Tranexamic acid loaded in a physically crosslinked trilaminate dressing for local hemorrhage control: Preparation, characterization, and in-vivo assessment using two different animal models.

This work aimed at formulating a trilaminate dressing loaded with tranexamic acid. It consisted of a layer of 3 % sodium hyaluronate to initiate hemostasis. It was followed by a mixed porous layer of 5 % polyvinyl alcohol and 2 % kappa-carrageenan. This layer acted as a drug reservoir that controlled its release. The third layer was 5 % ethyl cellulose backing layer for unidirectional release of tranexamic acid towards the wound. The 3 layers were physically crosslinked by hydrogen bonding as confirmed by Infrared spectroscopy. Swelling and release studies were performed, and results proposed that increasing number of layers decreased swelling properties and sustained release of tranexamic acid for 8 h. In vitro blood coagulation study was performed using human blood and showed that the dressing significantly decreased coagulation time by 70.5 % compared to the negative control. In vivo hemostatic activity was evaluated using tail amputation model in Wistar rats. Statistical analysis showed the dressing could stop bleeding in a punctured artery of the rat tail faster than the negative control by 59 %. Cranial bone defect model in New Zealand rabbits was performed to check for bone hemostasis and showed significant decrease in the hemostatic time by 80 % compared to the control.

The cost-utility of intraoperative tranexamic acid in adult spinal deformity patients undergoing long posterior spinal fusion.

PURPOSE: This study aims to evaluate the cost-utility of intraoperative tranexamic acid (TXA) in adult spinal deformity (ASD) patients undergoing long posterior (≥ 5 vertebral levels) spinal fusion. METHODS: A decision-analysis model was built for a hypothetical 60-year-old adult patient with spinal deformity undergoing long posterior spinal fusion. A comprehensive review of the literature was performed to obtain event probabilities, costs and health utilities at each node. Health utilities were utilized to calculate Quality-Adjusted Life Years (QALYs). A base-case analysis was carried out to obtain the incremental cost and effectiveness of intraoperative TXA. Probabilistic sensitivity analysis was performed to evaluate uncertainty in our model and obtain mean incremental costs, effectiveness, and net monetary benefits. One-way sensitivity analyses were also performed to identify the variables with the most impact on our model. RESULTS: Use of intraoperative TXA was the favored strategy in 88% of the iterations. The mean incremental utility ratio for using intraoperative TXA demonstrated higher benefit and lower cost while being lower than the willingness-to-pay threshold set at $50,000 per quality adjusted life years. Use of intraoperative TXA was associated with a mean incremental net monetary benefit (INMB) of $3743 (95% CI 3492-3995). One-way sensitivity analysis reported cost of blood transfusions due to post-operative anemia to be a major driver of cost-utility analysis. CONCLUSION: Use of intraoperative TXAs is a cost-effective strategy to reduce overall perioperative costs related to post-operative blood transfusions. Administration of intraoperative TXA should be considered for long fusions in ASD population when not explicitly contra-indicated due to patient factors.

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.

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial.

BACKGROUND: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. METHODS: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. FINDINGS: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82-1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). INTERPRETATION: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Characterization of a large cohort of patients with unclassified bleeding disorder; clinical features, management of haemostatic challenges and use of global haemostatic assessment with proposed recommendations for diagnosis and treatment.

INTRODUCTION: There is an unmet need to characterize the diagnosis and management of patients with an unclassified bleeding disorder (UBD). METHODS: Retrospective review of registered patients with UBD at our centre. Assessment including rotational thromboelastometry (ROTEM) and thrombin generation (TG) were used. RESULTS: A total of 124 patients were identified; 91% female. Mean age of presentation was 38.3 years. Mean bleeding score was 8.8 (standard deviation [SD] 3.8); 6.6 in men (SD 1.4) and 9.7 in women (SD 3.3), which was significantly different (P < .05). In women, after deduction of scores for menorrhagia and postpartum haemorrhage, the mean score was 6.4 which was not significantly different to the male score (P = .11). Twenty-three percent of patients have been transfused, 61% women had treatment for menorrhagia and 17% for epistaxis. TxA and desmopressin were effective at preventing bleeding in 69 procedures and 13 deliveries. TG revealed 26% patients with a long lag time and 19% with a decreased endogenous thrombin potential but no diagnostic pattern was seen. ROTEM (NATEM) was unable to characterize patients; 9% had a prolonged clot time or maximum lysis. ThromboGenomics was normal in 45 tested patients. CONCLUSIONS: We provide data which shows the bleeding score is biased towards gynaecological bleeding but which remains elevated even when the bleeding score is deducted. Tranexamic acid and desmopressin are effective as haemostatic prophylaxis but there is an urgent need for clinical trials. In conclusion, we describe the use of the bleeding score in these patients and phenotype, diagnosis (including ThromboGenomic testing) and management with practice recommendations.

Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial.

BACKGROUND: Tranexamic acid reduces surgical bleeding and decreases mortality in patients with traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury (TBI) and can cause brain herniation and death. We aimed to assess the effects of tranexamic acid in patients with TBI. METHODS: This randomised, placebo-controlled trial was done in 175 hospitals in 29 countries. Adults with TBI who were within 3 h of injury, had a Glasgow Coma Scale (GCS) score of 12 or lower or any intracranial bleeding on CT scan, and no major extracranial bleeding were eligible. The time window for eligibility was originally 8 h but in 2016 the protocol was changed to limit recruitment to patients within 3 h of injury. This change was made blind to the trial data, in response to external evidence suggesting that delayed treatment is unlikely to be effective. We randomly assigned (1:1) patients to receive tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was head injury-related death in hospital within 28 days of injury in patients treated within 3 h of injury. We prespecified a sensitivity analysis that excluded patients with a GCS score of 3 and those with bilateral unreactive pupils at baseline. All analyses were done by intention to treat. This trial was registered with ISRCTN (ISRCTN15088122), ClinicalTrials.gov (NCT01402882), EudraCT (2011-003669-14), and the Pan African Clinical Trial Registry (PACTR20121000441277). RESULTS: Between July 20, 2012, and Jan 31, 2019, we randomly allocated 12 737 patients with TBI to receive tranexamic acid (6406 [50·3%] or placebo [6331 [49·7%], of whom 9202 (72·2%) patients were treated within 3 h of injury. Among patients treated within 3 h of injury, the risk of head injury-related death was 18·5% in the tranexamic acid group versus 19·8% in the placebo group (855 vs 892 events; risk ratio [RR] 0·94 [95% CI 0·86-1·02]). In the prespecified sensitivity analysis that excluded patients with a GCS score of 3 or bilateral unreactive pupils at baseline, the risk of head injury-related death was 12·5% in the tranexamic acid group versus 14·0% in the placebo group (485 vs 525 events; RR 0·89 [95% CI 0·80-1·00]). The risk of head injury-related death reduced with tranexamic acid in patients with mild-to-moderate head injury (RR 0·78 [95% CI 0·64-0·95]) but not in patients with severe head injury (0·99 [95% CI 0·91-1·07]; p value for heterogeneity 0·030). Early treatment was more effective than was later treatment in patients with mild and moderate head injury (p=0·005) but time to treatment had no obvious effect in patients with severe head injury (p=0·73). The risk of vascular occlusive events was similar in the tranexamic acid and placebo groups (RR 0·98 (0·74-1·28). The risk of seizures was also similar between groups (1·09 [95% CI 0·90-1·33]). INTERPRETATION: Our results show that tranexamic acid is safe in patients with TBI and that treatment within 3 h of injury reduces head injury-related death. Patients should be treated as soon as possible after injury. FUNDING: National Institute for Health Research Health Technology Assessment, JP Moulton Charitable Trust, Department of Health and Social Care, Department for International Development, Global Challenges Research Fund, Medical Research Council, and Wellcome Trust (Joint Global Health Trials scheme). TRANSLATIONS: For the Arabic, Chinese, French, Hindi, Japanese, Spanish and Urdu translations of the abstract see Supplementary Material.

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.

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.

Effects of modification of trauma bleeding management: A before and after study.

OBJECTIVE: We hypothesised that the association of tranexamic acid (TXA) administration and thromboelastometry-guided haemostatic therapy (TGHT) with implementation of Damage Control Resuscitation (DCR) reduced blood products (BP) use and massive transfusion (MT). METHODS: Retrospective comparison of 2 cohorts of trauma patients admitted in a university hospital, before (Period 1) and after implementation of DCR, TXA (first 3-hours) and TGHT (Period 2). Patients were included if they received at least 1 BP (RBC, FFP or platelet) or coagulation factor concentrates (fibrinogen or prothrombin complex) during the first 24-hours following the admission. RESULTS: 380 patients were included. Patients in Period 2 (n = 182) received less frequently a MT (8% vs. 33%, P < 0.01), significantly less BP (RBC: 2 units [1-5] vs. 6 [3-11]; FFP: 0 units [0-2] vs. 4 [2-8]) but more fibrinogen concentrates (3.0 g [1.5-4.5] vs. 0.0 g [0.0-3.0], P < 0.01). Multivariate logistic regression analysis identified Period 1 as being associated with an increased risk of receiving MT (OR: 26.1, 95% CI: 9.7-70.2) and decreased survival at 28 days (OR: 2.0, 95% CI: 1.0-3.9). After propensity matching, the same results were observed but there was no difference for survival and a significant decrease for the cost of BP (2370 ± 2126 vs. 3284 ± 3812 €, P: 0.036). CONCLUSION: Following the implementation of a bundle of care including DCR, TGHT and administration of TXA, we observed a decrease to the use of blood products, need for MT and an improvement of survival.

Novel use of tranexamic acid to reduce the need for Nasal Packing in Epistaxis (NoPac) randomised controlled trial: research protocol.

INTRODUCTION: Patients presenting to emergency departments (EDs) with epistaxis uncontrolled by subsequent simple first aid measures or application of topical vasoconstrictors will typically undergo anterior nasal packing. Packing is effective, but can be extremely painful and unpleasant and patients usually need hospital admission. Tranexamic acid (TXA) is a cheap, safe, readily available antifibrinolytic agent known to be beneficial in a variety of clinical settings where uncontrolled bleeding may be a problem. Anecdotal evidence suggests that topical TXA may be of value in persistent epistaxis; however, further evaluation is required. METHODS AND ANALYSIS: This is a multicentre, double-blind, parallel group, randomised, controlled trial comparing the use of topical intranasal TXA with indistinguishable placebo in adults presenting to UK EDs with persistent atraumatic epistaxis. Follow-up is at 1 week by structured telephone review. The primary outcome measure is the subsequent need for anterior nasal packing in the ED. Key secondary outcomes include the need for hospital admission, blood transfusion and/or further treatment for epistaxis during the index ED attendance. Recruiting 450 patients will provide 90% power to demonstrate an absolute reduction in packing rate from 95% to 85%. An improvement of this magnitude would be of significant benefit to patients and healthcare providers and justify a change to standard practice. Given the low cost of TXA and its short administration time, a full economic evaluation is not being undertaken. ETHICS AND DISSEMINATION: The study has been approved by the South West-Bristol Research Ethics Committee (reference 17/SW/0010). We aim to publish the findings in a high impact, international peer-reviewed journal. Results will also be shared with the Hereditary Haemorrhagic Telangiectasia foundation and telangiectasia UK for dissemination through appropriate related forums. TRIAL REGISTRATION NUMBER: ISRCTN34153772 and EudraCT No: 2016-001530-10.

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.

Effect of pharmacist intervention on blood conservation therapy in total knee arthroplasty: A retrospective, observational study.

BACKGROUND: Total knee arthroplasty (TKA) is associated with blood loss and an increased risk of transfusion. Guidelines for antifibrinolytic drug tranexamic acid (TXA) treatment in TKA patients are available. We evaluated the effects of anticoagulant pharmacist intervention on perioperative blood conservation treatment in TKA patients. METHODS: In a retrospective, observational experimental study, patients admitted for TKA were allocated into the control or pharmacist intervention group. In the intervention phase, multiple interventions of TXA treatment based on guidelines were implemented. The primary endpoint was blood loss. Other outcome included postoperative haemoglobin and haematocrit levels, allogeneic blood transfusion, cost savings and safety. RESULTS: A total of 177 patients were included (88 and 89 in the control and intervention group, respectively). In the intervention group, 24.72% orders of TXA dosage, 20.22% orders of drug choice, 26.97% orders of TXA timing and 30.34% orders of TXA administration manner were adjusted. Eighty-nine (100%) patients received blood conservation therapy compared with 21 (23.86%) patients in the control group (P < 0.001). Total blood loss was 1133.31 ± 627.08 mL in the control group compared with 604.34 ± 459.09 mL in the intervention group (P < 0.001). Postoperative drops in haemoglobin and haematocrit in the control group were greater than in the intervention group (P < 0.001). The rate of allogeneic blood transfusion was 40.91% in the control group compared with 21.35% in the intervention group (P = 0.01). Pharmacist intervention was conducted to cost savings resulting from reduced transfusion, but with comparable safety profile. CONCLUSIONS: Anticoagulant pharmacist intervention on blood conservation treatment of TKA patients leads to favourable clinical and economic outcome.

Assessment of combined fractional CO2 and tranexamic acid in melasma treatment.

BACKGROUND: Melasma continues to be a disease that is difficult to treat with no fully satisfactory results. The role of a fractional CO2 laser in its treatment is controversial. The addition of tranexamic acid (TXA) might be helpful. OBJECTIVES: To assess the efficacy of a low-power fractional CO2 laser alone versus its combination with tranexamic acid used either topically or intradermally for melasma treatment. METHODS: A randomized comparative split-face study included a total of thirty female patients with bilateral, symmetrical melasma. The whole face was subjected to treatment via a low-power (12 Watts) fractional ablative CO2 laser. One side was randomly assigned to topical application of tranexamic acid solution after the session immediately or intradermal microinjection of tranexamic acid prior to the laser session. Sessions were conducted every 4-6 weeks for five consecutive sessions. Assessments were done using the melasma area severity index MASI score, melanin index (MI), and erythema index (EI) before sessions and 2 weeks after the final session. RESULTS: After treatment, there was significant reduction in the MASI score on both sides of the face; the side treated with the fractional CO2 laser alone and the side treated with fractional CO2 laser combined with TXA (topically or intradermal injection) (P-values 0.007, <0.001, and 0.016, respectively). MI was significantly lower on the side receiving fractional CO2 laser alone and the side receiving fractional CO2 laser combined with intradermal injection of TXA (P-values <0.001 and 0.003, respectively), while the EI showed significant improvement only on the side receiving fractional CO2 laser alone (P-value = 0.023). Although patients reported no differences in improvement on either treated side, the degree of improvement regarding the MASI score was better on the side receiving fractional CO2 laser alone. Regarding MI, the degree of improvement was higher on the side receiving fractional CO2 laser combined with intradermal injection of TXA than on the side receiving fractional CO2 laser alone; however, this improvement did not reach statistical significance. Minimal complications occurred in the form of mild pain. CONCLUSION: A low-power fractional CO2 laser is an effective, safe treatment for melasma. However, the addition of tranexamic acid (either topically or intradermally) to a fractional CO2 laser should be further studied. Lasers Surg. Med. 51:27-33, 2019. © 2018 Wiley Periodicals, Inc.

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.

Assessment of the effect of addition of 24 hours of oral tranexamic acid post-operatively to a single intraoperative intravenous dose of tranexamic acid on calculated blood loss following primary hip and knee arthroplasty (TRAC-24): a study protocol for a randomised controlled trial.

BACKGROUND: While it is has been proven that tranexamic acid (TXA) reduces blood loss in primary total hip and knee arthroplasty (THA and TKA), there is little published evidence on the use of TXA beyond 3 h post-operatively. Most blood loss occurs after wound closure and the primary aim of this study is to determine if the use of oral TXA post-operatively for up to 24 h will reduce calculated blood loss at 48 h beyond an intra-operative intravenous bolus alone following primary THA and TKA. To date, most TXA studies have excluded patients with a history of thromboembolic disease. METHODS/DESIGN: This is a phase IV, single-centred, open-label, parallel-group, randomised controlled trial. Participants are randomised to one of three groups: group 1, an intravenous (IV) bolus of TXA peri-operatively plus oral TXA post-operatively for 24 h; group 2, an IV bolus of TXA peri-operatively or group 3, standard care (no TXA). Eligible participants, including those with a history of thromboembolic disease, are allocated to these groups with a 2:2:1 allocation ratio. The primary outcome is the indirectly calculated blood loss 48 h after surgery. Researchers and patients are not blinded to the treatment; however, staff processing blood samples are. Originally 1166 participants were required to complete this study, 583 THA and 583 TKA. However, following an interim analysis after 100 THA and 100 TKA participants had been recruited to the study, the data monitoring ethics committee recommended stopping group 3 (standard care). DISCUSSION: TRAC-24 will help to determine whether an extended TXA dosing regimen can further reduce blood loss following primary THA and TKA. By including patients with a history of thromboembolic disease, this study will add to our understanding of the safety profile of TXA in this clinical situation. TRIAL REGISTRATION: ISRCTN registry, ISRCTN58790500 . Registered on 3 June 2016, EudraCT: 2015-002661-36.

Topical use of tranexamic acid in open heart surgery.

OBJECTIVE: To determine the efficacy of topical pouring of tranexamic acid in reducing post-operative mediastinal bleeding, requirement for blood products and the rate of re-exploration for re-securing haemostasis or relief of pericardial tamponade after open heart surgery. METHODS: The prospective, randomised, placebo-controlled, double-blind comparative study was conducted from March 2013 to September 2015 at Rehmatul-lil-Alameen Institute of Cardiology, Punjab Employees Social Security Institution, Lahore, and comprised patients scheduled for primary isolated elective or urgent open heart surgery. The subjects were divided into two equal groups. The hetranexamic acid group received cardiac bath with 2gm of tranexamic acid diluted in 50mlof normal saline, while the placebo group received cardiac bath without tranexamic acid. Before the closure of sternum, the solution was poured into pericardial cavity as cardiac bath while the chest tubes were temporarily clamped. Data was entered into a pre-designed proforma. RESULTS: Of the 100 subjects, there were 50(50%) in each of the two groups. There was no difference in surgical characteristics and perioperative complications in the groups (p>0.05). After 48 post-operative hours, total blood loss was significantly less in the tranexamic acid group compared to the placebo group (p<0.05). Significantly less number of blood pints were transfused in the acid group than the placebo group (p<0.05). No patient in the acid group was re-explored for excessive bleeding compared to 4(8%) in the placebo group. CONCLUSIONS: There was significant reduction in post-operative blood drainage, need of blood products and rate of re-exploration after topical use of tranexamic acid in open heart surgery.

Efficacy of oral tranexamic acid on blood loss in primary total hip arthroplasty using a direct anterior approach: a prospective randomized controlled trial.

BACKGROUND: Tranexamic acid (TXA), delivered intravenously or topically, has been shown to reduce blood loss, the need for transfusion, and relevant healthcare costs when administered in primary standard total hip arthroplasty (THA). Whether the same is true of oral TXA is unclear, the purpose of this study was to determine if oral tranexamic acid is equivalent to intravenous TXA in the case of patients undergoing THA via the direct anterior approach. METHODS: In this prospective randomized controlled trial, 120 patients undergoing primary THA by the direct anterior approach were randomized to receive oral TXA (two doses of 20 mg/kg), intravenous TXA (two doses of 15 mg/kg), or no TXA. Primary outcomes were haemoglobin drop, haematocrit levels, total blood loss, intra-operative blood loss, need for transfusion, and volume transfused. Secondary outcomes included thromboembolic events, wound complications, the length of post-operative hospital stay, and 30-day readmission. RESULTS: Demographic characteristics were similar among the three patient groups (p > 0.05, n = 40 per group). Haemoglobin drop, haematocrit levels, total blood loss, and intra-operative blood loss were similar in the oral and intravenous groups (p > 0.05), and significantly smaller than in the control group (p < 0.05). Transfusions were given to significantly fewer patients in the oral group (3%) and intravenous group (6%) than in the control group (27%, p = 0.01). Costs of TXA and transfusions were significantly lower in the oral group than the intravenous group (p < 0.05). The three groups were similar in thromboembolic events, wound complications, the length of post-operative hospital stay, and 30-day readmission (p > 0.05). CONCLUSION: Oral TXA shows similar efficacy and safety as intravenous TXA for reducing haemoglobin drop, haematocrit levels, total blood loss, and transfusion rate following THA by the direct anterior approach. Therefore, the much less-expensive oral formulation may be superior to the intravenous form.

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.