Can you please summarize the literature on the use of 1 dose or 2 doses of tranexamic acid in the intraoperative setting for total knee or total hip arthroplasty (total joint revision).

Comment by InpharmD Researcher

In the setting of total hip or knee arthroplasty, meta-analyses have generally found no difference in outcomes between 1 and 2 doses of tranexamic acid (TXA), but comparisons are limited due to a lack of comprehensive literature. Studies which directly compared one and two doses of intravenous TXA in patients undergoing total joint revision typically indicate a lack of significant difference in most outcomes; notably, one study found the two dose group had a significantly higher rate of readmission and reoperation within 30 days.

Background

A 2023 systematic review and meta-analysis assessed the efficacy and safety of single and double-dose intravenous tranexamic acid (TXA) in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). The investigation focused on comparing the effectiveness of a single fixed dose of 1 g TXA administered intravenously with two doses of 1 g each. The primary endpoints included total blood loss, postoperative hemoglobin drop, blood transfusion rate, length of hospital stay, and the incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE). The results indicated no significant difference between the single and double-dose TXA regimens across the observed outcomes. Both dosing strategies demonstrated similar efficacy in reducing total blood loss, blood transfusion rates, and maintaining postoperative hemoglobin levels, as well as similar lengths of hospital stay. Additionally, the risk of DVT and PE did not significantly differ between the single and double dosing regimens. The authors concluded that both TXA dosing strategies are similarly effective and safe, recommending a single dose due to its comparable efficacy and potential cost-saving benefits. However, they noted the need for further high-quality randomized controlled trials to establish definitive dosing guidelines for TXA in joint arthroplasty. [1]

A 2018 meta-analysis evaluated the efficacy and safety of multiple versus single doses of intravenous TXA in patients undergoing total joint arthroplasty (TJA). The primary outcomes focused on hidden blood loss (HBL), transfusion rates, and the incidence of DVT and PE. Secondary outcomes included total blood loss (TBL), postoperative drainage volume, and length of hospital stay (LOH). Data indicated that multiple doses of intravenous TXA significantly reduced TBL, HBL, transfusion rates, and postoperative drainage volume compared to a single dose. Additionally, the results suggested a shorter LOH for patients receiving multiple doses, with no significant increase in DVT or PE incidents. The analysis highlighted that multiple doses of TXA, especially when administered thrice, resulted in more pronounced reductions in blood loss metrics. The transfusion rate was notably lower in the multiple-dose group, suggesting a consequent reduction in the need for allogeneic blood transfusions without compromising safety. These findings underscore the potential benefits of adopting a multiple-dose TXA regimen in TJA to optimize perioperative outcomes while maintaining a favorable safety profile. [2]

A 2021 abstract evaluated the efficacy of single versus two-dose intravenous TXA regimens in TJA. The retrospective study was based on patients who underwent primary TKA and THA between January 2017 and July 2019. Patients were divided into two groups: a single-dose group receiving a 1-g intravenous bolus of TXA before incision, and a two-dose group receiving an additional 1-g bolus during wound closure. The cohort consisted of 873 procedures with two doses of TXA and 647 with a single dose. The study analyzed postoperative hemoglobin levels, transfusion rates, hospital length of stay, and 30-day postoperative complications. The results indicated that a single dose of TXA was comparable to two doses, with no significant differences observed in postoperative hemoglobin values, length of stay, transfusion rates, or complication rates within 30 days post-surgery. Although the group receiving two doses exhibited a trend towards reduced transfusion requirements, this was not statistically significant. Furthermore, no preoperative hemoglobin threshold was identified to suggest a greater benefit from two doses over one. Despite the retrospective nature of the study and some variability in perioperative protocols, the findings suggest that a streamlined, single-dose TXA regimen may offer equivalent clinical outcomes to a two-dose approach in TJA, potentially yielding substantial cost savings without increased risk of thromboembolic events. [3]

Literature Review

A search of the published medical literature revealed 6 studies investigating the researchable question:

Can you please summarize the literature on the use of 1 dose or 2 doses of tranexamic acid in the intraoperative setting for total knee or total hip arthroplasty (total joint revision).

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-6 for your response.

The Optimal Dosing Regimen for Tranexamic Acid in Revision Total Hip Arthroplasty
Design	Prospective, multicenter, randomized trial N= 175
Objective	To determine the optimal dosing regimen of tranexamic acid (TXA) to minimize perioperative blood loss in revision total hip arthroplasty
Study Groups	1 g intravenous (IV) TXA (n= 43) 2 g IV TXA (n= 40) 1 g IV and 1 g topical TXA (n= 46) 1,950 mg oral TXA (n= 46)
Inclusion Criteria	Patients scheduled for revised total hip arthroplasty
Exclusion Criteria	Patients scheduled for modular head and polyethylene liner revision; exhibited the following health conditions: prior thromboembolic event, anticoagulant medication (excluding aspirin) within 5 days prior to the surgical procedure, New York Heart Association Class-III or IV heart failure, myocardial infarction or cardiac stenting within 6 months of the surgical procedure, hepatic failure, renal failure requiring dialysis, pulmonary disease requiring supplemental oxygen, documented allergy to TXA, acquired disturbances of color vision, and the refusal to receive blood products.
Methods	Patients were randomized into one of four intervention groups: 1g IV TXA: single-dose of 1g IV TXA prior to incision during preparation and draping 2g IV TXA: double-dose of 1g IV TXA with the first dose administered during preparation and draping and the second dose given at time of skin closure 1g IV and 1g topical TXA: single-dose of 1g IV TXA during preparation and draping along with one dose of 1g intra-articular TXA immediately following arthrotomy closure 1,950 mg oral TXA: three doses of oral TXA given as 3 tablets 650 mg each. The first was given 2 hours prior to incision, the second was given 6 hours postoperatively, and the last was given on the morning of postoperative day 1
Duration	Study enrollment period: July 2016 to August 2019 Follow-up: blood loss calculated before postoperative day 5
Outcome Measures	Primary: postoperative decrease in hemoglobin Secondary: calculated blood loss, patients that require blood transfusions
Baseline Characteristics		1 g IV TXA (n= 43)	2 g IV TXA (n= 40)	1 g IV and 1 g topical TXA (n= 46)	1,950 mg oral TXA (n= 46)
	Age, years	66.8 ± 12.0	67.8 ± 13.2	66.5 ± 14.4	64.0 ± 12.3
	Female	47%	55%	59%	44%
	Weight, kg	85.0 ± 25.0	78.0 ± 19.7	85.2 ± 23.8	91.6 ± 28.2
	Body mass index, kg/m²	27.9 ± 5.93	26.9 ± 4.72	29.5 ± 6.43	29.7 ± 6.37
	American Society of Anesthesiologists class	2.5	2.5	2.5	2.4
	Preoperative Hemoglobin, g/dL Hematocrit Platelets, x10³/μL International normalized ratio Prothrombin time, seconds	12.8 39 250 1.1 15	12.9 39 253 1.1 12	13.0 39 227 1.0 12	13.3 40 293 1.3 12
	Operating room time, min Length of stay, days	134 ± 57 2.7 ± 1.6	152 ± 66 3.5 ± 2.7	155 ± 57 3.3 ± 3.4	148 ± 46 2.9 ± 2.3
Results	Endpoint	1 g IV TXA (n= 43)	2 g IV TXA (n= 40)	1 g IV and 1 g topical TXA (n= 46)	1,950 mg oral TXA (n= 46)	p-value
	Hemoglobin difference, g/dL	3.35 ± 1.47	3.55 ± 1.24	3.52 ± 1.69	3.40 ± 1.38	0.912
	Calculated blood loss, mL	1,567.03 ± 778.79	1,498.14 ± 620.45	1,587.77 ± 856.2	1,426.25 ± 1,012.72	0.794
	Need for transfusions	6 (14.0%)	7 (17.5%)	8 (17.4%)	8 (17.4%)	0.955
Adverse Events	None reported which includes additional venous thromboembolic complications, cerebrovascular events, transient ischemic attacks
Study Author Conclusions	All 4 TXA groups tested had equivalent blood-sparing properties in the setting of revision total hip arthroplasty, with a single venous thromboembolism reported in this high-risk population. Based on the equivalence between groups, surgeons should utilize whichever of the 4 investigated regimens is best suited for their practice and hospital setting. Given the transfusion rate in revision total hip arthroplasty despite TXA utilization, further work is required in this area.
InpharmD Researcher Critique	Patients were not blinded to treatment, likely due to the difficulty of administering four different types of treatment and placebo equivalents. Blood loss could be calculated before the fifth postoperative day, presenting risk of hemodilution and altering the report of actual blood loss. While no adverse events were observed, the study had a small patient population for each group. Whether those that received a double dose, totaling to 2 g of IV TXA are at a greater risk of complications compared to those who only received a single dose of 1 g IV TXA remains uncertain.

References:
[1] [1] Sershon RA, Fillingham YA, Abdel MP, et al. The Optimal Dosing Regimen for Tranexamic Acid in Revision Total Hip Arthroplasty: A Multicenter Randomized Clinical Trial. J Bone Joint Surg Am. 2020;102(21):1883-1890. doi:10.2106/JBJS.20.00010

One Versus Two Doses of Intravenous Tranexamic Acid in Total Knee Arthroplasty
Design	Retrospective cohort review N= 1,191
Objective	To compare one versus two doses of tranexamic acid (TXA) in primary TKA and its effect on postoperative transfusion rate
Study Groups	One dose (n= 891) Two dose (n= 300)
Inclusion Criteria	Age 18-95 years at time of surgery, underwent primary unilateral TKA, received TXA perioperatively
Exclusion Criteria	History of a bleeding disorder, simultaneous bilateral TKA, staged TKA done 1 week apart, revision or conversion TKA, patients who received therapeutic anticoagulation postoperatively (including warfarin, therapeutic doses of enoxaparin, rivaroxaban, or apixaban)
Methods	Patients were identified from medical records using procedural code for TKA. Data was compiled from two arthroplasty centers within a single institution, but with differing TXA protocols: single dose vs. two perioperative doses, each using 1 g intravenous (IV) TXA. At both hospitals, patients were administered a 1 g dose of IV TXA given over a 10-minute infusion after entering the operating room and before tourniquet inflation. At one of the hospitals, an additional 1 g dose of IV TXA was administered in the recovery room before transfer to the surgical floor. Multimodal pain regimens, physical therapy parameters, and rehabilitation protocols were identical between groups. Patients were permitted to receive prophylactic anticoagulation: aspirin 325 mg twice daily, subcutaneous heparin 5,000 units three times daily, or enoxaparin 30 mg twice daily.
Duration	Underwent primary TKA between April 2013 and September 2016
Outcome Measures	Primary: rate of postoperative transfusion Secondary: mean calculated postoperative blood volume loss, mean length of stay (LOS), rate of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 30 days, readmissions within 30 days, and reoperations within 30 days
Baseline Characteristics		One dose (n= 891)	Two dose (n= 300)	p-value
	Age, years	62.6	62	NS
	Female	608 (68.2%)	217 (72.3%)	NS
	Race White Black Asian Hispanic	377 (43.7%) 436 (50.6%) 29 (3.4%) 18 (2.1%)	144 (50%) 124 (43%) 6 (2.1%) 14 (4.9%)	0.016
	DVT prophylaxis Aspirin Enoxaparin Heparin	617 (69.2%) 290 (32.5%) 4 (0.5%)	246 (82%) 9 (3%) 1 (1%)	< 0.001 < 0.001 0.28
	Preoperative hemoglobin, g/dL	13.4	12.9	< 0.001
Results	Endpoint	One dose (n= 891)	Two doses (n= 300)	Odds ratio (2 vs. 1 dose)	p-value
	Rate of transfusion	50 (5.6%)	11 (3.7%)	0.64	0.18
	DVT within 30 days	4 (0.5%)	1 (0.3%)	0.74	0.8
	PE within 30 days	5 (0.6%)	2 (0.7%)	1.19	0.83
	Readmission within 30 days	21 (2.4%)	20 (6.7%)	2.96	< 0.001
	Reoperation within 30 days	5 (0.6%)	6 (2%)	3.61	0.024
				Mean difference	p-value
	LOS, days	3.6	3.1	–0.55	0.08
	Blood volume loss, mL	942	990	42	0.23
	In a multivariate analysis, two doses of TXA significantly increased risk for readmission (odds ratio [OR] 3.14; p < 0.001) and reoperation (OR 3.65; p= 0.034). Male gender was predictive of need for postoperative transfusion (OR 3.57; p= 0.001) and obesity was predictive of a lower rate of transfusion (OR 0.48; p= 0.025). Based on preoperative hemoglobin, every 1 g/dL increase in preoperative hemoglobin was predictive of a lower rate of transfusion (OR 0.35; p < 0.001). In a subgroup analysis of patients receiving prophylaxis with aspirin only, no difference was found in transfusion rate and thromboembolic events. The two-dose group was still at a significantly higher risk of readmission (6.5 vs. 1.9%, OR 3.51, p< 0.001) and reoperation (2.4 vs. 0.5%, OR 5.12, p= 0.022). Subgroup analysis of female patients found those receiving two doses were at significantly higher risk of readmission (6.45 vs. 2.14%, OR 3.16, p= 0.003), but LOS was statistically significantly shorter (mean difference –0.29 days, p= 0.036). In male patients, those receiving two doses experienced significantly higher calculated blood volume loss (mean difference 227 mL, p= 0.004) than patients receiving one dose.
Adverse Events	N/A
Study Author Conclusions	In unilateral TKA, there is no difference in transfusion rate with one or two doses of perioperative TXA. There was no increased risk of thromboembolic events between groups, although the two-dose group had a higher rate of readmission and reoperation. Given the added cost without clear benefit, these findings may support administration of one rather than two doses of TXA during primary TKA.
InpharmD Researcher Critique	This study was performed at a high-volume institution, allowing for a large cohort. However, a substantial number of patients who underwent a TKA at this institution were excluded from the study. Additionally, procedures were performed by seven different surgeons whose surgical approach may have varied. Finally, the timing of the second TXA dose was not reported, and may have varied.

References:
[1] [1] Charette RS, Bernstein JA, Sloan M, Nchako CM, Kamath AF, Nelson CL. One Versus Two Doses of Intravenous Tranexamic Acid in Total Knee Arthroplasty. J Knee Surg. 2021;34(7):749-754. doi:10.1055/s-0039-1700805

A Comparison Study between 1 gram and 2 grams of Tranexamic Acid for Reducing Blood Loss and Transfusion Requirements in Total Knee Arthroplasty
Design	Retrospective cohort review N= 50
Objective	To compare the effectiveness between 1 g and 2 g of tranexamic acid (TXA) on blood loss and packed red cell transfusion requirements in total knee arthroplasty (TKA) in Thai patients
Study Groups	1 g TXA (n= 25) 2 g TXA (n= 25)
Inclusion Criteria	Patients who underwent primary TKA for osteoarthritis
Exclusion Criteria	Severe ischemic heart disease, pulmonary embolism, deep vein thrombosis, coagulopathy, hepatic or renal failure
Methods	In both groups, patients received 1 g or 2 g of TXA 15 minutes before incision. All patients also received low-molecular-weight heparin (LMWH) for the prevention of deep vein thrombosis. A single surgeon performed all the surgeries.
Duration	Unspecified for blood loss. Possibly up to 24 hours
Outcome Measures	Blood loss, tourniquet time, hematocrit, packed red blood cells (PRC) transfused, deep vein thrombosis
Baseline Characteristics		1 g TXA (n= 25)	2 g TXA (n= 25)	p-value
	Age, years	68.5 ± 7.2	67.6 ± 6.1	0.614
	Male/female	25/0	25/0	1.000
	Preoperative hematocrit. %	39.2 ± 2.6	41.3 ± 3.9	0.028
	Body mass index, kg/m²	24.5 ± 3.1	26.1 ± 2.8	0.064
Results	Endpoint	1 g TXA (n= 25)	2 g TXA (n= 25)	p-value
	Perioperative blood loss, cc	73.6 (0 to 200)	61.2 (10 to 200)	0.422
	Postoperative blood loss, cc	399.6 (150 to 850)	228.2 (20 to 400)	< 0.001
	Total blood loss, cc	473.2 (200 to 950)	290.6 (30 to 500)	< 0.001
	Tourniquet time, min	110.5 ± 21.2	112.2 ± 18.5	0.767
	Postoperative 24 hour hematocrit, %	33.6 ± 3.0	37.0 ± 4.4	0.002
	Total of PRC transfused, units	2	2	1.000
	Deep vein thrombosis	0	0	--
Study Author Conclusions	TXA 2 g can reduce total blood loss more than TXA 1 g significantly without increasing the risk of postoperative DVT.
InpharmD Researcher Critique	Both doses were administered before incision. There were no female patients. The study was performed in Thailand which may not reflect the U.S. healthcare landscape.

References:
[1] Vanasbodeekul P. A comparison study between 1 gram and 2 grams of tranexamic acid for reducing blood loss and transfusion requirements in total knee arthroplasty. The Thai Journal of Orthopaedic Surgery. 2021;45(1-2):27-31.

2019 Mark Coventry Award: A Multicentre Randomized Clinical Trial of Tranexamic Acid in Revision Total Knee Arthroplasty
Design	Multicentre randomized clinical trial N= 233
Objective	To determine the optimal regimen to maximize the blood-sparing properties of Tranexamic Acid (TXA) in revision Total Knee Arthroplasty (TKA).
Study Groups	Single-dose IV TXA (n= 46) Double-dose IV TXA (n= 44) Combined IV/topical TXA (n= 47) Multi-dose oral TXA (n= 49)
Inclusion Criteria	Patients scheduled to undergo unilateral revision TKA, including isolated femoral or tibial component revision, revision of both components, removal of component and implantation of a spacer for deep infection, second-stage reimplantation, or conversion of a unicompartmental knee arthroplasty to TKA.
Exclusion Criteria	Isolated polyethylene exchange, known allergy to TXA, acquired disturbances of colour vision, preoperative use of anticoagulant therapy (excluding aspirin) within five days before surgery, history of arterial or venous thromboembolic event, placement of an arterial stent or myocardial infarction within the past six months, severe heart failure, history of renal impairment, hepatic failure, severe pulmonary disease, or refusal to participate or receive blood products
Methods	Patients were randomized to one of four TXA regimens: 1 g of intravenous (IV) TXA given prior to the skin incision, a double-dose regimen of 1 g IV TXA given both prior to skin incision and at time of wound closure, a combination of 1 g IV TXA given prior to skin incision and 1 g of intraoperative topical TXA, or three doses of 1950 mg oral TXA given two hours preoperatively, six hours postoperatively, and on the morning of postoperative day one. Randomization was based on the type of revision procedure to ensure equivalent distribution among groups.
Duration	July 2016 to May 2018
Outcome Measures	Primary: Postoperative decrease in haemoglobin Secondary: Calculated blood loss, rate of transfusion, number of patients transfused ≥ 2 units of pRBC, length of hospitalization
Baseline Characteristics		Single-dose IV TXA group	Double-dose IV TXA group	Combined IV/ topical TXA group	Multi-dose oral TXA group	p-value
	Patients, n	46	44	47	49
	Mean age, yrs (sd)	63.3 ± 8.8	63.7 ± 11.8	63.8 ± 8.0	62.5 ± 10.7	0.91
	Male:female sex, n (%)	26:20 (56.5:43.5)	23:21 (52.3:47.7)	18:29 (38.3:61.7)	24:25 (49.0:51.0)	0.34
	Mean weight, kg (sd)	99.6 ± 27.4	95.4 ± 21.8	99.2 ± 27.6	90.2 ± 21.2	0.22
	Mean height, m (sd)	1.7 ± 0.1	1.7 ± 0.1	1.7 ± 0.1	1.7 ± 0.1	0.52
	Mean body mass index, kg/m2 (sd)	33.4 ± 7.8	32.5 ± 6.8	33.5 ± 7.2	31.7 ± 7.3	0.58
	Mean predicted blood volume, l (sd)	5.5 ± 1.3	5.3 ± 1.0	5.4 ± 1.3	5.1 ± 1.0	0.30
	ASA class, n (%) 1 2 3 4	1 (2.2) 26 (56.5) 18 (39.1) 1 (2.2)	2 (4.5) 29 (65.9) 12 (27.3) 1 (2.3)	1 (2.1) 29 (61.7) 17 (36.2) 0 (0)	1 (2.0) 26 (53.1) 22 (44.9) 0 (0)	0.90
	Mean preoperative Hb, g/dl (sd)	13.1 ± 2.1	13.3 ± 1.5	13.2 ± 1.7	13.2 ± 1.8	0.98
	Type of revision TKA,n (%)
	Femoral component only Tibial component only Both components Explantation and cement spacer Second-stage reimplantation UKA to TKA conversion	1 (2.2) 3 (6.5) 24 (52.2) 6 (13.0) 10 (21.7) 6 (13.0)	2 (4.5) 4 (9.1) 20 (45.5) 8 (18.2) 8 (18.2) 6 (13.6)	3 (6.4) 5 (10.6) 22 (46.8) 8 (17.0) 5 (10.6) 5 (10.6)	2 (4.1) 4 (8.2) 20 (40.8) 9 (18.4) 8 (16.3) 8 (16.3)	1.00
	Tourniquet use, n (%)	46 (100.0)	44 (100.0)	44 (93.6)	47 (95.9)	1.00
	Drain use, n (%)	9 (19.6)	9 (20.5)	9 (19.1)	11 (22.4)	0.98
	Mean operative time, mins (sd)	145 ± 40	133 ± 48	130 ± 36	135 ± 47	0.24
	Non-aspirin DVT prophylaxis, n (%)	4 (8.7)	6 (13.6)	8 (17.0)	8 (16.3)	0.66
Results		Single-dose IV TXA group	Double-dose IV TXA group	Combined IV/topical TXA group	Multi-dose oral TXA group	p-value
	Mean reduction of haemoglobin, g/dl (sd)	2.8 ± 0.8	2.6 ± 1.0	2.6 ± 1.0	2.9 ± 1.1	0.001*
	Mean calculated blood loss, ml	1324 (472)	1184 (590)	1212 (636)	1283 (558)	0.65†
	Rate of transfusion, n (%)	2 (4.4)	1 (2.3)	1 (2.1)	2 (4.1)	0.95‡
	≥ 2 units pRBC transfused, n (%)	1 (2.2)	1 (2.3)	0 (0)	1 (2.0)	0.80‡
	Mean length of hospital stay, days (sd)	2.9 ± 2.0	2.6 ± 1.3	2.3 ± 1.7	2.4 ± 1.4	0.25†
	*Equivalence testing based on a 1 g/dl minimal clinically important difference (MCID); for this test, a p-value < 0.05 would demonstrate equivalence between treatments †Analysis of variance (ANOVA) ‡Fisher’s exact test IV, intravenous; TXA, tranexamic acid; pRBC, packed red blood cells
Adverse Events	No specific adverse events reported in the study
Study Author Conclusions	Despite the higher risk of blood loss in revision TKA, all TXA regimens tested had equivalent blood-sparing properties. Surgeons should consider using the lowest effective dose and least costly TXA regimen in revision TKA.
Critique	The study was well-designed with a multicentre approach and a robust sample size, which enhances the generalizability of the findings. However, the lack of blinding and absence of a control group may introduce bias. Additionally, the study did not include thromboembolic events as an outcome measure, which could be a limitation given the potential risks associated with TXA use. The financial implications of different TXA regimens were considered, which is a strength in terms of practical application.

References:
[1] [1] Fillingham YA, Darrith B, Calkins TE, et al. 2019 Mark Coventry Award: A multicentre randomized clinical trial of tranexamic acid in revision total knee arthroplasty: does the dosing regimen matter?. Bone Joint J. 2019;101-B(7_Supple_C):10-16. doi:10.1302/0301-620X.101B7.BJJ-2018-1451.R1

One Dose of Intravenamic Acid Is Equivalent to Two Doses in Total Hip and Knee Arthroplasty
Design	Retrospective cohort study N= 3,778
Objective	To identify whether 1 dose of intravenous tranexamic acid (TXA) is equivalent to 2 doses for reducing blood loss and transfusion rates following total hip arthroplasty (THA) and total knee arthroplasty (TKA) without an increase in complications.
Study Groups	THA without TXA (n= 592) THA with 1 dose TXA (n= 454) THA with 2 doses TXA (n= 690) TKA without TXA (n= 744) TKA with 1 dose TXA (n= 499) TKA with 2 doses TXA (n= 799)
Inclusion Criteria	Patients who underwent primary unilateral THA or TKA from 2012 to 2016
Exclusion Criteria	Patients who underwent simultaneous bilateral, revision, or conversion arthroplasty; history of venous thromboembolism, thrombotic stroke, cardiac stent in the last 2 years, atrial fibrillation, or long-term anticoagulation therapy.
Methods	Patients were divided into three groups: no TXA, 1 dose of 1-g IV TXA, and 2 doses of 1-g IV TXA. The change in hemoglobin levels, rate of allogeneic blood transfusions, and rate of complications were assessed. Multivariate analysis controlled for age, sex, and preoperative hemoglobin level
Duration	2012 to 2016
Outcome Measures	Primary: Change in hemoglobin levels Secondary: Rate of complicatrate of allogeneic blood transfusionsions
Baseline Characteristics		No TXA	1 TXA Dose	2 TXA Doses
	THA - Female (%)	57.9	58.6	53.8
	THA - Age (yr)	68.4 ± 10.7	67.4 ± 11.0	66.9 ± 10.6
	THA - Osteoarthritis (%)	89.8	93.6	89.9
	TKA - Female (%)	64.8	64.5	64.6
	TKA - Age (yr)	70.3 ± 9.6	69.5 ± 8.9	68.9 ± 9.6
	TKA - Osteoarthritis (%)	96.7	98.5	96.5
Results		No TXA	1 TXA Dose	2 TXA Doses	p-value
	THA - Change in hemoglobin (g/dL)	-3.6 ± 1.2	-2.9 ± 1.0	-3.1 ± 1.1	<0.001
	THA - Transfusion rate (%)	12.5	0	0.7	<0.001
	TKA - Change in hemoglobin (g/dL)	-2.9 ± 1.1	-2.4 ± 0.9	-2.4 ± 0.9	<0.001
	TKA - Transfusion rate (%)	4.3	0.4	0.3	<0.001
Adverse Events	Similar rates of perioperative complications occurred among all groups. No increase in thromboembolic events was observed with TXA administration.
Study Author Conclusions	One dose of TXA was as effective as two doses for decreasing blood loss and transfusion rates after THA and TKA without an increase in complications.
Critique	The study's large sample size and prospective data collection are strengths, but its retrospective design and lack of randomization are limitations. Exclusion of high-risk patients limits generalizability. Variability in postoperative prophylaxis and reinfusion practices may have influenced results.

References:
[1] [1] Wilde JM, Copp SN, McCauley JC, Bugbee WD. One Dose of Intravenous Tranexamic Acid Is Equivalent to Two Doses in Total Hip and Knee Arthroplasty. J Bone Joint Surg Am. 2018;100(13):1104-1109. doi:10.2106/JBJS.17.00641

One Dose Versus Two Doses of Intravenous Tranexamic Acid in Revision Total Joint Arthroplasty
Design	Retrospective study N= 340
Objective	To compare single-dose and two-dose regimens on postoperative hemoglobin levels, transfusion rates, and 30-day complication rates in patients who underwent revision TJA
Study Groups	One dose (n= 189) Two doses (n= 151)
Inclusion Criteria	Patients ≥18 years old who underwent revision THA or revision TKA between April 2014 and November 2020
Exclusion Criteria	Patients who underwent primary, conversion, or simultaneous bilateral arthroplasty or did not receive perioperative TXA.
Methods	Patients were divided into two cohorts based on TXA dosages. The first cohort received two doses of 1-g intravenous TXA, one before incision and one during wound closure. The second cohort received a single 1-g intravenous dose before incision. Postoperative hemoglobin levels were measured on days 1 to 3, and transfusion was considered for hemoglobin levels <7.0 g/dL or symptomatic anemia.
Duration	April 2014 to November 2020
Outcome Measures	Primary: Postoperative hemoglobin levels Secondary: Transfusion rates, length of hospital stay, 30-day postoperative complication rates
Baseline Characteristics		One Dose (n= 189)	Two Doses (n= 151)
	Sex Male Female	96 (50.8%) 93 (49.2%)	70 (46.4%) 81 (53.6%)
	Type of surgery TKA THA	95 (50.3%) 94 (49.7%)	75 (49.7%) 76 (50.3%)
	Type of anesthesia Regional General Combined	66 (34.9%) 86 (45.5%) 37 (19.6%)	58 (38.4%) 69 (45.7%) 24 (15.9%)
	Transfusion orders No Yes	138 (73%) 51 (27%)	120 (79.5%) 31 (20.5%)
Results	Statistical comparison between two cohorts			p-value
	Postoperative hemoglobin levels (b)	-0.18 (95% CI: 20.39 to 0.03)		0.09
	Transfusion rates (OR)	0.74 (95% CI: 0.39 to 1.38)		0.34
	Length of hospital stay (RR)	0.95 (95% CI: 0.84 to 1.08)		0.43
	30-day postoperative complication rates (OR)	1.30 (95% CI: 0.54 to 3.15)		0.56
Adverse Events	No notable differences in thromboembolic events (DVT or PE), myocardial infarctions, cerebrovascular accidents, or wound hematomas between the two cohorts.
Study Author Conclusions	A single dose of perioperative intravenous TXA just before incision during revision TJA had comparable postoperative hemoglobin levels, length of hospital stay, 30-day complication rates, and transfusion incidence when compared with two doses. Although this study suggests that there is no benefit to routinely giving a second intraoperative dose of TXA in revision arthroplasty, it does seem to be safe for those surgeons who prefer administering the additional dose.
Critique	The study's retrospective design may introduce biases, and the lack of data on variables such as urinary output and intraoperative blood loss limits the assessment of hydration status and blood loss. Differences in perioperative management among surgeons could affect results, although these were controlled for in analyses. The study's focus on intravenous TXA may limit generalizability to other administration routes.

References:
[1] [1] Grayson W, Seddio AE, Sontag-Milobsky I, Adams WH, Brown NM. One Dose Versus Two Doses of Intravenous Tranexamic Acid in Revision Total Joint Arthroplasty. J Am Acad Orthop Surg Glob Res Rev. 2025;9(12):e25.00241. Published 2025 Dec 5. doi:10.5435/JAAOSGlobal-D-25-00241