Choosing the Appropriate Antithrombotic Agent for the Prevention and Treatment of VTE: A Case-Based Approach

Geerts WH , Pineo GF , Heit JA . Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(3 suppl): 338S–400S.

Silverstein MD , Heit JA , Mohr DN . Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998;158:585–93. DOI 10.1001/archinte.158.6.585

Kniffin WD. Jr. , Baron JA , Barrett J , Birkmeyer JD , Anderson FA. Jr. The epidemiology of diagnosed pulmonary embolism and deep venous thrombosis in the elderly. Arch Intern Med 1994;154:861–6. DOI 10.1001/archinte.154.8.861

Prandoni P , Lensing AW , Cogo A. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996;125:1–7.

Hansson PO , Sorbo J , Eriksson H. Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors. Arch Intern Med 2000;160:769–74. DOI 10.1001/archinte.160.6.769

Goldhaber SZ . Pulmonary embolism. N Engl J Med 1998;339:93–104. DOI 10.1056/NEJM199807093390207

Anderson FA. Jr. , Spencer FA . Risk factors for venous thromboembolism. Circulation 2003;107:19–16. DOI 10.1161/01.CIR.0000046771.12875.6C

Alikhan R , Cohen AT , Combe S. Risk factors for venous thromboembolism in hospitalized patients with acute medical illness: analysis of the MEDENOX Study. Arch Intern Med 2004;164:963–8. DOI 10.1001/archinte.164.9.963

Turpie AG , Chin BS , Lip GY . ABC of antithrombotic therapy: venous thromboembolism: treatment strategies. BMJ 2002;325:948–50. DOI 10.1136/bmj.325.7370.948

Powers PJ , Gent M , Jay RM . 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;149:771–4. DOI 10.1001/archinte.149.4.771

Snook GA , Chrisman OD , Wilson TC . Thromboembolism after surgical treatment of hip fractures. Clin Orthop Relat Res 1981;155:21–4.

Agnelli G , Cosmi B , Di Filippo P. A randomised, double-blind, placebo-controlled trial of dermatan sulphate for prevention of deep vein thrombosis in hip fracture. Thromb Haemost 1992;67:203–8.

Todd CJ , Freeman CJ , Camilleri-Ferrante C. Differences in mortality after fracture of hip: the east Anglian audit. Br Med J 1995;310:904–8.

Haake DA , Berkman SA . Venous thromboembolic disease after hip surgery. Risk factors, prophylaxis, and diagnosis. Clin Orthop Relat Res 1989;242:212–31.

Lassen MR , Borris LC , Christiansen HM . Prevention of thromboembolism in 190 hip arthroplasties. Comparison of LMW heparin and placebo. Acta Orthop Scand 1991;62:33–8.

Guyatt G , Schunemann HJ , Cook D , Jaeschke R , Pauker S. Applying the grades of recommendation for antithrombotic and thrombolytic therapy: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(suppl):179S–87S. DOI 10.1378/chest.126.1.179

Package insert. Innohep (tinzaparin sodium). Boulder, CO: Pharmion, January 2003.

Package insert. Lovenox (enoxaparin sodium). Bridgewater, NJ: Aventis Pharmaceuticals, July 2004.

Package insert. Arixtra (fondaparinux sodium). Research Triangle Park, NC: GlaxoSmithKline, May 2005.

Package insert. Heparin sodium injection. Kalamazoo, MI: Pharmacia & Upjohn, December 2000.

Package insert. Warfarin sodium tablets. Pomona, NY: Barr Laboratories, November 2002.

Package insert. Fragmin (dalteparin sodium). Kalamazoo, MI: Pharmacia & Upjohn, December 2003.

Buller HR , Agnelli G , Hull RD , Hyers TM , Prins MH , Raskob GE . Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(suppl):401S–28S. DOI 10.1378/chest.126.3_suppl.401S

Hirsh J , Dalen J , Anderson DR , Poller L , Bussey H , Ansell J. Oral anticoagulants: mechanism of action; clinical effectiveness, and optimal therapeutic range. Chest 2001;119:8S–21S. DOI 10.1378/chest.119.1_suppl.8S

Walenga JM , Frenkel EP , Bick RL . Heparin-induced thrombocytopenia, paradoxical thromboembolism, and other adverse effects of heparin-type therapy. Hematol Oncol Clin North Am 2003;17:259–82, viii-ix. DOI 10.1016/S0889-8588(02)00088-6

Hyers TM . Management of venous thromboembolism: past, present, and future. Arch Intern Med 2003;163:759–68. DOI 10.1001/archinte.163.7.759

Merli G , Spiro TE , Olsson CG . Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease. Ann Intern Med 2001;134:191–202.

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. ENOXACAN Study Group. Br J Surg 1997; 84: 1099–103. DOI 10.1046/j.1365-2168.1997.d01-3882.x

Bergqvist D , Agnelli G , Cohen AT . Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med 2002;346:975–80. DOI 10.1056/NEJMoa012385

Agnelli G , Bergqvist D , Cohen AT , Gallus AS , Gent M. Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg 2005;92:1212–20. DOI 10.1002/bjs.5154

Eriksson BI , Bauer KA , Lassen MR , Turpie AG . Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med 2001;345:1298–304. DOI 10.1056/NEJMoa011100

Geerts WH , Heit JA , Clagett GP . Prevention of venous thromboembolism. Chest 2001;119(suppl 1):132S–75S. DOI 10.1378/chest.119.1_suppl.132S

Handoll HH , Farrar MJ , McBirnie J , Tytherleigh-Strong G , Milne AA , Gillespie WJ . 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: CD000305. DOI 10.1002/14651858.CD000305

Eriksson BI , Lassen MR . Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery: a multicenter, randomized, placebo-controlled, double-blind study. Arch Intern Med 2003;163:1337–42. DOI 10.1001/archinte.163.11.1337

Samama MM , Cohen AT , Darmon JY . A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N Engl J Med 1999;341:793–800. DOI 10.1056/NEJM199909093411103

Mismetti P , Laporte-Simitsidis S , Tardy B. Prevention of venous thromboembolism in internal medicine with unfractionated or low-molecular-weight heparins: a meta-analysis of randomised clinical trials. Thromb Haemost 2000;83:14–9.

Kleber FX , Witt C , Vogel G , Koppenhagen K , Schomaker U , Flosbach CW . Randomized comparison of enoxaparin with unfractionated heparin for the prevention of venous thromboembolism in medical patients with heart failure or severe respiratory disease. Am Heart J 2003;145:614–21. DOI 10.1067/mhj.2003.189

Leizorovicz A , Cohen AT , Turpie AG , Olsson CG , Vaitkus PT , Goldhaber SZ . Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004;110:874–9. DOI 10.1161/01.CIR.0000138928.83266.24

Cohen AT , Davidson BL , Gallus AS . Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 2006;332:325–9. Epub 2005 Jan 26. DOI 10.1136/bmj.38733.466748.7C

Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. The Columbus Investigators. N Engl J Med 1997; 337: 657–62. DOI 10.1056/NEJM199709043371001

Gould MK , Dembitzer AD , Doyle RL , Hastie TJ , Garber AM . Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials. Ann Intern Med 1999;130:800–9.

Dolovich LR , Ginsberg JS , Douketis JD , Holbrook AM , Cheah G. A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism: examining some unanswered questions regarding location of treatment, product type, and dosing frequency. Arch Intern Med 2000;160:181–8. DOI 10.1001/archinte.160.2.181

Buller HR , Davidson BL , Decousus H. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: a randomized trial. Ann Intern Med 2004;140:867–73.

Simonneau G , Sors H , Charbonnier B. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. Tinzaparine ou Heparine Standard: Evaluations dans l'Embolie Pulmonaire. N Engl J Med 1997;337:663–9. DOI 10.1056/NEJM199709043371002

Hull RD , Raskob GE , Brant RF . Low-molecular-weight heparin vs heparin in the treatment of patients with pulmonary embolism. American–Canadian Thrombosis Study Group. Arch Intern Med 2000;160:229–36. DOI 10.1001/archinte.160.2.229

Buller HR , Davidson BL , Decousus H. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med 2003;349:1695–702. DOI 10.1056/NEJMoa035451

Wells PS , Anderson DR , Rodger MA . A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism. Arch Intern Med 2005;165:733–8. DOI 10.1001/archinte.165.7.733

Zahn HR , Skinner JA , Porteous MJ . The preoperative prevalence of deep vein thrombosis in patients with femoral neck fractures and delayed operation. Injury 1999;30:605–7. DOI 10.1016/S0020-1383(99)00163-1

Eriksson H , Wahlander K , Gustafsson D , Welin LT , Frison L , Schulman S. A randomized, controlled, dose-guiding study of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for the treatment of acute deep vein thrombosis: THRIVE I. J Thromb Haemost 2003;1:41–7. DOI 10.10467/j.1538-7836.2003.00034.x

Eriksson BI , Agnelli G , Cohen AT . The direct thrombin inhibitor melagatran followed by oral ximelagatran compared with enoxaparin for the prevention of venous thromboembolism after total hip or knee replacement: the EXPRESS study. J Thromb Haemost 2003;1:2490–6. DOI 10.1111/j.1538-7836.2003.00494.x

Rogers FB . Venous thromboembolism in trauma patients: a review. Surgery 2001;130:1–12. DOI 10.1067/msy.2001.114558

Landefeld CS , Cook EF , Flatley M , Weisberg M , Goldman L. Identification and preliminary validation of predictors of major bleeding in hospitalized patients starting anticoagulant therapy. Am J Med 1987;82:703–13. DOI 10.1016/0002-9343(87)90004-0

Raskob GE , Hirsh J. Controversies in timing of the first dose of anticoagulant prophylaxis against venous thromboembolism after major orthopedic surgery. Chest 2003;124(suppl):379S–85S. DOI 10.1378/chest.124.6_suppl.379S

Turpie AG , Bauer KA , Eriksson BI , Lassen MR . Efficacy and safety of fondaparinux in major orthopedic surgery according to the timing of its first administration. Thromb Haemost 2003;90:364–6.

Colwell CW. Jr. , Kwong LM , Turpie AG , Davidson BL . Flexibility in administration of fondaparinux for prevention of symptomatic venous thromboembolism in orthopaedic surgery. J Arthroplasty 2006;21:36–45.

Hull R , Raskob G , Pineo G. A comparison of subcutaneous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation. N Engl J Med 1993;329:1370–6. DOI 10.1056/NEJM199311043291902

Colwell CW. Jr. , Collis DK , Paulson R. Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty. Evaluation during hospitalization and three months after discharge. J Bone Joint Surg Am 1999;81:932–40. DOI 10.1302/0301-620X.81B5.10316

De Wal H , Su E , Hiebert R , Di Cesare P. Factors influencing post-operative surgical drain output and time to a dry wound following total knee arthroplasty (abstract). Presented at: American Academy of Orthopaedic Surgeons, New Orleans, LA, February 5–9, 2003.

Sanchez-Ballaster J , Smith MG , Kershaw S. Wound infection in the management of hip fractures: a comparison between subcutaneous low-molecular-weight heparin and no thromboprophylaxis (abstract). Presented at: American Academy of Orthopaedic Surgeons, New Orleans, LA, February 5–9, 2003.

Waldman BJ . Advancements in minimally invasive total hip arthroplasty. Orthopedics 2003;26(suppl 8):S833–6.

Peters PC. Jr. , Nutescu E , Andersen J. Wound pharmacobiology. Orthopedics 2003;26(8 suppl):s837–42.

Dager WE , Andersen J , Nutescu E. Special considerations with fondaparinux therapy: heparin-induced thrombocytopenia and wound healing. Pharmacotherapy 2004;24(suppl):88S–94S.

Kearon C. Duration of venous thromboembolism prophylaxis after surgery. Chest 2003;124(suppl):386S–92S. DOI 10.1378/chest.124.6_suppl386S

Thaler HW , Roller RE , Greiner N , Sim E , Korninger C. Thromboprophylaxis with 60 mg enoxaparin is safe in hip trauma surgery. J Trauma 2001;51:518–21.

Bergqvist D , Benoni G , Bjorgell O. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996;335:696–700. DOI 10.1056/NEJM199609053351002

Prandoni P , Bruchi O , Sabbion P. Prolonged thromboprophylaxis with oral anticoagulants after total hip arthroplasty: a prospective controlled randomized study. Arch Intern Med 2002;162:1966–71. DOI 10.1001/archinte.162.17.1966

Levine M , Gent M , Hirsh J. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996;334:677–81. DOI 10.1056/NEJM199603143341101

Koopman MM , Prandoni P , Piovella F. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. The Tasman Study Group. N Engl J Med 1996;334:682–7. DOI 10.1056/NEJM 199603143341102

Hull R , Delmore T , Genton E. Warfarin sodium versus low-dose heparin in the long-term treatment of venous thrombosis. N Engl J Med 1979;301:855–8.

Lee AY , Levine MN , Baker RI . Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003;349:146–53. DOI 10.1056/NEJMoa025313

Hull R , Pineo G , Man A , Brant RF . A randomized trial evaluating long-term low-molecular-weight heparin therapy for three months versus intravenous heparin followed by warfarin sodium (abstract). Blood 2002;100:148a.

Hull RD , Pineo GF , Stein PD . Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review. Ann Intern Med 2001;135:858–69.

Lee AY , Rickles FR , Julian JA . Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol 2005;23:2123–9. DOI 10.1200/JCO.2005.03.133

Warkentin TE , Greinacher A. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(suppl):311S–37S. DOI 10.1378/chest.126.1.311

Dager WE , White RH . Pharmacotherapy of heparin-induced thrombocytopenia. Expert Opin Pharmacother 2003;4:919–40. DOI 10.1517/14656566.4.6.919

Srinivasan AF , Rice L , Bartholomew JR . Warfarin-induced skin necrosis and venous limb gangrene in the setting of heparin-induced thrombocytopenia. Arch Intern Med 2004;164:66–70. DOI 10.1001/archinte.164.1.66

Warkentin TE . Heparin-induced thrombocytopenia: pathogenesis and management. Br J Haematol 2003;121:535–55. DOI 10.1046/j.1365-2141.2003.04334.x

Warkentin TE , Sheppard JA , Horsewood P , Simpson PJ , Moore JC , Kelton JG . Impact of the patient population on the risk for heparin-induced thrombocytopenia. Blood 2000;96:1703–8.

Kelton JG , Smith JW , Warkentin TE , Hayward CP , Denomme GA , Horsewood P. Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4. Blood 1994;83:3232–9.

Warkentin TE . Heparin-induced thrombocytopenia. Pathogenesis, frequency, avoidance and management. Drug Saf 1997;17:325–41.

Quader MA , Stump LS , Sumpio BE . Low molecular weight heparins: current use and indications. J Am Coll Surg 1998;187:641–58. DOI 10.1016/S1072-7515(98)00255-5

Amiral J , Lormeau JC , Marfaing-Koka A. Absence of cross-reactivity of SR90107A/ORG31540 pentasaccharide with antibodies to heparin-PF4 complexes developed in heparin-induced thrombocytopenia. Blood Coagul Fibrinolysis 1997;8:114–7.

Savi P , Chong BH , Greinacher A. Effect of fondaparinux on platelet activation in the presence of heparin-dependent antibodies: a blinded comparative multicenter study with unfractionated heparin. Blood 2005;105:139–44. DOI 10.1182/blood-2004-05-2010

Weitz JI , Hirsh J , Samama MM . New anticoagulant drugs: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126(suppl):265S–86S. DOI 10.1378/chest.126.3_suppl.265S

Dager WE , White RH . Treatment of heparin-induced thrombocytopenia. Ann Pharmacother 2002;36:489–503. DOI 10.1345/aph.1A204

Hauptmann J. Pharmacokinetics of an emerging new class of anticoagulant/antithrombotic drugs. A review of small-molecule thrombin inhibitors. Eur J Clin Pharmacol 2002;57:751–8. DOI 10.1007/s00228-001-0392-7

Gustafsson D , Nystrom J , Carlsson S. The direct thrombin inhibitor melagatran and its oral prodrug H 376/95: intestinal absorption properties, biochemical and pharmacodynamic effects. Thromb Res 2001;101:171–81. DOI 10.1016/S0049-3848(00)00399-6

D'amico EA , Villaca PR , Gualandro SF , Bassitt RP , Chamone DA . Successful use of Arixtra in a patient with paroxysmal nocturnal hemoglobinuria, Budd–Chiari syndrome and heparin-induced thrombocytopenia. J Thromb Haemost 2003;1:2452–3. DOI 10.1046/j.1538-7836.2003.0468c.x

Kuo KHM , Kovacs MJ . Successful treatment of heparin-induced thrombocytopenia (HIT) with fondaparinux (abstract). Blood 2003;102:319a.

Chamberlin JR , Lewis B , Leya F. Successful treatment of heparin-associated thrombocytopenia and thrombosis using Hirulog. Can J Cardiol 1995;11:511–4.

Cohen A , Alikhan R , Arcelus JI . A risk assessment model for identifying medical patients who should receive thromboprophylaxis (abstract). J Thromb Haemost 2003;(suppl 1):OC437.

Samama M , Dahl OE , Mismetti P. Individualizing the risk of venous thromboembolism in medical and surgical patients: development of the decision matrix for VTE prophylaxis (abstract). J Thromb Haemost 2003;1(suppl):OC436.

Belch JJ , Lowe GD , Ward AG , Forbes CD , Prentice CR . Prevention of deep vein thrombosis in medical patients by low-dose heparin. Scott Med J 1981;26:115–7.

Bergmann JF , Neuhart E. A multicenter randomized double-blind study of enoxaparin compared with unfractionated heparin in the prevention of venous thromboembolic disease in elderly in-patients bedridden for an acute medical illness. The Enoxaparin in Medicine Study Group. Thromb Haemost 1996;76:529–34.

Harenberg J , Roebruck P , Heene DL . Subcutaneous low-molecular-weight heparin versus standard heparin and the prevention of thromboembolism in medical inpatients. The Heparin Study in Internal Medicine Group. Haemostasis 1996;26:127–39.

Lechler E , Schramm W , Flosbach CW . The venous thrombotic risk in non-surgical patients: epidemiological data and efficacy/safety profile of a low-molecular-weight heparin (enoxaparin). The Prime Study Group. Haemostasis 1996;26(suppl 2):49–56.

Harenberg J , Schomaker U , Flosbach CW . Enoxaparin is superior to unfractionated heparin in the prevention of venous thromboembolic events in medical patients at increased thromboembolic risk (abstract). Blood 1999;94(suppl 1):399a.

Hillborn M , Erila T , Sotaniemi K. Comparison of the efficacy and safety of the low-molecular-weight heparin enoxaparin with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke (abstract). Blood 1999;94(suppl 1):183a.