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Reading List: Thromboprophylaxis by Mr D Warwick
Steele N, Dodenhoff RM, Ward AJ, Morse MH. Thromboprophylaxis in pelvic and acetabular trauma surgery: the role of early treatment with low-molecular-weight heparin. J Bone Joint Surg [Br] 2005;87-B:209-12.
This paper has several useful messages:
Silbersack Y, Taute B-M, Hein W, Podhaisky H. Prevention of deep-vein thrombosis after total hip and knee replacement: low-molecular-weight heparin in combination with intermittent pneumatic compression. J Bone Joint Surg [Br] 2005;86-B:809-12. It seems obvious that a combination of mechanical and chemical prophylaxis will be more effective than either alone. Two sides of Virchow’s triangle are being addressed. However, it may be a surprise that this principle has not been closely studied in the previous literature. The authors use a proper randomised trial to show that, indeed, the addition of pneumatic compression to LMWH considerably improves the efficacy. The risk reduction for knee replacement (from 40% with LMWH to 0% with the addition of pneumatic compression stockings) is particularly impressive. Knee replacement patients are particularly prone to thrombosis; the efficacy of LMWH, warfarin and Foot Pumps is limited (although older studies show some optimism for pneumatic compression stockings). This paper suggests that knee replacement patients can receive much better protection with combined methods. Whilst there are many ongoing studies looking at the efficacy of one particular chemical or another in knee replacement, it would be more helpful for Grant bodies and Editors to look for work that confirms this paper’s conclusion. Warwick D, Samama MM. The contrast between venographic and clinical endpoints in trials of thromboprophylaxis in hip replacement. J Bone Joint Surg [Br] 2000;82-B:480-2. In this paper, the authors challenged the perceived wisdom which had underpinned the profusion of thromboprophylaxis trials during the 1980s and 1990s. Dozens of studies had been conceived, pursued and published which compared one method with another; venography was an outcome measure that would allow some sort of objective comparison. However, the authors proposed that on closer inspection, the venogram was not quite as robust as had been assumed. In particular there was no established basis on which to relate venographic events to clinical events, thus confounding a proper risk-benefit and cost-benefit analysis of any particular prophylaxis method. Furthermore, the venogram gave just a snapshot in time - providing data on prevalence rather than incidence. Thus the real effect of an intervention on the frequency of thrombosis remained unknown. This paper supported the view of those who were sceptical about the benefits of prophylaxis, particularly chemical.
As it happened, this paper soon became outdated. A meta-analysis of the prolonged-duration LMWH studies in hip surgery1 proved that a reduction in venographic deep-vein thrombosis (DVT) correlated directly with a reduction in symptomatic DVT. Thereafter, the venogram had greater credibility.
1. Cohen A, Bailey CS, Alikhan R, Cooper DJ. Extended thromboprophylaxis with low molecular weight heparin reduces symptomatic venous thromboembolism following lower limb arthroplasty: a meta-analysis. Thrombo Haemost 2001;85:940-1.
Murray DW, Britton AR, Bulstrode CJK. Thromboprophylaxis and death after total hip replacement. J Bone Joint Surg [Br] 1996;78-B:863-70. In the mid 1990s, it could be observed that opinions on chemical thromboprophylaxis in orthopaedics were polarising. One view (perhaps most keenly espoused by some groups in the UK) was that the benefit of prophylaxis was not only unproven but indeed that the risks of bleeding outweighed the reduction in thromboembolism. The opposite view (perhaps most keenly promoted in Europe and particularly by some authors of LMWH prophylaxis studies) was that the risk of thrombosis is so high that the comparative risk of chemical prophylaxis was negligible. In this paper, the authors reviewed a larger number of thromboprophylaxis studies to establish the death rate in the control arm and treatment arm. They showed that the death rate was not influenced by the treatment arm and it was exceedingly low, thereby annulling the need for thromboprophylaxis. This paper provided superficially-convincing support for the anti-prophylaxis camp. However, in my view the validity of the conclusions was vulnerable and perhaps not sufficiently challenged. There are at least five potential flaws. Firstly, the authors overlooked the cost and morbidity of non-fatal thromboembolism; death is not the only issue. Secondly, the authors opportunistically used randomised trials with radiological outcomes to establish mortality outcomes. This is questionable. Thirdly, randomised studies have exclusion criteria such that the highest risk patients are likely to be excluded so the real death rate would probably have been higher. Fourthly, two thirds of fatal pulmonary emboli after hip replacement occur beyond the second week, by which time the study was finished; the study may have underestimated the death rate by a very considerable proportion. Finally, if a patient died during the study period, they would not have been available for radiological assessment and would thereby have been excluded from the study. Thus their death would not have been recorded. Warwick DJ. New concepts in orthopaedic thromboprophylaxis. J Bone Joint Surg [Br] 2004;86-B:788-92. There have been several advances in knowledge about orthopaedic thromboprophylaxis. However, these advances have in general been published in the non-orthopaedic literature. Orthopaedic surgeons are perhaps a little busy to read beyond their own journals and indeed may believe that if clinical research was of relevance to them, it would be published in their own journals.
In this paper, the author tried to bring to the attention of the readership some important issues which some surgeons may have overlooked. Perhaps of most significance was the clearly-emerging evidence that the risk of symptomatic thromboembolism after hip surgery persists for at least five weeks and that symptomatic risk could be reduced by 2/3 if prophylaxis were prolonged. This risk-reduction is likely to be even higher now that patients are often discharged after only four or fivedays. Other issues included the weak evidence on which the widespread use of aspirin prophylaxis is based, the relationship between safety-efficacy and the time after surgery when prophylaxis is given, and finally the potential for new drugs such as pentasaccharide.
Kim Y-H, Oh S-H, Kim J-S. Incidence and natural history of deep-vein thrombosis after total hip arthroplasty: a prospective and randomised clinical study. J Bone Joint Surg [Br] 2003;85-B:661-5. The authors have devised a study on a group of Korean patients which provides some intriguing information. They performed a venogram on the sixth or seventh post-operative day and when the venogram was positive they gave no treatment; they just watched the patients and did another venogram six months later.; the six-month venogram showed that the thrombi had all resolved. Not one patient developed symptoms of either DVT or pulmonary embolism in the interim. Perhaps this study would have struggled to receive Ethics Committee approval in most European or American institutions. The overall DVT frequency of around 25% is about half that which would be expected without prophylaxis in Europe and the United States, confirming data elsewhere in the literature that Asian patients have, for whatever reason, a lower risk of venous thromboembolism after orthopaedic surgery. However, the intriguing point is that the natural history of thrombosis after hip replacement appears to be, at least in Koreans, benign. Mr David Warwick, Consultant Orthopaedic Surgeon |
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