ORALE, CHIRURGIA E MANOVRE INVASIVERACCOMANDAZIONI DELLA FCSA Bridging nei pazien/ ad Alto Rischio Giorno 5: sospensione TAO Giorno 4: inizio eparina se il paziente era in acenocumarolo (se paziente in range terapeu2co al momento della sospensione) Giorno 3: inizio eparina se il paziente era in warfarin (se paziente in range terapeu2co al momento della sospensione) Usare dosi di EBPM ogni 12 ore secondo il peso corporeo Ul2ma somministrazione almeno 12 ore prima dell intervento Controllo INR prima dell intervento Intervento con INR <1.5 Riprendere eparina alle stesse dosi la mahna successiva (se almeno 12 ore dopo l uscita dalla sala e se emostasi sicura). Giorno + 1: riprendere TAO ad una dose del 50% superiore a quella abituale (se emostasi sicura e se il paziente è in grado di assumere farmaci per os). Giorno + 2: proseguire TAO ad una dose del 50% superiore a quella abituale (se emostasi sicura) Giorno + 3 e successivi: proseguire TAO alla dose abituale (se emostasi sicura). Sospendere l eparina dopo due giorni con INR superiore a 2 (o a 2.5 per pazien2 a target 3).

25 Bridging nei pazien/ a Rischio Basso Moderato Giorno 5: sospensione TAO Giorno 4: inizio eparina se il paziente era in acenocumarolo (se paziente in range terapeu2co al momento della sospensione) Giorno 3: inizio eparina se il paziente era in warfarin (se paziente in range terapeu2co al momento della sospensione) Usare dosi di eparina profilahche ogni 24 ore: nadroparina : < 50 Kg: 2850 U, Kg: 3800 U, > 70 Kg: 5700 U enoxaparina 4000 U Ul2ma somministrazione almeno 12 ore prima dell intervento Controllo INR prima dell intervento Intervento con INR <1.5 Riprendere eparina a dosi profilahche la mahna successiva (se almeno 12 ore dopo l uscita dalla sala e se emostasi sicura). Giorno + 1: riprendere TAO ad una dose del 50% superiore a quella abituale (se emostasi sicura e se il paziente è in grado di assumere farmaci per os). Giorno + 2: proseguire TAO ad una dose del 50% superiore a quella abituale (se emostasi sicura) Giorno + 3 e successivi: proseguire TAO alla dose abituale (se emostasi sicura). Sospendere l eparina dopo due giorni con INR superiore a 2 (o a 2.5 per pazien2 a target 3)

26 Standardized Low Molecular Weight Heparin Bridging Regimen in Outpa/ents on Oral An/coagulants Undergoing Invasive Procedure or Surgery. An Incep/on Cohort Management Study V. Pengo, MD; U. Cucchini, MD; G. Denas, MD; N. Erba, MD; G. Guazzaloca, MD; L. La Rosa, MD; V. De Micheli, MD; S. Testa, MD; R. Frontoni, MD; D. Prisco, MD; G. Nante, MD; S. Iliceto, MD; for the Italian Federa2on of Centers for the Diagnosis of Thrombosis and Management of An2thrombo2c Therapies (FCSA) STUDY DESIGN Table 1. An/coagula/on Protocols Applied According to Pa/ent Thromboembolic Risk Protocol A: Pa/ents at High TE Risk, IU Weight, kg Nadroparin* (Twice Daily, SC) Enoxaparin* (Twice Daily, SC) < Protocol B: Pa/ents at Low to Intermediate TE Risk, IU Weight, kg Nadroparin* (Once Daily, SC) Enoxaparin (Once Daily, SC) < TE indicates thromboembolic. *Dosages (units of an2 factor Xa) varying according to body weight. Prophylac2c dosage that is independent of body weight.

27 Table 3. Types of Procedures According to the Bleeding Risk Surgery/Procedure n %* High bleeding risk (n369) Abdominal Orthopedic Maxillofacial Urologic Vascular Gynecologic Ocular Mammary Neurosurgery Low bleeding risk (n893) Gastrointes2nal Endoscopy Cutaneous surgery Cistoscopy Biopsies Hand surgery Angiography Ocular procedures ENT procedures Gynecologic procedures PM/ICD implanta2on Miscellaneous Hepa2c procedures Arthroscopy ENT indicates ear, nose, and throat; PM/ICD, pacemaker/implantable cardioverter defibrillator. *Percentage with respect to the group total. Micrographic surgery, cutaneous oncology, and other surgery requiring hospitaliza2on

28 Primary safety outcome: MAJOR BLEEDING Results There were 15 episodes of major bleeding (1.2%; 95% CI, 0.7 to 2.0). All events were postprocedural, and none was fatal. Most of the bleeding episodes (11 of 15) were overt surgical site bleeding, and 9 required the transfusion of 2 U packed red blood cells. Of the 15 major bleeding events, 8 occurred in the 295 cases bridged with protocol A (2.7%) and 7 in the 967 cases bridged with protocol B (0.7%; P0.011). 7 major bleeding events occurred in 369 cases of high bleeding risk procedures (1.9%), and the remaining 8 occurred in 893 cases of low bleeding risk procedures (0.9%; P0.16). On exact logisxc regression analysis, protocol A predicted the occurrence of major bleeding (odds ra2o, 4.6; 95% CI, 1.0 to 19.1; P0.047). Table 4. Thromboembolic Event Details Pa2ent Sex Age, y Indica2on Procedure Event Event Day* Comments 1 F 64 DVT Hemicolectomy PE 5 Thrombosis of the pulmonary artery segmental branches 2 F 63 AF+MVR Saphenectomy PE 0 No preopera2ve bridging with LMWH because day 4 INR3.1 3 F 83 PE Femoral PE (fatal) 6 History of PE osteosynthesis 4 F 57 AVR+ Saphenectomy Systemic 3 No postopera2ve LMWH because of a MV repair embolism considerablesurgical site hematoma 5 F 70 AF+stroke+MVR Colonoscopy TIA 13 Day 10 INR2.7 DVT indicates deep vein thrombosis; PE, pulmonary embolism; AF, atrial fibrilla2on; MVR, mitral valve replacement; AVR, aor2c valve replacement; and TIA, transient ischemic a=ack. *Number of days aner the procedure.

29 Patients Requiring Interruption of Long-Term Oral Anticoagulant Therapy: The Use of Fixed Sub-Therapeutic Doses of Low-Molecular Weight Heparin 1 Alessandra Malato, 1 Giorgia Saccullo, 1 Lucio Lo Coco, 1 Domenica Caramazza, 1 Ignazio Abbene, 1 Giuseppina Pizzo, 2 Alessandra Casuccio and 1 Sergio Siragusa STUDY DESIGN Pa/ents Characteris/cs (no. 328) Findings Mean age (range, y) 62.3 (25/89) M/F (%) 53/47 Weight, mean +SD (Kg) Bridging therapy with nadroparin, n (%) 142 (43.2%) Bridging therapy with enoxaparin, n (%) 186 (56.7%) All Venous Thromboembolism (VTE) events, n (%) 45 (13.7%) Events las2ng < 3 months 18 Events las2ng > 3 months 27 Atrial Fibrilla2on without previous stroke (AF NoAT), n (%) Atrial Fibrilla2on with previous stroke (AF AT), n (%) 122 (37.1%) 58 (17.6%) Prosthe2c Aor2c Valves (PAV), n (%) 35 (10.6%) Prostethic Mitralic Valves (PMV), n (%) 44 (13.4%) Study protocol. LMWH, low molecular weight heparin; VKA, vitamin K antagonist. Note: LMWH means 3800 UI an2 FXa of nadroparin or 4000 UI of enoxaparin an2 FXa; LMWH was started preopera2vely when INR 1.5; LMWH was stopped postopera2vely when there was an INR value of at least 2.0; VKA was started as the pa2ents usual daily dose prior to hospitaliza2on. Others (arterial hypertension, dilata2ve myocardiopathy, valvulopathy, miocardial infarc2on, coronary artery by pass gran), n (%) 24 (7.1%)

30 Results Pa2ents n (%) TE total, n (%) 95%CI Arterial, n (%) 95%CI Venous, n (%) 95% CI Thromboembolic events in Low Risk, High risk groups and total pa2ents Low risk group 182 (55.4%) 1 (0.54) 0.54 to (0.75) 0.45 to 1.95 High risk group 146 (44.6%) 5 (3.4) 0.5 to (2.0) to (1.3) ** 0.5 to 3.1 Total 328 (100%) 6 (1.8) 0.4 to (0.9) 0.1 to (0.9) 0.1 to 1.9 P value* *Fishers exact test. +Three events (one peripheral arterial thromboembolism and two transient ischemic a=acks) occurred in AF AT pa2ents. **Two events (isolated pulmonary embolism and deep vein thrombosis) occurred in VTE pa2ents. One event (DVT) occurred in AF AT pa2ents. TE, thromboembolism; AF AT, atrial fibrilla2on with previous stroke; VTE, venous thrombo embolism; CI, confidence intervals. Incidence of major bleeding events in low and high risk group accordingly to type of procedures Type of procedures (328) Major surgery (103) n (%) 95% Confidence Interval Low risk group (182) 1/35 (2.8) 2.6 to 8.2 High risk group (146) 6/68 (8.8) TKR, n (%) 0 2 (2.9) THR, n (%) 1 (2.8) 2 (2.9) Abdominal hernia repair, n (%) Aortofemoral construc2on, n (%) Minor surgery*(225) n (%) 0 1 (1.4) 0 1 (1.4) 0/147 0/78 P value 2.1 to *Fishers exact test. See text for defini2on and descrip2on. TKR, total knee replacement; THR, total hip replacement.

31 Bridging therapy with fixed doses of low molecular weight heparin in cancer pa2ents on long term warfarin 1 Giorgia Saccullo, 1 Alessandra Malato, 1 Lucio Lo Coco, 1 Simona Raso, 1 Marco Santoro, 1 Valen2na Zammit, 2 Antonio Russo, and 1 Sergio Siragusa Ca=edra ed U.O. di Ematologia con trapianto, Policlinico Universitario di Palermo STUDY DESIGN Pa/ents characteris/cs (n=156) Mean age (range, y) 66.6(32/89) M/F (%) 84/72 Weight, mean + SD (Kg) Solid cancer, n (%) 98 (62.8) Haematological cancer, n (%) 58 (37.2) Advanced/metasta2c cancer, n (%) 101 (64.7) Bridging therapy with nadroparin, n (%) 71 (45.5) Bridging therapy with enoxaparin, n (%) 79 (50.6) Bridging therapy with others heparin compounds, n (%) 6 (3.8) Low risk for TE 88 (56.4) Pa2ents on chemotherapy induced platelet deple2on 22 High risk for TE 68 (43.5) Pa2ents on chemotherapy induced platelet deple2on 17 Venous thromboembolism, n (%) 52 (33.3) Events las2ng < 3 months, n (%) 28 Events las2ng > 3 months, n (%) 24 Atrial fibrilla2on without previous stroke (AF NoAT), n (%) 48 (30.7) Atrial fibrilla2on with previous stroke (AF AT), n (%) 21 (13.4) Prosthe2c aor2c/mitral valves (PAV), n (%) 19 (12.1) Others (arterial hypertension, dilata2ve myocardiopathy, 16 (10.2) valvulopathy, myocardial infarc2on, coronary artery by pass gran), n (%)

32 Results Thromboembolic events in the low risk, high risk and total pa/ent groups Events, n (%) TE total, n (%, 95%CI) Arterial, n (%, 95% CI Venous, n (%, 95% CI) Low risk group (68) 1 (1.4, 95% CI ) 0 1 (1.4, 95% CI ) High risk group (88) 4^ (4.5, 95% CI ) 1 (1.1, 95% CI ) 3 (3.4, 95% CI ) Total (156) 5 (3.2, 95% CI (0.6, 95% CI ) 4 (2.5, 95% CI ) Fisher s exact test. ^ One event occurred in this group during chemotherapy induced thrombocytopenia. Abbrevia2ons: TE, thromboembolism; AF AT, atrial fibrilla2on with previous stroke; VTE, venous thromboembolism; CI, confidence interval P value among low and highrisk group Incidence of major bleeding events in the low and high risk groups accordingly to type of procedure Type of procedure (n) Low risk group High risk group Major surgery (54) n (%, 95% CI) 0 3 (5.5, 95% CI ) Non major surgery (63) n (%, 95% CI) 0 0 Chemotherapy induced thrombocytopenia (49) n (%, 95% CI) 0 2 (4.1, 95% CI )

33 TAO e terapia perioperatoria, un approccio mul2disciplinare Individualizzata sul rischio tromboembolico ed emorragico Considerare le scelte del chirurgo, anestesista, cardiologo Considerare la preferenza del paziente

34 Platelet inhibitory drugs: dura/on of bleeding risk* *Based on minimal data; no Xme points between 2 hours and 4 days Konkle BA. Acquired disorders of platelet funcxon. EducaXonal Session. Hematology 2011:

35 Terapia an/aggregante 3.4. In pa/ents who are receiving acetylsalicylic acid (ASA) for the secondary preven/on of cardiovascular disease and are having minor dental or dermatologic procedures or cataract surgery, we suggest con/nuing ASA around the /me of the procedure instead of stopping ASA 7 to 10 days before the procedure (Grade 2C) In pa/ents at moderate to high risk for cardiovascular events who are receiving ASA therapy and require noncardiac surgery, we suggest con/nuing ASA around the /me of surgery instead of stopping ASA 7 to 10 days before surgery (Grade 2C). In pa/ents at low risk for cardiovascular events who are receiving ASA therapy, we suggest stopping ASA 7 to 10 days before surgery instead of con<nua<on of ASA (Grade 2C) In pa/ents who are receiving ASA and require coronary artery bypass grau (CABG) surgery, we suggest con/nuing ASA around the /me of surgery instead of stopping ASA 7 to 10 days before surgery (Grade 2C). In pa/ents who are receiving dual an/platelet drug therapy and require CABG surgery, we suggest con/nuing ASA around the /me of surgery and stopping clopidogrel/prasugrel 5 days before surgery instead of con<nuing dual an<platelet therapy around the /me of surgery (Grade 2C). CHEST 2012; 141(2)(Suppl):7S 47S

36 Ematologia Policlinico Universitario di Palermo Università degli Studi di Palermo Palazzo Chiaramonte Steri Par2colare soffi=o ligneo La Vucciria R. Gu=uso 1974 Cor2le Interno

37 Managing OAT in pa2ents with mechanical heart valves undergoing elec2ve surgery: Results of a survey conducted among Italian physicians Minor surgery: pre operaxve management Stop OAT without heparin 12 (16.7%) Full dose sc UFH or LMWH 38 (52.8%) Full dose iv UFH 0 Other 22 (30.5%) Ageno et al. Blood Coagul Fibrinolysis 2004

38 Minor surgery: post operaxve management Resume OAT without heparin 1 (1.4%) Full dose sc UFH or LMWH 23 (31.9%) Low dose sc UFH or LMWH 44 (61.1%) Full dose iv UFH 0 Other 4 (5.5%)

39 Descrip2on of major events Pa2ent group alloca2on Event Type of surgery Time of occurrence (days INR value Treatment (index diseases*) aner surgery) High risk (AF AT) Peripheral arterial TE Vascular Angioplasty plus an2platelets plus VKA High risk (AF AT) TIA Gastrectomy VKA High risk (AF AT) TIA GI endoscopy VKA High risk (VTE < 3 months) Isolated PE Hemicolectomy Full dose of LMWH plus VKA High risk (AF AT) DVT Prostatectomy Full dose of LMWH plus VKA Low risk (VTE > 3 months) DVT Hysterectomy Full dose of LMWH plus VKA High risk (PMV) Wound haematoma TKR 1 < 1.2 Re interven2on plus ST* High risk (AF AT) Wound haematoma THR 0 < 1.2 ST High risk (AF AT) Overt surgical site bleed THR 0 < 1.2 ST High risk (AF AT) Overt surgical site bleed Abdominal hernia repair 1 < 1.2 ST High risk (AF AT) Wound haematoma TKR 1 < 1.2 ST High risk (VTE < 3 months) Overt surgical site bleed Aortofemoral construc2on 2 < 1.2 ST Low risk (AF NoAT) Overt surgical site bleed THR 3 < 1.2 ST *See text for explana2on. INR, interna2onal normalized ra2o; TE, thromboembolism; VKA, vitamin K antagonist; TIA, transient ischemic a=ack; GI, gastrointes2nal; LMWH, low molecular weight heparin; ST, standard treatment means packed red cell transfusion and vitamin K administra2on; TKR, total knee replacement; THR, total hip replacement.