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Heparins and mechanical methods for thromboprophylaxis in colorectal surgery
Peer Wille-Jørgensen, Morten Schnack Rasmussen, Betina Ristorp Andersen, Lars Borly
DOI:10.1002/14651858.CD001217
Peer Wille-Jørgensen, Morten Schnack Rasmussen, Betina Ristorp Andersen, Lars Borly
DOI:10.1002/14651858.CD001217
Date received: July 22, 2008
Cite this comment as: http://www.cochranefeedback.com/cf/cda/citation.do?id=9854#9854
I thank Dr. Wille-Jørgensen for the reply.
The clinical relevance of the surrogate endpoint of asymptomatic DVT prevention with anticoagulants correlating with a lower incidence of clinical DVT and fatal PE is hardly settled by Kakkar’s 1977 article in the Seminars of Nuclear Medicine, ‘Fibrinogen Uptake Test for Detection of Deep Vein Thrombosis’ review’1 (reference 1 of the reply).
While you have demonstrated a positive correlation between asymptomatic post operative DVT with later postphlebitic syndrome,2 this does not prove that post phlebitic syndrome is prevented by prophylactic anticoagulants. It may be that rebound hypercoagulation related DVT after stopping heparin increases VTE and subsequently the post phlebitic syndrome.
Regarding the efficacy of long-term postoperative prophylaxis with orthopaedic procedures, RCTs comparing heparins for 6-10 days post op versus extending the prophylaxis for an additional 3-4 weeks at home generally do not have data on outcomes after the completion of the extended prophylaxis. This misses outcome events due to post heparin rebound hypercoagulability. In the six RCTs reviewed by Hull and colleagues,3 none had an unanticoagulated arm to see the effect of short term prophylaxis itself. This meta-analysis included only 1953 patients and fatal PE occurred in only 2/862 placebo-treated patients (possibly due to rebound hypercoagulability) versus 0/1091 who received extended prophylaxis. This makes the Goldhaber study,4 about which Dr. Wille-Jørgensen had no comment, particularly relevant. Out of about 80,000 hospitalizations of patients followed for at least 2 months (i.e., capturing rebound hypercoagulability events), 12/13 cases of fatal PE occurred in patients given prophylaxic anticoagulants.
Regarding the reference to the data on the association between fatal PE and omission of prophylaxis from the Bispebjerg Hospital, University of Copenhagen, Denmark,5 despite the statistical significance of the data (p < .05), little can be concluded from an observational study with 20 cases of post operative fatal PE out of 4881 surgeries. The abstract of this study states, ‘Antithrombotic prophylaxis was applied routinely according to standard instructions.’ At least some of those not given antithrombotic prophylaxis may have had contraindications.
In a much larger study of autopsy verified fatal PE cases of all surgical patients in Malmo, Sweden, during the period from 1951 to 1988 in whom pulmonary emboli were found at autopsy (391 cases),6 the incidence of previous prophylaxis with anticoagulants in people with autopsy-proven FPE increased from 50% in 1971-1975 to 76% in 1976-1980, 85% in 1979-1983, and 94% in 1984-1988. The overall incidence of venous thromboembolism in this hospital had not changed from 1957 to 1987.7 Again, these data suggest the possibility of rebound hypercoagulability causing FPE.
While methodologically correct for its time, the ‘International Multicentre Trial’8 was before the era of early mobilization and mechanical VTE prophylaxis. The followup period was only until discharge from hospital, so the deaths due to rebound hypercoagulation on stopping the heparin were missed.
1. Kakkar VV. Fibrinogen Uptake Test for Detection of Deep Vein Thrombosis - A review of Current Practice. Sem Nucl Med. 1977;7:229-244.
2. Wille-Jorgensen P, Jorgensen LN, Crawford M. Asymptomatic postoperative deep vein thrombosis and the development of postthrombotic syndrome. A systematic review and meta-analysis. Thromb Haemost. 2005;93(2):236-241.
3. Hull RD, Pineo GF, Stein PD, et al. Extended Out-of-Hospital Low-Molecular-Weight Heparin Prophylaxis against Deep Venous Thrombosis in Patients after Elective Hip Arthroplasty: A Systematic Review. Ann Intern Med. 2001;135:858-869.
4. Goldhaber SZ, Dunn K, MacDougall RC. New Onset of Venous Thromboembolism Among Hospitalized Patients at Brigham and Women’s Hospital Is Caused More Often by Prophylaxis Failure Than by Withholding Treatment. Chest. 2000;118:1680-1684.
5. Rasmussen MS, Wille-Jorgensen P, Jorgensen LN. Postoperative fatal pulmonary embolism in a general surgical department. Am J Surg. 1995;169(2):214-216.
6. Lindblad B, Eriksson A, Bergqvist D. Autopsy-verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988. British Journal of Surgery. 1991;78(7):849-852.
7. Lindblad B, Sternby NH, Bergqvist D. Incidence of venous thromboembolism verified by necropsy over 30 years. BMJ. 1991;302(6778):709-711.
8. Kakkar VV, Corrigan TP, Fossard DP, Sutherland I, Thirwell J. Prevention of Fatal Postoperative pulmonary embolism by low doses of heparin. Reappraisal of results of international multicentre trial. Lancet. 1977;1(8011):567-569.