Should patients post-cardiac surgery be given low molecular weight heparin for deep vein thrombosis prophylaxis
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《血管的通路杂志》
a Department of Cardiothoracic Surgery, James Cook University Hospital, Middlesbrough, UK
b Department of Cardiothoracic Surgery, Blackpool Victoria Hospital, Whinney Heys Road, Blackpool, UK
c Freeman Hospital, Newcastle-upon-Tyne, UK
Abstract
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether the use of prophylactic postoperative low molecular weight heparin (LMWH) or unfractionated heparin after cardiac surgery would significantly reduce morbidity by reducing the incidence of deep vein thromboses (DVTs) and pulmonary emboli (PEs). Altogether 390 papers were identified on Medline. Relevant major guidelines were also searched together with their reference lists. Sixteen papers represented the best evidence on the topic. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses were tabulated. We conclude that the benefit of heparin prophylaxis for the prevention of DVTs and PEs is well established in non-cardiac surgery with reductions in the incidence of DVTs reported to be of the order of 50–70% in orthopaedic, general and obstetric surgery and in general medicine. No studies have yet been performed in cardiac surgery, but contrary to the view that DVTs are rare, in fact the incidence of DVT post-cardiac surgery is up to 15–20% and the incidence of PE is around 0.5 to 4% although many of these occur after discharge and many may be difficult to detect clinically. This is similar to the incidence of patients undergoing high risk general surgery. There is no evidence that heparin prophylaxis started the day after surgery increases the risk of pericardial effusions and the risk of bleeding complications is estimated to be 4%. Thus, we recommend that all patients post-cardiac surgery be commenced on heparin prophylaxis the day after their surgery and continue this up to discharge even if mobile. The particular regime should be guided by the ACCP recommendations for prophylaxis in high risk general surgical patients.
Key Words: Low molecular weight heparin; Venous thrombosis; Pulmonary embolism
1. Introduction
A best evidence topic was constructed according to the structured protocol. This protocol is fully described in the ICVTS [1].
2. Clinical scenario
You are at a weekly hospital lecture meeting and a guest lecturer has come to discuss the current treatment of pulmonary embolus. The discussion turns to prophylaxis protocols for DVTs in your hospital. It becomes evident that the general physicians, and all non-cardiac surgeons are routinely using low-molecular-weight-heparin for all their patients. The lecturer asks one of your colleagues why you do not use it in cardiac surgery, and he replies that the incidence is very low in cardiac surgery due to the clotting derangements post-operatively and anyway we would give all our patients pericardial effusions if we did. You are not sure that he is correct and therefore resolve to look up the answer.
3. Three-part question
In [patients undergoing cardiac surgery], would the use of [Low molecular weight Heparin] result in [a significantly reduced number of DVTs and PEs without bleeding complications].
4. Search strategy
Medline 1966–May 2006 using the OVID interface
[exp Venous Thrombosis/OR DVT.mp OR exp Pulmonary Embolism/OR PE.mp OR Pulmonary embol$.mp] AND [Cardiac surgical procedures.mp OR exp cardiac surgical procedures/OR exp Coronary Artery Bypass/OR Coronary art$ bypass.mp OR heart surgery.mp OR exp Thoracic surgery/OR Cardiac surgery.mp OR CABG.mp] AND [exp postoperative complications/OR complication$.mp OR adverse event$.mp] limit to humans.
5. Search outcome
Altogether 390 papers were identified on Medline. Relevant major guidelines were also searched together with their reference lists. Sixteen papers represented the best evidence on the topic ([2–17] and Table 1).
6. Results
There are three main issues when considering the possibility of DVT prophylaxis in patients post-cardiac surgery. Firstly, whether there is a significant morbidity and mortality associated with DVTs and PEs in patients post-cardiac surgery. Secondly, whether prophylaxis can significantly reduce the incidence of DVT and PE. Thirdly, whether DVT prophylaxis might cause an increase in post-operative bleeding complications.
6.1. Prevalence and morbidity of DVTs and PEs after cardiac surgery
Shammas in 2000 [7] performed a literature review to obtain an estimate of the incidence of DVTs and PEs after cardiac surgery. Eight studies were identified comprising over 18,000 patients [8–15] and it was found that if routine USS or venography was performed the incidence of DVT was 22%, and proximal DVT 15%. In addition, the incidence of PE was 0.8% with 29 fatal PEs. Interestingly, the clinical detection of DVTs was <2% and half of DVTs were in the non-harvested leg.
Ambrosettia et al. [5] in 2004 performed serial ultrasound of 270 consecutive patients post CABG attending three rehabilitation programmes. They found an incidence of DVT of 17%, an incidence of proximal DVT of 2.6% and two patients suffered a pulmonary embolus. Half of DVTs were in the leg where the saphenous vein was not harvested. They also analysed their data for protection of DVT with heparin and found a weak relationship but their numbers were too small to definitively prove this link.
Ramos et al. [6] in 1996 performed a large PRCT comparing heparin 5000 IU sc bd with heparin and 4–5 days of intermittent compression stockings. They decreased the incidence of PE from 4 to 1.5% with this intervention. This study showed that even with good prophylaxis, the incidence of PE after cardiac surgery was around 3%.
6.2. Risk reduction of DVTs and PEs with heparin
Considering whether prophylaxis significantly reduces the incidence of DVT and PE, we could find no clinical trials that assessed the impact of DVT prophylaxis in patients post-cardiac surgery. However, the American College of Chest Physicians(ACCP) [2] in 2001 published a comprehensive systematic review and guideline on DVT prophylaxis in other specialties. In general surgery 68 trials in nearly 20,000 patients have shown that either heparin or LMWH reduces the relative risk of DVT by 70%. In hip replacement surgery in over 40 trials with 7000 patients LMWH or heparin reduced the risk by up to 78%. Three ICU trials showed at least a halving of DVT, and three studies post-MI also showed a reduction. The general surgery trials have also demonstrated a reduction in proximal DVT, PE and fatal pulmonary embolus. Thus, across the whole range of surgical and medical conditions the incidence of DVT is high and prophylaxis significantly reduces the incidence of DVT and the incidence of its sequelae.
6.3. Complications of heparin therapy
Gutt et al. [3] in 2005 performed a systematic review of DVT prophylaxis in general surgery. They looked at the increase in bleeding complications and stated that LMWH at doses around 3400 IU or lower, reduced bleeding risk compared to heparin but above this, the risk was higher. They did not quantify this risk.
Bergqvist [4] in 2003 performed a systematic review in general surgery, and looked at efficacy and safety of LMWH versus unfractionated heparin. It was found that the rate of bleeding was 4–12% and severe bleeding was around 1%. It was concluded that the safety profile of LMWH was superior to unfractionated heparin at lower doses of LMWH, but this did rise as the dose increased.
Malouf et al. [16] assessed the impact of anticoagulation on pericardial effusions. They assessed 141 patients with serial echo of patients having warfarinisation post surgery. Sixty-seven Controls had an incidence of 4% of large effusions, but warfarinised patients had a 32% incidence, with 12 delayed tamponades. As a caveat, 41 patients had excessive anticoagulation at some stage and this study was in patients receiving full warfarin anticoagulation rather than prophylaxtic heparin.
Kulik et al. [17] in 2006 performed a systematic review of early anticoagulation strategies after mechanical valve replacements. They compared commencement of warfarin alone, with subcutaneous heparin and warfarin, LMWH and warfarin and intravenous heparin and warfarin. The bleeding rate was highest with intravenous heparin at 8% and was lower if s/c or LMW heparin was used at around 4%.
7. Clinical bottom line
The incidence of thromboembolism after cardiac surgery is similar to the incidence in patients undergoing high risk general surgery. The ACCP guidelines recommend heparin prophylaxis for this risk group and we conclude that patients post-cardiac surgery should be treated equivalently, with prophylaxis using heparin or LMWH starting on the first post-operative day.
References
Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: Best BETS. Interact Cardiovasc Thorac Surg 2003; 2:405–409.
Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA Jr, Wheeler HB. Prevention of venous thromboembolism. Chest 2001; 119:132–175.
Gutt CN, Oniu T, Wolkener F, Mehrabi A, Mistry S, Büchler MW. Prophylaxis and treatment of deep vein thrombosis in general surgery. Am J Surg 2005; 189:14–22.
Bergqvist D. Low molecular weight heparin for the prevention of venous thromboembolism after abdominal surgery. Br J Surg 2004; 91:965–974.
Ambrosetti M, Salerno M, Zambelli M, Mastropasqua F, Tramarin R, Pedretti RFE. Deep vein thrombosis among patients entering cardiac rehabilitation after coronary artery bypass surgery. Chest 2004; 125:191–196.
Ramos R, Salem BI, De Pawlikowski MP, Coordes C, Eisenberg S, Leidenfrost R. The efficacy of pneumatic compression stockings in the prevention of pulmonary embolism after cardiac surgery. Chest 1996; 109:82–85.
Shammas NW. Pulmonary embolus after coronary artery bypass surgery: a review of the literature. Clin Cardiol 2000; 23:637–644.
Reis SE, Polak JF, Hirsch DR, Cohn LH, Creager MA, Donovan BC, Goldhaber SZ. Frequency of deep venous thrombosis in asymptomatic patients with coronary artery bypass grafts. Am Heart J 1991; 122:478–482.
Josa M, Siouffi SY, Silverman AB, Barsamian EM, Khuri SF, Sharma GV. Pulmonary embolism after cardiac surgery. J Am Coll Cardiol 1993; 21:990–996.
Goldhaber SZ, Hirsh DR, MacDougall RC, Polak JF, Creager MA, Cohn LH. Prevention of venous thrombosis after coronary artery bypass surgery (a randomized trial comparing two mechanical prophylaxis strategies). Am J Cardiol 1995; 76:993–996.
Delaria GA, Hunter JA. Deep vein thrombosis. Implications after open heart surgery. Chest 1991; 99:284–288.
Wisoff BG, Hartstein ML, Aintablian A, Hamby R. Risk of coronary surgery. Two hundred consecutive patients with no hospital deaths. J Thorac Cardiovasc Surg 1975; 69:669–673.
Rao G, Zikria EA, Miller WH, Samadani SR, Ford WB. Incidence and prevention of pulmonary embolism after coronary artery surgery. J Vasc Surg 1975; 9:37–45.
Pouplard C, May M-A, Iochmann S, Amiral J, Vissac A-M, Marchand M, Gruel Y. Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular weight heparin. Clinical implications for heparin-induced thrombocytopenia. Circulation 1999; 99:2530–2536.
Gillinov AM, Davis EA, Alberg AJ, Rykiel M, Gardner TJ, Cameron DE. Pulmonary embolism in the cardiac surgical patient. Ann Thorac Surg 1992; 53:988–991.
Malouf JF, Alam S, Gharzeddine W, Stefadouros MA. The role of anticoagulation in the development of pericardial effusion and late tamponade after cardiac surgery [erratum appears in Eur Heart J 1994 Apr;15(4):583–4]. Eur Heart J 1993; 14:1451–1457.
Kulik A, Rubens FD, Wells PS, Kearon C, Mesana TG, van Berkom J, Lam BK. Early postoperative anticoagulation after mechanical valve replacement: a systematic review. Ann Thorac Surg 2006; 81:770–781.(Victoria Close, Manoj Pur)
b Department of Cardiothoracic Surgery, Blackpool Victoria Hospital, Whinney Heys Road, Blackpool, UK
c Freeman Hospital, Newcastle-upon-Tyne, UK
Abstract
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether the use of prophylactic postoperative low molecular weight heparin (LMWH) or unfractionated heparin after cardiac surgery would significantly reduce morbidity by reducing the incidence of deep vein thromboses (DVTs) and pulmonary emboli (PEs). Altogether 390 papers were identified on Medline. Relevant major guidelines were also searched together with their reference lists. Sixteen papers represented the best evidence on the topic. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses were tabulated. We conclude that the benefit of heparin prophylaxis for the prevention of DVTs and PEs is well established in non-cardiac surgery with reductions in the incidence of DVTs reported to be of the order of 50–70% in orthopaedic, general and obstetric surgery and in general medicine. No studies have yet been performed in cardiac surgery, but contrary to the view that DVTs are rare, in fact the incidence of DVT post-cardiac surgery is up to 15–20% and the incidence of PE is around 0.5 to 4% although many of these occur after discharge and many may be difficult to detect clinically. This is similar to the incidence of patients undergoing high risk general surgery. There is no evidence that heparin prophylaxis started the day after surgery increases the risk of pericardial effusions and the risk of bleeding complications is estimated to be 4%. Thus, we recommend that all patients post-cardiac surgery be commenced on heparin prophylaxis the day after their surgery and continue this up to discharge even if mobile. The particular regime should be guided by the ACCP recommendations for prophylaxis in high risk general surgical patients.
Key Words: Low molecular weight heparin; Venous thrombosis; Pulmonary embolism
1. Introduction
A best evidence topic was constructed according to the structured protocol. This protocol is fully described in the ICVTS [1].
2. Clinical scenario
You are at a weekly hospital lecture meeting and a guest lecturer has come to discuss the current treatment of pulmonary embolus. The discussion turns to prophylaxis protocols for DVTs in your hospital. It becomes evident that the general physicians, and all non-cardiac surgeons are routinely using low-molecular-weight-heparin for all their patients. The lecturer asks one of your colleagues why you do not use it in cardiac surgery, and he replies that the incidence is very low in cardiac surgery due to the clotting derangements post-operatively and anyway we would give all our patients pericardial effusions if we did. You are not sure that he is correct and therefore resolve to look up the answer.
3. Three-part question
In [patients undergoing cardiac surgery], would the use of [Low molecular weight Heparin] result in [a significantly reduced number of DVTs and PEs without bleeding complications].
4. Search strategy
Medline 1966–May 2006 using the OVID interface
[exp Venous Thrombosis/OR DVT.mp OR exp Pulmonary Embolism/OR PE.mp OR Pulmonary embol$.mp] AND [Cardiac surgical procedures.mp OR exp cardiac surgical procedures/OR exp Coronary Artery Bypass/OR Coronary art$ bypass.mp OR heart surgery.mp OR exp Thoracic surgery/OR Cardiac surgery.mp OR CABG.mp] AND [exp postoperative complications/OR complication$.mp OR adverse event$.mp] limit to humans.
5. Search outcome
Altogether 390 papers were identified on Medline. Relevant major guidelines were also searched together with their reference lists. Sixteen papers represented the best evidence on the topic ([2–17] and Table 1).
6. Results
There are three main issues when considering the possibility of DVT prophylaxis in patients post-cardiac surgery. Firstly, whether there is a significant morbidity and mortality associated with DVTs and PEs in patients post-cardiac surgery. Secondly, whether prophylaxis can significantly reduce the incidence of DVT and PE. Thirdly, whether DVT prophylaxis might cause an increase in post-operative bleeding complications.
6.1. Prevalence and morbidity of DVTs and PEs after cardiac surgery
Shammas in 2000 [7] performed a literature review to obtain an estimate of the incidence of DVTs and PEs after cardiac surgery. Eight studies were identified comprising over 18,000 patients [8–15] and it was found that if routine USS or venography was performed the incidence of DVT was 22%, and proximal DVT 15%. In addition, the incidence of PE was 0.8% with 29 fatal PEs. Interestingly, the clinical detection of DVTs was <2% and half of DVTs were in the non-harvested leg.
Ambrosettia et al. [5] in 2004 performed serial ultrasound of 270 consecutive patients post CABG attending three rehabilitation programmes. They found an incidence of DVT of 17%, an incidence of proximal DVT of 2.6% and two patients suffered a pulmonary embolus. Half of DVTs were in the leg where the saphenous vein was not harvested. They also analysed their data for protection of DVT with heparin and found a weak relationship but their numbers were too small to definitively prove this link.
Ramos et al. [6] in 1996 performed a large PRCT comparing heparin 5000 IU sc bd with heparin and 4–5 days of intermittent compression stockings. They decreased the incidence of PE from 4 to 1.5% with this intervention. This study showed that even with good prophylaxis, the incidence of PE after cardiac surgery was around 3%.
6.2. Risk reduction of DVTs and PEs with heparin
Considering whether prophylaxis significantly reduces the incidence of DVT and PE, we could find no clinical trials that assessed the impact of DVT prophylaxis in patients post-cardiac surgery. However, the American College of Chest Physicians(ACCP) [2] in 2001 published a comprehensive systematic review and guideline on DVT prophylaxis in other specialties. In general surgery 68 trials in nearly 20,000 patients have shown that either heparin or LMWH reduces the relative risk of DVT by 70%. In hip replacement surgery in over 40 trials with 7000 patients LMWH or heparin reduced the risk by up to 78%. Three ICU trials showed at least a halving of DVT, and three studies post-MI also showed a reduction. The general surgery trials have also demonstrated a reduction in proximal DVT, PE and fatal pulmonary embolus. Thus, across the whole range of surgical and medical conditions the incidence of DVT is high and prophylaxis significantly reduces the incidence of DVT and the incidence of its sequelae.
6.3. Complications of heparin therapy
Gutt et al. [3] in 2005 performed a systematic review of DVT prophylaxis in general surgery. They looked at the increase in bleeding complications and stated that LMWH at doses around 3400 IU or lower, reduced bleeding risk compared to heparin but above this, the risk was higher. They did not quantify this risk.
Bergqvist [4] in 2003 performed a systematic review in general surgery, and looked at efficacy and safety of LMWH versus unfractionated heparin. It was found that the rate of bleeding was 4–12% and severe bleeding was around 1%. It was concluded that the safety profile of LMWH was superior to unfractionated heparin at lower doses of LMWH, but this did rise as the dose increased.
Malouf et al. [16] assessed the impact of anticoagulation on pericardial effusions. They assessed 141 patients with serial echo of patients having warfarinisation post surgery. Sixty-seven Controls had an incidence of 4% of large effusions, but warfarinised patients had a 32% incidence, with 12 delayed tamponades. As a caveat, 41 patients had excessive anticoagulation at some stage and this study was in patients receiving full warfarin anticoagulation rather than prophylaxtic heparin.
Kulik et al. [17] in 2006 performed a systematic review of early anticoagulation strategies after mechanical valve replacements. They compared commencement of warfarin alone, with subcutaneous heparin and warfarin, LMWH and warfarin and intravenous heparin and warfarin. The bleeding rate was highest with intravenous heparin at 8% and was lower if s/c or LMW heparin was used at around 4%.
7. Clinical bottom line
The incidence of thromboembolism after cardiac surgery is similar to the incidence in patients undergoing high risk general surgery. The ACCP guidelines recommend heparin prophylaxis for this risk group and we conclude that patients post-cardiac surgery should be treated equivalently, with prophylaxis using heparin or LMWH starting on the first post-operative day.
References
Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: Best BETS. Interact Cardiovasc Thorac Surg 2003; 2:405–409.
Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA Jr, Wheeler HB. Prevention of venous thromboembolism. Chest 2001; 119:132–175.
Gutt CN, Oniu T, Wolkener F, Mehrabi A, Mistry S, Büchler MW. Prophylaxis and treatment of deep vein thrombosis in general surgery. Am J Surg 2005; 189:14–22.
Bergqvist D. Low molecular weight heparin for the prevention of venous thromboembolism after abdominal surgery. Br J Surg 2004; 91:965–974.
Ambrosetti M, Salerno M, Zambelli M, Mastropasqua F, Tramarin R, Pedretti RFE. Deep vein thrombosis among patients entering cardiac rehabilitation after coronary artery bypass surgery. Chest 2004; 125:191–196.
Ramos R, Salem BI, De Pawlikowski MP, Coordes C, Eisenberg S, Leidenfrost R. The efficacy of pneumatic compression stockings in the prevention of pulmonary embolism after cardiac surgery. Chest 1996; 109:82–85.
Shammas NW. Pulmonary embolus after coronary artery bypass surgery: a review of the literature. Clin Cardiol 2000; 23:637–644.
Reis SE, Polak JF, Hirsch DR, Cohn LH, Creager MA, Donovan BC, Goldhaber SZ. Frequency of deep venous thrombosis in asymptomatic patients with coronary artery bypass grafts. Am Heart J 1991; 122:478–482.
Josa M, Siouffi SY, Silverman AB, Barsamian EM, Khuri SF, Sharma GV. Pulmonary embolism after cardiac surgery. J Am Coll Cardiol 1993; 21:990–996.
Goldhaber SZ, Hirsh DR, MacDougall RC, Polak JF, Creager MA, Cohn LH. Prevention of venous thrombosis after coronary artery bypass surgery (a randomized trial comparing two mechanical prophylaxis strategies). Am J Cardiol 1995; 76:993–996.
Delaria GA, Hunter JA. Deep vein thrombosis. Implications after open heart surgery. Chest 1991; 99:284–288.
Wisoff BG, Hartstein ML, Aintablian A, Hamby R. Risk of coronary surgery. Two hundred consecutive patients with no hospital deaths. J Thorac Cardiovasc Surg 1975; 69:669–673.
Rao G, Zikria EA, Miller WH, Samadani SR, Ford WB. Incidence and prevention of pulmonary embolism after coronary artery surgery. J Vasc Surg 1975; 9:37–45.
Pouplard C, May M-A, Iochmann S, Amiral J, Vissac A-M, Marchand M, Gruel Y. Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular weight heparin. Clinical implications for heparin-induced thrombocytopenia. Circulation 1999; 99:2530–2536.
Gillinov AM, Davis EA, Alberg AJ, Rykiel M, Gardner TJ, Cameron DE. Pulmonary embolism in the cardiac surgical patient. Ann Thorac Surg 1992; 53:988–991.
Malouf JF, Alam S, Gharzeddine W, Stefadouros MA. The role of anticoagulation in the development of pericardial effusion and late tamponade after cardiac surgery [erratum appears in Eur Heart J 1994 Apr;15(4):583–4]. Eur Heart J 1993; 14:1451–1457.
Kulik A, Rubens FD, Wells PS, Kearon C, Mesana TG, van Berkom J, Lam BK. Early postoperative anticoagulation after mechanical valve replacement: a systematic review. Ann Thorac Surg 2006; 81:770–781.(Victoria Close, Manoj Pur)