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Exchange Information Implementation Guide Professional Development Resource Room Project Team Main Resource Room Home Venous Thromboembolism Resource Room

Literature Review

Key Literature

Table of Contents

Annotative Bibliography

Annotative Bibliography


Clinical Guidelines

Prevention of symptomatic pulmonary embolism in patients undergoing total hip and knee arthroplasty: clinical guideline of the American Academy of Orthopaedic Surgeons.
Lachiewicz PF. Instr Course Lect. 2009;58:795-804. PMID: 19385587

Deep venous thrombosis prophylaxis in total joint replacement: American College of Chest Physicians versus American Academy of Orthopaedic Surgeons guidelines.
Marchetto N. (2009) Current Orthopaedic Practice 20(1).

The Joint Commission Specifications Manual for National Hospital Quality Measures  Surgical Care Improvement Project (SCIP)
http://www.jointcommission.org/surgical_care_improvement_project/ Accessed June 2, 2009.

  • SCIP VTE-1 (SCIP VTE Measure #1: Surgery Patients with Recommended Venous Thromboembolism Prophylaxis Ordered)
  • SCIP VTE-2 (Surgery Patients Who Received Appropriate Venous Thromboembolism Prophylaxis Within 24 Hours Prior to Surgery to 24 Hours After Surgery)

Low-Molecular-Weight Heparins in Renal Impairment and Obesity: Available Evidence and Clinical Practice Recommendations  Across Medical and Surgical Settings (June) (CE).
Nutescu EA, Spinler SA, Wittkowsky A, Dager WE. Ann Pharmacother. 2009 May 19. [Epub ahead of print]. PMID: 19458109

Key articles and guidelines for the prevention of venous thromboembolism.
Dobesh PP, Wittkowsky AK, Stacy Z, Dager WE, Haines ST, Lopez LM, Nutescu E, Phillips KW, Trujillo TC, Vondracek T.
Pharmacotherapy. 2009 Apr;29(4):410-58. PMID: 19323620

American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
Antithrombotic and Thrombolytic Therapy, 8th Ed: ACCP Guidelines: June 2008; Vol. 133, No. 6_suppl.
Available at: http://www.chestjournal.org/content/vol133/6_suppl/index.shtml?etoc last accessed July 9, 2008.

Management of Venous Thromboembolism: A Clinical Practice Guideline from the American College of Physicians and the American Academy of Family Physicians
Snow, V, Qaseem, A, Barry, P, et al., and the Joint American College of Physicians/American Academy of Family Physicians Panel on Deep Venous Thrombosis/Pulmonary Embolism, Ann Intern Med. 2007;146:204-210. Accessed at: The Annals of Internal Medicine (January 31, 2007)

American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
Antithrombotic and Thrombolytic Therapy, 8th Ed: ACCP Guidelines: June 2008; Vol. 133, No. 6_suppl.
Available at: http://www.chestjournal.org/content/vol133/6_suppl/index.shtml?etoc last accessed July 9, 2008.

Venous Thromboembolism Guidebook, fourth addition.
Gelfand Eli, Piazza Gregory, Goldhaber Samuel. Venous Thromboembolism Guidebook, fourth addition. 2003;2:247-265. PMID: 18340128

Antihrombolic Therapy for Venous Thromboelbolic Disease.
Antithrombotic and thrombolytic therapy: from evidence to application: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):688S-696S. Review. PMID: 15383490

Thromboprophylaxis in Medical and Surgical Patients Undergoing Physical Medicine and Rehabilitation. Consensus Recommendations.
Ginzburg E, Banovac K Epstein B et al. Am J Phys Med Rehab. Feb 2006 85(2): 159 – 166. PMID: 16428908

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Etiology

Cardiovascular risk factors and venous thromboembolism: a meta-analysis.
Ageno W, Becattini C, et, al. Circulation. 2008 Jan 1;117(1):93-102. Epub 2007 Dec 17. PMID: 18086925  

Venous thromboembolism in children.
Parasuraman S, Goldhaber SZ. Circulation. 2006 Jan 17;113(2):e12-6. PMID: 16418440

Venous Thromboembolism Guidebook Fifth Edition
Piazza, G and Goldhaber SZ.Crit Pathways in Cardio l2006;5: 211–227. PMID: 18340238

Acute Pulmonary Embolism: Part I: Epidemiology and Diagnosis
Piazza G and Goldhaber SZ. Circulation 2006; 114;28-32. PMID: 16831989 No abstract available.

Hormonal factors and risk of recurrent venous thrombosis: the prevention of recurrent venous thromboembolism trial.
Cushman M, Glynn RJ, et, al. J Thromb Haemost. 2006 Oct;4(10):2199-203. Epub 2006 Jul 26. PMID: 16869933

Homocysteine-lowering therapy and risk for venous thromboembolism: a randomized trial.
Ray JG, Kearon C, et, al. Ann Intern Med. 2007 Jun 5;146(11):761-7. Epub 2007 Apr 30. PMID: 17470822

Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: prevalence and risk factors.
Tillie-Leblond I, Marquette CH, et, al. Ann Intern Med. 2006 Mar 21;144(6):390-6. PMID: 16549851

Risk of thromboembolism in heart failure: an analysis from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).
Freudenberger RS, Hellkamp AS, et, al. Circulation. 2007 May 22;115(20):2637-41. Epub 2007 May 7. PMID: 17485579

Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality.
Cohen AT, Agnelli G, Thromb Haemost. 2007 Oct;98(4):756-64. PMID: 17938798

No difference in risk for thrombocytopenia during treatment of pulmonary embolism and deep venous thrombosis with either low-molecular-weight heparin or unfractionated heparin: a metaanalysis.
Morris TA, Castrejon S, et, al. Chest. 2007 Oct;132(4):1131-9. Epub 2007 Jul 23. PMID: 17646239

So, does low-molecular-weight heparin cause less heparin-induced thrombocytopenia than unfractionated heparin or not?
Warkentin TE, Greinacher A. Chest. 2007 Oct;132(4):1108-10. PMID: 17934108 No abstract available.

Venous thromboembolism in the outpatient setting.
Spencer FA, Lessard D, et, al. Arch Intern Med. 2007 Jul 23;167(14):1471-5. PMID: 17646600

Risk factors for venous thromboembolic events in cancer patients.
Kröger K, Weiland D, et, al. Ann Oncol. 2006 Feb;17(2):297-303. Epub 2005 Nov 9. PMID: 16282243

A Prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis.
Goldhaber SZ, Tapson VF Am J Cardiol 2004;93:259-262. PMID: 14715365

Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting.
Smeeth L, Cook C, Thomas S et al Lancet April 1 2006 367:1075-1079. PMID: 16581406

How frequently is venous thromboembolism in heparin treated patients associated with HIT?
Levine RL, McCollum D, Hursting MJ Chest 2006;130;681-687. PMID: 16963663

Thrombosis during pregnancy and the postpartum period.
James AH, Tapson VF, Goldhaber SZ Am J Obs Gyn 2005;193:216-219. PMID: 16021082

Hormonal factors and the risk of recurrent venous thrombosis: The PREVENT Trial.
Cushman M, Glynn RJ, Goldhaber SZ J of Thromboses and Haemostasis 2006; 4:2199-203. PMID: 16869933

Greater fish, fruit, and vegetable intakes are related to lower incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology.
Steffen LM, Folsom AR, et, al. Circulation. 2007 Jan 16;115(2):188-95. Epub 2006 Dec 18. PMID: 17179018

The risk of venous thromboembolism is markedly elevated in patients with diabetes.
Petrauskiene V, Falk M, Waernbaum I, et al. Diabetologia 2005;48:1017-21. Epub March 19, 2005. PMID: 15778859

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Heparin Induced Thrombocytopenia (HIT)

HIT (Heparin Induced Thrombocytopenia).
Arepally GM, Ortel T L. NEJM August 24, 2006, 355(8): 809-817. PMID: 16928996 No abstract available.

Heparin Induced Thrombocytopenia.
Baroletti SA and Goldhaber SZ Circulation 2006; 114: 355-6. PMID: 16923760 No abstract available.

Heparin-Induced Thombocytopenia Diagnosis & Management
Warkentin TE, Heparin-induced thrombocytopenia: diagnosis and management. Circulation. 2004 Nov 2;110(18):e454-8. PMID: 15520327 No abstract available.

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Prevention/Patient Safety

A large-scale, global observational study of VTE risk and prophylaxis in the acute hospital care setting: the ENDORSE study
Cohen, AT, Tapson, VF, Bergman JF et al.  2007 Congress of the International Society on Thrombosis and Hemostasis.  July 6-12, 2007.  Geneva Switzerland.  Abstract 1STH 2007 0-S-002. PMID: 18242412

...highlighting underutilization of prophylaxis in 32 countries

Thromboprophylaxis rates in US medical centers: success or failure?
Amin A, Stemkowski S, Lin J, Yang G.  J Thromb Haemost 2007; 5: 1610–6. PMID: 17663733

The current challenge of venous thromboembolism (VTE) in the hospitalized patient. Part II: Treatment and prevention of DVT and PE - evolving risk-stratification and prophylaxis strategies for hospital-based medicine.
Bosker G, Poponick J, Emerman CL, et al. Available at: www.thrombosis-consult.com . Accessed October 28, 2003.

A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis.
Goldhaber, SZ, Tapson VF; for the DVT FREE Steering Committee. Am J Cardiol 2004a;93:259-262. PMID: 14715365

Venous thromboembolism: an ounce of prevention (editorial).
Goldhaber SZ. Mayo Clin Proc 2005;80:725-726 . Available at: Mayo Clinic Proceedings - Medical journal specializing in Internal Medicine published by Mayo Foundation for Medical Education and Research (www.mayoclinicproceedings.com/ ). Accessed December 3, 2005.

The Hospitalist Viewpoint: The New CMS VTE Prophylaxis Standards
McKean, S. North American Thrombosis Forum (NATF) online. Accessed October 14, 2008 http://www.natfonline.org/ethrombosis.php

Anticoagulant prophylaxis in special populations with an indwelling epidural catheter or renal insufficiency.
Douketis JD, Rabbat C, et, al. J Crit Care. 2005 Dec;20(4):324-9. PMID: 16310603

Thromboprophylaxis in medical and surgical patients undergoing physical medicine and rehabilitation: consensus recommendations.
Ginzburg E, Banovac K, et, al. Am J Phys Med Rehabil. 2006 Feb;85(2):159-66. PMID: 16428908

D-dimer, factor VII coagulant activity, low-intensity warfarin and risk of recurrent venous thromboembolism.
Shrivastava S, Ridker PM, Glynn R, et al.  J of Thrombosis and Haemostasis, 2006, 4:1208-1214. PMID: 16706961

Acute Pulmonary Embolism: Part II: Treatment and Prophylaxis.
Piazza G and Goldhaber SZ Circulation 2006; 114;42-47. PMID: 16847156 No abstract available.

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.
[No authors listed]. Br J Surg. 1997 Aug;84(8):1099-103. PMID: 9278651  

Greater fish, fruit, and vegetable intakes are related to lower incidence of venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology.
Steffen LM, Folsom AR, et, al. Circulation. 2007 Jan 16;115(2):188-95. Epub 2006 Dec 18. PMID: 17179018

Effectiveness of a guideline for venous thromboembolism prophylaxis in elderly post-acute care patients: a multicenter study with systematic ultrasonographic examination.
Sellier E, Labarere J, et, al. Arch Intern Med. 2006;166:2065-2071. PMID: 17060535

Prevention of Venous Thromboembolism
Goldhaber, SZ. Kardiovaskuläre Medizin 2006;9:102–108.

Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study.
Glynn RJ, Ridker PM, et, al. Circulation. 2007 Sep 25;116(13):1497-503. Epub 2007 Sep 10. PMID: 17846285

Preventing pulmonary embolism and deep vein thrombosis: a 'call to action' for vascular medicine specialists.
Goldhaber SZ. J Thromb Haemost 2007; 5: 1607–9. PMID: 17663732 No abstract available.

Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients.
Dentali F, Douketis JD, et, al. Ann Intern Med. 2007 Feb 20;146(4):278-88. PMID: 17310052

Twice vs three times daily heparin dosing for thromboembolism prophylaxis in the general medical population: A metaanalysis.
King CS, Holley AB, et, al. Chest. 2007 Feb;131(2):507-16. PMID: 17296655

Multicenter evaluation of the use of venous thromboembolism prophylaxis in acutely ill medical patients in Canada.
Kahn SR, Panju A, et, al. Thromb Res. 2007;119(2):145-55. Epub 2006 Mar 3. PMID: 16516275

Hospitals' compliance with prophylaxis guidelines for venous thromboembolism.
Yu HT, Dylan ML, et, al. Am J Health Syst Pharm. 2007 Jan 1;64(1):69-76. PMID: 17189583

Venous thromboembolism risk among hospitalized patients: magnitude of the risk is staggering.
Goldhaber SZ. Am J Hematol. 2007 Sep;82(9):775-6. PMID: 17626256

Estimated annual numbers of US acute-care hospital patients at risk for venous thromboembolism.
Anderson FA Jr, Zayaruzny M, et, al. Am J Hematol. 2007 Sep;82(9):777-82. PMID: 17626254

A prospective long-term study of 220 patients with a retrievable vena cava filter for secondary prevention of venous thromboembolism.
Mismetti P, Rivron-Guillot K, et, al. Chest. 2007 Jan;131(1):223-9. PMID: 17218580

Clinical outcome of patients with venous thromboembolism and renal insufficiency. Findings from the RIETE registry.
Falgá C, Capdevila JA, et, al. Thromb Haemost. 2007 Oct;98(4):771-6. PMID: 17938800

Clinical practice. Prophylaxis for thromboembolism in hospitalized medical patients.
Francis, CW. N Engl J Med. 2007 Apr 5;356(14):1438-44. PMID: 17409325 No abstract available.

Double trouble for 2,609 hospitalized medical patients who developed deep vein thrombosis: prophylaxis omitted more often and pulmonary embolism more frequent.
Piazza G, Seddighzadeh A, Goldhaber SZ. Chest. 2007 Aug;132(2):554-61. Epub 2007 Jun 15. PMID: 17573518

Venous thromboembolism prophylaxis in acutely ill hospitalized medical patients: findings from the International Medical Prevention Registry on Venous Thromboembolism.
Tapson VF, Decousus H, et, al. Chest. 2007 Sep;132(3):936-45. Epub 2007 Jun 15. PMID: 17573514

Inferior vena cava filters in venous thromboembolism.
Weichman K, Ansell JE. Prog Cardiovasc Dis. 2006 Sep-Oct;49(2):98-105. PMID: 17046435

Pharmacological venous thromboembolism prophylaxis in hospitalized medical patients: a meta-analysis of randomized controlled trials.
Wein L, Wein S, et, al. Arch Intern Med. 2007 Jul 23;167(14):1476-86. PMID: 17646601

Prevention of Deep Vein Thrombosis & Pulmonary Embolism.
Goldhaber SZ and Fanikos J. Cardiology patient pagesPrevention of deep vein thrombosis and pulmonary embolism. Circulation. 2004 Oct 19;110(16):e445-7. PMID: 15492324 No abstract available.
Seminar: Pulmonary Embolism.  Goldhaber, SZ.  Lancet 363:1296-1305 (April, 2004)

American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
Antithrombotic and Thrombolytic Therapy, 8th Ed: ACCP Guidelines: June 2008; Vol. 133, No. 6_suppl.
Available at: http://www.chestjournal.org/content/vol133/6_suppl/index.shtml?etoc last accessed July 9, 2008.

Thromboprophylaxis during pregnancy, labour, and after vaginal delivery.
Royal College of Obstetricians and Gynecologists.
Available at www.rcog.org.uk. Accessed 16 August 2005

Thromboprophylaxis in Medical and Surgical Patients Undergoing Physical Medicine and Rehabilitation. Consensus Recommendations.
Ginzburg E, Banovac K Epstein B et al. Am J Phys Med Rehab. Feb 2006 85(2): 159 – 166. PMID: 16428908

Effectiveness of a Guideline for VTE Prophylaxis in Elderly Post-Acute Care Patients:
A Multi-Center Study with Systematic Ultrasonographic Examination.
Sellier, E, Labarere J, Bosson, J et al.Arch Intern Med 2006;166:2065-2071. PMID: 17060535

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Randomized Control Trials

Residual thrombosis on ultrasonography to guide the duration of anticoagulation in patients with deep venous thrombosis. A randomized trial.
Prandoni P, Prins MH, Lensing AW, Ghirarduzzi A, Ageno W, Imberti D; et al.  Ann Intern Med. 2009;150:577-585. PMID: 19414836  Editorial:
Optimal Duration of Anticoagulation After Venous Thromboembolism: Fixed and Evidence-Based, or Flexible and Personalized?
Goldhaber SZ. Ann Intern Med. 2009 May 5;150(9):644-6. No abstract available. PMID: 19414845

The Prince Study:  Prevention in Cardiopulmonary Diseases with Enoxaparin.
The Prince Study:  Prevention in Cardiopulmonary Diseases with Enoxaparin, Kleber, F.X. et al. Am Heart J 2003; 145:614-21.

The MEDENOX Trial:  A Comparison of Enoxaparin with Placebo for the prevention of Venous Thromboembolism in Acutely ill Medical Patients.
Samama MM, Cohen AT, Darmon JY, Desjardins L, Eldor A, Janbon C, Leizorovicz A, Nguyen H, Olsson CG, Turpie AG, Weisslinger N. 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 Sep 9;341(11):793-800. PMID: 10477777

The PRIME Study:  The Venous Thrombotic Risk in Non-Surgical Patients: Epidemiological Data and Efficacy/Safety Profile of LMWH (Enoxaparin).
The PRIME Study:  The Venous Thrombotic Risk in Non-Surgical Patients: Epidemiological Data and Efficacy/Safety Profile of LMWH (Enoxaparin), Lechler, E. et al.  Haemostasis 1996; 26(suppl 2): 49-56.

The Prevent Trial: Randomized, Placebo-Controlled trial of Dalteparian for Prevention of Venous Thromboembolism in Acutely ill medical Patients.
Leizorovicz Alain, Cohen Alexander, Turpie Alexander, Gustav-Olsson Carl, Vaitkus Paul and Goldhauber Samuel. Circulation. 2004 Aug 17;110(7):874-9. Epub 2004 Aug 02. PMID: 10477777

The ARTEMIS Trial:  Arixtra for ThromboEmbolism Prevention in a Medical Indications Study.
The ARTEMIS Trial:  Arixtra for ThromboEmbolism Prevention in a Medical Indications Study.  Cohen, A. et al. J Thromb Haemost 2003;1(suppl 1):P2046.

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Therapeutics

Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism.
Ridker PM, Goldhaber SZ, Danielson E, Rosenberg Y, Eby CS, Deitcher SR, Cushman M, Moll S, Kessler CM, Elliott CG, Paulson R, Wong T, Bauer KA, Schwartz BA, Miletich JP, Bounameaux H, Glynn RJ; PREVENT Investigators.N Engl J Med. 2003 Apr 10;348(15):1425-34. Epub 2003 Feb 24. PMID: 12601075

A Randomized Trial of Rosuvastatin in the Prevention of Venous Thromboembolism
Glynn RJ, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Ridker PM. N Engl J Med. 2009 Apr 30;360(18):1851-61. Epub 2009 Mar 29. PMID: 19329822

Genetic testing before anticoagulation? A systematic review of pharmacogenetic dosing of warfarin.
Kangelaris KN, Bent S, Nussbaum RL, et al. J Gen Intern Med. 2009 May;24(5):656-64. Epub 2009 Mar 21. (Review) PMID: 19306050

Once-daily fondaparinux monotherapy without warfarin for long-term treatment of venous thromboembolism.
Shetty R, Seddighzadeh A, et, al. Thromb Haemost. 2007;98(6):1384-1386. PMID: 18064344 No abstract available.

Percutaneous mechanical thrombectomy for massive pulmonary embolism: improve safety and efficacy by sharing information.
Goldhababer, SZ. Catheter Cardiovasc Interv. 2007 Nov 15;70(6):807-8. PMID: 18022903

The risk for fatal pulmonary embolism after discontinuing anticoagulant therapy for venous thromboembolism.
Douketis JD, Gu CS, et, al. Ann Intern Med. 2007 Dec 4;147(11):766-74. PMID: 18056660  

Venous thromboembolism in children.
Parasuraman S, Goldhaber SZ. Circulation. 2006 Jan 17;113(2):e12-6. PMID: 16418440

Venous Thromboembolism Guidebook Fifth Edition
Piazza, G and Goldhaber SZ.Crit Pathways in Cardiol 2006;5: 211–227.

Individual time within target range in patients treated with vitamin K antagonists: main determinant of quality of anticoagulation and predictor of clinical outcome. A retrospective study of 2300 consecutive patients with venous thromboembolism.
Veeger NJ, Piersma-Wichers M, et, al. Br J Haematol. 2005 Feb;128(4):513-9. PMID: 15686461

Trials that matter: can patients with venous thromboembolism be treated with fixed-dose subcutaneous unfractionated heparin?
Goldhaber SZ, Berkwits M. Ann Intern Med. 2006;145:929-931. PMID: 17179061 No abstract available.

Warfarin maintenance dosing patterns in clinical practice: implications for safer anticoagulation in the elderly population.
Garcia D, Regan S, et, al. Chest. 2005 Jun;127(6):2049-56. PMID: 15947319  

Differences between low-molecular-weight and unfractionated heparin for venous thromboembolism prevention following ischemic stroke: a meta-analysis.
Shorr AF, Jackson WL, et, al. Chest. 2008 Jan;133(1):149-55. Epub 2007 Oct 9. PMID: 17925410

Dalteparin Reduced Recurrent Venous Thromboembolism More then Oral Anticoagulation in Patients with Cancer.
Dalteparin reduced recurrent venous thromboembolism more than oral anticoagulation in patients with cancer. ACP J Club. 2004 Jan-Feb;140(1):10. PMID: 14711281 No abstract available.

Fondaparinux was not inferior to unfractioned heparin for symptomatic pulmonary embolism.
Baller HR, Davidson BL, Decousus H, et al. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med. 2003;349:1695-702. PMID: 14585937

High- and moderate-intensity warfarin regimens did not differ for preventing thrombosis in the antiphospholipid antibody syndrome.
Crowther MA, Ginsberg JS, Julian J, et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med. 2003;349:1133-8. PMID: 13679527

Comparison of a single end point to determine optimal initial warfarin dosing (5 versus 10 mg) for venous thromboembolism.
Quiroz R, Gerhard-Herman M, Kosowsky JM et al Am J Card 2006; 98:535-7. PMID: 16893712

Acute Pulmonary Embolism: Part II: Treatment and Prophylaxis.
Piazza G and Goldhaber SZ Circulation 2006; 114;42-47. PMID: 16847156 No abstract available.

Thrombolytic therapy of pulmonary embolism: a meta-analysis.
Thabut G, Thabut D, Myers RP et al. J Am Coll Cardiol 2002; 40:1660-1667. PMID: 12427420

Massive pulmonary embolism.
Kucher N, Rossi E, De Rosa M et al. Circulation 2006; 113:577-582. PMID: 16432055

Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism.
Konstantinides S, Geibel A, Heusel G et al. NEJM 2002;347:1143-1150. PMID: 12374874

A comparison of low-molecular weight heparin with unfractionated heparin for acute pulmonary embolism.
Simonneau G, Sors H, Charbonnier B et al. NEJM 1997; 337:663-9. 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. PMID: 9278462

Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism.
Buller HR, Davidson BL, Decousus H et al. NEJM 2003; 349:1695-1702. PMID: 14585937

Extended enoxaparin monotherapy for acute symptomatic pulmonary embolism.
Kucher N, Quiroz R, McKean S et al. Vascular Medicine 2005; 10:1-6. PMID: 16444853

Enoxaparin in the treatment of deep vein thrombosis with or without pulmonary embolism: an individual patient data meta-analysis.
Mismetti P, Quenet S, Levine M et al Chest October 2005 128(4) 22032210. PMID: 16236875

Low-molecular-weight heparin compared with intravenous unfractionated heparin for the treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials.
Quinlan DJ, McQuillan A, Eikelboom JW. Ann Intern Med 2004; 140: 175-183. PMID: 14757615

A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis.
Levine M, Gent M, Hirsh J et al. NEJM March 14, 1996 334:677-681. PMID: 8594425

Effects of a low-molecular-weight heparin on thrombus regression and recurrent thromboembolism in patients with deep-vein thrombosis.
Breddin HK, Hach-Wunderle V, Nakow RN et al. NEJM March 1, 2001 344(9):62631. PMID: 11228276

New concepts in optimal management of anticoagulant therapy for extended treatment of venous thromboembolism.
Schulman Sam and Ogren Mats Thromb Haemost 2006; 96:258-66. PMID: 16953265

Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism.
Ridker PM, Goldhaber SZ, Danielson E et al NEJM 2003; 348:1425-1434. PMID: 12601075

Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism.
Kearon C, Ginsberg JS, Kovacs MJ et al. NEJM 2003: 349;631-639. PMID: 12917299

Extended oral anticoagulant therapy after a first episode of pulmonary embolism.
Agnelli G, Prandoni P, Becattini C, et al. Ann Intern Med 2003; 139:19-25. PMID: 12834314

The CLOT Trial: Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.
Lee AYY, Levine MN, Baker RI et al. NEJM July 10, 2003; 349;146-153. PMID: 12853587
Meyer G et al. Arch Intern Med 2002; 162:1729-1735.

Long-term management of patients after venous thromboembolism.
Kearon C Circulation 2004 Aug 31: 110(9 Suppl 1):I10-8. PMID: 15339876

Prevention of recurrent idiopathic venous thromboembolism. (i.e. duration of treatment)
Goldhaber GZ Circulation 2004 Dec 14:110(24 Suppl 1):IV20-4. PMID: 15598644

Heparin and low-molecular-weight heparin therapy for venous thromboembolism: will unfractionated heparin survive?
Hull RD, Pineo GF. Semin Thromb Hemost 2004 Feb;30 Suppl 1:11-23. PMID: 15085462

Influence of patient characteristics and renal function on factor Xa inhibition pharmacokinetics and pharmacodynamics after enoxaparin administration in non-ST-segment elevation acute coronary syndromes.
Becker RC, Spencer FA, Gibson, SM et al. Am Heart J 2002;143:753-759. PMID: 12040334

Retrospective evaluation of a pharmacokinetic program for adjusting enoxaparin in renal impairment.
Kruse MW, Lee JJ Am Heart J 2004; 148:582-589. PMID: 15459586

Venous Thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies.
Lepercq J, Conard J, Borel-Derlon A, et al. Br J Obstet Gynaecol 2001; 108:1134-1140. PMID: 11762651

New concepts in optimal management of anticoagulant therapy for extended treatment of venous thromboembolism.
Schulman S, Ogren M. Thromb Haemost. 2006 Sep;96(3):258-66. PMID: 16953265

Extended-duration VTE prophylaxis in acutely ill med pts with related reduced mobility.  The EXCLAIM study.
Hull, RD, Schellong,SM, Tapson VT et al.  2007 Congress of the International Society of Thrombosis and Hemostasis; July 7-13, 2007.  Geneva Switzerland.  Late breaking clinical trials, abstract 0-S-001. 

Extended-duration thromboprophylaxis in acutely ill medical patients with reduced mobility: Methodology for the EXCLAIM study.
Hull, RD, Schellong SM, Tapson, VT et al.   J Thromb Thrombolysis 2006; 22: 31-8. PMID: 16786230

Extended prophylaxis RCT for additional 28 days.  44% reduction in VTE.  At 90 days after enrollment, the VTE rates for extended prophylaxis were 3% and 5.2% respectively (p = 0.0015)

The use of low molecular weight heparins in the prevention of venous thromboembolic disease.
Morris BA, Colwell CW, Hardwick ME. Orthop Nurs 1998;17:23-29. PMID: 10095646

Treatment of venous thromboembolism: emerging trends in anticoagulation.
Nutescu EA. Available at: www.pharmacytimes.com . Accessed March 10, 2006.

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Diagnosis

Venous thromboembolism in children.
Parasuraman S, Goldhaber SZ. Circulation. 2006 Jan 17;113(2):e12-6. PMID: 16418440

Venous Thromboembolism Guidebook Fifth Edition
Piazza, G and Goldhaber SZ.Crit Pathways in Cardiol 2006;5: 211–227.

Diagnosing pulmonary embolism with improved certainty and simplicity.
Hull RD. JAMA. 2006 Jan 11;295(2):213-5. PMID: 16403934 No abstract available.

Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography.
van Belle A, Büller HR, et, al. JAMA. 2006 Jan 11;295(2):172-9. PMID: 16403929  

HIT (Heparin Induced Thrombocytopenia).
Arepally GM, Ortel T L. NEJM August 24, 2006, 355(8): 809-817. PMID: 16928996 No abstract available.

Heparin-induced thrombocytopenia.
Baroletti SA, Goldhaber SZ. Circulation. 2006 Aug 22;114(8):e355-6. PMID: 16923760 No abstract available.

D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review.
Stein PD, Hull RD, et, al. Ann Intern Med. 2004 Apr 20;140(8):589-602. PMID: 15096330  

Time-resolved MR angiography: a primary screening examination of patients with suspected pulmonary embolism and contraindications to administration of iodinated contrast material.
Ersoy H, Goldhaber SZ, et, al. AJR Am J Roentgenol. 2007 May;188(5):1246-54. PMID: 17449767

Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis.
Wells PS, Anderson DR, Rodger M, et al. D-dimer testing reduced the need for ultrasonographic imaging in outpatients with suspected deep venous thrombosis. N Engl J Med. 2003;349:1227-35. PMID: 14507948

D-dimer, factor VII coagulant activity, low-intensity warfarin and risk of recurrent venous thromboembolism.
Shrivastava S, Ridker PM, Glynn R, et al.  J of Thrombosis and Haemostasis, 2006, 4:1208-1214. PMID: 16706961

Acute Pulmonary Embolism: Part I: Epidemiology and Diagnosis
Piazza G and Goldhaber SZ Circulation 2006; 114;28-32. PMID: 16831989 No abstract available.

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Prognosis

Validation of a model to predict adverse outcomes in patients with pulmonary embolism.
Aujesky D, Roy PM, et, al. Eur Heart J. 2006 Feb;27(4):476-81. Epub 2005 Oct 5. PMID: 16207738

The natural course of hemodynamically stable pulmonary embolism: Clinical outcome and risk factors in a large prospective cohort study.
Nijkeuter M, Söhne M, et, al. Chest. 2007 Feb;131(2):517-23. PMID: 17296656

Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER).
Goldhaber SZ, Visani L, De Rosa M. Lancet 1999; 353:1386-1389. PMID: 10227218

Right Ventricular Enlargement on Chest Computed Tomography – Prognostic Role in Acute Pulmonary Embolism.
Quiroz Rene, Kucher Nils, Shoeph Joseph, Kipfmueller Florian, Solomon Scott, Costello Phillip, and Goldhaber Samuel. Right Ventricular Enlargement on Chest Computed Tomography: Prognostic Role in Acute Pulmonary Embolism. 2004;109:2401-2404. PMID: 15148278

Men had greater risk for recurrent venous thromboembolism than women.
Men had greater risk for recurrent venous thromboembolism than women. ACP J Club. 2004 Nov-Dec;141(3):78. PMID: 15518462  No abstract available.

Right Ventricular Enlargement on Chest Computed Tomography – A Prediction of Early Death in Acute Pulmonary Embolism.
Shoeph Joseph, Kucher Nils, Kipfmueller Florian, Quiroz Rene, Costello Phillip, and Goldhaber Samuel. Right Ventricular Enlargement on Chest Computed Tomography: A Predictor of Early Death in Acute Pulmonary Embolism. 2004;110:3276-3280. PMID: 15533868

A population- based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism: the Worcester DVT Study.
Anderson FA, Wheeler HB, Goldberg RJ, et al. Arch Intern Med 1991;151:933-938. PMID: 2025141

Recurrent venous thromboembolism after deep vein thrombosis: incidence and risk factors.
Hansson P-O, Sorbo J, Eriksson H. Arch Intern Med 2000;160(6):769-774. PMID: 10737276

Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based, cohort study.
Heit JA, Silverstein MD, Mohr DN, et al. Arch Intern Med 1999;159:445-453. PMID: 10074952

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Patient Education

Cardiology Patient Page: Prevention of deep vein thrombosis and pulmonary embolism
Goldhaber Samuel and Fanikos John.  Circulation. 2004 Oct 19;110(16):e445-7. PMID: 15492324 No abstract available.

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Economics

Cost Implications of Using Unfractionated Heparin or Enoxaparin in Medical Patients
at Risk for Venous Thromboembolic Events.
Weinberg, R, Lichtig, L, et, al. P&T®. June 2006;Vol. 31 No. 6.

Measuring Clinical Effectiveness Using Common Hospital Data.
Lichtig, L, Weinberg, R, et, al. P&T®. May 2004; Vol. 29 No. 5.

Low-Molecular-Weight Heparins Compared with Unfractionated Heparin for the Treatment of Acute Deep Venous Thrombosis. A Cost-Effectiveness Analysis.
Gould M, Dembitzer AD, Sanders GD et al. Annals of Int Med May 18, 1999 130(10): 789-809. PMID: 10366368

Management of Acute Proximal Deep Vein Thrombosis: Pharmacoeconomic Evaluation of Outpatient Treatment with Enoxaparin vs Inpatient Treatment with Unfractionated Heparin
Spyropoulos AC, Hurley JS, Ciesla GN et al. Chest 2002;122:108-114. PMID: 12114345

Cost effectiveness of thromboprophylaxis with a low-molecular-weight heparin versus unfractionated heparin in acutely ill medical inpatients
McGarry LJ, Thompson D, Weinstein MC et al. The American Journal of Managed Care September 2004; 10:632-642. PMID: 15515996

Comparing the costs, risks, and benefits of competing strategies for the primary prevention of venous thromboembolism.
Avorn J, Winkelmayer WC. Circulation. 2004 Dec 14;110(24 Suppl 1):IV25-32. PMID: 15598645

Cost of venous thromboembolism following major orthopedic surgery in hospitalized patients.
Ollendorf DA, Vera-Llonch M, Oster G. J Health Sys Pharm 2002; 59:1750-1754. PMID: 12298113

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Surgical VTE Prophylaxis

Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients: a double-blind, randomized comparison. The North American Fragmin Trial Investigators.
Hull RD, Pineo GF, et, al. Arch Intern Med. 2000 Jul 24;160(14):2199-207. PMID: 10904464

Low-molecular-weight heparin prophylaxis using dalteparin extended out-of-hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients: a double-blind, randomized comparison. North American Fragmin Trial Investigators.
Hull RD, Pineo GF, et, al. Arch Intern Med. 2000 Jul 24;160(14):2208-15. PMID: 10904465

Antithrombotic therapy in gynecologic surgery and gynecologic oncology.
von Tempelhoff GF, Heilmann L. Hematol Oncol Clin North Am. 2000 Oct;14(5):1151-69, ix. PMID: 11005039  

Prevention of pulmonary embolism in general surgery patients.
Zurawska U, Parasuraman S, et, al. Circulation. 2007 Mar 6;115(9):e302-7. PMID: 17339555

Venous thromboembolism prevention in gynecologic cancer surgery: a systematic review.
Einstein MH, Pritts EA, Hartenbach EM. Gynecol Oncol. 2007 Jun;105(3):813-9. Epub 2007 Apr 20. PMID: 17449089

Rivaroxaban for thromboprophylaxis after orthopaedic surgery: pooled analysis of two studies.
Fisher WD, Eriksson BI, et, al. Thromb Haemost. 2007 Jun;97(6):931-7.  PMID: 17549294

Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies.
Turpie AG, Bauer KA, et, al. Arch Intern Med. 2002 Sep 9;162(16):1833-40. PMID: 12196081

Risk of venous thromboembolism in patients undergoing cancer surgery and options for thromboprophylaxis.
Bergqvist D. J Surg Oncol. 2007 Feb 1;95(2):167-74. PMID: 17262765

Venous thromboembolism in patients undergoing surgery: Low rates of prophylaxis and high rates of filter insertion.
Seddighzadeh, A, Zurawska, U, et al. Thromb Haemost 2007; 98: 1220–1225. PMID: 18064317  

Venous Thromboembolism  in the outpatient setting.
Spencer FA, Lessard D, Emergy C, Reed G, Goldberg, RJ.  Arch Intern Med 2007; 167:1471-1475. PMID: 17646600

...37% of all outpatient VTE are related to hospitalization and 5% to outpatient surgery within prior 3 months. 
...2/3rd of these cased within prior 1 month.
...of those hosp that subsequently dev VTE, only 43% had received prophylaxis during hospitalization implication inpt VTE prophylaxis can reduce community-based BTE rate for up to 3 months following hosp or outpt surger

Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery.
Agnelli G, Piovella F, Buoncristiani P, et al. N Engl J Med 1998;339:80-85. PMID: 9654538

A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project.
Agnelli G, Bolis G, Capussotti L, et al. Ann Surg 2006;243:89-95. PMID: 16371741

American Society of Anesthesiologists Physical Classification System.
Available at: www.asahq.org . Accessed May 2006.

Imagerie des complications mécaniques des filtres caves inférieurs [Imaging mechanical complications of inferior vena cava filters].
Arrive L, Rotenberg L, Monnier-Cholley L, et al. J de Radiology 2001;82:231-235. PMID: 11287853

Deep vein thrombosis and low-dose heparin prophylaxis in neurosurgical patients.
Cerrato D, Ariano C, Fiacchino F. J Neurosurg 1978;49:378-381. PMID: 681999

Deep venous thrombosis after total joint arthroplasty: the role of compression ultrasonography and the importance of the experience of the technician.
Garino JP, Lotke PA, Kitziger KJ, et al. J Bone Joint Surg Am 1996;78:1359-1365. PMID: 8816651

A prospective study of venous thromboembolism after major trauma.
Geerts WH, Code KI, Jay RM, et al. N Engl J Med 1994;331:1601-1606. PMID: 7969340

A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma.
Geerts WH, Jay RM, Code KI, et al. N Engl J Med 1996;335:701-707. PMID: 8703169

American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
Antithrombotic and Thrombolytic Therapy, 8th Ed: ACCP Guidelines: June 2008; Vol. 133, No. 6_suppl.
Available at: http://www.chestjournal.org/content/vol133/6_suppl/index.shtml?etoc last accessed July 9, 2008.

Low-molecular-weight heparinoid orgaran is more effective than aspirin in the prevention of venous thromboembolism after surgery for hip fracture.
Gent M, Hirsh J, Ginsberg JS, et al. Circulation 1996;93:80-84. PMID: 8616946

A prospective study of risk factors for pulmonary embolism in women.
Goldhaber SZ, Grodstein F, Stampfer MJ, et al.  JAMA 1997 Jun 25;277(24):1933. PMID: 9039882

Pulmonary embolism after coronary artery bypass grafting.
Goldhaber SZ, Schoepf UJ. Circulation 2004;109;2712-2715. PMID: 15184296 No abstract available.

RD heparin (ardeparin sodium) vs aspirin to prevent deep venous thrombosis after hip or knee replacement surgery (abstract)
Graor RA, Stewart JH, Lotke PA, et al. Chest 1992; 102:118S.

When should prophylactic anticoagulation begin after hip fracture?
Grant PJ and Jaffer 1-minute consult: Q: Cleveland Clinic Journal of Medicine, 2006, 73(9):785-792. PMID: 16970132 No abstract available.

Ardeparin Arthroplasty Study Group. Efficacy and safety of low molecular weight heparin (ardeparin sodium) compared to warfarin for the prevention of venous thromboembolism after total knee replacement surgery: a double-blind, dose-ranging study.
Heit JA, Berkowitz SD, Bona R, et al; Thromb Haemost 1997;77:32-38. PMID: 9031445

The thromboembolic risk in surgery.
Hoffmann R. Hepatogastroenterol 1991;38:272-278. PMID: 1937369

Deep vein thrombosis during prolonged mechanical ventilation despite prophylaxis.
Ibrahim EH, Iregui M, Prentice D, et al. Crit Care Med 2002;30:771-774. PMID: 11940743

Duration of anesthesia and venous thromboembolism after hip and knee arthroplasty.
Jaffer AK, Barsoum WK, Krebs V, et al. Mayo Clin Proc 2005;80:732-738. PMID: 15945526

Venous thromboembolism after trauma.
Knudson MM, Ikossi DG. Curr Opin Crit Care 2004;10:539-548. PMID: 15616398

Increased use of prophylactic vena cava filters in trauma patients failed to decrease overall incidence of pulmonary embolism.
McMurty AL, Owings JT, Anderson JT, et al. J Am Coll Surg 1999;189:314-320. PMID: 10472933

A potentially expanded role for enoxaparin in preventing venous thromboembolism in high risk blunt trauma patients.
Norwood SH, McAuley CE, Berne JD, et al. J Am Coll Surg 2001;192:161-167. PMID: 11220715

Prospective evaluation of the safety of enoxaparin prophylaxis for venous thromboembolism in patients with intracranial hemorrhagic injuries.
Norwood SH, McAuley CE, Berne JD, et al. Arch Surg 2002;137:696-702. PMID: 12049541

Low molecular weight heparin and compression stockings in the prevention of venous thromboembolism in neurosurgery.
Nurmohamed MT, van Riel AM, Henkens CMA, et al. Thromb Haemost 1996;75:233-238. PMID: 8815566

Educational campaign to improve the prevention of postoperative venous thromboembolism.
Peterson GM, Drake CI, Jupe DM, et al. J Clin Pharm Therapeutics 1999;24:279-287. PMID: 10475986

Spinal Cord Injury Thromboprophylaxis Investigators. Prevention of venous thromboembolism in the rehabilitation phase after spinal cord injury: Prophylaxis with low-dose heparin or enoxaparin.
J Trauma 2003;54:1111-1115. PMID: 12813331

Duplex screening for quality assurance of postoperative thromboembolism prophylaxis in neurosurgery: Krefeld Study, Thrombo 2000 (abstract).
Van den Berg E, Bahr W, Hess J, et al. J Thromb Haemost 2003; 1(suppl):P1460.

Prevention of venous thromboembolism after injury: an evidence-based report: Part I. Analysis of risk factors and evaluation of the role of vena caval filters.
Velmahos GC, Kern J, Chan LS, et al. J Trauma 2000; 49:132-139. PMID: 10912869

Prevention of venous thromboembolism after injury: an evidence-based report: Part II. Analysis of risk factors and evaluation of the role of vena caval filters.
Velmahos GC, Kern J, Chan LS, et al. J Trauma 2000;49:140-144. PMID: 10912870

Accuracy of ultrasound for the diagnosis of deep vein thrombosis in asymptomatic patients after orthopedic surgery: A meta-analysis.
Wells PS, Lensing AWA, Davidson BS, et al. Ann Intern Med 1995;122:47-53. PMID: 7985896

Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures.
White RH, Zhou H, Romano PS. Thromb Haemost. 2003;90:446-455. PMID: 12958614

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Quality & Improvement Strategies

Physician alerts to prevent symptomatic venous thromboembolism in hospitalized patients.
Piazza G, Rosenbaum EJ, Pendergast W, et al.  Circulation. 2009 Apr 28;119(16):2196-201. Epub 2009 Apr 13. (Original) PMID: 19364975

SHM VTE Implementation Guide: Preventing Hospital-Acquired Venous-Thromboembolism, A Guide for Effective Quality Improvement, Version 3.3.
Stein, J, Maynard G. Society of Hospital Medicine website, Venous Thromboembolism Quality Improvement Resource Room http://www.hospitalmedicine.org/vte accessed February 26, 2009.

Awareness Improves Prevalence of VTE Prophylaxis on Multiple Nursing Units.
Stein J, Chernetsky Tejedor S, Shabbir H, O'Malley E. J Hosp Med. 2008: Vol 3(S1): 41.

Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies.
KG, McDonald KM, Wachter RM, Owens DK. Rockville, MD: Agency for Healthcare Research and Quality; 2004.

No magic bullets: a systematic review of 102 trials of interventions to improve professional practice.
Oxman AD, Thomson MA, Davis DA, Haynes RB. CMAJ 1995; 153:1423–1431. PMID: 7585368

Clinical assessment of venous thromboembolic risk in surgical patients.
Caprini JA, Arcelus JI, Hasty JH, et al. Semin Thromb Haemost 1991; 17(suppl 3):304–312. PMID: 1754886

Computerized order entry sets and intensive education improve the rate of prophylaxis for deep vein thrombophlebitis.
Levi D, Kupfter Y, Seneviratne C, Tessler S. Chest 1998;114S:280S.

Audit guided action can improve the compliance with thromboembolic prophylaxis prescribing to hospitalized, acutely ill
older adults.
Timmons S, O’Callaghan C, O’Connor M, et al. J Thromb Haemost 2005; 3:2112–2113. PMID: 16102124

The effect of a computerized reminder system on the prevention of postoperative venous thromboembolism.
Mosen D, Elliott CG, Egger MJ, et al. Chest 2004; 125:1635–1641. PMID: 15136370

The Hospitalist Viewpoint: The New CMS VTE Prophylaxis Standards
McKean, S. North American Thrombosis Forum (NATF) online. Accessed October 14, 2008 http://www.natfonline.org/ethrombosis.php

Electronic alerts for hospitalized high-VTE risk patients not receiving prophylaxis: a cohort study.
Baroletti S, Munz K, et, al. J Thromb Thrombolysis. 2007 Nov 17 [Epub ahead of print]. PMID: 18026689

Bridging the Gap Between Evidence and Practice in Venous Thromboembolism
Prophylaxis: The Quality Improvement Process.
Michota FA. J Gen Intern Med. 2007 Sep 22; [Epub ahead of print] PMID: 17891516

Translating evidence-based guidelines into performance measures for venous thromboembolism and acute coronary syndrome.
Groce JB 3rd. Am J Health Syst Pharm. 2007 Jun 1;64(11 Suppl 7):S25-9. PMID: 17519443

Improved use of thromboprophylaxis for deep vein thrombosis following an educational intervention.
Cohn SL, Adekile A, Mahabir V. J Hosp Med. 2006 Nov;1(6):331-8. PMID: 17219525

Curriculum development: the venous thromboembolism quality improvement resource room.
McKean S, Stein J, Maynard G, et al. J Hosp Med. 2006 Mar;1(2):124-32. PMID: 17219483

Brief hospital quality improvement program: preventing venous thromboembolism. Fitzsimmons AB, Hall LW. Mo Med. 2006 Mar-Apr;103(2):162-4. PMID: 16703717

Effect of a clinical pharmacy education program on improvement in the quantity and quality of venous thromboembolism prophylaxis for medically ill patients.
Dobesh PP, Stacy ZA. J Manag Care Pharm. 2005 Nov-Dec;11(9):755-62. PMID: 16300419

Management of suspected venous thromboembolism: the impact of a multifaceted intervention.
Salaun PY, Couturaud F, Lacut K, et al. Int J Qual Health Care. 2005 Oct;17(5):433-8. Epub 2005 May 4. PMID: 15872025

Minimizing errors of omission: behavioural reenforcement of heparin to avert venous emboli: the BEHAVE study.
J. McMullin, MD; D. Cook, MD; L. Griffith, MSc; E. McDonald, RN; F. Clarke, RRT; G. Guyatt, MD. Crit Care Med. 2006 Mar;34(3):694-9. PMID: 16505655

A computerized reminder system to increase the use of preventive care for hospitalized patients.
Dexter PR, Perkins S, Overhage JM, Maharry K, Kohler RB, McDonald CJ. N Engl J Med. 2001 Sep 27;345(13):965-70. PMID: 11575289

Electronic medical alerts--so simple, so complex.
Durieux P. N Engl J Med. 2005 Mar 10;352(10):1034-6. PMID: 15758015

A clinical decision support system for prevention of venous thromboembolism: effect on physician behavior.
Durieux P, Nizard R, Ravaud P, Mounier N, Lepage E. JAMA. 2000 Jun 7;283(21):2816-21. PMID: 10838650

Compliance with recommended prophylaxis for venous thromboembolism: improving the use and rate of uptake of clinical practice guidelines.
Kakkar AK, Davidson BL, Haas SK; The Investigators Against Thromboembolism (INATE) Core Group. J Thromb Haemost. 2004 Feb;2(2):221-7. PMID: 14995982

Electronic alerts to prevent venous thromboembolism among hospitalized patients.
Kucher N, Koo S, Quiroz R, Cooper JM, Paterno MD, Soukonnikov B, Goldhaber SZ. N Engl J Med. 2005 Mar 10;352(10):969-77. PMID: 15758007

A systematic review of strategies to improve prophylaxis for venous thromboembolism in hospitals.
Tooher R, Middleton P, Pham C, Fitridge R, Rowe S, Babidge W, Maddern G. Ann Surg. 2005 Mar;241(3):397-415. PMID: 15729062

Innovative approaches to increase deep vein thrombosis prophylaxis rate resulting in a decrease in hospital-acquired deep vein thrombosis at a tertiary-care teaching hospital.
Bullock-Palmer RP, Weiss S, Hyman C. J Hosp Med. 2008 Mar;3(2):148-55. PMID: 18438791

An overview of venous thromboembolism: impact, risks, and issues in prophylaxis.
Jaffer AK. Cleve Clin J Med. 2008 Apr;75 Suppl 3:S3-6. PMID: 18494222

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Annotative Bibliography

Clinical Importance of Venous Thrombembolism (VTE) in Hospitalized Medical Patients

  • Thromboembolism is common and kills more people than AIDS, Breast Cancer, and Highway Fatalities combined
    • Extrapolating the Worcester DVT Study data from 16 hospitals in Worcester, Massachusetts, to the United States, approximately 200,000 cases of VTE deaths may occur per year. Up to 10% of hospital deaths result from acute pulmonary embolism. Anderson FA et al. A population-based perspective of the hospital incidence and case-fatality rates of DVT and PE. Arch Intern Med 1991; 151:933-938. PMID: 2025141
  • Prospective long-term follow-up of 528 symptomatic patients
    • Mortality from VTE: should show data ICOPER cumulative mortality after diagnosis
    • 17.5% mortality 90 days after diagnosis first PE Goldhaber, S. et al. Acute PE: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999;353:1386-89. PMID: 10227218
  • Predicting who will have a pulmonary embolism (PE) is difficult and venous thromboembolism is under diagnosed in the United States
    • In one retrospective review acute pulmonary embolism as the cause of death was only diagnosed in 11.9% of patients subsequently shown to have PE at autopsy. Stein, P. et al. Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. Chest 1995; 108:978-981. PMID: 7555172
    • Sudden death may be the first presentation of acute pulmonary embolism. Clagett, C. et al. Prevention of venous thromboembolism. Chest. 1998; 114:531S-560S.
  • Initial diagnosis of PE carries a significant mortality that extends beyond the acute event
    • Long-term follow up of patients diagnosed with PE revealed a high mortality rate of 17.5% at 3 months from diagnosis. Prandoni,P. et al. The clinical course of DVT. Prospective long-term follow-up of 528 symptomatic patients. Haematologica 1997;82:423-428. PMID: 9299855 Goldhaber, S. et al. Acute PE: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999;353:1386-89. PMID: 10227218

VTE Poses a Significant Economic Burden Due to the Initial Cost, Sequelae, and Disease Prevalence

  • Initial cost of management for patients admitted with pulmonary embolism is approximately $12K with inpatient management of deep venous thrombosis $7K based on national data 1994 for DRG related groups. Accessed on Statistics From the HCUP-3 Nationwide Inpatient Sample for 1994: Diagnosis-Related Groups
  • There is a high incidence of long term sequelae of venous thromboembolism: recurrent VTE (30% cumulative incidence) and postthrombotic syndrome (29.6% cumulative incidence). Prandoni, et al. The long-term clinical course of acute deep venous thrombosis. Ann of Intern Med 1996 Jul 1;125(1):1-7. PMID: 8644983
  • The postthrombotic syndrome of pain, swelling, ulceration, hyperpigmentation affects daily activity and ability to work and may lower the quality of life. Kahn, S et al. Effect of postthrombotic syndrome on health-related quality of life after DVT. Arch Int Med. 2002 162:1144-1148. PMID: 12020185

Failure to Prescribe VTE Prophylaxis for Hospitalized Medical Patients: Adequate, Evidence-based VTE prophylaxis is Still Underutilized

  • Omitting prophylaxis is a much greater problem in medical than in surgical patients. In particular, non-ICU general medical patients often receive inadequate prophylaxis, usually b.i.d. mini-dose UFH, which has never been validated in a randomized, control trial
    • 183 sites: 5,451 patients o 3,894 (71%) did not receive prophylaxis
    • Of the 2,726 inpatients diagnosed with DVT, 58% had not received prophylaxis
    • More than twice as many medical patients failed to receive prophylaxis as surgical patients
    • Among inpatients with inadequate prophylaxis 6% received tid mini dose heparin versus 94% who received bid minidose heparin
  • Goldhaber, S. New onset of VTE among hospitalized patients at Brigham and Women’s Hospital is caused more often by prophylaxis failure than by withholding treatment. Chest. 2000 Dec;118(6):1680-4. PMID: 11115458
    • New onset VTE among hospitalized patients admitted to Brigham and Women’s Hospital for another reason is caused more often by prophyaxis failure than by withholding treatment.
  • Goldhaber, S., Tapson, V.F., DVT Free Steering Committee. A Prospective Registry of 5, 451 patients with ultrasound-confirmed deep vein thrombosis. Amer J Card. 2004 Jan 15;93(2):259-62. PMID: 14715365
    • Of the 2,726 patients who had their DVT diagnosed while hospitalized at 183 US sites, only 1,147 (42 %) received prophylaxis within 30 days before diagnosis. Medical patients were much less likely to receive prophylaxis compared with surgical patients.
  • Until recently, VTE risk was not well-defined and there were few well-designed studies of prophylaxis for general medical patients. o
    • Without prophylaxis the range of DVT risk is between
      • 10-26% in general medical patients (Cade et al. High risk of the critically ill for venous thromboembolism. Crit Care Med. 1982 Jul;10(7):448-50. PMID: 7044682) and Belch, J et al. Prevention of deep vein thrombosis in medical patients by low-dose heparin. Scott Med J. 1981; 26:115-117. PMID: 7291971 ),
      • 17-34% in patients with myocardial infarction (Nicolaides, A. et al. Int Angiol. 1997: 16:3- 38),
      • 20-40% in patients with congestive heart failure (Anderson et al. The effect of dicumarol upon the mortality and incidence of thromboembolic complications in congestive heart failure. Amer Heart J. 1950; 39:697-702. PMID: 15413578 ),
      • 11-75% in patients with stroke (Nicolaides, A. et al. Int Angiol. 1997: 16:3-38) and
      • 25-42% in general medical intensive care patients (Hirsh, D et al. Prevalence of deep venous thrombosis among patients in medical intensive care. JAMA 1995; 274:335-337. PMID: 7609264).
    • The use of "mini-dose heparin" as the standard of care has been based on insufficient evidence in medical hospitalized patients.
      • At the time of the study design for MEDENOX and PREVENT trials, review of published data in support of unfractionated heaparin (UFH) in low dose (UFH 5000 IU q 8-12 hours SQ) by US and European regulatory agencies concluded the use of minidose UFH was not evidenced based for medical inpatients.
      • Neither UFH nor low molecular weight heparin (LMWH) was FDA approved for this patient population at that time.
      • The predominantly European studies were limited by small populations, variations in endpoint measurements, and open label, non-randomized design.
      • Belch, J. et al. Prevention of DVT in medical inpatients by low dose heparin. Scott Med J 1981; 26: 115-7 PMID: 7291971
      • In a randomized, prospective, open-label, controlled study of a small group of 80 medical inpatients with heart failure and/or pulmonary infection demonstrated 4% incidence of DVT in patients receiving UFH 5000 IU q 8h compared to 26% in the no treatment group.
      • Gardlund, B. et al. Randomised, control trial of low dose heparin for prevention of fatal pulmonary embolism in patients with infectious disease. Lancet. 1996; 347: 1357-1361. PMID: 8637340
      • In a randomized, prospective, unblinded, controlled study of 11,693 patients with infectious disease demonstrated no significant difference in the necropsy-defined PE rate between treatment with UFH 5000 IU q 12 hours and the no treatment group.

Current Evidence: Prophylactic Doses of Heparins to Reduce the Incidence of DVT and Clinical PE in Hospitalized Medical Patients

  • THE PRINCE Study: Thromboembolism - Prevention in Cardiopulmonary Diseases with Enoxaparin, Kleber, F. X. et al. 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. PMID: 12679756
    • Enoxaparin 40 mg q d is at least as effective as UFH 5,000U t.i.d. in the prevention of VTE in patients with CHF NYHA III/IV or severe respiratory disease and as safe as UFH regarding hemorrhage.
  • The MEDENOX Study: A Comparison of Enoxaparin With Placebo for The Prevention of Venous Thromboembolism in Acutely Ill Medical Patients, Samama, M. et al. NEJM 1999; 341: 793-800. PMID: 10477777
    • Enoxaparin 40 mg q d for 6-14 days more effective than placebo in reducing the risk of VTE by 63% without increased hemorrhage or thrombocytopenia, a benefit maintained at 3 month follow-up. However, enoxaparin 20 mg q d for the same time period is not superior to placebo. Acutely ill medical patients are at a significant risk of VTE (15% total VTE, 5% proximal VTE).

Acutely ill medical patients are at significant risk of VTE (15% total VTE, 5% proximal DVT) Enoxaparin 40 mg once-daily given subcutaneously for 6-14 days was effective in reducing the risk of VTE by 63% compared to placebo

Benefit was maintained at 3 month follow-up

This result was achieved with no increase in adverse events, hemorrhage or decreased platelets

  • The PRIME Study: The Venous Thrombotic Risk in Non-Surgical Patients: Epidemiological Data and Efficacy/Safety Profile of LMWH (Enoxaparin), Lechler, E. et al. Haemostasis 1996; 26(suppl 2): 49-56. PMID: 8707167
    • Enoxaparin 40 mg q d versus UFH 5,000 IU t.i.d. over 7 days is equally efficacious in high risk patients and at least as safe as UFH.
  • The PREVENT Trial: The Prospective Evaluation of Dalteparin Efficacy for The Prevention of VTE in Immobilized Patients Trial.
    • Dalteparin is more effective than placebo in the prevention of VTE in acutely ill patients hospitalized for at least 4 days with CHF (NYHA III, IV), acute respiratory failure, or with acute severe systemic disease plus one risk factor (RRR = 0.55). Leizorovicz, A et al. Randomized Placebo-Controlled Trial of Dalteparin for the Prevention of Venous Thromboembolism in Acutely Ill Medical Patients. Circulation. 2004;110:874-9. PMID: 15289368
      • Confirmed findings of earlier Medenox trial that acutely ill medical patients are at significant risk of VTE
      • Dalteparin 5000 IU subcutaneously q day for 12-14 days was effective in reducing the risk of VTE (risk ratio 0.55, p=0.0015) compared to placebo
      • This result was achieved with no increase in adverse events
  • In summary whatever the baseline VTE risk and the type of patient, prophylactic doses of heparins will reduce the incidence of DVT and PE. The appropriate dose of heparins should be used to ensure the approximately 50% risk reduction of VTE achieved in clinical trials of medical inpatients. For minidose heparin, UFH 5000 IU q 8 hours is more effective than no treatment. Evidence is less convincing that UFH 5000 IU U q 12 hours is more effective than placebo. For LMWH, the MEDENOX Trial demonstrated a significant benefit using 40mg of enoxaparin once daily and the PREVENT trial demonstrated a significant benefit using 5000 IU of dalteparin once daily compared with placebo.
  • The ARTEMIS Trial: Arixtra for ThromboEmbolism Prevention in a Medical Indications Study.
    • Fondaparinux, a pentassaccharide, 2.5 mg daily subcutaneously, reduces the incident of DVT by 49% compared to placebo without any increase in major bleeding. Cohen, A. et al. Fondaparinux vs placebo for the prevention of venous thromboembolism in acutely ill medical patients (ARTEMIS). J Thromb Haemost 2003;1(suppl 1):P2046.
  • Antihrombolic Therapy for Venous Thromboelbolic Disease
    Antithrombotic and thrombolytic therapy: from evidence to application: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):688S-696S. PMID: 15383490

Patient Safety Now on the Radar Screen

  • The Joint Commission
  • 2001 the Agency for Health Care Research and Quality published a patient safety practices report that VTE prophylaxis decreases adverse patient outcomes and health costs.
    • VTE prophylaxis in patients at risk ranked first in order of need for widespread implementation for hospitalized patients - ahead of perioperative B-blocker use, maximum sterile barriers during central intravenous catheters, antibiotic prophylaxis in surgical patients, and verification of patient understanding during informed consent.
  • Making Health Care Safer: A Critical Analysis of Patient Safety Practices: Evidence Report/Technology Assessment No. 43, AHRQ Publication No. 01-EO58.

Risk Assessment: Total Eligible Population Much Greater Than Simply High Risk Subgroups

  • Specific medical conditions alone are not accurate predictors of VTE Risk
    • Specific disease is not the only factor affecting risk; for the same condition, moderate and high risk overlap depending on severity of disease. Multiple risk factors also affect total risk in medical patients.
  • Patient-related risk factors are at least as important as the admitting diagnosis
    • Advanced age, immobility, malignancy, pregnancy, estrogens, PMH VTE, inherited and acquired molecular risk factors, and metabolic abnormalities increase risk.
  • Medical interventions further increase VTE Risk o Chemotherapy, invasive medical technologies, and immobilization of the patient compound risk.
  • DVT-Free Prospective Registry confirmed that prior DVT, surgery, cancer, and immobility are the most common risk factors for hospital acquired VTE.
    • Goldhaber, S. Tapson, V.F., DVT Free Steering Committee. A Prospective Registry of 5, 451 patients with ultrasound-confirmed deep vein thrombosis. Amer J Card 93(2):259-262, Jan 15, 2004. PMID: 14715365

Challenges Prediction and Detection of PE

  • Diagnosis may not be suspected with vague symptoms
  • Silent, fatal disease (unsuspected in 70-80%, diagnosed at autopsy)
  • Universal measures to prevent postoperative VTE of paramount importance

Estimated lives saved if effective prophylaxis used = 80,0000 patients per year

Guidelines

Management of Venous Thromboembolism: A Clinical Practice Guideline from the American College of Physicians and the American Academy of Family Physicians
Snow, V, Qaseem, A, Barry, P, et al., and the Joint American College of Physicians/American Academy of Family Physicians Panel on Deep Venous Thrombosis/Pulmonary Embolism, Ann Intern Med. 2007;146:204-210. Accessed at: The Annals of Internal Medicine (January 31, 2007)

 

 

 

 

Venous Thromboembolism Resource Room Project Team
This resource room is sponsored in part by a non-educational sponsorship from sanofi-aventis US, LLC

Disclaimer
The Venous Thromboembolism (VTE) Resource Room is an online resource for visitors to the Society of Hospital Medicine’s website. All content and links have been reviewed by the VTE Resource Room Project Team, however the Society of Hospital Medicine does not exercise any editorial control over content associated with the external links that have been made available via this website.

The contributions of Dr. Maynard and his UCSD collaborators in the development of the SHM VTE Prevention Resource Room and the VTE Prevention Implementation Guide were supported by grant number 1U18HS015826-01 from the Agency for Healthcare Research and Quality (AHRQ). The contents of this product are solely the responsibility of Dr. Maynard and the SHM VTE Resource Room team, and do not necessarily represent the official view of or imply endorsement by AHRQ or the U.S. Department of Health and Human Services.

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