The Use of Tranexamic Acid in Anterior Cruciate Ligament Reconstruction: A Systematic Review

Round 1

Reviewer 1 Report

Applied Sciences, Review of The use of tranexamic acid in anterior cruciate ligament reconstruction decreases postoperatives bleeding and pain levels: a systematic review

 

This is an interesting, well written, short review of a limited amount of information. I only have a limited number of comments that could potentially improve the manuscript in a short revision. There are only a few randomised clinical trials on tranexamic acid (TXA) use in ACL reconstruction, most have been published in the last 7 years. In general positive findings have been reported for this procedure. Further studies are still warranted to optimise the procedure and identify suitable candidates for TXA administration in ACL reconstruction. Functional aspects of the material properties of the repaired ACL tissue also need to be standardised to demonstrate how effective the healing process has been. Two studies the authors need to include in their study are :-

1. Goldstein K, Jones C, Kay J, Shin J, de Sa D. Tranexamic Acid Administration in Arthroscopic Surgery Is a Safe Adjunct to Decrease Postoperative Pain and Swelling: A Systematic Review and Meta-Analysis. Arthroscopy. 2021 Oct 14:S0749-8063(21)00891-4.
2. Kalina R, Fidler E, Béreš M, Zeman P, Sigmund M, Gallo J. Efekt jednorázového podání kyseliny tranexamové při rekonstrukci předního zkříženého vazu hamstringy: randomizovaná klinická studie [Effect of a Single Dose of Tranexamic Acid Administered during Anterior Cruciate Ligament Reconstruction Using Hamstrings: a Randomized Clinical Study]. Acta Chir Orthop Traumatol Cech. 2021;88(3):184-190.

 

The structural formula for tranexamic acid should be included in the revision.

 

The ACL stabilises the knee-joint, a major multidirectional weight bearing articulatory structure. Anteriomedial and posteriolateral ACL bundles resist anterior tibial translation providing rotational stability but are frequently injured during high impact sporting activities. Ruptured ACLs do not spontaneously heal and are common in the US with over 100,000 tears occurring annually. Establishment of normal kinematics and stabilisation are important in the injured knee, since an unstable knee may develop premature OA.The ACL exists in a hostile weighted environment, torsional knee movement and tangential synovial fluid flow prevent initial fibrin clot formation which normally stabilises the defect site early in wound repair. Although diverging from the central issue of the efficacy of TXA for the promotion of ACL repair processes and may be deemed by the authors to fall outwith the major aim of their study an issue the authors might have also discussed is the hostile ACL repair environment and ACL stabilization and how these effect ACL repair. An ACL rupture model in rats has shown that if knee kinematics and tibial translation are controlled spontaneous ACL repair and recovery of 50% of the ACL biomechanical properties occurred in an 8 week recovery period [Kokobun et al 2016]. Rapid repair would also minimize blood loss and alleviate pain. Biological interventions with growth factors are also of promise and may further improve such procedures.

 

Kokubun, T., Kanemura, N, Murata, K, Moriyama, H, Morita, S, Jinno, T, Ihara, H, Takayanagi, K. , Effect of Changing the Joint Kinematics of Knees With a Ruptured Anterior Cruciate Ligament on the Molecular Biological Responses and Spontaneous Healing in a Rat Model. Am J Sports Med 2016, 44, 2900-2910.

 

 

Author Response

Dear reviewers and editor,

Attached you will find the response with the changes we have made answering the issues of the 1st reviewer.

Author Response File: Author Response.pdf

Reviewer 2 Report

Thank you for permitting me to review this manuscript 

 

The title is suggestive that Tranexamic acid decrease blood loss and pain , however in the end it appears that only 6 paper assessed this issue I think the title should change according to real findings as the authors state themselves that this issue need more long term outcomes to be studied and especially it needs more focus on side effects which indeed can appear in the long term results. 

It appears that in half of the studies the method of injection is different IA versus IV , therefore in my point of view evidence is not enough to proceed with one type or another type of administration this should clearly highlighted and conclusion should really be balanced. 

Line 141.

The difference significantly reported in drain output might not be clinically relevant they can only be relevant if drainage is not installed  

the amount of bleeding should be discussed. 

 

Line 241  please rephraze as it sounds inconsistant (lack of heterogenity of AT administration 

 

Please report more data on postoperative pain evaluation especially if  this assessement were dynamic or static or both of them , which kind of postoperative analgesic technique was used? , we know that if regional anesthesia is used it is far more superior than miltimodal IV regimen only this should be rechecked and compared and reported.

Author Response

Dear reviewers and editor,

Attached you will find the response to Reviewer number 2's observations.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

The authors have improved the manuscript and made all changes requested