Tranexamic acid utilization remains low in anatomical and reverse total shoulder arthroplasty despite decreased postoperative complications: A propensity-matched analysis

Abstract

Background

This study investigated the effect of tranexamic acid (TXA) on postoperative outcomes in anatomic total shoulder (aTSA) or reverse total shoulder arthroplasty (rTSA) surgery.

Methods

We queried the TriNetX network for patients who underwent TSA from 2000 to 2025. Patients were 1:1 matched into aTSA or rTSA cohorts and subcategorized into TXA or non-TXA groups. Yearly trends in TXA utilization by TSA procedure were reported. Postoperative complications at 90 days and 2 years were assessed.

Results

TXA utilization increased 7% in aTSA and 11% in rTSA from 2020 to 2024. Within 90 days, TXA patients in both cohorts had a reduced risk of transfusions, acute post-hemorrhagic anemia, and hospital readmission. TXA patients in the aTSA cohort had a reduced risk of pulmonary embolism within 90 days. At 2 years, TXA patients in both cohorts had a reduced risk of transfusions, surgical site infection, pulmonary embolism, and hospital readmission. TXA patients in the rTSA cohort had a higher risk of periprosthetic loosening at both follow-ups.

Discussion

Patients receiving TXA had a significantly reduced risk of postoperative complications. TXA has a similar impact on outcomes in both TSA variations, and utilization should be considered as part of a comprehensive management strategy.

Keywords

Perioperative interventions postoperative outcomes shoulder replacement arthroplasty total shoulder replacement tranexamic acid

Introduction

Total shoulder arthroplasty (TSA) is an orthopaedic procedure that has continued to steadily increase in prevalence in the United States over the past 3 decades.^1–3 Within the two main variants of TSA, anatomic total shoulder arthroplasty (aTSA) has been mainly indicated for patients with primary osteoarthritis with a healthy rotator cuff, whereas reverse total shoulder arthroplasty (rTSA) has been reserved for patients with rotator cuff arthropathy.^4,5 However, the indications for rTSA have broadened, as it is now also used to treat patients who would have traditionally been treated with an aTSA, leading to increased rTSA adoption.^6–10 Therefore, there is a considerable need to evaluate how procedural variations influence postoperative outcomes.

Tranexamic acid (TXA) is a synthetic derivative of the amino acid lysine and acts as an anti-fibrinolytic agent by competitively inhibiting the conversion of plasminogen into plasmin.^11–13 Due to the well-characterized complication of intraoperative blood loss during joint replacement procedures and subsequent need for transfusions, TXA has become a popular pharmacologic agent to minimize blood loss and the rate of postoperative transfusions in arthroplasty.^14,15 Although TXA is well-studied in total hip arthroplasty (THA) and total knee arthroplasty (TKA), its role in TSA is less clearly defined.^16–20 The risk of blood loss in TSA is less than in lower extremity arthroplasty, but transfusion rates in TSA have been reported to range from 4.5% to 43%, with patients undergoing rTSA having an even higher risk of transfusions and developing hematomas.^6,21–26

Although prior research has established TXA as an effective pharmacological agent in TSA for reducing postoperative issues, the literature on the association between TXA and operative outcomes in TSA is still very limited. The scope of analysis in most of these studies was limited to hematological issues, including changes in blood loss, hemoglobin, and hematocrit, and none assessed the risks related to the prosthesis or surgery itself.^17,18,27,28 As the use of TXA continues to grow in shoulder arthroplasty, it is imperative to further investigate its broader clinical impact, particularly across the aTSA and rTSA populations.^29–32

The objective of this study was to investigate the utilization of TXA and the association of TXA administration with postoperative medical, surgical, and prosthetic complications following aTSA and rTSA. We hypothesized that TXA use would be associated with a lower risk of complications in both procedure types.

Methods

For this retrospective cohort study, we queried the TriNetX Research Network (Cambridge, Massachusetts, USA), a database that contains de-identified electronic health records and clinical data such as demographics, diagnoses (International Classification of Diseases, 10th Revision [ICD-10] codes), procedures (Current Procedural Terminology [CPT] codes), and medications of over 100 million patients across more than 50 healthcare organizations. The de-identification of the data is consistent with the Health Insurance Portability and Accountability Act Privacy Rule, and all data is reported as aggregate counts and statistical summaries to protect patients’ privacy and sensitive information. Due to the use of solely de-identified information in this study, it was exempt from Institutional Review Board approval.

The TriNetX database was queried on June 21, 2025 using CPT and ICD-10 codes for patients 18 years or older who underwent either an aTSA or rTSA from January 1, 2000 to January 1, 2025. Cohort 1 was defined as patients undergoing an aTSA, and Cohort 2 was defined as patients undergoing an rTSA. Both cohorts were then subcategorized into two groups as follows: (1) patients who were administered TXA within 24 h prior to their TSA procedure and (2) patients who were not administered TXA. Further information on cohort construction is available in Appendix 1.

Both cohorts were then matched 1:1 based on patient demographics (age, gender, ethnicity, race), existing comorbidities, and the use of antithrombotic medications using a propensity-score matching method, which is a statistical technique that aims to minimize the confounding bias by balancing the population in each cohort using logistic regression. Characteristics for propensity-matching were chosen based on their ability to influence outcomes of interest.^2,25,33 Comorbidities were identified using the Elixhauser Comorbidity Index.³⁴ Statistical significance was defined as a two-tailed alpha value < 0.05.

This study analyzed the complications at the 90-day and 2-year follow-up points to investigate short- and long-term outcomes. Chi-square analysis was performed to determine the risk of surgical and prosthetic complications, including surgical site infections (SSI), wound dehiscence, prosthetic dislocation, prosthetic loosening, prosthetic fracture, and prosthetic joint infections (PJI), and medical complications including myocardial infarction (MI), pulmonary embolism (PE), deep vein thrombosis (DVT), hematoma, transfusions, shoulder stiffness, and hospital readmission. Additionally, rates of revision surgery were assessed at the 2-year mark. The index event, defined as the point at which analysis started for each patient, was the date of the aTSA or rTSA procedure. The outcomes between the two cohorts were reported through risk ratios (RR) and 95% confidence intervals (95% CI), using t tests and chi-squared tests with an alpha level of 0.05 for analysis. A Bonferroni correction was performed to account for multiple testing.

Before matching, our search results identified a total of 18,977 patients in the aTSA cohort, including 5636 patients in the TXA group (29.7%) and 13,341 patients in the non-TXA group (70.3%). For the rTSA cohort, our search identified 38,119 patients, including 13,963 patients in the TXA group (36.6%) and 24,156 patients in the non-TXA cohort (63.4%). Within both cohorts, the TXA group was significantly more likely to have used tobacco and have a diagnosis of diabetes mellitus, hypertensive diseases, or hypothyroidism (P < 0.001), and more likely to use apixaban, fondaparinux, heparin, or aspirin (P < 0.001) compared to the non-TXA group.

After matching, the aTSA cohort consisted of 5551 patients. There were no significant differences in terms of comorbidities or antithrombotic usage. The mean age was 66 years, and 50% were males. Across both the TXA and non-TXA groups, approximately 52% of patients had hypertensive diseases, 16% had diabetes mellitus, and 14% had hypothyroidism. The rTSA cohort consisted of 13,892 patients. There were also no significant differences in comorbidities or antithrombotic usage. The mean age was 71 years, and 57% were females. In both groups, 63% of patients had hypertensive disease, 23% had diabetes mellitus, and 19% had hypothyroidism. Comprehensive information on patient demographics, comorbidities, and medications before propensity matching is shown in Appendix 2, and characteristics after propensity matching are shown in Tables 1 –4.

Table 1.

Anatomic total shoulder arthroplasty patient demographic characteristics (after match).

	TXA cohort	Non-TXA cohort
Characteristic	N (mean or % of cohort)	N (mean or % of cohort)	P
Age at index	5551 (65.9 ± 9.5)	5551 (65.9 ± 10)	0.860
Sex
Male	2806 (50.5)	2773 (50)	0.531
Female	2584 (46.6)	2631 (47.4)	0.371
Race and ethnicity
White	4486 (80.8)	4477 (80.7)	0.829
Black or African American	354 (6.4)	349 (6.3)	0.846
Hispanic or Latino	139 (2.5)	138 (2.5)	0.951
Not Hispanic or Latino	4551 (82)	4613 (83.1)	0.121
Asian	131 (2.4)	133 (2.4)	0.901
Native Hawaiian or other Pacific Islander	20 (0.4)	18 (0.3)	0.745
American Indian or Alaska Native	10 (0.2)	10 (0.2)	1
Other race	126 (2.3)	125 (2.3)	0.949
Unknown race	425 (7.7)	440 (7.9)	0.595
Unknown ethnicity	861 (15.5)	800 (14.4)	0.105

TXA: tranexamic acid.

Table 2.

Anatomic total shoulder arthroplasty patient comorbidities and medications (after match).

	TXA cohort	Non-TXA cohort
	N (mean or % of cohort)	N (mean or % of cohort)	P
Comorbidity
Tobacco use	162 (2.9)	162 (2.9)	1
Diabetes mellitus	899 (16.2)	842 (15.2)	0.137
Heart failure	281 (5.1)	279 (5)	0.931
Hypertensive diseases	2865 (51.6)	2891 (52.1)	0.621
Chronic rheumatic heart diseases	157 (2.8)	167 (3)	0.573
Other peripheral vascular diseases	198 (3.6)	197 (3.5)	0.959
Other pulmonary heart diseases	121 (2.2)	124 (2.2)	0.846
Other hypothyroidism	765 (13.8)	764 (13.8)	0.978
Viral hepatitis	104 (1.9)	96 (1.7)	0.568
Other diseases of liver	300 (5.4)	290 (5.2)	0.672
HIV	23 (0.4)	29 (0.5)	0.404
Malignant neoplasms of hematopoietic tissue	65 (1.2)	62 (1.1)	0.789
Malignant neoplasms of other unspecified sites	97 (1.7)	92 (1.7)	0.714
Other rheumatoid arthritis	220 (4)	229 (4.1)	0.665
Coagulation defects, purpura and other hemorrhagic conditions	294 (5.3)	299 (5.4)	0.833
Mental and behavioral disorders due to psychoactive substance use	739 (13.3)	752 (13.5)	0.717
Alcohol-related disorders	210 (3.8)	210 (3.8)	1
Psychotic disorders	58 (1)	56 (1)	0.851
Depressive episode	1023 (18.4)	1019 (18.4)	0.922
Medication
Apixaban	191 (3.4)	187 (3.4)	0.834
Dabigatran etexilate	30 (0.5)	32 (0.6)	0.799
Dalteparin	23 (0.4)	31 (0.6)	0.275
Fondaparinux	56 (1)	49 (0.9)	0.492
Warfarin	420 (7.6)	388 (7)	0.242
Heparin	942 (17)	899 (16.2)	0.273
Rivaroxaban	227 (4.1)	222 (4)	0.810
Enoxaparin	766 (13.8)	742 (13.4)	0.506
Aspirin	2078 (37.4)	2051 (36.9)	0.596

TXA: tranexamic acid.

Table 3.

Reverse total shoulder arthroplasty patient demographic characteristics (after match).

	TXA cohort	Non-TXA cohort
Characteristic	N (mean or % of cohort)	N (mean or % of cohort)	P
Age at index	13,892 (70.9 ± 8.8)	13,892 (70.8 ± 9.1)	0.519
Sex
Male	5589 (40.2)	5624 (40.5)	0.669
Female	7899 (56.9)	7925 (57)	0.753
Race and Ethnicity
White	11,485 (82.7)	11,456 (82.5)	0.647
Black or African American	898 (6.5)	897 (6.5)	0.981
Hispanic or Latino	562 (4)	571 (4.1)	0.785
Not Hispanic or Latino	10,754 (77.4)	10,978 (79)	0.001
Asian	166 (1.2)	169 (1.2)	0.869
Native Hawaiian or other Pacific Islander	24 (0.2)	18 (0.1)	0.354
American Indian or Alaska Native	50 (0.4)	50 (0.4)	1
Other race	359 (2.6)	265 (2.6)	0.821
Unknown race	910 (6.6)	937 (6.7)	0.516
Unknown ethnicity	2576 (18.5)	2343 (16.9)	<0.001

TXA: tranexamic acid.

Table 4.

Reverse total shoulder arthroplasty patient comorbidities and medications (after match).

	TXA cohort	Non-TXA cohort
	N (mean or % of cohort)	N (mean or % of cohort)	P
Comorbidity
Tobacco use	436 (3.1)	449 (3.2)	0.657
Diabetes mellitus	3302 (23.8)	3238 (23.3)	0.365
Heart failure	1398 (10.1)	1371 (9.9)	0.589
Hypertensive diseases	8697 (62.6)	8721 (62.8)	0.766
Chronic rheumatic heart diseases	709 (5.1)	691 (5)	0.622
Other peripheral vascular diseases	927 (6.7)	889 (6.4)	0.356
Other pulmonary heart diseases	565 (4.1)	556 (4)	0.784
Other hypothyroidism	2604 (18.7)	2566 (18.5)	0.558
Viral hepatitis	290 (2.1)	284 (2)	0.800
Other diseases of liver	1078 (7.8)	1031 (7.4)	0.287
HIV	36 (0.3)	41 (0.3)	0.568
Malignant neoplasms of hematopoietic tissue	259 (1.9)	251 (1.8)	0.721
Malignant neoplasms of other unspecified sites	392 (2.8)	387 (2.8)	0.856
Other rheumatoid arthritis	924 (6.7)	910 (6.6)	0.735
Coagulation defects, purpura and other hemorrhagic conditions	1046 (7.5)	984 (7.1)	0.153
Mental and behavioral disorders due to psychoactive substance use	2380 (17.1)	2363 (17)	0.774
Alcohol = related disorders	698 (5)	696 (5)	0.956
Psychotic disorders	197 (1.4)	191 (1.4)	0.759
Depressive episode	3429 (24.7)	2408 (24.5)	0.770
Medication
Apixaban	808 (5.8)	787 (5.7)	0.588
Dabigatran etexilate	64 (0.5)	56 (04)	0.464
Dalteparin	105 (0.8)	103 (0.7)	0.889
Fondaparinux	131 (0.9)	107 (0.8)	0.118
Warfarin	1281 (9.2)	1258 (9.1)	0.632
Heparin	3425 (24.7)	3353 (24.1)	0.315
Rivaroxaban	622 (4.5)	612 (4.4)	0.771
Enoxaparin	2771 (19.9)	2742 (19.7)	0.663
Aspirin	6179 (44.5)	6243 (44.9)	0.440

TXA: tranexamic acid.

Results

Anatomic TSA cohort

90-day postoperative complications

Within 90 days following the aTSA procedure, patients who received TXA were significantly less likely to have a transfusion (RR: 0.45; CI: 0.27, 0.75; P = 0.002), PE (RR: 0.61; CI: 0.38, 0.97; P = 0.036), acute post-hemorrhagic anemia (RR: 0.52; CI: 0.41, 0.65; P < 0.001), and hospital readmission (RR: 0.20; CI: 0.10, 0.39; P < 0.001). There were no significant differences between the TXA and non-TXA groups in terms of risk for SSI, prosthetic dislocation, prosthetic loosening, prosthetic fracture, PJI, shoulder stiffness, wound dehiscence, MI, DVT, or hematoma (Table 5).

Table 5.

Anatomic total shoulder arthroplasty complications at 90-day follow-up.

Outcome	TXA (n)	Non-TXA (n)	% of TXA cohort	% of non-TXA cohort	Risk ratio	CI	P
Surgical site infections	19	26	0.34%	0.47%	0.73	(0.41, 1.32)	0.296
Prosthetic dislocation	73	65	1.32%	1.17%	1.12	(0.81, 1.57)	0.493
Prosthetic loosening	27	18	0.49%	0.32%	1.50	(0.83, 2.72)	0.179
Prosthetic fracture	38	33	0.68%	0.59%	1.15	(0.72, 1.83)	0.552
Prosthetic joint infections	86	79	1.55%	1.42%	1.09	(0.80, 1.47)	0.583
Shoulder stiffness	255	242	4.59%	4.36%	1.05	(0.89, 1.25)	0.551
Wound disruption	19	17	0.34%	0.31%	1.12	(0.58, 2.15)	0.738
Transfusion	21	47	0.38%	0.85%	0.45	(0.27, 0.75)	0.002
Myocardial infarction	16	27	0.29%	0.49%	0.59	(0.32, 1.10)	0.093
Pulmonary embolism	28	46	0.50%	0.83%	0.61	(0.38, 0.97)	0.036
Deep vein thrombosis	46	53	0.83%	0.95%	0.87	(0.59, 1.29)	0.48
Post-hemorrhagic anemia	105	203	1.89%	3.66%	0.52	(0.41, 0.65)	<0.001
Hematoma*	0	10	0.00%	0.18%	NA	NA	0.002
Readmission*	10	51	0.18%	0.92%	0.20	(0.10, 0.39)	<0.001

*TriNetX reports data points with ≤10 patients as “NA” to protect de-identified patient information. CI: confidence interval; TXA: tranexamic acid.

2-year postoperative complications

Within 2 years following the aTSA procedure, TXA-receiving patients were significantly less likely to have an SSI (RR: 0.65; CI: 0.46, 0.91; P = 0.011), transfusion (RR: 0.67; CI: 0.50, 0.91; P = 0.009), PE (RR: 0.59; CI: 0.44, 0.79; P < 0.001), and hospital readmission (RR: 0.19; CI: 0.12, 0.31; P < 0.001). There were no significant differences between the two groups in terms of risk for prosthetic dislocation, prosthetic loosening, prosthetic fracture, PJI, shoulder stiffness, MI, DVT, or hematoma. Additionally, the risk of revision was not significantly different between the TXA and non-TXA groups (Table 6).

Table 6.

Anatomic total shoulder arthroplasty complications at 2-year follow-up.

Outcome	TXA (n)	Non-TXA (n)	% of TXA cohort	% of non-TXA cohort	Risk ratio	CI	P
Surgical site infection	55	85	0.99%	1.53%	0.65	(0.46, 0.91)	0.011
Prosthetic dislocation	142	142	2.56%	2.56%	1.00	(0.80, 1.26)	1
Prosthetic loosening	79	67	1.42%	1.21%	1.18	(0.85, 1.63)	0.317
Prosthetic fracture	81	86	1.46%	1.55%	0.94	(0.70, 1.27)	0.697
Prosthetic joint infection	148	152	2.67%	2.74%	0.97	(0.78, 1.22)	0.815
Shoulder stiffness	325	349	5.85%	6.29%	0.93	(0.80, 1.08)	0.34
Transfusion	69	103	1.24%	1.86%	0.67	(0.50, 0.91)	0.009
Myocardial infarction	82	83	1.48%	1.50%	0.99	(0.73, 1.34)	0.937
Pulmonary embolism	71	120	1.28%	2.16%	0.59	(0.44, 0.79)	<0.001
Deep vein thrombosis	118	134	2.13%	2.41%	0.88	(0.69, 1.13)	0.308
Hematoma*	10	10	0.18%	0.18%	1.00	(0.42, 2.40)	1
Readmission	19	100	0.34%	1.80%	0.19	(0.12, 0.31)	<0.001
Revision	94	97	1.69%	1.75%	0.98	(0.74, 1.30)	0.884

CI: confidence interval; TXA: tranexamic acid.

Reverse TSA cohort

90-day postoperative complications

Within 90 days following the rTSA procedure, patients receiving TXA were significantly less likely to have a transfusion (RR: 0.54; CI: 0.45, 0.64; P < 0.001), acute post-hemorrhagic anemia (RR: 0.61; CI: 0.54, 0.67; P < 0.001), and hospital readmission (RR: 0.11; CI: 0.07, 0.16; P < 0.001). However, the TXA group was at an increased risk for prosthetic loosening (RR: 1.36; CI: 1.01, 1.84; P = 0.045). There were no significant differences between the two groups in terms of risk for SSI, prosthetic dislocation, prosthetic fracture, PJI, shoulder stiffness, wound dehiscence, MI, PE, DVT, or hematoma (Table 7).

Table 7.

Reverse total arthroplasty complications at 90-day follow-up.

Outcome	TXA (n)	Non-TXA (n)	% of TXA cohort	% of non-TXA cohort	Risk ratio	CI	P
Surgical site infection	97	106	0.70%	0.76%	0.92	(0.70, 1.20)	0.526
Prosthetic dislocation	328	341	2.36%	2.45%	0.96	(0.83, 1.12)	0.611
Prosthetic loosening	98	72	0.71%	0.52%	1.36	(1.01, 1.84)	0.045
Prosthetic fracture	145	157	1.04%	1.13%	0.92	(0.74, 1.16)	0.487
Prosthetic joint infection	285	323	2.05%	2.33%	0.88	(0.75, 1.03)	0.119
Shoulder stiffness	599	557	4.31%	4.01%	1.08	(0.96, 1.20)	0.207
Wound disruption	63	52	0.45%	0.37%	1.21	(0.84, 1.75)	0.304
Transfusion	173	323	1.25%	2.33%	0.54	(0.45, 0.64)	<0.001
Myocardial infarction	150	130	1.08%	0.94%	1.15	(0.91, 1.46)	0.23
Pulmonary embolism	134	164	0.96%	1.18%	0.82	(0.65, 1.03)	0.081
Deep vein thrombosis	196	207	1.41%	1.49%	0.95	(0.78, 1.15)	0.581
Post-hemorrhagic anemia	512	846	3.69%	6.09%	0.61	(0.54, 0.67)	<0.001
Hematoma	13	11	0.09%	0.08%	1.18	(0.53, 2.64)	0.683
Readmission	26	238	0.19%	1.71%	0.11	(0.07, 0.16)	<0.001

CI: confidence interval; TXA: tranexamic acid.

2-year postoperative complications

Within 2 years following the rTSA procedure, patients receiving TXA were significantly less likely to have an SSI (RR: 0.81; CI: 0.68, 0.96; P = 0.016), transfusion (RR: 0.61; CI: 0.53, 0.70; P < 0.001), PE (RR: 0.81; CI: 0.70, 0.95; P = 0.011), and hospital readmission (RR: 0.26; CI: 0.21, 0.33; P < 0.001). However, the TXA group was at increased risk of prosthetic loosening (RR: 1.25; CI: 1.04, 1.50; P = 0.017). There were no significant differences between the two groups in terms of risk for prosthetic dislocation, prosthetic fracture, PJI, shoulder stiffness, MI, DVT, hematoma, or revision surgery (Table 8).

Table 8.

Reverse total shoulder arthroplasty complications at 2-year follow-up.

Outcome	TXA (n)	Non-TXA (n)	% of TXA cohort	% of non-TXA cohort	Risk ratio	CI	P
Surgical site infection	220	273	1.58%	1.97%	0.81	(0.68, 0.96)	0.016
Prosthetic dislocation	524	533	3.77%	3.84%	0.98	(0.87, 1.11)	0.778
Prosthetic loosening	250	200	1.80%	1.44%	1.25	(1.04, 1.50)	0.017
Prosthetic fracture	331	311	2.38%	2.24%	1.06	(0.91, 1.24)	0.425
Prosthetic joint infection	472	531	3.40%	3.82%	0.89	(0.79, 1.00)	0.058
Shoulder stiffness	813	871	5.85%	6.27%	0.93	(0.85, 1.02)	0.145
Transfusion	337	553	2.43%	3.98%	0.61	(0.53, 0.70)	<0.001
Myocardial infarction	414	376	2.98%	2.71%	1.10	(0.96, 1.26)	0.17
Pulmonary embolism	272	334	1.96%	2.40%	0.81	(0.70, 0.95)	0.011
Deep vein thrombosis	396	435	2.85%	3.13%	0.91	(0.80, 1.04)	0.17
Hematoma	38	38	0.27%	0.27%	1.00	(0.64, 1.57)	1
Readmission	88	338	0.63%	2.43%	0.26	(0.21, 0.33)	<0.001
Revision	313	311	2.25%	2.24%	1.01	(0.86, 1.17)	0.943

CI: confidence interval; TXA: tranexamic acid.

Trends in TXA usage

Our study uniquely tracked trends in TXA use by TSA technique from 2020–2024 (Figures 1 and 2). In this time period, TXA use increased from 43% to 54% in rTSA and from 44% to 51% in aTSA.

Figure 1.

Rates of TXA utilization in aTSA procedures from 2020 to 2024.

Figure 2.

Rates of TXA utilization in rTSA procedures from 2020 to 2024.

Discussion

Due to the growing number of shoulder arthroplasties nationwide, expanding indications for TSA, and growing TXA use, there is a need to further characterize the risk profile of TXA in the context of shoulder replacements.^2,35,36 To our knowledge, this study of 57,096 patients represents the largest analysis of the role of TXA in postoperative TSA complications stratified by procedure type. To date, only four studies have compared TXA outcomes in aTSA versus rTSA; however, their investigations were limited to hematological complications.^17,18,27,28

Our study showed that at 90 days and 2 years postoperatively, TXA patients in both the aTSA and rTSA cohort had a lower risk of receiving a transfusion, having acute post-hemorrhagic anemia, and lower readmission rates compared to the non-TXA patients. At 2 years, patients receiving TXA in both cohorts were also at a lower risk for SSI and PE. These findings were consistent with our hypothesis and expand on the previous literature with the addition of surgical and prosthetic complications.

Regarding infection, TXA was associated with a significantly lower risk of SSI but an equivocal risk of PJI. Only one study has previously investigated the effects of TXA on SSIs in TSA and found no difference in infection rates between the TXA and non-TXA groups.²⁷ In contrast, TXA was associated with lower postoperative SSI risk after THA and TKA in a meta-analysis of 31 studies and a prospective study of 57 patients.^37,38 The protective role of TXA against SSI in arthroplasty may be due to the decreased need for transfusions, lower rate of hematomas, or interaction with plasmin-mediated immune pathways.^39–42 Additionally, TXA is established to protect against PJI in THA and TKA through possible antimicrobial properties and decreased blood loss, transfusion risk, wound drainage, and hematomas.^36–38^,43 However, this is not seen in TSA in our study or previous literature despite a decrease in transfusions and anemia.

The only significant prosthetic complication seen was increased risk of loosening in the TXA group following rTSA, a complication not described in previous THA studies.^23,44 However, this is more likely attributable to older average age of rTSA patients who are already at a higher risk of postoperative prosthetic complications, or due to a higher survival rate in rTSA patients which allowed for the loosening.^33,45 There were also similar levels of wound dehiscence in all groups. The effect of TXA on wound healing in arthroplasty is unclear, as some studies have reported a decrease in postoperative wound complications while others have found no difference.^32,46,47

We found that the TXA patients in both TSA cohorts had significantly lower transfusion rates at all follow-ups. This is a finding consistent with the anti-fibrinolytic properties of TXA that allow it to mitigate blood loss during surgical procedures.^48,49 These findings are notable, as the impact of TXA on transfusions in TSA was previously unclear. Three separate randomized control trials and a retrospective cohort study by Kissin et al.²⁸ found that the use of TXA in TSA was not associated with a decreased risk of postoperative transfusions.^11,19,50 In contrast, three retrospective cohort studies reported that TXA usage was associated with a significant decrease in need for postoperative transfusion compared to non-TXA groups.^35,51,52 Although all of these studies assessed the risk of transfusions, none stratified their results by the type of TSA procedure. Our study further contributes new evidence by demonstrating the risk associated with each subtype of TSA.

TXA was also associated with a decreased risk of PE and acute postoperative anemia in both cohorts. Our PE results are a novel finding, as no previous TSA study has demonstrated a PE benefit.^28,35 Additionally, several meta-analyses have found TXA administration in TSA procedures to be associated with a decrease in total postoperative blood loss, need for transfusion, changes in hemoglobin and hematocrit, and length of hospital stay.^29,53,54 Due to its efficacy in promoting hemostasis and decreasing blood loss, the use of TXA can play a crucial role in preventing postoperative anemia in both variations of TSA, as shown by our findings. There was no difference in the rates of MI or DVT across all cohorts. These findings are supported by prior studies reporting no effect of TXA on thromboembolic events in patients undergoing TSA.^35,51

Our study found an increase in TXA utilization from 2020 to 2024 in both aTSA and rTSA procedures, aligning with trends of increased TXA popularity seen in other orthopaedic subspecialties such as lower extremity, spine, and orthopaedic trauma.^14,22,43,46 Previous concern regarding the possible thromboembolic risks of TXA use, particularly in high-risk patients, has not been borne out in the literature, as multiple studies describe no increased risk of adverse outcomes after TXA use in high-risk patients after TSA.^2,29,35 As the usage and efficacy of TXA continue to increase, we observe that this trend extends to both variations of TSA. Although further investigation is needed to fully understand the hazards in high-risk patient populations, this safety data may explain the steady increase in TXA use and offer reassurance to surgeons incorporating TXA into their practice protocols.

Overall, this study has strong clinical implications. Our results support the routine use of TXA in both rTSA and aTSA given its association with reduced transfusion rates, anemia, SSI, PE, and hospital readmissions without an observed increase in thromboembolic complications. As the population undergoing TSA continues to grow in size and medical complexity, TXA may offer a safe and effective option to improve perioperative outcomes and reduce healthcare utilization. These results may inform clinical protocols and preoperative decision-making, especially in our high-risk and elderly patients, where the benefits of meticulous hemostasis and reduced infection may be more pronounced.

The strengths of our study include our extensive outcome analysis, comprehensive statistical testing, and large sample size. Utilizing the propensity-matching technique and Elixhauser Comorbidity Index allowed our study to minimize the influence of external confounders and mitigate bias, while enhancing the internal validity of the results. However, limitations still exist. As with any other retrospective database analysis, the data used in this study comes from patient coding in electronic health records, which may be subject to error. Administrative patient coding for procedures, medications and comorbidities may be incorrectly entered or missed, which could impact the results of the study. While the Elixhauser Comorbidity Index helps adjust for comorbidities, unmeasured cofounders may still exist. In addition, TXA can be administered through a topical or intravenous method of delivery, and our study did not stratify results based on this, as TriNetX does not allow for that analysis. However, a retrospective cohort study by Budge⁷ found both topical and intravenous TXA to be equivalently effective in controlling post-operative hemoglobin reductions in both rTSA and aTSA.

Further research on this topic is warranted. Prospective trials stratifying by topical versus intravenous TXA administration routes and dosing regimens are indicated to determine the most effective and safest approach. Further subgroup analysis in high-risk patients may also help refine specific risk profiles. Finally, incorporating patient-reported outcome scores and functional scores could offer further insight into whether the perioperative benefits of TXA affect short or long-term quality of life following TSA.

In this large, propensity-matched study, preoperative administration of TXA was associated with significantly lower rates of transfusion, anemia, SSI, PE, and hospital readmission following both anatomic and reverse TSA. These findings support the routine use of TXA as a safe and effective adjunct in TSA, with benefits that extend beyond hematologic outcomes to include reductions in infectious and thromboembolic complications.

As TSA volumes continue to rise and surgical indications broaden, TXA offers a cost-effective strategy to improve perioperative safety, enhance patient recovery, and reduce healthcare utilization. Future research should focus on patient outcome scores, the optimal route and dosing of TXA in TSA, and its safety in high-risk and medically complex patients. These efforts will be critical to inform evidence-based guidelines and ensure high-value care across all TSA populations.

Footnotes

ORCID iDs

Natalie R Black

Jeremy S Somerson

Ethical approval

This study used anonymized data and was exempt from Institutional Review Board approval.

Informed consent

Not applicable, as this study used de-identified data from the TriNetX database.

Contributorship

JS, NRB, and JSS contributed to the conceptualization, formal analysis, investigation, methodology, writing of the original draft, and review and editing of the final draft. NRB and JSS additionally provided supervision. All authors reviewed and edited the manuscript and approved the final version of the manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Guarantor

JSS

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