Thromboprophylaxis in patients with acute spinal injuries: an evidence-based analysis.

BACKGROUND The increased risk for venous thromboembolic events following spinal trauma is well established. The purpose of the present study was to examine the literature in order to determine the optimum thromboprophylaxis regimen for patients with acute spinal injuries with or without spinal cord injury. METHODS EMBASE, MEDLINE, and Cochrane databases were searched from the earliest available date to April 2008 for clinical trials comparing different methods of thromboprophylaxis in adult patients following acute spinal injuries (with or without spinal cord injury). Outcome measures included the prevalences of deep-vein thrombosis and pulmonary embolism and treatment-related adverse events. RESULTS The search yielded 489 studies, but only twenty-one of them fulfilled the inclusion criteria. The prevalence of deep-vein thrombosis was significantly lower in patients without spinal cord injury as compared with patients with spinal cord injury (odds ratio = 6.0; 95% confidence interval = 2.9 to 12.7). Patients with an acute spinal cord injury who were receiving oral anticoagulants had significantly fewer episodes of pulmonary embolism (odds ratio = 0.1; 95% confidence interval = 0.01 to 0.63) than those who were not receiving oral anticoagulants (either untreated controls or patients managed with low-molecular-weight heparin). The start of thromboprophylaxis within the first two weeks after the injury resulted in significantly fewer deep-vein-thrombosis events than delayed initiation did (odds ratio = 0.2; 95% confidence interval = 0.1 to 0.4). With regard to heparin-based pharmacoprophylaxis in patients with spinal trauma, low-molecular-weight heparin significantly reduced the rates of deep-vein thrombosis and bleeding episodes in comparison with the findings in patients who received unfractionated heparin, with odds ratios of 2.6 (95% confidence interval = 1.2 to 5.6) and 7.5 (95% confidence interval = 1.0 to 58.4) for deep-vein thrombosis and bleeding, respectively. CONCLUSIONS The prevalence of deep-vein thrombosis following a spine injury is higher among patients who have a spinal cord injury than among those who do not have a spinal cord injury. Therefore, thromboprophylaxis in these patients should start as early as possible once it is deemed safe in terms of potential bleeding complications. Within this population, low-molecular-weight heparin is more effective for the prevention of deep-vein thrombosis, with fewer bleeding complications, than unfractionated heparin is. The use of vitamin K antagonists appeared to be effective for the prevention of pulmonary embolism.

[1]  Clifford W Colwell,et al.  Prevention of Venous Thromboembolism* American College of Chest Physicians Evidence- Based Clinical Practice Guidelines (8th Edition) , 2008 .

[2]  M. Clementi,et al.  Vitamin K antagonists and pregnancy outcome , 2006, Thrombosis and Haemostasis.

[3]  P. Franks,et al.  Venous thromboembolism after spinal cord injury: incidence, time course, and associated risk factors in 16,240 adults and children. , 2005, Archives of physical medicine and rehabilitation.

[4]  C. Colwell,et al.  Prevention of venous thromboembolism. , 1994, Chest.

[5]  Clifford W Colwell,et al.  Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. , 2004, Chest.

[6]  H. Yanar,et al.  Venous Thromboembolism Prophylaxis after Head and Spinal Trauma: Intermittent Pneumatic Compression Devices Versus Low Molecular Weight Heparin , 2004, World Journal of Surgery.

[7]  W. Donovan,et al.  Comparison of Dalteparin and Enoxaparin for Deep Venous Thrombosis Prophylaxis in Patients with Spinal Cord Injury , 2003, American journal of physical medicine & rehabilitation.

[8]  Andrea Furlan,et al.  Updated Method Guidelines for Systematic Reviews in the Cochrane Collaboration Back Review Group , 2003, Spine.

[9]  G. Velmahos,et al.  Prevention of Venous Thromboembolism in the Acute Treatment Phase after Spinal Cord Injury: A Randomized, Multicenter Trial Comparing Low-Dose Heparin Plus Intermittent Pneumatic Compression with Enoxaparin , 2003 .

[10]  P. Iversen,et al.  Impaired circadian variations of haemostatic and fibrinolytic parameters in tetraplegia , 2002, British journal of haematology.

[11]  B. Eriksson,et al.  Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. , 2002, Archives of internal medicine.

[12]  P. Thumbikat,et al.  A comparison of heparin/warfarin and enoxaparin thromboprophylaxis in spinal cord injury: the Sheffield experience , 2002, Spinal Cord.

[13]  A. Pieri,et al.  Primary prevention of deep venous thrombosis and pulmonary embolism in acute spinal cord injured patients , 2002, Spinal Cord.

[14]  M. Fehlings,et al.  Epidemiology, demographics, and pathophysiology of acute spinal cord injury. , 2001, Spine.

[15]  U. Lohmann,et al.  [Prevention of thromboembolism in spinal fractures with spinal cord injuries. Standard heparin versus low-molecular-weight heparin in acute paraplegia]. , 2001, Zentralblatt fur Chirurgie.

[16]  K. Deep,et al.  Prophylaxis of thromboembolism in spinal injuries–results of enoxaparin used in 276 patients , 2001, Spinal Cord.

[17]  P. Jacobs,et al.  A Randomized Blinded Comparison Of Two Methods Used For Venous Antistasis In Tetraplegia , 2000, The journal of spinal cord medicine.

[18]  M. Devivo,et al.  Recent trends in mortality and causes of death among persons with spinal cord injury. , 1999, Archives of physical medicine and rehabilitation.

[19]  O. Agu,et al.  Graduated compression stockings in the prevention of venous thromboembolism , 1999, The British journal of surgery.

[20]  A. Iorio,et al.  Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. , 1998, The New England journal of medicine.

[21]  M. Knudson,et al.  Use of low molecular weight heparin in preventing thromboembolism in trauma patients. , 1996, The Journal of trauma.

[22]  D. Chen,et al.  Enoxaparin for thromboembolism prophylaxis in spinal injury: preliminary report on experience with 105 patients. , 1996, American journal of physical medicine & rehabilitation.

[23]  P. Haentjens.  Thromboembolic prophylaxis in orthopaedic trauma patients: a comparison between a fixed dose and an individually adjusted dose of a low molecular weight heparin (nadroparin calcium) , 1996, Injury.

[24]  H. Büller,et al.  Low Molecular Weight Heparin and Compression Stockings in the Prevention of Venous Thromboembolism in Neurosurgery , 1996, Thrombosis and Haemostasis.

[25]  J. Szalai,et al.  A prospective study of venous thromboembolism after major trauma. , 1994, The New England journal of medicine.

[26]  J. Chmiel,et al.  Prevention of thromboembolism in spinal cord injury: role of low molecular weight heparin. , 1994, Archives of physical medicine and rehabilitation.

[27]  I. Perkash,et al.  Persistent hypercoagulation associated with heterotopic ossification in patients with spinal cord injury long after injury has occurred , 1993, Paraplegia.

[28]  B. Üstünsöz,et al.  Deep vein thrombosis in spinal cord injured patients , 1993, Paraplegia.

[29]  A. Comerota,et al.  Why does prophylaxis with external pneumatic compression for deep vein thrombosis fail? , 1992, American journal of surgery.

[30]  J. Ditunno,et al.  Mechanical plus pharmacological prophylaxis for deep vein thrombosis in acute spinal cord injury , 1992, Paraplegia.

[31]  J. Vandenbroucke,et al.  Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis , 1992, The Lancet.

[32]  D. Green,et al.  Prevention of Thromboembolism After Spinal Cord Injury , 1991, Seminars in thrombosis and hemostasis.

[33]  B. Eriksson,et al.  Prevention of deep-vein thrombosis and pulmonary embolism after total hip replacement. Comparison of low-molecular-weight heparin and unfractionated heparin. , 1991, The Journal of bone and joint surgery. American volume.

[34]  S. Eiskjær,et al.  Prevention of thromboembolism in 190 hip arthroplasties. Comparison of LMW heparin and placebo. , 1991, Acta orthopaedica Scandinavica.

[35]  T. Pang,et al.  Prevention of thromboembolism after spinal cord injury using low-molecular-weight heparin. , 1990, Annals of internal medicine.

[36]  P. Myllynen,et al.  Fibrinolysis and spinal injury. Relationship to post-traumatic deep vein thrombosis. , 1989, Acta chirurgica Scandinavica.

[37]  G. Yarkony,et al.  Fixed- vs adjusted-dose heparin in the prophylaxis of thromboembolism in spinal cord injury. , 1988, JAMA.

[38]  J. Ditunno,et al.  Deep vein thrombosis: prophylaxis in acute spinal cord injured patients. , 1988, Archives of physical medicine and rehabilitation.

[39]  P. Wille-Jørgensen,et al.  Heparin with and without graded compression stockings in the prevention of thromboembolic complications of major abdominal surgery: A randomized trial , 1985, The British journal of surgery.

[40]  O. Böstman,et al.  Deep venous thrombosis and pulmonary embolism in patients with acute spinal cord injury: a comparison with nonparalyzed patients immobilized due to spinal fractures. , 1985, The Journal of trauma.

[41]  E. Rossi,et al.  Deep vein thrombosis in spinal cord injury: effect of prophylaxis with calf compression, aspirin,and dipyridamole , 1982, Paraplegia.

[42]  S. Törngren.  Low dose heparin and compression stockings in the prevention of postoperative deep venous thrombosis , 1980, The British journal of surgery.

[43]  E. Rossi,et al.  Sequential Changes in Factor VIII and Platelets Preceding Deep Vein Thrombosis in Patients with Spinal Cord Injury , 1980, British journal of haematology.

[44]  A. Perkash.  Experience with the management of deep vein thrombosis in patients with spinal cord injury , 1980, Paraplegia.

[45]  I. Perkash,et al.  Experience with the management of thromboembolism in patients with spinal cord injury: part I. incidence, diagnosis and role of some risk factors , 1978, Paraplegia.

[46]  K. Moser,et al.  Venous thrombosis in acute spinal cord paralysis. , 1977, The Journal of trauma.

[47]  N. Watson.  Anticoagulant therapy in the treatment of venous thrombosis and pulmonary embolism in acute spinal injury , 1974, Paraplegia.

[48]  J. Silver.  The prophylactic use of anticoagulant therapy in the prevention of pulmonary emboli in one hundred consecutive spinal injury patients , 1974, Paraplegia.

[49]  H. Hachen.  Anticoagulant therapy in patients with spinal cord injury , 1974, Paraplegia.

[50]  F. Naso.  Pulmonary embolism in acute spinal cord injury. , 1974, Archives of physical medicine and rehabilitation.

[51]  E. Husni.  Pathogenesis of venous thrombosis. , 1971, JAMA.

[52]  A. Moulton,et al.  Prophylactic Anticoagulant Therapy against Pulmonary Emboli in Acute Paraplegia , 1970, British medical journal.

[53]  Christopher,et al.  Early acute management in adults with spinal cord injury: a clinical practice guideline for health-care professionals. , 2008, The journal of spinal cord medicine.

[54]  Prevention of venous thromboembolism in the rehabilitation phase after spinal cord injury: prophylaxis with low-dose heparin or enoxaparin. , 2003, The Journal of trauma.

[55]  T. Ryken,et al.  Guidelines for the management of acute cervical spine and spinal cord injuries. , 2002, Clinical neurosurgery.

[56]  A. Sachdeva,et al.  Elastic compression stockings for prevention of deep vein thrombosis. , 2000, The Cochrane database of systematic reviews.

[57]  T. Therneau,et al.  Prevention of venous thromboembolism in patients with spinal cord injury: effects of sequential pneumatic compression and heparin. , 1999, The journal of spinal cord medicine.

[58]  R. Ramos,et al.  The efficacy of pneumatic compression stockings in the prevention of pulmonary embolism after cardiac surgery. , 1996, Chest.

[59]  J. Heit,et al.  Prevention of venous thromboembolism. , 1995, Chest.

[60]  M. Monreal,et al.  Comparison of Subcutaneous Unfractionated Heparin with a Low Molecular Weight Heparin (Fragmin®) in Patients with Venous Thromboembolism and Contraindications to Coumarin , 1994, Thrombosis and Haemostasis.

[61]  P. Wille-Jørgensen,et al.  Prophylaxis of deep venous thrombosis after acute abdominal operation. , 1991, Surgery, gynecology & obstetrics.

[62]  W. Waring,et al.  Acute spinal cord injuries and the incidence of clinically occurring thromboembolic disease , 1991, Paraplegia.

[63]  W. Masri,et al.  Prophylactic anticoagulant therapy in patients with spinal cord injury , 1981, Paraplegia.

[64]  A. Sasahara,et al.  Low dose heparin prophylaxis for deep venous thrombosis in acute spinal cord injury patients: a controlled study , 1981, Paraplegia.