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Volume:2 Issue:2 Number:28 ISSN#:2563-5476
ACE Report #5781

Antifibrinolytic agents reduce blood loss and transfusion requirements in spine surgery

Study Type:Meta analysis
OE Level Evidence:1
Journal Level of Evidence:N/A

Efficacy and safety of using antifibrinolytic agents in spine surgery: a meta-analysis

PLoS One. 2013 Nov 22;8(11):e82063

Contributing Authors: C Yuan H Zhang S He

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9 randomized controlled studies, with a total of 664 patients, were included in this meta-analysis to compare antifibrinolytic agents such as tranexamic acid (TXA) and epsilonaminocaproic acid (EACA), to a placebo in regards to blood loss, transfusion requirements and deep vein thrombosis incidence in patients who underwent spine surgery. The antifibrinolytic agents were effective in reducing total blood loss, total blood transfusion and ratio of blood transfusion; additionally, the incidence of deep vein thrombosis was comparable between the antifibrinolytic agents and the placebos used.

Publication Funding Details +
None disclosed

Risk of Bias


Reporting Criteria


Fragility Index


Were the search methods used to find evidence (original research) on the primary question or questions stated?

Was the search for evidence reasonably comprehensive?

Were the criteria used for deciding which studies to include in the overview reported?

Was the bias in the selection of studies avoided?

Were the criteria used for assessing the validity of the included studies reported?

Was the validity of all of the studies referred to in the text assessed with use of appropriate criteria (either in selecting the studies for inclusion or in analyzing the studies that were cited)?

Were the methods used to combine the findings of the relevant studies (to reach a conclusion) reported?

Were the findings of the relevant studies combined appropriately relative to the primary question that the overview addresses?

Were the conclusions made by the author or authors supported by the data and or analysis reported in the overview?

How would you rate the scientific quality of this evidence?

Yes = 1

Uncertain = 0.5

Not Relevant = 0

No = 0

The Reporting Criteria Assessment evaluates the transparency with which authors report the methodological and trial characteristics of the trial within the publication. The assessment is divided into five categories which are presented below.




Accessing Data


Analysing Data





Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA. J Clin Epidemiol. 1992;45:255-65

The Fragility Index is a tool that aids in the interpretation of significant findings, providing a measure of strength for a result. The Fragility Index represents the number of consecutive events that need to be added to a dichotomous outcome to make the finding no longer significant. A small number represents a weaker finding and a large number represents a stronger finding.

Why was this study needed now?

Spine surgery, particularly multilevel spinal fusion, deformity correction and anterior-posterior spinal fusion, are associated with significant blood loss and transfusion requirements. Transfusions can be the cause of a variety of complications which can be decreased with autologous blood donations, application of cell saver-systems or the use of erythropoietin; however, these solutions are expensive and logistically challenging. Intraoperative administration of antifibrinolytics such as tranexamic acid (TXA), epsilonaminocaproic acid (EACA) and aprotinin are becoming more popular in spine surgery. Recent high-quality evidence provides reason to conduct a current meta-analysis on the topic; therefore, this study was conducted to determine the effects of antifibrinolytic agents on reducing perioperative blood loss in spine surgery.

What was the principal research question?

What are the effects of antifibrinolytic agents such as tranexamic acid (TXA) and epsilonaminocaproic acic (EACA) on perioperative blood loss and transfusion requirements in patients undergoing spine surgery?

Study Characteristics -
Data Source:
The search was performed using MEDLINE, EMBASE and the Cochrane Library databases for all studies written in English published by October 2012. WHO International Clinical Trials Registry Platform, UK National Research Register Archive and Current Controlled Trials from their inception to October 2012 for unpublished trials. All reference lists were searched for relevant articles.
Index Terms:
Spine surgery, spinal surgery, antifibrinolytic agents, tranexamic acid, and epsilonaminocaproic acid
Study Selection:
9 randomized controlled trials that compared TXA or EACA to a placebo in spine surgery and reported on at least one of blood loss, blood transfusion, ratio of blood transfusion, or incidence of deep vein thrombosis (DVT) were independently selected by two reviewers; discrepancies were resolved through discussion.
Data Extraction:
Data extraction of authors, year of publication, country, sample size, age, gender, drug dosage, transfusion indication, duration of surgery, total blood loss, blood transfusion, ratio of blood transfusion, and incidence of DVT.
Data Synthesis:
Data analyses were performed with Review Manager Version 5.2. Continuous outcomes were pooled as weight mean difference (WMD) with 95% confidence intervals (CI) and risk ratios (RR) with 95% CIs were used to evaluate dichotomous data. Significant outcomes had a p value of less than 0.05. A fixed-effects model was used for data that was not significantly heterogeneous (p>0.05) and a random-effects model was used significantly heterogeneous data (p<0.05).

What were the important findings?

  • 8 studies reported on total blood loss, the overall effect was significantly different in favour of the intervention (WMD =-288.8, 95 % CI -46.49 to -110.19; p = 0.002).Subgroup analyses of 6 studies that examined TXA and 2 studies evaluating EACA resulted in similar conclusions (WMD =-285.3, 95 % CI -506.99 to -63.65; p = 0.01 and WMD =-338.1, 95 % CI -583.03 to -93.33; p = 0.007, respectively).
  • The 9 studies that reported on total blood transfusion and found a significant difference in favour of antifibrinolytic agents(WMD =-242.76, 95 % CI -422.5 to -62.95; p = 0.008). Subgroup analysis of 6 studies involving TXA indicated significant differences in favour of TXA (WMD=-242.76, 95 % CI -422.5 to -62.95; p = 0.008) and 3 studies display improved results with EACA as well compared to a placebo (WMD =-358.1, 95 % CI -608.49 to -107.71; p = 0.005)
  • Ratio of blood transfusion was available in 7 studies and overall antifibrinolytic agents proved superior over the placebo (RR = 0.73, 95% CI 0.58 to 0.93; p = 0.010). A subgroup analysis of TXA alone resulted in similar findings (RR =0.71, 95 % CI 0.54 to 0.92; p= 0.01).
  • 9 Studies examined the DVT incidence and found no difference between groups (RR 0.25, 95 % CI 0.03 to 2.22; p= 0.21).

What should I remember most?

The antifibrinolytic agents tranexamic acid (TXA) and epsilonaminocaproic acid (EACA) were both effective in reducing total blood loss, total blood transfusion and ratio of blood transfusion. The incidence of deep vein thrombosis was comparable between the antifibrinolytic agents and the placebos used.

How will this affect the care of my patients?

Results of this study suggest that patients undergoing spine surgery can benefit from the administration of antifibrinolytic agents such as tranexamic acid and epsilonaminocaproic acid in terms of reducing blood loss and transfusion requirements. This study was limited by the small sample sizes of the included trials and the heterogeneity in variation in drug dose, surgical procedure, operation time, age of patients, protocol for estimating blood loss and transfusion indication. All of the included studies featured intravenous administration of the study drugs; whether there is a role of topical agents in spine surgery remains to be determined.

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