Safety and Efficacy of Anti-Fibrinolytics in Orthopedic Surgery: A Meta-Analysis of Randomized Trials.

Background: Minimizing blood transfusions following elective orthopedic procedures is desirable given the risks associated with transfusion, including cost, infection, and allergic reactions. Anti-fibrinolytic agents may reduce perioperative blood loss but are used infrequently possibly due to a lack of data supporting their efficacy and concerns about increased risks for venous thromboembolism (VTE). We performed a meta-analysis to determine whether anti-fibrinolytic agents reduce perioperative blood loss in patients undergoing total hip replacement (THR) or total knee arthroplasty (TKA).

Data sources: MEDLINE (1966 to May Week 3 2006), EMBASE (1980 to 2006 Week 21), Cochrane Database of Systematic Reviews, ACP Journal Club, Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials (the latter four databases to May 29, 2006) were searched. Additional trials were identified by manual searches. Authors and/or pharmaceutical companies were contacted if required. Study selection was based on the following criteria: prospective randomized clinical trials in which tranexamic acid, epsilon-aminocaproic acid, or aprotinin were administered. Two independent reviewers abstracted transfusion requirements, total blood loss, and venous thromboembolism. Study quality was assessed using the Jadad Quality Assessment scale. Data was pooled using the Mantel-Haenszel method and a random effects model.

Results: In 25 studies involving 1332 patients, the weighted mean difference (WMD) in total blood loss in patients treated with anti-fibrinolytic agents compared to patients receiving placebo was −409.50 mL (95%CI, −548.17 to −270.82; P< 0.00001, I² = 89.6%). In 1557 patients, the relative risk (RR) for transfusion was 0.52 (95%CI, 0.42 to 0.64; P<0.00001, I² = 58.0%). VTE did not appear to be increased in patients who received anti-fibrinolytic agents (RR 0.972 (95%CI, 0.885 to 1.06).

Conclusions: Patients undergoing TKR or THA who receive anti-fibrinolytic agents appear to have reductions in blood loss and need for transfusion. Whether these medications increase VTE risk cannot be determined due to limited data. Study characteristics were heterogeneous and the optimal timing, dose, and type of anti-fibrinolytic therapy have yet to be determined. Further studies in this area are warranted.