Preventing Postsurgical Venous Thromboembolism: Pharmacological Approaches

Antonella Tufano; Antonio Coppola; Anna Maria Cerbone; Carlo Ruosi; Massimo Franchini

doi:10.1055/s-0031-1273089

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2011; 37(3): 252-266
DOI: 10.1055/s-0031-1273089

Preventing Postsurgical Venous Thromboembolism: Pharmacological Approaches

Antonella Tufano¹ , Antonio Coppola¹ , Anna Maria Cerbone¹ , Carlo Ruosi² , Massimo Franchini³

¹Regional Reference Centre for Coagulation Disorders, Department of Clinical and Experimental Medicine, Federico II University Hospital, Naples
²Department of Orthopedics, Federico II University Hospital, Naples
³Immunohematology and Transfusion Center, Department of Pathology and Laboratory Medicine, University Hospital, Parma; Italy

Abstract

ABSTRACT

The use of antithrombotic drugs for the prevention of venous thromboembolism (VTE) in patients undergoing surgery is presently based on solid principles and high-level scientific evidence. This article reviews current strategies of pharmacological thromboprophylaxis. The level of VTE risk following surgery depends on a variety of factors that the surgeon should take into account, including the type of surgery and the presence of additional risk factors, such as elderly age and cancer. In patients undergoing minor general surgery, early mobilization is sufficient as prophylaxis, whereas in those undergoing major general surgery, thromboprophylaxis with low molecular weight heparin (LMWH), low-dose unfractionated heparin, or the pentasaccharide fondaparinux is recommended. Patients undergoing major orthopedic surgery have a particularly high risk of VTE, and routine thromboprophylaxis with LMWH, fondaparinux, or a vitamin K antagonist (international normalized ratio target: 2.0 to 3.0) is the standard of care in this group of patients. Recently, two new oral anticoagulants, rivaroxaban (a factor Xa inhibitor) and dabigatran etexilate (a direct thrombin inhibitor) have been licensed to be used for thromboprophylaxis after orthopedic surgery in Europe. Mechanical methods of thromboprophylaxis (compression stockings, intermittent pneumatic compression, vena cava filters), not discussed in detail in this review, should always be considered in patients at high thrombotic risk, in association with the pharmacolocical strategies, or in cases of contraindications to antocoagulants, as in patients or procedures at high risk of bleeding.

KEYWORDS

Antithrombotic drugs - prevention - venous thromboembolism - surgery - heparin - fondaparinux - rivaroxaban - dabigatran.

Full Text

References

REFERENCES

1 Geerts W H, Bergqvist D, Pineo G F American College of Chest Physicians et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008; 133 (6, Suppl) 381S-453S
2 Naess I A, Christiansen S C, Romundstad P, Cannegieter S C, Rosendaal F R, Hammerstrøm J. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost. 2007; 5 (4) 692-699
3 Anderson Jr F A, Wheeler H B, Goldberg R J, Hosmer D W, Forcier A. The prevalence of risk factors for venous thromboembolism among hospital patients. Arch Intern Med. 1992; 152 (8) 1660-1664
4 Rosendaal F R. Risk factors for venous thrombotic disease. Thromb Haemost. 1999; 82 (2) 610-619
5 Anderson Jr F A, Spencer F A. Risk factors for venous thromboembolism. Circulation. 2003; 107 (23, Suppl 1) I9-I16
6 Samama M M, Dahl O E, Quinlan D J, Mismetti P, Rosencher N. Quantification of risk factors for venous thromboembolism: a preliminary study for the development of a risk assessment tool. Haematologica. 2003; 88 (12) 1410-1421
7 Kucher N, Tapson V F, Goldhaber S Z. DVT FREE Steering Committee . Risk factors associated with symptomatic pulmonary embolism in a large cohort of deep vein thrombosis patients. Thromb Haemost. 2005; 93 (3) 494-498
8 Kearon C. Natural history of venous thromboembolism. Circulation. 2003; 107 (23, Suppl 1) I22-I30
9 Sullivan S D, Kahn S R, Davidson B L, Borris L, Bossuyt P, Raskob G. Measuring the outcomes and pharmacoeconomic consequences of venous thromboembolism prophylaxis in major orthopaedic surgery. Pharmacoeconomics. 2003; 21 (7) 477-496
10 Caprini J A, Botteman M F, Stephens J M et al.. Economic burden of long-term complications of deep vein thrombosis after total hip replacement surgery in the United States. Value Health. 2003; 6 (1) 59-74
11 Avorn J, Winkelmayer W C. Comparing the costs, risks, and benefits of competing strategies for the primary prevention of venous thromboembolism. Circulation. 2004; 110 (24, Suppl 1) IV25-IV32
12 Nurmohamed M T, Rosendaal F R, Büller H R et al.. Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis. Lancet. 1992; 340 (8812) 152-156
13 Kakkar V V, Cohen A T, Edmonson R A The Thromboprophylaxis Collaborative Group et al. Low molecular weight versus standard heparin for prevention of venous thromboembolism after major abdominal surgery. Lancet. 1993; 341 (8840) 259-265
14 Koch A, Ziegler S, Breitschwerdt H, Victor N. Low molecular weight heparin and unfractionated heparin in thrombosis prophylaxis: meta-analysis based on original patient data. Thromb Res. 2001; 102 (4) 295-309
15 Haas S, Wolf H, Kakkar A K, Fareed J, Encke A. Prevention of fatal pulmonary embolism and mortality in surgical patients: a randomized double-blind comparison of LMWH with unfractionated heparin. Thromb Haemost. 2005; 94 (4) 814-819
16 Baglin T. Defining the population in need of thromboprophylaxis—making hospitals safer. Br J Haematol. 2010; 149 (6) 805-812
17 Lijfering W M, Rosendaal F R, Cannegieter S C. Risk factors for venous thrombosis—current understanding from an epidemiological point of view. Br J Haematol. 2010; 149 (6) 824-833
18 Hirsh J, Bauer K A, Donati M B, Gould M, Samama M M, Weitz J I. American College of Chest Physicians . Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008; 133 (6, Suppl) 141S-159S
19 Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. American College of Chest Physicians . Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008; 133 (6, Suppl) 160S-198S
20 Patrono C, Baigent C, Hirsh J, Roth G. American College of Chest Physicians . Antiplatelet drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008; 133 (6, Suppl) 199S-233S
21 Antiplatelet Trialists' Collaboration . Collaborative overview of randomised trials of antiplatelet therapy—III: Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. Antiplatelet Trialists' Collaboration. BMJ. 1994; 308 (6923) 235-246
22 Lotke P A, Palevsky H, Keenan A M et al.. Aspirin and warfarin for thromboembolic disease after total joint arthroplasty. Clin Orthop Relat Res. 1996; 324 (324) 251-258
23 Pulmonary Embolism Prevention (PEP) Trial Collaborative Group . Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet. 2000; 355 (9212) 1295-1302
24 Hovens M M, Snoep J D, Tamsma J T, Huisman M V. Aspirin in the prevention and treatment of venous thromboembolism. J Thromb Haemost. 2006; 4 (7) 1470-1475
25 McKenna R, Galante J, Bachmann F, Wallace D L, Kaushal P S, Meredith P. Prevention of venous thromboembolism after total knee replacement by high-dose aspirin or intermittent calf and thigh compression. BMJ. 1980; 280 (6213) 514-517
26 Powers P J, Gent M, Jay R M et al.. A randomized trial of less intense postoperative warfarin or aspirin therapy in the prevention of venous thromboembolism after surgery for fractured hip. Arch Intern Med. 1989; 149 (4) 771-774
27 Westrich G H, Sculco T P. Prophylaxis against deep venous thrombosis after total knee arthroplasty. Pneumatic plantar compression and aspirin compared with aspirin alone. J Bone Joint Surg Am. 1996; 78 (6) 826-834
28 Laux V, Perzborn E, Heitmeier S et al.. Direct inhibitors of coagulation proteins—the end of the heparin and low-molecular-weight heparin era for anticoagulant therapy?. Thromb Haemost. 2009; 102 (5) 892-899
29 Nishio H, Ieko M, Nakabayashi T. New therapeutic option for thromboembolism—dabigatran etexilate. Expert Opin Pharmacother. 2008; 9 (14) 2509-2517
30 Perzborn E, Strassburger J, Wilmen A et al.. In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939—an oral, direct factor Xa inhibitor. J Thromb Haemost. 2005; 3 (3) 514-521
31 Gulseth M P, Michaud J, Nutescu E A. Rivaroxaban: an oral direct inhibitor of factor Xa. Am J Health Syst Pharm. 2008; 65 (16) 1520-1529
32 Piccini J P, Patel M R, Mahaffey K W, Fox K A, Califf R M. Rivaroxaban, an oral direct factor Xa inhibitor. Expert Opin Investig Drugs. 2008; 17 (6) 925-937
33 Weinz C, Schwarz T, Kubitza D, Mueck W, Lang D. Metabolism and excretion of rivaroxaban, an oral, direct factor Xa inhibitor, in rats, dogs, and humans. Drug Metab Dispos. 2009; 37 (5) 1056-1064
34 Kakkar A K, Brenner B, Dahl O E RECORD2 Investigators et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008; 372 (9632) 31-39
35 Eriksson B I, Borris L C, Friedman R J RECORD1 Study Group et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008; 358 (26) 2765-2775
36 Lassen M R, Ageno W, Borris L C RECORD3 Investigators et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008; 358 (26) 2776-2786
37 Turpie A GG, Lassen M R, Davidson B L RECORD4 Investigators et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009; 373 (9676) 1673-1680
38 Mismetti P, Laporte S, Darmon J Y, Buchmüller A, Decousus H. Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg. 2001; 88 (7) 913-930
39 Koch A, Bouges S, Ziegler S, Dinkel H, Daures J P, Victor N. Low molecular weight heparin and unfractionated heparin in thrombosis prophylaxis after major surgical intervention: update of previous meta-analyses. Br J Surg. 1997; 84 (6) 750-759
40 Agnelli G, Bergqvist D, Cohen A T, Gallus A S, Gent M. PEGASUS investigators . Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg. 2005; 92 (10) 1212-1220
41 Turpie A G, Bauer K A, Caprini J A, Comp P C, Gent M, Muntz J E. Apollo Investigators . Fondaparinux combined with intermittent pneumatic compression vs. intermittent pneumatic compression alone for prevention of venous thromboembolism after abdominal surgery: a randomized, double-blind comparison. J Thromb Haemost. 2007; 5 (9) 1854-1861
42 Bergqvist D, Agnelli G, Cohen A T ENOXACAN II Investigators et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med. 2002; 346 (13) 975-980
43 Rasmussen M S, Jorgensen L N, Wille-Jørgensen P FAME Investigators et al. Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study. J Thromb Haemost. 2006; 4 (11) 2384-2390
44 Dabrowiecki S, Rosc D, Jurkowski P. The influence of laparoscopic cholecystectomy on perioperative blood clotting and fibrinolysis. Blood Coagul Fibrinolysis. 1997; 8 (1) 1-5
45 Martinez-Ramos C, Lopez-Pastor A, Nùñez-Peña J R et al.. Changes in hemostasis after laparoscopic cholecystectomy. Surg Endosc. 1999; 13 (5) 476-479
46 Prisco D, De Gaudio A R, Carla R et al.. Videolaparoscopic cholecystectomy induces a hemostasis activation of lower grade than does open surgery. Surg Endosc. 2000; 14 (2) 170-174
47 Nguyen N T, Owings J T, Gosselin R et al.. Systemic coagulation and fibrinolysis after laparoscopic and open gastric bypass. Arch Surg. 2001; 136 (8) 909-916
48 Tincani E, Piccoli M, Turrini F, Crowther M A, Melotti G, Bondi M. Video laparoscopic surgery: is out-of-hospital thromboprophylaxis necessary?. J Thromb Haemost. 2005; 3 (2) 216-220
49 Bounameaux H, Didier D, Polat O, Desmarais S, de Moerloose P, Huber O. Antithrombotic prophylaxis in patients undergoing laparoscopic cholecystectomy. Thromb Res. 1997; 86 (3) 271-273
50 Baca I, Schneider B, Köhler T, Misselwitz F, Zehle A, Mühe F. Prevention of thromboembolism in minimal invasive interventions and brief inpatient treatment. Results of a multicenter, prospective, randomized, controlled study with a low molecular weight heparin. [in German] Chirurg. 1997; 68 (12) 1275-1280
51 Prystowsky J B, Morasch M D, Eskandari M K, Hungness E S, Nagle A P. Prospective analysis of the incidence of deep venous thrombosis in bariatric surgery patients. Surgery. 2005; 138 (4) 759-763 discussion 763-765
52 McCarty T M, Arnold D T, Lamont J P, Fisher T L, Kuhn J A. Optimizing outcomes in bariatric surgery: outpatient laparoscopic gastric bypass. Ann Surg. 2005; 242 (4) 494-498 discussion 498-501
53 Mason E E, Tang S, Renquist K E National Bariatric Surgery Registry (NBSR) Contributors et al. A decade of change in obesity surgery. Obes Surg. 1997; 7 (3) 189-197
54 Poulose B K, Griffin M R, Zhu Y et al.. National analysis of adverse patient safety for events in bariatric surgery. Am Surg. 2005; 71 (5) 406-413
55 Kalfarentzos F, Stavropoulou F, Yarmenitis S et al.. Prophylaxis of venous thromboembolism using two different doses of low-molecular-weight heparin (nadroparin) in bariatric surgery: a prospective randomized trial. Obes Surg. 2001; 11 (6) 670-676
56 Scholten D J, Hoedema R M, Scholten S E. A comparison of two different prophylactic dose regimens of low molecular weight heparin in bariatric surgery. Obes Surg. 2002; 12 (1) 19-24
57 Frederiksen S G, Hedenbro J L, Norgren L. Enoxaparin effect depends on body-weight and current doses may be inadequate in obese patients. Br J Surg. 2003; 90 (5) 547-548
58 Shepherd M F, Rosborough T K, Schwartz M L. Heparin thromboprophylaxis in gastric bypass surgery. Obes Surg. 2003; 13 (2) 249-253
59 Beksaç B, González Della Valle A, Salvati E A. Thromboembolic disease after total hip arthroplasty: who is at risk?. Clin Orthop Relat Res. 2006; 453 211-224
60 Mesko J W, Brand R A, Iorio R et al.. Venous thromboembolic disease management patterns in total hip arthroplasty and total knee arthroplasty patients: a survey of the AAHKS membership. J Arthroplasty. 2001; 16 (6) 679-688
61 Hull R D, Pineo G F, Francis C The North American Fragmin Trial Investigators et al. Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients: a double-blind, randomized comparison. Arch Intern Med. 2000; 160 (14) 2199-2207
62 Mismetti P, Laporte S, Zufferey P, Epinat M, Decousus H, Cucherat M. Prevention of venous thromboembolism in orthopedic surgery with vitamin K antagonists: a meta-analysis. J Thromb Haemost. 2004; 2 (7) 1058-1070
63 O'Donnell M, Julian J, Kearon C. Risk of bleeding with vitamin K antagonists compared with low-molecular-weight heparin after orthopedic surgery: a rebuttal. J Thromb Haemost. 2005; 3 (3) 606-608 author reply 609-610
64 Lassen M R, Bauer K A, Eriksson B I, Turpie A G. European Pentasaccharide Elective Surgery Study (EPHESUS) Steering Committee . Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison. Lancet. 2002; 359 (9319) 1715-1720
65 Turpie A G, Bauer K A, Eriksson B I, Lassen M R. PENTATHALON 2000 Study Steering Committee . Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial. Lancet. 2002; 359 (9319) 1721-1726
66 Turpie A G, Bauer K A, Eriksson B I, Lassen M R. Superiority of fondaparinux over enoxaparin in preventing venous thromboembolism in major orthopedic surgery using different efficacy end points. Chest. 2004; 126 (2) 501-508
67 Howard A W, Aaron S D. Low molecular weight heparin decreases proximal and distal deep venous thrombosis following total knee arthroplasty. A meta-analysis of randomized trials. Thromb Haemost. 1998; 79 (5) 902-906
68 Brookenthal K R, Freedman K B, Lotke P A, Fitzgerald R H, Lonner J H. A meta-analysis of thromboembolic prophylaxis in total knee arthroplasty. J Arthroplasty. 2001; 16 (3) 293-300
69 Bauer K A, Eriksson B I, Lassen M R, Turpie A G. Steering Committee of the Pentasaccharide in Major Knee Surgery Study . Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. 2001; 345 (18) 1305-1310
70 Turpie A G, Bauer K A, Eriksson B I, Lassen M R. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med. 2002; 162 (16) 1833-1840
71 Handoll H H, Farrar M J, McBirnie J, Tytherleigh-Strong G, Milne A A, Gillespie W J. Heparin, low molecular weight heparin and physical methods for preventing deep vein thrombosis and pulmonary embolism following surgery for hip fractures. Cochrane Database Syst Rev. 2002; (4) CD000305
72 Powers P J, Gent M, Jay R M et al.. A randomized trial of less intense postoperative warfarin or aspirin therapy in the prevention of venous thromboembolism after surgery for fractured hip. Arch Intern Med. 1989; 149 (4) 771-774
73 Borgstroem S, Greitz T, Van Der Linden W, Molin J, Rudics I. Anticoagulant prophylaxis of venous thrombosis in patients with fractured neck of the femur: a controlled clinical trial using venous phlebography. Acta Chir Scand. 1965; 129 500-508
74 Hamilton H W, Crawford J S, Gardiner J H, Wiley A M. Venous thrombosis in patients with fracture of the upper end of the femur. A phlebographic study of the effect of prophylactic anticoagulation. J Bone Joint Surg Br. 1970; 52 (2) 268-289
75 Eriksson B I, Bauer K A, Lassen M R, Turpie A G. Steering Committee of the Pentasaccharide in Hip-Fracture Surgery Study . Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med. 2001; 345 (18) 1298-1304
76 Eriksson B I, Lassen M R. PENTasaccharide in HIp-FRActure Surgery Plus Investigators . Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery: a multicenter, randomized, placebo-controlled, double-blind study. Arch Intern Med. 2003; 163 (11) 1337-1342
77 Wirth T, Schneider B, Misselwitz F et al.. Prevention of venous thromboembolism after knee arthroscopy with low-molecular weight heparin (reviparin): Results of a randomized controlled trial. Arthroscopy. 2001; 17 (4) 393-399
78 Michot M, Conen D, Holtz D et al.. Prevention of deep-vein thrombosis in ambulatory arthroscopic knee surgery: a randomized trial of prophylaxis with low molecular weight heparin. Arthroscopy. 2002; 18 (3) 257-263
79 Camporese G, Bernardi E, Prandoni P et al.. Graduated compression stocking (GCS) versus low-molecular-weight heparin (LMWH) for prevention of deep vein thrombosis (DVT) after knee arthroscopy (KA): a randomized study (KANT). J Thromb Haemost. 2007; 5 (Suppl 2) OT-052
80 Ramos J, Perrotta C, Badariotti G, Berenstein G. Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy. Cochrane Database Syst Rev. 2007; (2) CD005259
81 Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism. Lancet Oncol. 2005; 6 (6) 401-410
82 Bergqvist D, Burmark U S, Flordal P A et al.. Low molecular weight heparin started before surgery as prophylaxis against deep vein thrombosis: 2500 versus 5000 XaI units in 2070 patients. Br J Surg. 1995; 82 (4) 496-501
83 ENOXACAN Study Group . Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessment. Br J Surg. 1997; 84 (8) 1099-1103
84 McLeod R S, Geerts W H, Sniderman K W Canadian Colorectal Surgery DVT Prophylaxis Trial investigators et al. Subcutaneous heparin versus low-molecular-weight heparin as thromboprophylaxis in patients undergoing colorectal surgery: results of the Canadian colorectal DVT prophylaxis trial: a randomized, double-blind trial. Ann Surg. 2001; 233 (3) 438-444
85 Clark-Pearson D L, DeLong E, Synan I S, Soper J T, Creasman W T, Coleman R E. A controlled trial of two low-dose heparin regimens for the prevention of postoperative deep vein thrombosis. Obstet Gynecol. 1990; 75 (4) 684-689
86 Clarke-Pearson D L, Synan I S, Dodge R, Soper J T, Berchuck A, Coleman R E. A randomized trial of low-dose heparin and intermittent pneumatic calf compression for the prevention of deep venous thrombosis after gynecologic oncology surgery. Am J Obstet Gynecol. 1993; 168 (4) 1146-1153 discussion 1153-1154
87 Clarke-Pearson D L, Coleman R E, Synan I S, Hinshaw W, Creasman W T. Venous thromboembolism prophylaxis in gynecologic oncology: a prospective, controlled trial of low-dose heparin. Am J Obstet Gynecol. 1983; 145 (5) 606-613
88 Agnelli G, Bergqvist D, Cohen A T, Gallus A S, Gent M. PEGASUS investigators . Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg. 2005; 92 (10) 1212-1220
89 Bergqvist D, Agnelli G, Cohen A T ENOXACAN II Investigators et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med. 2002; 346 (13) 975-980
90 Rasmussen M S, Jorgensen L N, Wille-Jørgensen P FAME Investigators et al. Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study. J Thromb Haemost. 2006; 4 (11) 2384-2390
91 Kakkar V V, Balibrea J L, Martínez-González J, Prandoni P. CANBESURE Study Group . Extended prophylaxis with bemiparin for the prevention of venous thromboembolism after abdominal or pelvic surgery for cancer: the CANBESURE randomized study. J Thromb Haemost. 2010; 8 (6) 1223-1229
92 Mandalà M, Labianca R. European Society for Medical Oncology . Venous thromboembolism (VTE) in cancer patients. ESMO clinical recommendations for prevention and management. Thromb Res. 2010; 125 (Suppl 2) S117-S119
93 Ufer M. Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development. Thromb Haemost. 2010; 103 (3) 572-585
94 Coppola A, Tufano A, Cerbone A M, Di Minno G. Inherited thrombophilia: implications for prevention and treatment of venous thromboembolism. Semin Thromb Hemost. 2009; 35 (7) 683-694
95 Patnaik M M, Moll S. Inherited antithrombin deficiency: a review. Haemophilia. 2008; 14 (6) 1229-1239
96 Rodgers G M. Role of antithrombin concentrate in treatment of hereditary antithrombin deficiency. An update. Thromb Haemost. 2009; 101 (5) 806-812
97 Goldenberg N A, Manco-Johnson M J. Protein C deficiency. Haemophilia. 2008; 14 (6) 1214-1221
98 Amin A N, Stemkowski S, Lin J, Yang G. Preventing venous thromboembolism in US hospitals: are surgical patients receiving appropriate prophylaxis?. Thromb Haemost. 2008; 99 (4) 796-797
99 Cohen A T, Tapson V F, Bergmann J F ENDORSE Investigators et al. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet. 2008; 371 (9610) 387-394
100 Kakkar A K, Davidson B L, Haas S K. Investigators Against Thromboembolism (INATE) Core Group . Compliance with recommended prophylaxis for venous thromboembolism: improving the use and rate of uptake of clinical practice guidelines. J Thromb Haemost. 2004; 2 (2) 221-227
101 Warwick D, Friedman R J, Agnelli G et al.. Insufficient duration of venous thromboembolism prophylaxis after total hip or knee replacement when compared with the time course of thromboembolic events: findings from the Global Orthopaedic Registry. J Bone Joint Surg Br. 2007; 89 (6) 799-807
102 Struijk-Mulder M C, Ettema H B, Verheyen C C, Büller H R. Comparing consensus guidelines on thromboprophylaxis in orthopedic surgery. J Thromb Haemost. 2010; 8 (4) 678-683

Antonio CoppolaM.D.

Regional Reference Centre for Coagulation Disorders, Federico II University Hospital

Via S. Pansini, 5 - 80131 Naples, Italy

Email: antocopp@unina.it