In reply: Walters and Graham question the role of low-molecular-weight heparin (LMWH) as a replacement for unfractionated heparin during pregnancy, and cite the lack of randomised comparisons to support their view that the standard initial treatment for pulmonary embolism during pregnancy remains intravenous unfractionated heparin. We do not deny the lack of clinical trials of LMWH in pregnancy; we were simply referring to the increased use of LMWH.1,2

However, the lack of evidence of effectiveness does not equate with evidence of lack of effectiveness of LMWH in pregnancy. Clinical trials are needed to determine optimal anticoagulant strategies during pregnancy, particularly in patients with prosthetic heart valves. While awaiting the results of these trials, we believe that the major pharmaco-kinetic and safety advantages of LMWH over unfractionated heparin, coupled with an extensive body of evidence demonstrating their efficacy and safety in non-pregnant patients, should not be ignored in our pursuit of optimal anticoagulation therapies.

Williamson and Street question the validity of asymptomatic deep vein thrombosis as a surrogate for symptomatic venous thromboembolism in patients undergoing major orthopaedic surgery. Further, they cite a 0.1%–0.2% incidence of pulmonary embolism in patients undergoing hip replacement surgery without prophylaxis3 to support the conclusion that any effect of thromboprophylaxis on reducing symptomatic events is likely to be irrelevant for individual orthopaedic surgeons.

We believe that their argument is seriously flawed. Firstly, the "meta-analysis" they cite3 had major methodological limitations, as elegantly highlighted by "Sherlock Holmes" in his critical appraisal of systematic reviews of surgical thromboprophylaxis.4 Secondly, rigorously conducted randomised trials and meta-analyses of randomised trials have demonstrated the efficacy of antithrombotic therapy for the prevention of both symptomatic and fatal venous thromboembolism in high-risk surgical patients, including lower-limb orthopaedic surgery.5,6 Thirdly, the clear correlation between reduction in asymptomatic and symptomatic venous thromboembolism in patients undergoing elective joint replacement surgery7 suggests that asymptomatic thrombosis detected by screening venography is a valid surrogate for symptomatic events. Fourthly, we agree that an individual orthopaedic surgeon performing 50 joint replacements per year may remain unaware of a small reduction in fatal pulmonary emboli in his or her own practice (eg, a 0.1% absolute risk reduction would be equivalent to preventing one death in 20 years of practice).

Yet, on a population basis, even a 0.1% absolute reduction (which is likely to be an underestimate — the PEP study showed a 0.3% absolute reduction in fatal pulmonary embolism with aspirin5) equates to 50 preventable deaths per year in Australia alone8 and many thousands worldwide.

There is now overwhelming evidence of the efficacy of thromboprophylaxis for preventing venous thromboembolism, including symptomatic and fatal pulmonary embolism, in high-risk surgical patients. With the rapid ageing of the Australian population and the expected increase in joint replacement surgery in coming years,9 the failure to use effective thromboprophylaxis in orthopaedic patients will likely result in a growing burden of preventable morbidity and mortality from venous thromboembolism.