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    Effects of Tranexamic Acid on Bleeding in Total Knee Arthroplasty

    Bleeding is one of primary reasons for impaired recovery after total knee arthroplasty because it can cause:

    • Knee swelling
    • Increased pain
    • Restricted motion
    • Greater risk of wound complications

    Tranexamic acid (TXA) is now being used in major joint reconstruction to control bleeding. Is it having the desired effect on bleeding and, by extension, on recovery after TKA?

    At the ICJR Australia meeting in Sydney, Samuel J. MacDessi, MD, MBBS, FRACS, FAOA, from Sydney Knee Specialists, sought to answer that question.

    First, what is TXA? A synthetic amino acid marketed by Pfizer as Cyklokapron, TXA is an anti-fibrinolytic agent that:

    • Saturates the lysine binding sites of plasminogen
    • Inhibits plasminogen from binding to fibrin

    So TXA does not act in a “pro-thrombotic” way, but instead inhibits the breakdown of clots.

    IV Injections of TXA

    The current recommended dosing is 3 IV injections of 15mg/kg, as follows:

    • The first dosage is given prior to release of the tourniquet – within 5 minutes, or in a hip replacement within about 10 minutes of making the incision.
    • Two bolus injections are given at 8 and 16 hours after the initial dose.

    Not much is known about the timing of these injections, and Dr. MacDessi said that all papers on IV TXA have used different timing ratios: anywhere from a second dose within 2 hours (the half-life of TXA is 1.6 to 1.8 hours) to up to 8 hours, which is the current recommendation.

    Yang et al [1] did a systematic review of the literature that included 15 randomized controlled trials with a total of 837 patients. They found a decrease in weighted mean blood loss of -540mL when compared with placebo. They also found a weighted mean difference in transfusions of -1.43 units, and they found no increased risk of venous thromboembolism (VTE).

    This study, Dr. MacDessi concluded, demonstrates that it makes sense to use TXA in TKA.

    Of course, the use of an additional agent can have an economic impact. A study of 1,018 patients, 580 of whom received TXA, by Gillette et al [2] examined the mean direct hospital costs, including OR cost of using TXA, pathology cost, and pharmacy cost. For the TXA patients, the cost was $15,099, versus $15,978 for non-TXA patients, a saving of $879 for patients receiving TXA. This was statistically significant (P < 0.002).

    Intra-articular Use of TXA

    Dr. MacDessi said intra-articular use of TXA is an attractive option because it:

    • Targets blood loss locally and leads to less systemic absorption
    • Is a simple one-dose administration at time of surgery
    • Requires less nursing time for administration

    A systematic review of intra-articular TXA by Panteli et al [3] found the following:

    • Mean reduction in drain loss of -268mL
    • Mean reduction in hemoglobin drop of -0.94g/dL
    • Lower risk of transfusion with a Relative Ratio of 0.47
    • No increase in VTE

    Subgroup analysis showed that > 2g TXA significantly reduced transfusion requirements.

    The authors noted that not all the reviewed studies were Level 1, but instead were a combination of retrospective and prospective studies. The systematic review, however, showed a theme of potential benefits of intra articular TXA.

    Dose-dependent Study

    Dr. MacDessi also presented the results of his own TXA study, in which he compared the dose-dependent effects of intra-articular TXA on bleeding in TKA [4]. The purpose of the study was to observe the effect of varying dosages of intra-articular TXA on blood loss in TKA.

    The study was a prospective, non-randomized cohort of cases performed between June 2010 and April 2012. Only primary unilateral knee arthroplasties for osteoarthritis were included. All surgeries were performed at 1 institution by 2 surgeons with identical surgical technique. Excluded from the study were patients with:

    • Hematologic or thromboembolic diseases
    • Perioperative anticoagulation treatment
    • Concurrent hardware removal or extensive synovectomy
    • Lateral patellar retinacular release

    TXA administration occurred in a consecutive fashion, with the patients being divided into 3 groups:

    • Control group: first through 54th patients
    • 1,500mg TXA: next 56 patients
    • 3,000mg TXA: next 56 patients

    In all, 193 unilateral TKA were assessed for suitability. The researchers excluded 27 patients, leaving 166 patients in the study.

    The technique used in the study included the following:

    • No drains were used.
    • A tourniquet was used only for the initial surgical exposure of the knee joint
    • After the athrotomy was closed, TXA was injected into the joint space through a bactericidal filter and a 16-gauge epidural catheter.

    Analyzing the results, Dr. MacDessi found:

    • There was a statistically significant difference in hemoglobin among the 3 groups, getting stronger as the dosage increased.
    • Blood loss was reduced by 16% per 1,500mg of TXA administered, indicating a linear behavior.
    • The transfusion rate went down as the TXA dose increased.
    • There was only one DVT event in each group.
    • One patient in the 3,000mg of TXA group developed a pulmonary embolism.

    Dr. MacDessi said the results of the study had several limiting factors:

    • Non-randomized study
    • No routine scanning for deep vein thrombosis or pulmonary embolism
    • Serum TXA levels not measure

    In Dr. MacDessi’s study, intra-articular administration of 3,000 mg of TXA into the joint reduced blood loss by 32%, as well as reduced transfusion requirements.

    As a result Dr. MacDessi has stopped routine hemoglobin measurement on postoperative day 2. He has also found a remarkable decrease in swelling and bruising postoperatively, despite not using a drain.

    Dr. MacDessi’s presentation can be found here.

    References

    1. Effectiveness and Safety of Tranexamic Acid in Reducing Blood Loss in Total Knee Arthroplasty: A Meta-Analysis. Zhi-Gao Yang, MD, Wei-Ping Chen, MD, and Li-Dong Wu, PhD, MD. J Bone Joint Surg Am. 2012;94:1153-9
    2. Economic Impact of Tranexamic Acid in Healthy Patients Undergoing Primary Total Hip and Knee Arthroplasty. Blake P. Gillette, MD, Hilal Maradit Kremers, MD, MSc, Christopher M. Duncan, MD, Hugh M. Smith, PhD, Robert T. Trousdale, MD, Mark W. Pagnano, MD, Rafael J. Sierra, MD. The Journal of Arthroplasty 28 Suppl. 1 (2013) 137–139
    3. Topical tranexamic acid in total knee replacement: a systematic review and meta-analysis. Panteli M1, Papakostidis C, Dahabreh Z, Giannoudis PV. Knee. 2013 Oct;20(5):300-9. doi: 10.1016/j.knee.2013.05.014
    4. Dose-Dependent Effects of Intra-Articular Injection of Tranexamic Acid on Bleeding in Total Knee Arthroplasty. Samuel MacDessi and Darren Chen, Bob Jang, Martin T. Bohm, Ian Harris. Bone Joint J 2013 95-B:(SUPP 15) 34.