ACE Report #5044

Tranexamic acid reduces blood loss and transfusions in TKA and THA

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

Tranexamic acid and the reduction of blood loss in total knee and hip arthroplasty: a meta-analysis

BMC Res Notes. 2013 May 7;6:184. doi: 10.1186/1756-0500-6-184

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33 RCTs (1,957 patients), reporting the use of tranexamic acid (TXA) in total hip arthroplasty or total knee arthroplasty compared to a control, were selected in this meta-analysis. The findings calculating the efficacy of tranexamic acid in reducing in blood loss, number of patients requiring allogeneic blood transfusions, and risk of deep vein thrombosis (DVT) indicated better outcomes in favour of tranexamic acid for both THA and TKA.

Publication Funding Details +
Not Reported
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?

With the increasing number of TKAs and THAs being performed, the issue of blood loss and subsequent high risk of blood transfusions is an increasingly important issue. Substantial blood loss can lead to postoperative anemia, infections, cardiopulmonary events, and increased costs. To counteract these effects, tranexamic acid (TXA), applied topically or intravenously, has been used in many surgeries, but it's risk of causing deep vein thrombosis (DVT) is of some concern. Therefore, this meta-analysis was conducted to investigate the effects of TXA in reducing blood loss and allogenic transfusion requirements without causing DVT.

What was the principal research question?

Does tranexamic acid (TXA) reduce total blood loss and number of patients requiring allogenic blood transfusions, compared to a control, in patients undergoing THA and TKA?

Study Characteristics -
Data Source:
A search was conducted on Pubmed, Ovid MEDLINE and EMBASE online databases, as well as Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials and www.Clinicaltrials.gov. Additional search was done on archives of the American Academy of Orthopedic Surgeons (2001-2011), Knee Society (2001-2011), Canadian Orthopedic Association (2003-2011), and British Orthopedic Association (2002-2011).
Index Terms:
Key terms used were tranexamic acid OR TXA AND total knee replacement OR total hip replacement OR total knee arthroplasty OR total hip arthroplasty OR TKA OR THA OR TKR OR THR
Study Selection:
33 English and non-English RCTs (19 TKA, 14 THA with 1,957 patients), published from 1995-July 2012, were selected by two independent reviewers. They compared TXA to a control (placebo or no use) in unilateral TKA or THA (not minimally invasive) with outcome measures of total blood loss, number of patients requiring allogeneic blood transfusions, and the incidence of thromboembolic complications.
Data Extraction:
Data extracted were patient demographics, number of patients, dose of TXA, method of TXA administration, type of control (saline, non-TXA), TBL and/or number of patients receiving allogeneic transfusions, transfusion criteria, DVT screening method, thromboprophylaxis used, incidence of DVT and/or thromboembolic complications, and cost effectiveness.
Data Synthesis:
Comprehensive Meta-analysis version 2.0 software was used, and data was aggregated using random effects model. Weighted mean difference (WMD) was used for continuous outcomes, while odds ratio (OR) was used for discontinuous outcomes. Homogeneity was measured by Hedges and Olkin method, with p value < 0.1 accepted as statistical heterogeneity. The heterogeneity was measured using the I2 statistic. Funnel plot was used for publication bias.

What were the important findings?

  • In 14 studies with TKA, the combined total blood loss favoured TXA patients, WMD = -1.149 (p < 0.001; 95% CI −1.298 to -1.000). The heterogeneity of these results was high (p = 0.000, I2 = 85.710). After sensitivity analysis considering heterogeneity, TXA showed superiority over control; WMD = −1.706 (p < 0.001, 95% CI −1.949 to-1.463).
  • In 12 studies with THA, the combined total blood loss also favoured TXA, WMD = −0.504 (p<0.001; 95% CI, -0.672, -0.336). A moderate level of heterogeneity was found (p = 0.006, I2 = 58.000).
  • In 16 studies with TKA, the combined OR of number of patients receiving allogeneic blood transfusions was 0.145 (p < 0.001; 95% CI, 0.094, 0.223) in favour of TXA group. The results were homogenous (p =0.801, I2 = 0.000).
  • In 10 studies with THA, the combined OR for number of patients receiving allogeneic blood transfusions was 0.327 (p < 0.001; 95% CI, 0.208, 0.515) in favour of TXA. The heterogeneity of the results was moderate (p = 0.135, I2 = 34.089).
  • In 7 studies with TKA, the combined OR of number of patients who developed DVT was 1.030 (p = 0.946; 95% CI, 0.439, 2.420), showing no increase in DVT incidences with TXA use. The results were homogenous (p =0.615, I2 = 0.000).
  • In 5 studies with THA, the combined OR for the number of patients who developed a DVT was 1.070 (p = 0.895; 95% CI, 0.393, 2.911), showing no increase in DVT incidences with TXA use. The results were homogenous (p =0.677, I2 = 0.000).
  • In TXA groups, 30 DVT, 3 pulmonary embolisms (PE), 1 myocardial infarction, 3 wound infections, 9 wound hematomas, and 1 chest infection occurred. In control groups 20 DVT, 4 PE, 5 wound infections, and 6 wound hematomas occurred.

What should I remember most?

The use of TXA significantly reduced the total blood loss and number of patients requiring blood allogeneic blood transfusions after THA and TKA, without an increased risk of thromboembolic complications.

How will this affect the care of my patients?

The study supports the use of TXA in major surgeries such as TKA and THA. However, more meta-analyses with poolable data regarding thromboembolic complications are needed to confirm these findings.

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