What is the role of platelet-active drugs in deep venous thrombosis (DVT) prophylaxis for patients undergoing orthopedic surgery?

Updated: Jan 28, 2021
  • Author: David A Forsh, MD; Chief Editor: Vinod K Panchbhavi, MD, FACS, FAOA, FABOS, FAAOS  more...
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Platelet-active drugs such as aspirin or cyclooxygenase (COX)-1 inhibitors have been used to prevent thrombosis. [22] Aspirin is effective as a platelet inhibitor at very low dosages (50-100 mg/day). This dosage is significantly less than that necessary to produce an anti-inflammatory effect. However, a meta-analysis of the effect of aspirin following total hip replacement (THR) completed in 1994 had equivocal results. [23, 24]

A large study performed in Europe, the Pulmonary Embolism Prevention (PEP) study, found that the overall DVT rate was decreased 30% with low-dose aspirin compared with placebo, and the overall pulmonary thrombosis rate was decreased by 40%. This trial included 13,356 patients with hip fractures and 4088 patients with THR. [24]  Aspirin at 160 mg/day was compared with placebo and evaluated at day 35. Approximately 40% of the patients also were given low-density heparin or LMWH. [24]

In a concomitant study of 4088 patients with THRs, a 25% reduction of DVT was observed in comparison with the placebo control, but no decrease was noted in the rate of pulmonary embolism. [24] This trial did not show a clear benefit to using aspirin as the primary method of venous prophylaxis in patients undergoing either total hip or total knee surgery.

The Seventh ACCP Conference did not recommend the use of aspirin alone as a prophylactic agent for any patient group, because aspirin is less effective than other options. However, reports by Lotke and Lonner [25] and by Berend and Lombardi [26] suggested that the use of aspirin combined with optimally used IPC devices may be effective in some circumstances in preventing fatal pulmonary embolism.

Since these studies, the use of aspirin for prophylaxis has been evaluated further. A systematic review of eight studies (N = 43,012) by Mistry et al addressed the use of aspirin as thromboprophylaxis after knee and hip arthroplasty. [27]  Overall, only 283 (0.66%) of the patients given aspirin had symptomatic DVT. Aspirin was found to be cost-effective, to have a good side-effect profile, and to have a lower rate of complications (eg, bleeding and wound oozing) than anticoagulants.

In a meta-analysis of 13 randomized controlled trials (N = 20,115), Haykal et al assessed the clinical efficacy and safety of aspirin against those of placebo and anticoagulants in patients undergoing knee or hip arthroplasty. [28, 29]  The primary outcome was VTE incidence; secondary outcomes included any bleeding, major bleeding, and death. No significant differences among the three groups were noted with regard to the secondary outcomes. Aspirin was associated with a lower VTE incidence than anticoagulants, but the difference was not statistically significant. However, it was associated with a significantly lower incidence of VTE in comparison with placebo.

In a systematic review and meta-analysis of six studies (N = 4460) comparing the clinical effects of LMWH and aspirin with regard to DVT after orthopedic surgery, Chen and Hu found that LMWH was associated with a significantly lower incidence of DVT, though the incidence of postoperative bleeding did not differe between the two groups. [30]

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