Unravelling the Antifibrinolytic Mechanism of Action of the 1,2,3-Triazole Derivatives.

A new family of antifibrinolytic drugs has been recently discovered, combining a triazole moiety, an oxadiazolone, and a terminal amine. Two of the molecules of this family have shown activity that is greater than or similar to that of tranexamic acid (TXA), the current antifibrinolytic gold standard, which has been associated with several side effects and whose use is limited in patients with renal impairment. The aim of this work was to thoroughly examine the mechanism of action of the two ideal candidates of the 1,2,3-triazole family and compare them with TXA, to identify an antifibrinolytic alternative active at lower dosages. Specifically, the antifibrinolytic activity of the two compounds (1 and 5) and TXA was assessed in fibrinolytic isolated systems and in whole blood. Results revealed that despite having an activity pathway comparable to that of TXA, both compounds showed greater activity in blood. These differences could be attributed to a more stable ligand-target binding to the pocket of plasminogen for compounds 1 and 5, as suggested by molecular dynamic simulations. This work presents further evidence of the antifibrinolytic activity of the two best candidates of the 1,2,3-triazole family and paves the way for incorporating these molecules as new antifibrinolytic therapies.

Role of prophylactic tranexamic acid in reducing blood loss during cesarean section: A double-blind placebo-controlled randomized controlled trial.

Background: Postpartum hemorrhage (PPH) is defined by the World Health Organization as blood loss of ≥500 mL within 24 h of delivery. Globally, hemorrhage accounts for 27.1% of maternal deaths, making it the leading direct cause of maternal death. PPH has been identified in more than two-thirds of reported hemorrhage-related deaths, causing 38% of maternal deaths in India. Tranexamic acid, an antifibrinolytic, has been used to control bleeding after PPH is identified. Materials and Methods: Antenatal women admitted for elective cesarean section were randomized into two arms: the case group (received one gram of tranexamic acid 20 min prior to skin incision) and the control group (received a placebo), each group consisting of 36 participants. Clinical Trials Registry - India (CTRI) registration number - CTRI/2021/02/031579. Results: The mean (±standard deviation [SD]) intraoperative blood loss in the case group was 241.25 (±67.83) mL, and in the control group, it was 344.92 (±146.67) mL (P = 0.001), while postoperative blood loss did not differ significantly between the groups (P = 0.1470). In terms of the difference in hemoglobin, there was a significant difference between the two groups (P = 0.001). No significant maternal or neonatal side effects were found. Conclusion: Preoperative tranexamic acid, when given in elective cesarean section, significantly reduces intraoperative blood loss.

Efficacy of intraoperative use of tranexamic acid in reducing blood loss from telescoping nail application in osteogenesis imperfecta. A randomized controlled trial.

BACKGROUND: Osteogenesis imperfecta (O.I) is a rare disease caused by an abnormality in type 1 collagen synthesis leading to repeated fractures after low-energy trauma and progressive long bones deformity. Telescoping nail application and surgical correction of these deformities usually necessitates multiple osteotomies and significant bleeding occur due to weakened capillaries and impaired platelet activity. Tranexamic acid (TXA) has an antifibrinolytic effect which is useful in reducing bleeding and need for blood transfusions following several orthopaedic procedures. HYPOTHESIS: The use of intraoperative (Local and Intravenous) tranexamic acid reduces blood loss during femoral telescoping nail application in O.I. MATERIAL AND METHODS: A prospective randomized controlled study was carried out on 40 patients during applying femoral telescoping nail divided into Group A: (case TXA); 20 patients receiving intraoperative TXA and Group B: (control); 20 patients not receiving TXA. Blood loss and perioperative Hemoglobin (Hb) and Hematocrit Level (Hct) were assessed. RESULTS: The study included 29 males and 11 females with mean age 7.98 years. The number of osteotomies in both groups ranged from zero to 3 osteotomies with a median one osteotomy. A significant decrease in blood loss was observed in TXA group (mean 241.5 cc) compared to control group (mean 461.5 cc). Postoperative Hb was significantly lower in control group (mean 12.30 g/dL changed to 10.45 g/dL) compared to TXA group (mean 12.26 g/dL changed to 11.52 g/dL). Also, postoperative Hct was significantly lower in control group (m:ean 37.37 % changed to 32.03%) compared to TXA group (mean 36.53 % changed to 34.66 %). DISCUSSION: The use of TXA during femoral telescoping nail application in OI patients has contributed to a remarkable reduction in overall blood loss. Consideration of adding it to management protocol is advised. LEVEL OF EVIDENCE: II; Randomized Controlled Trial (RCT).

Incidence of Subclinical Deep Vein Thrombosis after Total Hip and Knee Arthroplasty Is Not Correlated with Number of Tranexamic Acid Doses.

Background: Recent studies increasingly highlight the efficacy of tranexamic acid administration in total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, the optimal dosage of tranexamic acid is still controversial. Methods: The current study analyzes the efficiency of tranexamic acid dosage and the number of administrations in THA and TKA. The objective of this study is to compare the incidence of deep vein thrombosis (DVT) based on the number of dosages. We divided the patients into two groups; one group received a single dosage, and the other group received two dosages. Doppler ultrasound examinations were conducted on the lower limbs of all patients at both six and thirty days postoperatively. The second objective is to compare the decrease in hemoglobin (Hb) in the two groups. Results: The results show that there is no difference in DVT incidence between the patients with different TXA numbers of dosages. There is no statistically significant decrease in Hb between the two groups at day one and day five postoperatively. Day one shows a statistically higher average in the two-dose group, approximately 0.06 g/dL, and day five shows a slightly elevated average in the single-dose group, approximately 0.06 g/dL. Blood transfusion requirements show no significant differences in the groups; one patient in the single-dose tranexamic acid group needed transfusion at day five postoperatively, while two patients in each group required immediate postoperative transfusion. Conclusion: There was no increase in the incidence of deep vein thrombosis among patients receiving two dosages of tranexamic acid.

Safety and Efficacy of Tranexamic Acid in Spinal Surgery: A Systematic Review and Meta-Analysis.

Background: Tranexamic acid (TXA) has gained popularity in spinal surgery because of its potential to reduce blood loss. However, concerns regarding its safety and efficacy remain. This systematic review and meta-analysis aimed to evaluate the efficacy of TXA in reducing blood loss and its safety profile in spinal surgeries. Methods: A comprehensive search was conducted in electronic databases for randomized controlled trials and prospective studies evaluating the use of TXA in spinal surgery. The primary outcomes were intraoperative and total estimated blood loss (EBL), and the secondary outcomes included the incidence and types of complications associated with TXA use. Meta-analyses were performed using random-effects models. Results: Thirteen studies involving 1,213 participants were included in the meta-analysis. The use of TXA was associated with significant reductions in both intraoperative (mean difference: -46.56 mL [-73.85, -19.26], p<0.01]) and total EBL (mean difference: -210.17 mL [-284.93, -135.40], p<0.01) while also decreasing the need for blood transfusions (risk ratio: 0.68 [0.51, 0.90], p<0.01). No significant difference was found in the incidence and types of thrombotic complications when TXA was used in spinal surgery. Subgroup analysis showed consistent results in instrumentation and fusion surgery and different doses of TXA. Conclusions: TXA is effective in reducing intraoperative and overall blood loss in spinal surgery without increasing the risk of complications. These findings support the use of TXA to improve patient outcomes. However, caution should be exercised because of the heterogeneity among the included studies. Further research is needed to confirm these findings and explore potential long-term complications.

Effect of Tranexamic Acid on Hidden Blood Loss in Percutaneous Endoscopic Transforaminal Lumbar Interbody Fusion: A Retrospective Study.

Purpose: Percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) has become one of the most popular minimally invasive surgeries today. However, the issue of hidden blood loss (HBL) in this surgery has received little attention. This study aims to examine the HBL in PE-TLIF surgery and the effect of tranexamic acid (TXA) on blood loss. Methods: In our research, We conducted a retrospective analysis of 300 patients who underwent PE-TLIF from September 2019 to August 2023. They were divided into 2 groups based on whether they received intravenous TXA injection before surgery. The variables compared included: demographic data, pre-and postoperative hemoglobin (HB), hematocrit (HCT), platelets (PLT), red blood cells (RBC), total blood loss (TBL), visible blood loss (VBL), HBL, operation time, postoperative hospital stay, inflammatory markers, coagulation parameters, and adverse events. Results: Regarding demographic characteristics, besides the operation time, no significant differences were observed between the two groups. Compared with the control group, the TXA group showed a significant reduction trend in TBL, HBL, and VBL (P < 0.05). On the first day after surgery, there were significant differences in prothrombin (PT), activated partial thromboplastin time (APTT), and D-dimer (D-D) levels between the two groups. Similarly, HCT also found similar results on the third day after surgery. No adverse events occurred in either group. Conclusion: Research has found that there is a significant amount of HBL in patients undergoing PE-TLIF. Intravenous injection of TXA can safely and effectively reduce perioperative HBL and VBL. Additionally, compared to the control group, the TXA group shows a significant reduction in operation time.

Venous Thromboembolic Events in Adult Trauma Patients Receiving Balanced Hemostatic Resuscitation (BHR): An Analysis of Their Incidence, Predictors, and Associated Mortality Rates at a Level 1 Trauma Center.

Background and objective Studies assessing the incidence of venous thromboembolic (VTE) events in the setting of massive balanced transfusions and/or tranexamic acid (TXA) infusion have yielded varied outcomes. In light of this, we conducted this study to examine the incidence of VTEs in trauma patients requiring blood products, and to identify the risk factors for VTE and mortality in this population. Methods We performed a retrospective analysis of trauma patients admitted to our level 1 trauma center from January 2013 to September 2023. Clinical characteristics were compared between patients who developed VTE and those who did not. A regression analysis of potential variables associated with the development of VTEs and mortality was performed. Results Among 1305 patients (mean age: 42.4 ± 18.8 years) receiving blood products within the initial 24 hours, 4.3% (56 patients) developed a VTE. Patients with VTE experienced prolonged ICU and hospital stays and ventilation duration (p<0.001). They were also noted to have delayed initiation of VTE prophylaxis (104.2 vs. 50.3 hours, p<.001). Prolonged ventilation >7 days was the sole significant factor associated with VTE in multivariate regression analysis [odds ratio (OR): 6.2, p=0.004]. Early TXA administration (within four hours) showed a higher association with VTE than TXA within 24 hours (OR: 2.1, p=0.07 vs. OR 1.6, p=0.22). Massive transfusion was found to increase VTE risk (OR: 2.65, p<0.001). Severe head and neck (OR: 6.0, p=0.002) and chest (OR: 3.8, p=0.01) injuries were key predictors of mortality, while TXA was not significantly associated with mortality in the multivariate model. Conclusions Our study revealed an elevated risk of VTE in patients requiring massive transfusion protocol (MTP, ≥6 units). Early TXA administration was neither associated with increased VTE risk in MTP patients nor increased mortality risk. Strategies directed at reducing the risk of VTE in massively transfused patients while maintaining the survival benefits of balanced resuscitation and TXA need to be devised.

Therapeutic efficiency and safety assessment of intradermal platelet-rich plasma combined with oral tranexamic acid in patients with facial melasma.

BACKGROUND: Melasma is a chronic, acquired hypermelanosis that primarily affects the face. Platelet-rich plasma (PRP) and tranexamic acid (TXA) are promising treatments for melasma. However, only a few randomized clinical trials have examined the efficacy and safety of combining these therapies for melasma. OBJECTIVES: We aimed to compare the efficacy and safety of combining PRP and oral TXA with those of PRP alone in the treatment of facial melasma. MATERIAL AND METHODS: A randomized controlled trial was conducted at Walailak University Hospital, Nakhon Si Thammarat, Thailand, between March and September 2023. Participants with mixed-type melasma were randomly allocated in a 1:1 ratio to either group A (PRP injection alone without placebo) or group B (PRP injection with oral TXA). Therapeutic efficacy and safety assessments were performed over a 12-week follow-up period. RESULTS: The study included 26 participants (mean age: 45.9 years, standard deviation (±SD): 5.0) who were predominantly female (84.6%). In group A, the modified Melasma Area and Severity Index (mMASI) scores significantly decreased from a median of 4.30 interquartile range (IQR): 4.10) to 3.60 (IQR: 3.10) between week 0 and week 12, respectively. In group B, the median mMASI decreased from 6.40 (IQR: 7.80) to 3.60 (IQR: 3.70) over the same period. The median change in mMASI scores in group B (2.90, IQR: 2.40) was significantly larger than in group A (0.90, IQR: 0.60) (p < 0.001, U = 160.50). However, there were no significant differences in the physicians' global assessment (PGA), melasma quality of life scale (MelasQoL) or patient satisfaction during follow-up. Four patients (15.4%) experienced transient erythema and swelling. In group B, 1 participant (7.7%) experienced transient mild gastrointestinal discomfort after receiving oral TXA. CONCLUSIONS: The combination of intradermal PRP injection and oral TXA is effective for melasma, even in patients with poor prognostic treatment response factors. No serious adverse reactions were observed in either group.

Tranexamic acid-loaded catechol-modified hyaluronic acid/carboxymethyl chitosan double cross-linked porous gel micropowders for rapid hemostasis and wound healing.

Acquiring rapid and effective hemostasis remains a critical clinical challenge. Current researches focus on concentrating blood components to speed up the hemostatic while ignore the effect of anti-fibrinolysis in promoting blood coagulation. Herein, we designed a novel tranexamic acid (TA)-loaded physicochemical double cross-linked multifunctional catechol-modified hyaluronic acid-dopamine/carboxymethyl chitosan porous gel micropowders (TA&Fe3+@HA-DA/CMCS PGMs) for rapid hemostasis and wound healing. TA&Fe3+@HA-DA/CMCS PGMs exhibited high water absorption rate (505.9 ± 62.1 %) and rapid hemostasis (79 ± 4 s) in vivo. Catechol groups, Fe3+ and the protonated amino groups of CMCS induced bacterial death. Moreover, TA&Fe3+@HA-DA/CMCS PGMs displayed sufficient adhesion to a variety of wet rat tissues. TA&Fe3+@HA-DA/CMCS PGMs on various bleeding wounds, including rat liver injury and tail severed models showed excellent hemostasis performance. The TA&Fe3+@HA-DA/CMCS PGMs could promote the healing of full-thickness skin wounds on the backs of rats. The advantages of TA&Fe3+@HA-DA/CMCS PGMs including rapid hemostasis, effective wound healing, good tissue adhesion, antibacterial properties and ease of use make it potentially valuable in clinical application.

Potential Role of Tranexamic Acid in Rosacea Treatment: conquering Flushing Beyond Melasma.

Rosacea is a chronic inflammatory skin disease that affects a patient's appearance and quality of life. It mainly affects the midface region and presents as erythema, flushing, telangiectasia, papules, pustules, and rhinophyma. Despite its prevalence, the precise pathophysiology of rosacea remains unknown, and novel pharmacological therapies are currently under investigation. Tranexamic acid (TA) is a synthetic, lysine-like compound that competitively inhibits fibrinogen production by synthesizing fibrinolytic enzymes. In addition to its popular application in hemorrhage treatment, TA has been used to manage a number of skin conditions, including melasma, chronic urticaria, and angioedema. TA is a better option for melasma treatment. However, the role of TA in treating rosacea has not yet been systematically elucidated. In this study, we reviewed all available literature on the use of TA for rosacea treatment. The included articles examined the therapeutic effects of TA in patients with rosacea, including traditional methods such as oral and topical administration and more novel approaches such as intradermal injections, microneedling, and laser-assisted delivery. Several recent clinical studies demonstrated that TA alleviates rosacea symptoms by restoring the permeability barrier, ameliorating the immune reaction, and inhibiting angiogenesis. In this review, we summarized the function and potential application of TA in rosacea treatment, aiming to facilitate the implementation of clinical applications.

Clinical Efficacy of Intra-articular Tranexamic Acid Injection in the Management of Hemophilia with Total Hip Arthroplasty: A 24-month Retrospective Cohort Study.

OBJECTIVE: Total hip arthroplasty (THA) effectively treats end-stage hemophilic hip arthropathy. Given hemophilia's unique characteristics, perioperative bleeding remains a significant risk for patients undergoing THA. Tranexamic acid (TXA), an efficient antifibrinolytic agent, may benefit the outcomes of THA for patients with hemophilia (PWH). This study aims to explore the clinical efficacy of intra-articular injection of TXA in treating perioperative bleeding in PWH and assess its additional clinical benefits. METHODS: The retrospective study comprised data of PWH who received THA from January 2015 to December 2021 in the research center. A total of 59 individuals were included in the study, divided into a TXA group (n = 31) and a non-TXA group (n = 28). We compared various parameters, including total blood loss (TBL), visible blood loss (VBL), occult blood loss (OBL), intraoperative coagulation factor VIII (FVIII) consumption, perioperative total FVIII consumption, hemoglobin (HB), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), length of hospital stay, hospitalization costs, length of surgery, total protein, activated partial thromboplastin time (APTT), D-dimer, rate of joint swelling, hip joint range of motion (ROM), visual analogue scale (VAS), and Harris hip joint function scale (HHS) between the two groups. Follow-up assessments were conducted for up to 24 months. A Student's t test was utilized for the statistical analysis. RESULTS: This study demonstrated that intra-articular TXA effectively reduced TBL (1248.19 ± 439.88 mL, p < 0.001), VBL (490.32 ± 344.34 mL, p = 0.003), and OBL (757.87 ± 381.48 mL, p = 0.004) in PWH who underwent THA. TXA demonstrated effectiveness in reducing VAS scores on POD1, POD7, and POD14 and joint swelling rates on POD1, POD7, POD14, and at discharge (p < 0.05). Additionally, the TXA group achieved higher HHS ratings at all follow-up time points (p < 0.05), showing superior hip joint mobility, lower postoperative inflammation levels, reduced factor VIII consumption during surgery, and less postoperative nutritional loss. No statistically significant differences were observed between the two groups in terms of hospital stay, hospitalization costs, surgery duration, and coagulation indicators. CONCLUSION: Intra-articular injection of TXA reduces perioperative bleeding in PWH undergoing THA while also improving joint mobility, post-operative rehabilitation, and quality of life. This may provide value for the future application of TXA in PWH.

Tranexamic acid may benefit patients with preexisting thromboembolic risk undergoing total joint arthroplasty: a systematic review and meta-analysis.

Purpose: This study sought to determine if the use of tranexamic acid (TXA) in preexisting thromboembolic risk patients undergoing total joint arthroplasty (TJA) was linked to an increased risk of death or postoperative complications. Methods: We conducted a comprehensive search for studies up to May 2023 in PubMed, Web of Science, EMBASE, and the Cochrane Library. We included randomized clinical trials, cohort studies, and case-control studies examining the use of TXA during TJA surgeries on high-risk patients. The Cochrane Risk of Bias instrument was used to gauge the excellence of RCTs, while the MINORS index was implemented to evaluate cohort studies. We used mean difference (MD) and relative risk (RR) as effect size indices for continuous and binary data, respectively, along with 95% CIs. Results: Our comprehensive study, incorporating data from 11 diverse studies involving 812 993 patients, conducted a meta-analysis demonstrating significant positive outcomes associated with TXA administration. The findings revealed substantial reductions in critical parameters, including overall blood loss (MD = -237.33; 95% CI (-425.44, -49.23)), transfusion rates (RR = 0.45; 95% CI (0.34, 0.60)), and 90-day unplanned readmission rates (RR = 0.86; 95% CI (0.76, 0.97)). Moreover, TXA administration exhibited a protective effect against adverse events, showing decreased risks of pulmonary embolism (RR = 0.73; 95% CI (0.61, 0.87)), myocardial infarction (RR = 0.47; 95% CI (0.40-0.56)), and stroke (RR = 0.73; 95% CI (0.59-0.90)). Importantly, no increased risk was observed for mortality (RR = 0.53; 95% CI (0.24, 1.13)), deep vein thrombosis (RR = 0.69; 95% CI (0.44, 1.09)), or any of the evaluated complications associated with TXA use. Conclusion: The results of this study indicate that the use of TXA in TJA patients with preexisting thromboembolic risk does not exacerbate complications, including reducing mortality, deep vein thrombosis, and pulmonary embolism. Existing evidence strongly supports the potential benefits of TXA in TJA patients with thromboembolic risk, including lowering blood loss, transfusion, and readmission rates.

Intrafocal injection of tranexamic acid decreases early return to hospital after high tibial osteotomy.

INTRODUCTION: High tibial osteotomy (HTO) is a surgery performed to treat the symptoms and prevent the progression of medial osteoarthritis. Post-operative bleeding has led to early returns to hospital following surgery. Intrafocal injection of tranexamic acid (TXA) could reduce this bleeding complication. The objective of the study was to evaluate the effect of TXA during HTO on the incidence of post-operative complications and early returns to hospital. MATERIALS AND METHODS: This retrospective study included 251 cases of HTO performed between May 2012 and October 2021, with the use of TXA introduced in May 2017. The experimental (n = 102) and control (n = 149) groups were compared as to the rate of post-operative early returns. The influence of confounding factors was evaluated, including age, sex, body mass index (BMI), tobacco use, grade of medial femorotibial osteoarthritis (MFTO), magnitude of angular correction (MAC), and surgery duration. RESULTS: No statistically significant difference was found between the groups with regards to all variables except age. The experimental group was significantly older (54.4 years; σ = 7.5) than the control group (50.4 years; σ = 7.9; p < 0.001). We observed a decrease in emergency department (ED) visits in the experimental group (15.7%) compared to the control (30.2%; p = 0.008) and a decrease in early returns in the experimental group (28.4%) compared to the control (40.5%; p = 0.049). No statistically significant difference in demographic data, MFTO, or MAC was found among patients with and without an early return, in both the experimental and control groups. CONCLUSION: The intrafocal injection of TXA during HTO decreases early returns to hospital.

Tranexamic acid as a therapeutic option for melasma management: meta-analysis and systematic review of randomized controlled trials.

Purpose: This study aimed to evaluate the efficacy of tranexamic acid (TXA) in treating melasma through a meta-analysis and systematic review of randomized controlled trials (RCTs). The study focused on identifying associated adverse effects and comparing TXA's effectiveness with other melasma treatments.Materials and methods: Following PROSPERO and PRISMA guidelines, an extensive electronic search was conducted across four databases for RCTs on TXA use in melasma. Inclusion criteria encompassed full-text English articles with specific outcome measures, while studies with high bias risk or non-English publications were excluded. Data were extracted from 22 relevant studies and analyzed using the RevMan software, with heterogeneity identified using I² statistics and forest plots.Results: A total of 22 studies with 1280 patients were included. TXA was administered orally, topically, or via injection, with treatment durations ranging from 8 weeks to nearly 2 years. TXA significantly reduced melasma severity, evidenced by reductions in MASI, mMASI, MI, and hemi-MASI scores. Oral TXA showed the most substantial decrease in MASI scores, followed by injections and topical applications. However, studies exhibited high heterogeneity, particularly in combined treatments. Adverse effects included gastrointestinal discomfort, skin irritation, and menstrual irregularities.Conclusions: TXA is effective in treating melasma, either alone or combined with other treatments. Despite significant reductions in melasma severity, further research is necessary to standardize TXA administration methods and address long-term effects. The high heterogeneity observed suggests a need for more consistent treatment protocols.

Mesotherapy for Melasma - An Updated Review.

Mesotherapy is a popular novel therapeutic modality that delivers intradermal or subcutaneous microinjections of pharmaceutical compounds. Although this novel treatment method is used commonly in aesthetic dermatology, there is little information about the details of injections, efficacy, and side effects of mesotherapy in melasma. In this review, we evaluated the efficacy of various types of anti-pigmentation agents used with mesotherapy in the management of melasma.

Prolonged joint cavity retention of tranexamic acid achieved by a solid-in-oil-in-gel system: A preliminary study.

Tranexamic acid (TXA) is an anti-fibrinolysis agent widely used in postoperative blood loss management. As a highly water-soluble drug, TXA is suffering from rapid clearance from the action site, therefore, large amount of drug is required when administered either by intravenously or topically. In this study, a TXA preparation with prolonged action site residence was designed using the nano-micro strategy. TXA nanoparticles were dispersed in oil by emulsification followed by lyophilization to give a solid-in-oil suspension, which was used as the oil phase for the preparation of TXA-loaded solid-in-oil-in-water (TXA@S/O/W) system. The particle size of TXA in oil was 207.4 ± 13.50 nm, and the particle size of TXA@S/O/W was 40.5 µm. The emulsion-in-gel system (TXA@S/O/G) was prepared by dispersing TXA@S/O/W in water solution of PLGA-b-PEG-b-PLGA (PPP). And its gelling temperature was determined to be 26.6 ℃ by a rheometer. Sustained drug release was achieved by TXA@S/O/G with 72.85 ± 7.52 % of TXA released at 120 h. Formulation retention at the joint cavity was studied by live imaging, and the fluorescent signals dropped gradually during one week. Drug escape from the injection site via drainage and absorption was investigated by a self-made device and plasma TXA concentration determination, respectively. TXA@S/O/G showed the least drug drainage during test, while more than 70 % of drug was drained in TXA@S/O/W group and TXA solution group. Besides, low yet steady plasma TXA concentration (less than 400 ng/mL) was found after injecting TXA@S/O/G into rat knees at a dosage of 2.5 mg/kg, which was much lower than those of TXA dissolved in PPP gel or TXA solution. In conclusion, sustained drug release as well as prolonged action site retention were simultaneously achieved by the designed TXA@S/O/G system. More importantly, due to the steady plasma concentration, this strategy could be further applied to other highly water-soluble drugs with needs on sustained plasma exposure.

The necessity of suction drainage when intra-articular injection of tranexamic acid is used during primary total knee arthroplasty: a retrospective study.

BACKGROUND: Suction drainages are commonly used after total knee arthroplasty (TKA) procedures; however, their use is somewhat controversial. Recently, some reports have claimed that the administration of tranexamic acid (TXA) may prevent postoperative bleeding following TKAs. Although numerous studies have reported regarding different dosages, timings of administration, or drain clamping times for intravenous and intra-articular TXA injections (IA-TXAs), few have examined whether suction drainage is necessary when TXA is administered. In this study, we compared using suction drainage without TXA administration and IA-TXA without suction drainage and aimed to examine the need for suction drainage during IA-TXA. METHODS: This retrospective study was conducted on 217 patients who had received TKA for osteoarthritis; 104 were placed on suction drainage after TKA without TXA (Group A), whereas the remaining 113 received IA-TXA immediately after surgery without suction drainage (Group B). Our clinical evaluation included assessments of the need for transfusion, presence of postoperative complications, incidence of deep vein thrombosis (DVT), and changes in hemoglobin (Hb), hematocrit (Hct), and D-dimer levels. RESULTS: No significant differences were observed in terms of postoperative complications and preoperative Hb, Hct, or D-dimer levels between the two groups. Although the prevalence of DVT was significantly higher in Group B (p < 0.05), all cases were asymptomatic. Hb and Hct levels were significantly lower in Group A than in Group B at 1, 3, 7, and 14 days postoperatively (p < 0.05), although none of the cases required blood transfusions. D-dimer levels were significantly higher in Group A than in Group B at 1 and 3 days postoperatively (p < 0.05). CONCLUSION: Suction drainage might not be necessary when IA-TXA is administered after TKA procedures.

A randomised controlled trial assessing the effect of tranexamic acid on post-operative blood transfusions in patient with intra-capsular hip fractures treated with hemi- or total hip arthroplasty.

BACKGROUND: Intravenous tranexamic acid (TA) has proven efficacy in reducing blood loss and incidence of transfusion of blood products in elective total joint arthroplasty. However, evidence of efficacy in the setting of intracapsular hip fractures needing hip hemiarthroplasty (HA) or total hip arthroplasty (THA) are scarce. This study aimed to assess post-operative transfusion incidence in this clinical setting. METHODS: Over a five-year period 250 patients with intracapsular neck of femur fractures requiring arthroplasty were randomised to two groups. The treatment group received three-dose intravenous TA protocol and the control group received usual treatment without administration of TA. Blood loss was estimated from the change in Hb levels on day 1, 3 and 5 after surgery compared to preoperative levels. Transfusions of blood products were recorded when they were triggered by an a priori protocol. Post-operative complications were recorded during patient hospital admission. RESULTS: The intervention group showed significantly lower transfusion incidence of packed red blood cells (PRBC) (6 vs. 15, p = 0.04, OR = 0.37, 95%CI OR = 0.14 to 0.99) and in the group of patients who received a blood transfusion, a trend was observed for patients who received TA to have lesser number of units of PRBC (mean = 1.3 vs. 1.6, p = 0.51). A significant difference was noted in post-operative Hb levels of day 1,3 and 5. Backward stepwise multivariable regression analysis showed the use of TA was the most significant factor for reduction in postoperative blood transfusion (p = 0.047, OR = 0.37, 95% CI OR = 0.14 to 0.99). Assessment of the strength of the correlation showed modest correlation (Pearson correlation - 0.13 p = 0.04, 95% CI correlation= -0.25 to -0.01). There was no increase in adverse events in patients who received TA. CONCLUSION: The use of TA in setting of intracapsular hip fractures requiring arthroplasty reduces blood loss, the need for transfusion of blood products and may reduce surgical site complications without increasing the risk of VTE.

The hemostatic and anti-inflammatory effects of intravenous single-dose of tranexamic acid in double-segment posterior lumbar interbody fusion: a case control study.

This study aims to observe the hemostatic and anti-inflammatory effects of intravenous administration of tranexamic acid (TXA) in dual segment posterior lumbar interbody fusion (PLIF). The data of 53 patients with lumbar disease treated with double-segment PLIF were included in this study. The observation group was received a single-dose intravenous of TXA (1 g/100 mL) 15 min before skin incision after general anesthesia. The control group was not received TXA. The observation indicators included postoperative activated partial prothrombin time (APTT), thrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelets (PLT), and postoperative deep vein thrombosis in the lower limbs, surgical time, intraoperative bleeding volume, postoperative drainage volume, transfusion rate, postoperative hospital stay, red blood cell (RBC), hemoglobin (HB), hematocrit (HCT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) on the 1st, 4th, 7th, and last tested day after surgery. All patients successfully completed the operation, and there was no deep vein thrombosis after operation. There was no statistically significant difference in postoperative APTT, PT, TT, FIB, PLT, surgical time, and postoperative hospital stay between the two groups (p > 0.05). The intraoperative bleeding volume, postoperative drainage volume, and transfusion rate in the observation group were lower than those in the control group, and the differences were statistically significant (p < 0.05). There was no statistically significant difference in RBC, HB, HCT, CRP, and ESR between the two groups on the 1st, 4th, 7th, and last tested day after surgery (p > 0.05). Intravenous administration of TXA in dual segment PLIF does not affect coagulation function and can reduce bleeding volume, postoperative drainage volume, and transfusion rate. Moreover, it does not affect the postoperative inflammatory response.

Topical Tranexamic Acid to Control Vaginal Laceration Bleeding after Sexual Assault.

BACKGROUND: Sexual assault survivors may sustain vaginal trauma that requires intervention in the emergency department, or operating room. CASE REPORT: We describe the case of a 16-year-old female who was referred to the emergency department for evaluation of continued bleeding from a vaginal laceration following sexual assault 38 h prior. The bleeding limited the medical forensic medical examination, but she was hemodynamically stable. After the application of tranexamic acid (TXA)-soaked gauze, the patient's bleeding was controlled and the wound was able to be evaluated and the examination completed. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: To our knowledge, this is the first case in the literature that describes the use of topical TXA in a patient to achieve hemostasis in a vaginal laceration sustained from sexual violence.