Cost-Benefit Analysis of Using A Single Dose of Tranexamic Acid in Degenerative Lumbar Scoliosis Patients Undergoing Long-Segment Spinal Fusion Surgery: A Retrospective Study.

BACKGROUND Degenerative lumbar scoliosis (DLS) patients undergoing posterior long-segment spinal fusion surgery often require perioperative blood transfusions, and previous studies have reported that increased complications and additional costs accompany these transfusions. One method for decreasing transfusions is the administration of tranexamic acid (TXA). We sought to evaluate the costs and benefits of preoperative administration of 1 g of intravenous TXA, without maintenance, in DLS patients undergoing long-segment spinal fusion surgery. MATERIAL AND METHODS Patients who received TXA (TXA group) were compared with patients who did not receive TXA (NTXA group) with regard to blood loss, units of packed red blood cells (PRBC) transfused, hemostasis costs, and perioperative complications. The benefits and costs were estimated through analysis of the spending on NTXA and TXA patients, and were compared. The difference between the cost per patient in the 2 groups was designated as the net cost-benefit. Then, both groups were substratified into non-osteotomy and osteotomy subgroups for further analysis. RESULTS Of the 173 patients who met the inclusion criteria, 54 TXA patients had significantly reduced perioperative blood loss and total hemostasis costs compared with NTXA patients (n=119). In the group without osteotomy (n=72), TXA (n=13) reduced perioperative blood loss but did not significantly decrease PRBC units and hemostasis costs. However, in patients undergoing osteotomy (n=101), a remarkable net cost savings of ¥648.77 per patient was shown in the TXA group (n=41) (P<0.001). This was because patients undergoing osteotomy in the TXA group received fewer PRBC units (3.7 vs 5.7, P=0.001). CONCLUSIONS A single dose of TXA significantly decreased perioperative blood loss and total hemostasis costs for DLS patients undergoing osteotomy. Furthermore, TXA led to no additional net costs in patients without osteotomy.

An economic evaluation of tranexamic acid to prevent postpartum haemorrhage in women with vaginal delivery: the randomised controlled TRAAP trial.

OBJECTIVE: To estimate the cost-effectiveness of tranexamic acid (TXA) use to prevent postpartum haemorrhage. DESIGN: A trial-based economic evaluation. SETTING: Fifteen French university maternity hospitals. POPULATION: Women enrolled in the TRAAP randomised controlled trial comparing TXA versus placebo in women with vaginal delivery. TRAAP failed to show a reduction in postpartum haemorrhage of at least 500 ml in the intervention arm but evidenced significant lower rates of secondary outcomes related to blood loss. METHODS & MAIN OUTCOME MEASURES: We estimated direct medical costs from within-trial hospital resources collected prospectively from the study report form. All resources were costed at their value to the hospital. We estimated incremental cost per incremental haemorrhage averted. RESULTS: Among the 4079 women in the TRAAP trial, data necessary to calculate costs were available for 3836 (94.0%). The average total costs in the TXA and control groups were €2278 ± 388 and €2288 ± 409 per woman, respectively (P = 0.79). In women with postpartum haemorrhage of at least 500 ml (trial primary endpoint), costs were €2359 ± 354 and €2409 ± 525 (P = 0.14); for provider-assessed clinically significant postpartum haemorrhage and postpartum haemorrhage of at least 1000 ml, costs were respectively €2316 ± 347 versus €2381 ± 521 (P = 0.22) and €2321 ± 318 versus €2411 ± 590 (P = 0.35) in the tranexamic and placebo groups, respectively. The probabilistic sensitivity analysis showed that the use of TXA had a 65-73% probability of saving costs and improving outcome. CONCLUSIONS: Our findings support the use of TXA, as both bleeding events and cost may be reduced three out of four times. TWEETABLE ABSTRACT: Tranexamic acid at vaginal delivery reduces both costs and bleeding events 3 times out of 4.

Tranexamic acid in the routine treatment of postpartum hemorrhage in the United States: a cost-effectiveness analysis.

BACKGROUND: The World Maternal Antifibrinolytic trial demonstrated that tranexamic acid administered during postpartum hemorrhage reduces hemorrhage-related mortality and laparotomies. The World Health Organization has thus recommended early use of tranexamic acid in the treatment of postpartum hemorrhage. This recommendation has not been universally adopted in the United States, in part because of concerns about cost-effectiveness. OBJECTIVE: We aim to demonstrate the cost-effectiveness of routine tranexamic acid administration in the treatment of postpartum hemorrhage in the United States, where the rate of hemorrhage-related mortality is lower than that described in the World Maternal Antifibrinolytic trial. STUDY DESIGN: We constructed a decision tree comparing 3 strategies in women with a clinical diagnosis of postpartum hemorrhage: no tranexamic acid, tranexamic acid given at any time, and ideal use of tranexamic acid given within 3 hours of delivery. The study was performed from a health care institution perspective with a time horizon of delivery until 6 weeks postpartum. We included interventions that differed by arm in the World Maternal Antifibrinolytic trial (hemorrhage-related mortality, laparotomies, and brace or compression sutures) and incorporated probabilities and costs based on available data for a population of women with postpartum hemorrhage in the United States. In our base case, the rate of postpartum hemorrhage-related mortality was 0.0388%, and the cost of tranexamic acid was $37.80. We assumed that the relative risk reduction in death and laparotomy with tranexamic acid would be similar to the World Maternal Antifibrinolytic trial (19% and 36%, respectively). The primary outcome was incremental cost per hemorrhage-related death averted, and a main secondary outcome was incremental cost per laparotomy avoided under each strategy. Another planned secondary outcome was cost per quality-adjusted life-year. We anticipated that the risk reduction (benefit) because of tranexamic acid in the United States may be less than in the World Maternal Antifibrinolytic trial; thus, we performed 1-way and 2-way sensitivity analyses to explore the parameter uncertainty across a wide range of data-supported estimates. Probabilistic sensitivity analyses with Monte Carlo simulation were performed. RESULTS: Tranexamic acid strategies were dominant (more effective and cost saving) compared with no tranexamic acid for patients with postpartum hemorrhage in the United States. One-way analyses showed that tranexamic acid is cost saving as long as the relative risk reduction of death with tranexamic acid is greater than 4.7%; the model was not sensitive to any other variables. Threshold analyses outside the bounds defined in the model showed that tranexamic acid is cost saving as long as the relative risk reduction of laparotomy with tranexamic acid is greater than 7% or the cost of tranexamic acid is less than $194. A 2-way sensitivity analysis of the risk reduction of death because of tranexamic acid and the baseline risk of postpartum hemorrhage-related death confirmed that tranexamic acid is cost saving across a wide range of plausible estimates. Furthermore, probabilistic sensitivity analysis demonstrated that the tranexamic acid strategies are cost saving in >99.9% of 10,000 Monte Carlo simulations. Despite the initial cost of administration, the annual net cost savings expected from routine use of tranexamic acid for the treatment of postpartum hemorrhage in the United States is $11.3 million, and we estimate that 9 maternal deaths would be averted in 1 year with this strategy. Giving tranexamic acid within 3 hours would almost triple the cost savings and improve maternal outcomes much further. CONCLUSION: A policy of routine tranexamic acid early in the treatment of postpartum hemorrhage is likely to be cost saving in the United States. This conclusion holds true even when the relative risk reduction with tranexamic acid is significantly less than reported in the World Maternal Antifibrinolytic trial and when tranexamic acid is significantly more expensive than currently reported.

Clinical Impact of Routine Complete Blood Counts Following Total Knee Arthroplasty.

BACKGROUND: Routine laboratory studies are generally obtained following total knee arthroplasty (TKA), and often continued daily until discharge. This study aims to investigate the utility and cost-effectiveness of complete blood count (CBC) tests following TKA. METHODS: Retrospective review identified 484 patients who underwent primary TKA under a tourniquet at a single institution. Preoperative and postoperative CBC values were collected along with demographic data, use of tranexamic acid (TXA), and transfusion rates. Logistic regression models were calculated for all variables. RESULTS: Twenty-five patients required transfusion following TKA (5.2%). Patients requiring transfusion had significantly lower preoperative hemoglobin compared to patients who did not require transfusion (11.47 vs 13.58 g/dL, P = .005). Risk of transfusion was 5.2 times higher in patients with preoperative anemia (95% confidence interval 2.90-9.35, P < .001). Without TXA, patients were 2.75 times more likely to receive transfusion (95% confidence interval 1.43-5.30, P < .001). An average of 2.9 CBC tests were collected per patient who did not receive medical intervention, costing a total of $144,773.80 in associated hospital charges ($316.10 per patient). CONCLUSION: Ensuring quality, cost-effective patient care following total joint arthroplasty is essential in the era of bundled payments. Routine postoperative CBCs do not add value for patients with normal preoperative hemoglobin who receive TXA during TKA performed under tourniquet. Patients who are anemic preoperatively or do not receive TXA should obtain a postoperative CBC test. Daily CBCs are unnecessary if the first postoperative CBC does not prompt intervention.

Cost-benefit analysis of the use of tranexamic acid in total replacement hip surgery.

STUDY OBJECTIVE: To establish the best dose regimen for tranexamic acid (TXA) in total hip replacement surgery. DESIGN: Secondary analysis based on data from a multicenter double-blind randomized clinical trial. SETTING: Two hospitals in Spain. INTERVENTIONS: TXA (2 doses) versus placebo. PATIENTS: Consecutive adults who underwent uncemented unilateral total replacement hip surgery. MEASUREMENTS: We estimated the costs associated with TXA use (including consumables, drugs and nurse time) and allogeneic and autologous blood transfusions. For the cost-benefit analysis, we considered the spending on controls to estimate the benefits and the spending on patients in the intervention arms to estimate the costs. The net cost-benefit of TXA administration was calculated by subtracting the costs incurred per patient given TXA from the costs per patient given placebo. MAIN RESULTS: The median total costs per patient were €2.7 (2.4-3.0) in the single-dose group, €6.5 (6.5-7.1) in the two-dose group and €0 (0-190) in the control group (p = 0.001). The blood transfusion costs were €1607.8, €1041.8 and €3115.3 in the single-dose, two-dose and control groups, respectively. The administration of two doses of TXA achieved a greater net cost-benefit than a single dose, the difference being €566 in terms of overall costs. CONCLUSIONS: The administration of TXA is cost-effective, especially in the case of the two-dose regimen studied.

Transfusions and cost-benefit of oral versus intravenous tranexamic acid in primary total hip arthroplasty: A meta-analysis of randomized controlled trials.

BACKGROUND: The purpose of this study was to assess the cost benefit and transfusions of oral and IV tranexamic acid (TXA) in primary total hip arthroplasty (THA). METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) comparing oral and IV TXA in primary THA. Primary outcomes were total blood loss, maximum hemoglobin drop, transfusion requirements, and cost benefit. Secondary outcomes were length of stay, deep venous thrombosis (DVT) and/or pulmonary embolism (PE). RESULTS: Four independent RCTs were included involving 391 patients. There was no difference in the total blood loss (P = .99), maximum hemoglobin drop (P = .73), and the length of stay (P = .95) between the 2 groups. Transfusion requirements (P = .97) were similar. The total mean cost was the US $75.41 in oral TXA group and the US $580.83 in IV TXA group. The incidence of DVT (P = .3) did not differ significantly between the 2 groups, and no PE was reported in all studies. CONCLUSION: Oral TXA shows similar efficacy and safety as IV TXA in reducing total blood loss, maximum hemoglobin drop and transfusion requirements in primary THA. However, oral TXA may be more cost-benefit than IV TXA. LEVEL OF EVIDENCE: Level I, therapeutic study.

The Effect of Tranexamic Acid on Functional Outcomes: An Exploratory Analysis of the CRASH-2 Randomized Controlled Trial.

STUDY OBJECTIVE: Tranexamic acid improves survival in severely injured adults. However, its effectiveness on overall functional outcome is unknown. We hypothesized that tranexamic acid improves overall functional outcome compared with placebo in severely injured adults and conduct an exploratory analysis of the Clinical Randomization of an Antifibrinolytic in Significant Haemorrhage (CRASH-2) data to investigate this hypothesis. METHODS: We included injured adults from the CRASH-2 trial who were randomized 3 hours or less from injury. The primary outcome measure was functional status at hospital discharge or on day 28 if the subject was still in the hospital. Functional status was measured with the modified Oxford Handicap Scale, a 6-category ordinal functional outcome scale. We conducted 3 separate analyses using 3 different outcome measures to evaluate the effectiveness of tranexamic acid versus placebo on functional outcomes, including the mean utility-weighted modified Oxford Handicap Scale score (overall functional outcome), the area under the curve (based on functional outcome and rate of recovery), and a sliding dichotomy analysis (favorable versus unfavorable functional outcome) stratified by baseline mortality risk (stratified analysis). RESULTS: There were 13,432 patients (6,679 randomized to placebo and 6,753 to tranexamic acid) included in the study cohort. The mean utility-weighted modified Oxford Handicap Scale score was 0.66 (SD 0.33) for patients randomized to tranexamic acid compared with a mean of 0.64 (SD 0.34) for those randomized to placebo (mean difference 0.02; 95% confidence interval [CI] 0.01 to 0.03). The area under the curve analysis demonstrated that patients randomized to tranexamic acid had a higher 28-day mean utility-weighted modified Oxford Handicap Scale score compared with those randomized to placebo (mean score 0.55 [SD 0.30] versus 0.53 [SD 0.31]; mean difference 0.02 [95% CI 0.01 to 0.03]). The sliding dichotomy analysis demonstrated heterogeneity of treatment effects across risk groups. The overall proportion of patients with favorable functional outcomes was higher in the tranexamic acid group (5,360/6,753 [79.4%]; 95% CI 78.4% to 80.3%) compared with the placebo group (5,174/6,679 [77.5%]; 95% CI 76.5% to 78.5%; difference 1.9% [95% CI 0.5% to 3.3%]; number needed to treat=52). When each risk group was tested separately, only the lowest-risk group (<6% baseline mortality risk) demonstrated a statistically significant effect of tranexamic acid toward favorable functional outcomes (tranexamic acid versus placebo adjusted odds ratio 0.78; 95% CI 0.67 to 0.90). There were no differences between tranexamic acid and placebo in the other risk groups. CONCLUSION: Across 3 exploratory analyses, severely injured adult patients randomized within 3 hours from injury demonstrated better functional outcomes with tranexamic acid compared with placebo. When heterogeneity of treatment effects across risk groups was evaluated, only the lowest-risk group demonstrated a significant effect of tranexamic acid toward favorable outcomes. Given the overall safety and cost-effectiveness of tranexamic acid use in injured adults, our results further support the use of tranexamic acid for this population. Future trauma trials that evaluate tranexamic acid use should also consider functional status as an important outcome.

A Retrospective Comparative Study of Different Methods of Blood Management in Total Knee Replacement.

Perioperative blood management is essential to minimize allogeneic blood transfusion in total knee replacement. The effect of preoperative administration of erythropoietin, intraoperative cell saver, tranexamic acid, and restrictive transfusion strategies on allogeneic transfusion is studied in total knee replacement. A retrospective comparative study of 106 patients who underwent total knee replacement in different time periods was performed. Group A (n 1 = 45) underwent restrictive strategies of transfusion between 2009 and 2010. Group B (n 2 = 24) includes patients where erythropoietin of either 10.000 IU or 20.000 IU was given preoperatively. Patients of Group C (n 3 = 21) underwent autologous washed erythrocytes transfusion through a cell saver. Lastly, in Group D (n 4 = 15) tranexamic acid dose of 1 gr IV was given intraoperatively. The preoperative and discharge hemoglobin together with total units of blood transfusion and creatinine levels was studied. Tranexamic acid noted the least units of blood transfusion (mean = 0.82 units/patient, p < 0.001, CI 95%) in contrast to the two regimens of erythropoietin (1.16 units/patient) OrthoPAT (1.43 units/patient) and restrictive strategies (1.92 units/patient). The mean preoperative hemoglobin was 13.37 g/dL with no statistical difference among the groups of patients. The postoperative mean hemoglobin was 10.59 with no statistical difference among the groups of patients too. Additionally, the mean creatinine level was 0.93 mg/dL; however, no statistical difference among the groups of patients was noted. Finally, tranexamic acid seemed to be the most cost-effective regime. In our study, tranexamic acid proved its superiority concerning the postoperative blood transfusion on patients undergoing total knee replacement, in comparison with the other existing methods of perioperative blood management. This is a Level III, retrospective comparative study.

Efficacy and safety of oral compared with intravenous tranexamic acid in reducing blood loss after primary total knee and hip arthroplasty: a meta-analysis.

BACKGROUND: Tranexamic acid (TXA) is an anti-fibrinolytic agent successfully preventing blood loss when using intravenously (IV) in total hip arthroplasty (THA) and total knee arthroplasty (TKA). An oral administration, which is available on blood sparing, has been reported exhibit profound cost-saving benefits. The aim of this meta-analysis is to investigate whether the administration of oral and intravenous tranexamic acid postoperatively has equivalent blood-sparing properties in these patients. METHODS: The online electronic databases were searched for eligible literatures updated on September 2018. Studies assessing the effect between oral TXA and intravenous TXA (IV-TXA) in those undergoing TKA or THA were included. All the data were pooled with the corresponding 95% confidence interval (CI) using RevMan software. Based on the heterogeneity, we performed a systematic analysis to explore the overall results across the included studies. RESULTS: Nine studies met our inclusion criteria. No significant differences were identified with regard to the Hb drop (SMD = - 0.03,95%CI = - 0.18-0.12, P = 0.67), total Hb loss (SMD = 0.10,95%CI = - 0.06-0.26, P = 0.24), total blood loss (SMD = - 0.00,95%CI = - 0.20-0.20, P = 1.00), transfusion rate (OR = 0.77,95%CI = 0.54-1.10, P = 0.14), DVT rate (OR = 0.58,95%CI = 0.19-1.75, P = 0.33), and length of hospital stay (SMD = - 0.05,95%CI = - 0.28-0.17, P = 0.63) between the oral groups and intravenous group. CONCLUSION: The blood-sparing efficacy of oral TXA is similar to that of the intravenous forms in the setting of THA and TKA. Considering the cost-benefit superiority and ease of administration of oral TXA, further studies and clinical trials are required to further identify the optimal administration for THA and TKA.

Blood loss and cost-effectiveness of oral vs intravenous tranexamic acid in primary total hip arthroplasty: A randomized clinical trial.

BACKGROUND: To assess the blood loss and cost-effectiveness of the oral and intravenous (IV) administration of tranexamic acid (TXA) for the treatment of primary total hip arthroplasty (THA). METHODS: From January 2017 to August 2017, 100 patients undergoing primary THA were enrolled and randomly divided into two groups. In the oral TXA group (N = 50), 1 g of TXA (2 tablets of 500 mg) was given 2 h before the incision, and the same dose was repeated 3 h and 6 h postoperatively. In the IV TXA group (N = 50), 1 g of TXA was administered 10 min before the incision, and the same dose was repeated 3 h and 6 h postoperatively. The total follow-up period was 6 months. RESULTS: There were no statistically significant differences in total blood loss (863.3 ±â€¯272.5 mL and 886.1 ±â€¯200.2 mL, P = 0.66), maximum Hb drop (2.9 ±â€¯0.6 g/dl and 3.1 ±â€¯0.8 g/dl, P = 0.17), maximum Hct drop (7.4 ±â€¯2.1% and 7.7 ±â€¯1.8%, P = 0.48), transfusion rates (1 and 2, P = 1.00) and transfusion units (1.5 u and 3 u, P = 0.56) between the two groups. However, the costs of TXA in the oral group were significantly lower than those in the IV TXA group (¥600 and ¥3150, P < 0.01). There was no difference in the Hb levels on postoperative days 1 and 3. No significant differences were found for operating time, hospital length of stay, DVT and/or PE, and wound complications in the postoperative follow-up. CONCLUSIONS: The study demonstrated that the oral and IV administration of TXA in patients undergoing THA was proved to be an equivalent and effective method in reducing blood loss and transfusion rates. However, oral TXA is more cost-effectiveness than IV TXA, and it may be an alternative to the IV form.

Pharmacologic Hemostatic Agents in Total Joint Arthroplasty-A Cost-Effectiveness Analysis.

BACKGROUND: Total knee and hip arthroplasties can be associated with substantial blood loss, affecting morbidity and even mortality. Two pharmacological antifibrinolytics, ε-aminocaproic acid (EACA) and tranexamic acid (TXA) have been used to minimize perioperative blood loss, but both have associated morbidity. Given the added cost of these medications and the risks associated with then, a cost-effectiveness analysis was undertaken to ascertain the best strategy. METHODS: A cost-effectiveness model was constructed using the payoffs of cost (in United States dollars) and effectiveness (quality-adjusted life expectancy, in days). The medical literature was used to ascertain various complications, their probabilities, utility values, and direct medical costs associated with various health states. A time horizon of 10 years and a willingness to pay threshold of $100,000 was used. RESULTS: The total cost and effectiveness (quality-adjusted life expectancy, in days) was $459.77, $951.22, and $1174.87 and 3411.19, 3248.02, and 3342.69 for TXA, no pharmacologic hemostatic agent, and EACA, respectively. Because TXA is less expensive and more effective than the competing alternatives, it was the favored strategy. One-way sensitivity analyses for probability of transfusion and myocardial infarction for all 3 strategies revealed that TXA remains the dominant strategy across all clinically plausible values. CONCLUSION: TXA, when compared with no pharmacologic hemostatic agent and with EACA, is the most cost-effective strategy to minimize intraoperative blood loss in hip and knee total joint arthroplasties. These findings are robust to sensitivity analyses using clinically plausible probabilities.

Tranexamic acid for treatment of women with post-partum haemorrhage in Nigeria and Pakistan: a cost-effectiveness analysis of data from the WOMAN trial.

BACKGROUND: Sub-Saharan Africa and southern Asia account for almost 85% of global maternal deaths from post-partum haemorrhage. Early administration of tranexamic acid, within 3 h of giving birth, was shown to reduce the risk of death due to bleeding in women with post-partum haemorrhage in the World Maternal Antifibrinolytic (WOMAN) trial. We aimed to assess the cost-effectiveness of early administration of tranexamic acid for treatment of post-partum haemorrhage. METHODS: For this economic evaluation we developed a decision model to assess the cost-effectiveness of the addition of tranexamic acid to usual care for treatment of women with post-partum haemorrhage in Nigeria and Pakistan. We used data from the WOMAN trial to inform model parameters, supplemented by estimates from the literature. We estimated costs (calculated in 2016 US$), life-years, and quality-adjusted life-years (QALYs) with and without tranexamic acid, calculated incremental cost-effectiveness ratios (ICERs), and compared these to threshold values in each country. Costs were assessed from the health-care provider perspective and discounted at 3% per year in the base case analysis. We did a series of one-way sensitivity analyses and probabilistic sensitivity analysis to assess the robustness of the results to parameter uncertainty. FINDINGS: Early treatment of post-partum haemorrhage with tranexamic acid generated an average gain of 0·18 QALYs at an additional cost of $37·12 per patient in Nigeria and an average gain of 0·08 QALYs at an additional cost of $6·55 per patient in Pakistan. The base case ICER results were $208 per QALY in Nigeria and $83 per QALY in Pakistan. These ICERs were below the lower bound of the cost-effectiveness threshold range in both countries. The ICERs were most sensitive to uncertainty in parameter inputs for the relative risk of death due to bleeding with tranexamic acid, the discount rate, the cost of the drug, and the baseline probability of death due to bleeding. INTERPRETATION: Early treatment of post-partum haemorrhage with tranexamic acid is highly cost-effective in Nigeria and Pakistan, and is likely to be cost-effective in countries in sub-Saharan Africa and southern Asia with a similar baseline risk of death due to bleeding. FUNDING: London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation.

Craniosynostosis Surgery and the Impact of Tranexamic Acid Dosing.

Consensus does not exist regarding the best dosage regimen for using tranexamic acid (TXA) for patients undergoing open calvarial vault remodeling in craniosynostosis surgery. The purpose of this study was to evaluate 2 dosing protocols, as well as the cost of using TXA. Previously, the institutional protocol was to give patients undergoing open calvarial vault remodeling a loading infusion of TXA (10 mg/kg) at the start of their procedure, after which intravenous TXA (5 mg/kg/h) was given throughout surgery and for 24 hours postoperatively. In July 2015, the protocol changed to a reduced postoperative infusion time of 4 hours. A retrospective review was conducted of records of 30 patients who had surgery before the protocol change (24-hour group) and 23 patients whose surgery occurred after the protocol change (4-hour group). The following data were collected: blood volume transfused, hemoglobin levels, estimated blood loss, and intensive care days; and costs of TXA and blood transfusion. Results showed a 4-hour infusion was as effective as a 24-hour infusion for reducing blood loss in patients undergoing craniosynostosis. Transfusion requirements, hemoglobin and hematocrit levels, and estimated blood loss were not significantly different for the groups. The cost of TXA and transfusion in the 4-hour group was significantly less (P < 0.001) than in the 24-hour group. No significant difference in cost existed for patients who received blood transfusion alone versus patients who received the 4-hour TXA infusion.

A systematic review and meta-analysis comparing combined intravenous and topical tranexamic acid with intravenous administration alone in THA.

PURPOSE: To compare the effectiveness and safety of combined intravenous and topical tranexamic acid with intravenous use alone in THA. METHODS: The electronic databases MEDLINE, EMBASE, BIOSIS, Cochrane central, and further adapted for Google and Google Scholar internet, last updated on Dec 30, 2016, were searched. Evaluated outcomes included total blood loss, transfusion rate, maximum postoperative Hb drop, and incidence of thromboembolic complications. The standard mean difference (SMD) or the relative risk (RR) was calculated for continuous or dichotomous data respectively. The quality of the trial was assessed, and meta-analyses were performed with the Cochrane Collaboration's RevMan 5.0 software. RESULTS: Five RCTs with 457 patients were included. Combined TXA administration reduced blood loss (SMD, 1.39; 95%CI, 0.55 to 2.23; P<0.00001, I2 = 94%), hemoglobin decline (SMD, 0.84; 95%CI, 0.13 to 1.54; P = 0.01, I2 = 83%) and the need for transfusion (RR, 2.58; 95%CI, 1.59 to 4.18; P = 0.65, I2 = 0%) without increasing the rate of thromboembolic complications significantly (RR, 0.83; 95%CI, 0.27 to 2.54; P = 0.81, I2 = 0%). CONCLUSION: The present study has emphasized that combined TXA administration can effectively reduce blood loss, hemoglobin decline and the need for transfusion without increasing the rate of thromboembolic complications.

[Local Application of Tranexamic Acid in Total Hip Arthroplasty Decreases Blood Loss and Consumption of Blood Transfusion]. / Lokální aplikace kyseliny tranexamové u TEP kycle snizuje krevní ztráty a spotrebu krevních transfuzí.

PURPOSE OF THE STUDY The primary aim of our study was to identify the effects of local application of tranexamic acid (TXA, Exacyl) on the amount of postoperative blood loss and blood transfusion requirement in primary total hip arthroplasty. We also recorded the levels of postoperative haemoglobin and its drop in early period after surgery. In each patient, we monitored in detail the incidence of early complications (haematoma, wound exudate). Lastly, the economic aspect of TXA administration was also taken into account. MATERIAL AND METHODS The prospective study included a total of 312 patients (122 men and 190 women) undergoing primary total hip arthroplasty (THA) at our department between January 2012 and November 2015. The patients enrolled in the study were divided into the intervention group with local (intra-articular) application of TXA and the control group without using TXA. Each group had 156 patients. The mean age of patients in the group with TXA was 65.6 years and the most frequent indication for THA surgery was primary osteoarthritis (59.0 %). The groups did not show any differences in basic characteristics, which was statistically verified. In each patient the volume of postoperative drainage, total blood loss, including the hidden loss, was recorded. In postoperative period, we monitored the haemoglobin levels and haematocrit. On discharge of each patient from the hospital, the size and site of a haematoma, wound exudate if still present even after postoperative day 4 and early surgical revision were evaluated. RESULTS In the group with TXA the blood losses from drains were significantly lower compared to the control group (493.4 ± 357.1 ml vs. 777.3 ± 382.5 ml; p < 0.0001). The median value for total blood loss (i.e. drainage volume and hidden loss) in the group with TXA was by 29.5 % lower than the median in the group without TXA (689.2 vs. 977.1 ml). The mean total blood loss (intraoperative + postoperative) was 783.8 ± 478.6 ml (mean ± standard deviation) in the patients with TXA and 1079.7 ± 487.1 ml in the second group without TXA. The difference in the total blood loss volume was significant (p < 0.0001). In the group with TXA the consumption of blood transfusion was significantly lower by 50 % (20 vs. 40 units), (p = 0.0004). The patients with TXA also reported a significantly lower consumption of allogeneic blood (p = 0.004), a higher level of postoperative haemoglobin (p < 0.0001) and a lower mean drop of haemoglobin (p < 0.0001). We did not observe any significant differences in the incidence of haematomas (p = 0.644). No higher volume of wound drainage and joint swelling after postoperative day 4 in patients with TXA was found (p = 0.565; p = 0.242). The TXA group did not show a higher rate of surgical revision (p = 1.000). The total economic costs of blood transfusion requirements were significantly lower in the TXA group than in the control group (p = 0.004), including consumption of autologous transfusions and blood salvage (p < 0.0001). DISCUSSION The main effect of the local application of TXA is to reduce bleeding which should result in lower postoperative blood loss and consumption of allogenic blood transfusion. The advantage of the local application of TXA is its easy application and maximum concentration of TXA at the surgical site. In addition, a potential harm associated with a systemic administration of a higher TXA dose is reduced because of only minimal TXA resorption into the circulation. According to a number of recent studies, the local application of TXA achieves comparable results to its intravenous application. The economic benefit of TXA intervention is also worth considering. CONCLUSIONS The local application of TXA is an effective and, simultaneously, safe method to reduce perioperative blood loss and consumption of blood transfusions and also to decrease the costs of hospital stay in the patients after THA. Another advantage of the local application is the need to administer one dose only, whereas at least two doses need to be administered intravenously in order to achieve the same effect. No significant complications were observed in the patients with TXA. According to the recent literature, it is therefore appropriate to include the local application of TXA among the recommended procedures for THA, as is the case in total knee arthroplasty. Key words: tranexamic acid, local application, blood loss, hidden blood loss, THA, total hip arthroplasty, complications.

Oral Tranexamic Acid Reduces Transfusions in Total Knee Arthroplasty.

BACKGROUND: Tranexamic acid (TXA) reduces intraoperative blood loss and transfusions in patients undergoing total knee arthroplasty. Although numerous studies demonstrate the efficacy of intravenous and topical TXA in these patients, few demonstrate the effectiveness and appropriate dosing recommendations of oral formulations. METHODS: A retrospective cohort study was performed to evaluate differences in transfusion requirements in patients undergoing primary unilateral total knee arthroplasty with either no TXA (n = 866), a single-dose of oral TXA (n = 157), or both preoperative and postoperative oral TXA (n = 1049). Secondary outcomes included postoperative hemoglobin drop, total units transfused, length of stay, drain output, and cell salvage volume. RESULTS: Transfusion rates decreased from 15.4% in the no-oral tranexamic acid (OTA) group to 9.6% in the single-dose OTA group (P < .001) and 7% in the 2-dose group (P < .001), with no difference in transfusion rates between the single- and 2-dose groups (P = .390). In addition, postoperative hemoglobin drop was reduced from 4.2 g/dL in the no-OTA group to 3.5 g/dL in the single-dose group (P < .01) and to 3.4 g/dL in the 2-dose group (P < .01), without a difference between the single- and 2-dose groups (P = .233). CONCLUSION: OTA reduces transfusions, with greater ease of administration and improved cost-effectiveness relative to other forms of delivery.

Process Improvement Project Using Tranexamic Acid Is Cost-Effective in Reducing Blood Loss and Transfusions After Total Hip and Total Knee Arthroplasty.

BACKGROUND: Tranexamic acid (TXA) has been associated with decreased blood loss and transfusion after total hip arthroplasty (THA) and total knee arthroplasty (TKA). The purpose of this study was to examine both transfusion utilization and the economic impact of a Process Improvement Project implementing TXA for THA and TKA. METHODS: After standardization of TXA administration in THA and TKA patients, retrospective data were compared from 12 consecutive months before (group A, n = 336 procedures) and after (group B, n = 436 procedures) project initiation. RESULTS: TXA administration increased with project implementation (group A = 3.57%, group B = 86.01%) and was associated with reductions in perioperative hemoglobin decrement (20.2%), patients transfused (45%), and number of units transfused per patient (61.9%). Cost savings were notable per patient ($128) and annually program wide ($55,884) with the primary THA subgroup contributing the most to the savings. No increase in adverse effects was observed. CONCLUSION: Standardized administration of TXA is an effective and economically favorable blood-reduction strategy for patients undergoing elective THA or TKA. Although reduction in transfusions with TXA may be greater after TKA, the economic and clinical impact of transfusion reduction is more substantial in THA patients.

Topical Tranexamic Acid is Equivalent to Targeted Preoperative Autologous Blood Donation in Total Hip Arthroplasty.

BACKGROUND: Topical tranexamic acid (TXA) was introduced to replace the previous targeted preoperative autologous blood donation (PABD) program. This study aims to analyze the efficacy of topical TXA compared with targeted PABD in anemic patients undergoing primary total hip arthroplasty (THA). METHODS: Two thousand two hundred fifty-one patients underwent primary THA between 2009 and 2013 using targeted autologous blood donation for 280 anemic patients (12%; Hb <12.5 g/dL). One thousand nine hundred seventy-one nonanemic patients (88%; ≥12.5 Hb/dL) received no blood management intervention. Starting in 2014, 505 consecutive patients were operated using 3 grams of topical TXA and abandoning PABD. Ninety-one patients (18%) were anemic and 414 (82%) nonanemic. RESULTS: The utilization of topical TXA in anemic patients resulted in higher hemoglobin levels on the first postoperative day (P = .014), but not on the second postoperative day (P = .198) compared with PABD. There was no difference in allogeneic transfusion rates between both groups: 12% vs 13% (P = .848). In the nonanemic group, TXA significantly increased hemoglobin levels on the first postoperative day (P = .001) as well as on the second postoperative day (P < .001), and resulted in a reduction in allogeneic transfusion rates from 8% to 1%. CONCLUSION: The present study suggests that topical TXA is equivalent to PABD in anemic patients and reduces transfusion rates and increases Hb-levels in nonanemic patients.

Comparing ε-Aminocaproic Acid and Tranexamic Acid in Reducing Postoperative Transfusions in Total Knee Arthroplasty.

Multiple studies have shown tranexamic acid (TXA) to reduce blood loss and transfusion rates in patients undergoing total knee arthroplasty (TKA). Accordingly, TXA has become a routine blood conservation agent for TKA. In contrast, ε-aminocaproic acid (EACA), a similar acting antifibrinolytic to TXA, has been less frequently used. This study evaluated whether EACA is as efficacious as TXA in reducing postoperative blood transfusion rates and compared the cost per surgery between agents. A multicenter retrospective chart review of elective unilateral TKA from April 2012 through December 2014 was performed. Five hospitals within a health care system participated. Data collected included age, gender, severity of illness score, use of antifibrinolytic and dose, red blood cell (RBC) transfusions and the number of units, and preadmission and discharge hemoglobin (Hb). Dosing of the antifibrinolytic differed based on the agent used, 5 or 10 g (based on weight) for EACA versus 1 g for TXA. The institutional acquisition cost of each antifibrinolytic was obtained and averaged over the study period. Of 2,922 primary unilateral TKA cases, 820 patients received EACA, 610 patients received TXA, and 1,492 patients received no antifibrinolytic (control group). Compared with the control group both EACA and TXA groups had significantly fewer patients transfused (EACA 2.8% [p < 0.0001], TXA 3.2% [p < 0.0001] vs. control 10.8%) and lower mean RBC units transfused per patient (EACA 0.05 units/patient [pt] [p < 0.0001], TXA 0.05 units/pt [p < 0.0001] vs. control 0.19 units/pt]. There was no difference in mean RBC units transfused per patient, percentage of patients transfused, and discharge Hb levels between the EACA and TXA groups (p = 0.822, 0.236, and 0.322, respectively). Medication acquisition cost for EACA averaged $2.23 per surgery compared with TXA at $39.58 per surgery. Administration of EACA or TXA significantly decreased postoperative transfusion rates compared with no antifibrinolytic therapy. Utilization of EACA for unilateral TKA proved to be comparable to TXA in all studied aspects at a lower cost. The level of evidence for the study is Level 3.

[Intra-Articular Application of Tranexamic Acid Significantly Reduces Blood Loss and Transfusion Requirement in Primary Total Knee Arthroplasty]. / Lokální aplikace kyseliny tranexamové významne snizuje mnozství krevních ztrát a spotrebu krevních transfuzí po primární TEP kolena.

PURPOSE OF THE STUDY The aim of this prospective study was to investigate the effect of topical application of tranexamic acid (TXA, Exacyl) on the amount of post-operative blood loss, and blood transfusion requirement in patients undergoing primary total knee arthroplasty (TKA). Attention was paid to early complications potentially associated with TXA administration, such as haematoma, wound exudate, or knee swelling. In addition, the economic benefit of TXA treatment was also taken into account. MATERIAL AND METHODS The study included 238 patients (85 men and 153 women) who underwent primary total knee arthroplasty (TKA) at our department between January 2013 and November 2015. A group of 119 patients (41 men and 78 women) received intraarticular TXA injections according to the treatment protocol (TXA group). A control group matched in basic characteristics to the TXA group also consisted of 119 patients. The average age in the TXA group was 69.8 years, and the most frequent indication for TKA surgery was primary knee osteoarthritis (81.5%). In each patient, post-operative volume of blood lost from drains and total blood loss including hidden blood loss were recorded, as well as post-operative haemoglobin and haematocrit levels. On discharge of each patient from hospital, the size and site of a haematoma; wound exudate, if present after post-operative day 4; joint swelling; range of motion and early revision surgery, if performed, were evaluated. Requirements of analgesic drugs after surgery were also recorded. RESULTS In the TXA group, blood losses from drains were significantly lower than in the control group (456.7 ± 270.8 vs 640.5 ±448.2; p = 0.004). The median value for blood losses from drains was lower by 22% and the average value for total blood loss, including hidden losses, was also lower than in the control group (762.4 ± 345.2 ml vs 995.5 ± 457.3 ml). The difference in the total amount of blood loss between the two groups was significant (p = 0.0001), including hidden blood loss (p = 0.030). The TXA patients had significantly fewer requirements for allogeneic blood transfusion (p < 0.0004), higher post-operative haemoglobin levels (p = 0.014), lower incidence of haematomas (p = 0.0003), and a significantly higher flexion degree on discharge from hospital (p < 0.0001). No higher volume of wound drainage was found (p = 1.000). Only one patient of the TXA group underwent revision surgery due to wound healing disturbance. The total costs of blood transfusion requirements were significantly lower in the TXA group than in the control group (p = 0.0004). DISCUSSION Topical administration allows the antifibrinolytic effect of TXA to act directly at a bleeding site. Its advantages involve easy application, maximum TXA concentration at the site of application, no danger associated with administration of a higher TXA dose and minimal TXA resorption into the circulation. On the other hand, there are no exact instructions for an effective and safe topical application of TXA and some authors are concerned that a coagulum arising after TXA application might affect soft tissue behaviour (healing, swelling, rehabilitation) or result in infection. CONCLUSIONS The study showed the efficacy and safety of topical TXA administration resulting in lower peri-operative bleeding, fewer blood transfusion requirements and higher haemoglobin levels after TKA. The patients treated with TXA had less knee swelling, lower incidence of haematomas and used fewer analgesic drugs in the early post-operative period. The economic benefit is also worth considering. In agreement with the recent literature, it is suggested to add topical TXA application to the recommended procedures for TKA surgery. Key words: tranexamic acid, Exacyl, topical application, intra-articular application, blood loss, hidden blood loss, total knee arthroplasty, complications.