TXA and Shoulder Arthroplasty - what we wish we knew

For shoulder surgeons it's not so much about reducing total blood loss (which is usually <400cc and rarely requires transfusion) but rather it's about minimizing hematoma/brusing/swelling - especially when it is a priority to get the shoulder moving soon after arthroplasty, such as in anatomic arthroplasty for a preoperatively stiff shoulder.

Tranexamic acid (TXA) is a synthetic lysine derivative that competitively inhibits plasminogen activation, preventing its conversion to plasmin, and stabilizing fibrin clots; this is its anti-fibrinolytic effect. It can be administered intravenously, topically, or orally.

Much of what we have learned about TXA comes from hip and knee arthroplasty. Here's a summary of what can be pulled from that literature: 

1. Interestingly, more is not better - low dose IV TXA (total of 1 or 2 grams) is as effective as higher doses. 

2. Pre-incision administration is more effective than post incision administration.

3. A common protocol is1 gram pre-incision and 1 gram at closure. A protocol of 2 grams IV at incision plus 2 grams IV at closure (total 4 grams) is NOT standard and exceeds what most studies have investigated. 

4. The 2021 TRAC-24 Trial revealed that in addition to intraoperative IV TXA,  postoperative oral TXA reduced blood loss in total knee arthroplasty as well as reduced length of stay, lower readmission rates, ER visits and need for transfusion.

5. A 2024 randomized controlled trial showed that for total knees, 1 gram IV before and at closure plus1.95 grams orally daily on post operative days 1, 2 and 3 resulted in improved motion, less pain and better functional scores at 2 and 6 weeks in comparison to those receiving only the IV perioperative TXA. The authors suggested that the benefit resulted from an anti-inflamatory effect rather than diminished blood loss. This postoperative regimen significantly reduced CRP and IL-6 levels in TKA patients

Tranexamic acid attenuates inflammatory effect and modulates immune response in primary total knee arthroplasty: a randomized, placebo-controlled, pilot trial

The antifibrinolytic and anti‐inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial

Anti-inflammatory effect of multi-dose tranexamic acid in hip and knee arthroplasty: a systematic review and meta-analysis of randomized controlled trials

 

Safety Considerations

1. The 2018 guidelines provide STRONG evidence that TXA administration (IV, topical, and oral) does not increase the risk of venous thromboembolism in patients without known history of VTE. Direct meta-analysis of 77 high-quality and 1 moderate-quality randomized clinical trials (92% of which excluded patients with history of thromboembolic events) demonstrated no significant difference in VTE rates between TXA and placebo.

2. For high-risk patients - those with a history of VTE, myocardial infarction, cerebrovascular accident, or vascular stent placement - the guidelines provide only MODERATE support that TXA does not increase thromboembolic risk.

Extrapolating the hip and knee evidence to shoulder arthroplasty, a reasonable approach to the use of TXA in shoulder arthroplasty may be:

(1) One gram IV at the time of incision and one gram at closure (alternative: two grams IV at incision).

(2) For patients with a history of prior VTE, myocardial infarction, cerebrovascular accident, or vascular stent placement, avoid IV TXA and, after the wound has been irrigated, topically administer 2 grams TXA in 50 mL normal saline and close the wound without further irrigation.

(3) Consider oral tranexamic acid: three 650mg tablets once daily on postoperative days 1, 2, and 3 in an attempt to reduce postoperative brusing, improve motion, reduce pain and improve function. Check with patient's insurance company to be sure it is covered for this use.

Staying on top of the situation

Nesting Grebe

Montlake Fill

2024

REFERENCES

1. Fillingham YA, Ramkumar DB, Jevsevar DS, Yates AJ, Bini SA, Clarke HD, Schemitsch E, Johnson RL, Memtsoudis SG, Sayeed SA, Sah AP, Della Valle CJ. Tranexamic Acid Use in Total Joint Arthroplasty: The Clinical Practice Guidelines Endorsed by the American Association of Hip and Knee Surgeons, American Society of Regional Anesthesia and Pain Medicine, American Academy of Orthopaedic Surgeons, Hip Society, and Knee Society. J Arthroplasty. 2018 Oct;33(10):3065-3069.

2. Fillingham YA, Ramkumar DB, Jevsevar DS, Yates AJ, Shores P, Mullen K, Bini SA, Clarke HD, Schemitsch E, Johnson RL, Memtsoudis SG, Sayeed SA, Sah AP, Della Valle CJ. The Efficacy of Tranexamic Acid in Total Hip Arthroplasty: A Network Meta-Analysis. J Arthroplasty. 2018;33(10):3083-3089.

3. Fillingham YA, Ramkumar DB, Jevsevar DS, Yates AJ, Shores P, Mullen K, Bini SA, Clarke HD, Schemitsch E, Johnson RL, Memtsoudis SG, Sayeed SA, Sah AP, Della Valle CJ. The Efficacy of Tranexamic Acid in Total Knee Arthroplasty: A Network Meta-Analysis. J Arthroplasty. 2018;33(10):3090-3098.

4. Magill P, Hill JC, Bryce L, Martin U, Dorman A, Hogg R, Campbell C, Gardner E, McFarland M, Bell J, Benson G, Beverland D. Oral tranexamic acid for an additional 24 hours postoperatively versus a single preoperative intravenous dose for reducing blood loss in total knee arthroplasty: results of a randomized controlled trial (TRAC-24). Bone Joint J. 2021 Oct;103-B(10):1595-1603.

5. Magill P, Hill JC, Bryce L, Martin U, Dorman A, Hogg R, Campbell C, Gardner E, McFarland M, Bell J, Benson G, Beverland D. Oral tranexamic acid for an additional 24 hours postoperatively versus a single preoperative intravenous dose for reducing blood loss in total hip arthroplasty: results of a randomized controlled trial (TRAC-24). Bone Joint J. 2021 Jul;103-B(7):1197-1205.

6. Karayiannis PN, Agus A, Bryce L, Hill JC, Beverland D. Using tranexamic acid for an additional 24 hours postoperatively in hip and knee arthroplasty saves money: a cost analysis from the TRAC-24 randomized control trial. Bone Jt Open. 2022 Jul;3(7):536-542.

7. Mihalko WM, Brimmo O, Siddiqi A, Mannava S, Kremers HM, Sierra RJ. The AAHKS Clinical Research Award: Extended Postoperative Oral Tranexamic Acid in Total Knee Arthroplasty: A Randomized Controlled Pilot Study. J Arthroplasty. 2024 Sep;39(9S):S2-S8.

8. Yuenyongviwat V, Dissaneewate K, Iamthanaporn K. Efficacy of Extended Oral Tranexamic Acid on Blood Loss in Primary Total Knee Arthroplasty. Acta Ortop Bras. 2022 Jul-Aug;30(4):e245411.

9. Lloyd TD, Deakin AH, Gregg-Smith SJ, Melling L, Dall GF, Yates P, Hui ACW, et al. Perioperative administration of tranexamic acid in lower limb arthroplasty: a multicentre, prospective cohort study. Anaesthesia. 2020 Aug;75(8):1050-1058.

10. Grosso MJ, Boddapati V, Cooper HJ, Geller JA, Shah RP, Neuwirth AL, Rubin LE. One Dose Versus Two Doses of Intravenous Tranexamic Acid in Total Joint Arthroplasty. J Bone Joint Surg Am. 2021 Jun 2;103(11):e45.

11. Box HN, Tisano BS, Khazzam M. Tranexamic acid administration for anatomic and reverse total shoulder arthroplasty: a systematic review and meta-analysis. JSES Open Access. 2018 Feb 15;2(1):28-33.

12. Kirsch JM, Bedi A, Horner N, Wiater JM, Pauzenberger L, Koueiter DM, Miller BS, Bhandari M, Khan M. Tranexamic Acid in Shoulder Arthroplasty: A Systematic Review and Meta-Analysis. JBJS Rev. 2017 Sep;5(9):e3.

13. Friedman RJ, Gordon E, Butler RB, Mock L, Dumas B. Tranexamic acid decreases blood loss after total shoulder arthroplasty. J Shoulder Elbow Surg. 2016 Apr;25(4):614-8.

14. Pauzenberger L, Domej MA, Heuberer PR, Hexel M, Grieb A, Laky B, Blasl J, Anderl W. A single dose of tranexamic acid reduces blood loss after reverse and anatomic shoulder arthroplasty: a randomized controlled trial. J Shoulder Elbow Surg. 2021 Mar;30(3):e55-e67.

15. Sun C, Zhang X, Ma J, Jiang C, Xia Y, Xiong Y, Pan Z. Oral and intravenous tranexamic acid are equivalent at reducing blood loss following shoulder arthroplasty: A multicenter, double-blinded, randomized, placebo-controlled trial. J Shoulder Elbow Surg. 2022 May;31(5):907-915.

16. Abildgaard JT, McLemore R, Hattrup SJ. Tranexamic acid decreases blood loss in total shoulder arthroplasty and reverse total shoulder arthroplasty. J Shoulder Elbow Surg. 2016 Oct;25(10):1643-8.

17. Koutserimpas C, Chamakos E, Raptis K, Samoladas E. Tranexamic Acid in Shoulder Arthroplasty. A Comprehensive Review. Acta Biomed. 2021 Jun 7;92(3):e2021213.

18. StatPearls. Tranexamic Acid. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532909/

19. Hill J, Magill P, Dorman A, et al. Assessment of the effect of addition of 24 hours of oral tranexamic acid post-operatively to a single intraoperative intravenous dose of tranexamic acid on calculated blood loss following primary hip and knee arthroplasty (TRAC-24): a study protocol for a randomised controlled trial. Trials. 2018 Jul 31;19(1):422.

20. Jones AM, Greenwood R, Bochert M, Gibbons M. Effectiveness of oral versus intravenous tranexamic acid in primary total hip and knee arthroplasty: a randomised, non-inferiority trial. Br J Anaesth. 2023 Feb;130(2):234-242.

21. Budge M, et al. Topical and Intravenous Tranexamic Acid Are Equivalent in Decreasing Blood Loss in Total Shoulder Arthroplasty. J Shoulder Elbow Surg 2019.

Follow on twitter/X: https://x.com/RickMatsen
Follow on facebook: https://www.facebook.com/shoulder.arthritis
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Here are some videos that are of shoulder interest
Shoulder arthritis - what you need to know (see this link).
How to x-ray the shoulder (see this link).
The ream and run procedure (see this link)
The total shoulder arthroplasty (see this link)
The cuff tear arthropathy arthroplasty (see this link).
The reverse total shoulder arthroplasty (see this link).
The smooth and move procedure for irreparable rotator cuff tears (see this link)
Shoulder rehabilitation exercises (see this link).

What information can be gathered from a synovial fluid aspirate?

Synovial fluid aspiration is often used to gather information about a possible periprosthetic infection. 

When a sufficient volume is recovered, laboratory tests may help surgeons evaluate the likelihood of a periprosthetic infection; however the aspiration attempt may not yield fluid even if it is image guided. To be clinically useful, the aspiration needs to be carried out several weeks in advance of a potential surgical revision to allow sufficient time for laboratory tests and culture results to be finalized.

The authors of Synovial Fluid Cutibacterium acnes Antigen Is Detected Among Shoulder Samples with High Inflammation and Early Culture Growth presented a three pronged analysis of 1,365 de-identified synovial fluid samples, of which 1,150 were culture-negative and 215 were culture-positive.  94 of the culture positive samples were positive for Cutibacterium and 121 for other organisms.

The samples were analyzed by (1) time to culture positivity (known to be a reflection of the load of bacteria in the sample), (2) a validated  C. acnes antigen immunoassay test, and (3) a synovial fluid inflammation score calculated from 4 tests on synovial fluid: C reactive protein,  alpha-defensin, WBC count and percent polymorphonuclear cells.  

They found that 

(1) The samples tended to cluster into high inflammation and low inflammation groups for both all specimens

and for those in specimens that were culture positive for Cutibacterium

(2) C. acnes antigen levels demonstrated moderate-strong positive correlation with inflammation, with 166-fold higher levels of C. acnes antigen in high-inflammation samples compared with low-inflammation samples. 

(3) The days to C. acnes culture positivity demonstrated weak- inverse correlation with inflammation, with 1.5-fold earlier growth among the 67 high- inflammation samples compared to the low inflammation samples. Because a positive culture depends on discernible colonies on the culture plate and because the threshold for discernability relates to the number of bacteria present, low loads of bacteria in the sample are expected to have longer time to culture positivity. 

The relationship between C acnes antigen levels (left) and days to culture positivity (right) for samples with low inflammation and high inflammation is shown below.

(4) 19.0% of high-inflammation, culture-negative fluid samples demonstrated elevated C. acnes antigen.  Elevated C. acnes antigen was observed in only 0.38% of the low-inflammation culture-negative fluid samples and in only 4.9% of the high-inflammation non-C. acnes-positive cultures. 

Here it is of note that synovial fluid cultures are not uncommonly culture negative when tissue and explant cultures are positive. This may be because there may be Cutibacterium in biofilm form in tissue but not in planktonic (free floating) form in fluid. Thus these shoulders may not have been culture negative if tissue and explant cultures had been available. Absence of evidence is not evidence of absence.

Comment: One way to put these findings together is that low loads of Cutibacterium (as indicated by longer times before cultures become positive and by low antigen levels) may be insufficient to cause a tissue damaging inflammatory response on the part of the host. If one uses the definition of infection as "bacteria doing harm", these shoulders may not meet that definition, even though there are bacteria present. On the other hand, high loads of bacteria are likely to have shorter time to culture positivity, higher antigen levels and more inflammation.

You can support cutting edge shoulder research that is leading to better care for patients with shoulder problems, click on this link

Follow on twitter/X: https://x.com/RickMatsen
Follow on facebook: https://www.facebook.com/shoulder.arthritis
Follow on LinkedIn: https://www.linkedin.com/in/rick-matsen-88b1a8133/


Here are some videos that are of shoulder interest
Shoulder arthritis - what you need to know (see this link).
How to x-ray the shoulder (see this link).
The ream and run procedure (see this link).
The total shoulder arthroplasty (see this link).
The cuff tear arthropathy arthroplasty (see this link).
The reverse total shoulder arthroplasty (see this link).
The smooth and move procedure for irreparable rotator cuff tears (see this link).
Shoulder rehabilitation exercises (see this link). 

Rotator cuff tears - does inflammation account for the pain?

Association of synovial inflammation and inflammatory mediators with glenohumeral rotator cuff pathology

These authors point out that chronic inflammation has recently been recognized as a source of joint pain and dysfunction in those with pathologies previously considered purely degenerative. They hypothesized that patients with full-thickness rotator cuff tears would have greater synovial inflammation compared with those without rotator cuff tear pathology, with gene expression relating to histologic findings.

Synovial sampling was obtained from a common site within the rotator interval after anterior portal establishment in 19 patients with full thickness rotator cuff tears (RTC group) and in 11 patients without rotator cuff pathology (control group).

The synovitis score was significantly increased in the RTC group compared with controls. Immunofluorescence demonstrated significantly increased staining for CD31, CD45, and CD68 in the RTC vs control group. CD45+/68– cells were found perivascularly, with CD45+/68+ cells toward the joint lining edge of the synovium. Levels of matrix metalloproteinase-3 (MMP-3) and interleukin-6 were significantly increased in the RTC group, with a positive correlation between the synovitis score and MMP-3 expression. No correlation was found between the synovitis score and tear size or Goutallier classification nor between MMP-3 levels and AP tear size, amount of retraction, or Goutallier classification for those with cuff tears.

The authors concluded that shoulders with full-thickness rotator cuff tears had greater levels of synovial inflammation, angiogenesis, and MMP-3 upregulation compared with controls. Gene expression of MMP-3 correlated with the degree of synovitis.

Comment: These results indicate an association between synovial inflammation and cuff tears; they do not indicate whether synovial inflammation contributes to the development of cuff tears or vice versa. Nevertheless, this association may help understand the effectiveness of anti-inflammatory medications in the management of symptoms from rotator cuff pathology. It may also help explain the mechanism by which the smooth and move procedure (which includes the excision of inflammatory tissue in the humeroscapular motion interface) leads to improved comfort and function of shoulders with cuff tears, even though the tear itself is irreparable.

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Consultation for those who live a distance away from Seattle.

Check out the new Shoulder Arthritis Book - click here.

Click here to see the new Rotator Cuff Book

Use the "Search" box to the right to find other topics of interest to you.

You may be interested in some of our most visited web pages including:shoulder arthritis, total shoulder, ream and run, reverse total shoulder, CTA arthroplasty, and rotator cuff surgery as well as the 'ream and run essentials'

See from which cities our patients come.

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Shoulder arthritis and rotator cuff articles from Sept issue of the Journal of Shoulder and Elbow Surgery

In the September issue of JSES a number of interesting articles appear.
Shidle et al sought evidence of inflammatory markers in tissue samples from shoulders with rotator cuff tears. They found that the amount of inflammation correlates with tear size and was greater in full thickness than in partial thickness tears. This finding of inflammation may help explain the achy pain at rest experienced by patients with full thickness cuff years as well as the relief of symptoms from anti-inflammatory medications as well as from a 'smooth and move' procedure that removes the inflamed bursal tissue, even if the cuff tear itself is not repaired.


Gulotta et al considered the prognostic factors for clinical and ultrasound determination of cuff integrity at five years after rotator cuff repair surgery. As Harryman et al demonstrared 20 years ago in a very similar study, larger tears in older patients are likely to fail to heal after repair. In fact, the risk of healing failure increased over five times when the tear involved more than one tendon. However, as Harryman et al pointed out previously, many patients were clinically improved even though the repair failed. These results suggest that an option for treating large tears in older patients may be the 'smooth and move' procedure, sparing the patient from the need to protect an attempted repair after surgery, especially if the prognosis for healing is unfavorable. This study points out that a 'successful' rotator cuff surgery needs to be carefully defined in clinical research: does 'success' refer to healing of the tendon verified by cuff tendon imaging or by improvement in the comfort and function of the shoulder?

Finally, Warrender et al reported that in patients having rotator cuff repair, obesity was associated with worse functional outcomes, longer operative times and longer hospital stays.

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Use the "Search the Blog" box to the right to find other topics of interest to you.

You may be interested in some of our most visited web pages including:shoulder arthritis, total shoulder, ream and run, reverse total shoulder, CTA arthroplasty,  and rotator cuff surgery.

See the countries from which our readers come on this post.

Shoulder: arthritic or frozen?

There are three common conditions of the shoulder that are often confused: rotator cuff tear, shoulder arthritis and frozen shoulder. Shoulder stiffness is a common symptom of each of them. Shoulder stiffness is diagnosed as shown here.

A detailed discussion of rotator cuff problems can be found here.

A detailed discussion of shoulder arthritis can be found here. The reasons for stiffness in arthritis are shown here. The photo below shows an arthritic humeral head as seen at surgery.

A frozen shoulder is, like shoulder arthritis, one of the conditions that can result in a stiff shoulder. The difference is that in a frozen shoulder, the joint surfaces are normal and the shoulder motion is limited because the tissue around the joint - the joint capsule - has tightened down. Frozen shoulders are thought to arise from inflammation within the joint. Frozen shoulders can be particularly problematic in individuals with diabetes. It was once believed that frozen shoulder was associated with personality disorders, but recent evidence does not support this contention. We diagnose a frozen shoulder when the shoulder has limited motion, without a history of prior injury or surgery and with AP and Axillary x-rays showing a normal joint space as diagrammed below.



Frozen shoulders usually respond to home exercises.

Our basic approach to rehabilitation of a frozen shoulder is shown in the post on stretching (see this link) and in the post on strengthening (see this link)

If this is not successful, consideration can be given to a gentle manipulation under full muscle relaxation and anesthesia. If this is not successful an arthroscopic or open surgical release of the tight capsule can be considered.

You can support cutting edge shoulder research that is leading to better care for patients with shoulder problems, click on this link.

Follow on twitter: https://twitter.com/shoulderarth

Follow on facebook: click on this link

Follow on facebook: https://www.facebook.com/frederick.matsen

Follow on LinkedIn: https://www.linkedin.com/in/rick-matsen-88b1a8133/

Here are some videos that are of shoulder interest

Shoulder arthritis - what you need to know (see this link).

How to x-ray the shoulder (see this link).

The ream and run procedure (see this link).

The total shoulder arthroplasty (see this link).

The cuff tear arthropathy arthroplasty (see this link).

The reverse total shoulder arthroplasty (see this link).

The smooth and move procedure for irreparable rotator cuff tears (see this link).

Shoulder rehabilitation exercises (see this link).