The novel thromboxane prostanoid receptor mediates CTGF production to drive human nasal fibroblast self-migration through NF-κB and PKCδ-CREB signaling pathways.

Chronic rhinosinusitis without nasal polyp (CRSsNP) is characterized by tissue repair/remodeling and the subepithelial stroma region in whose nasal mucosa has been reported by us to have thromboxane A2 (TXA2) prostanoid (TP) receptor and overexpress connective tissue growth factor (CTGF). Therefore, this study aimed to investigate the relationship between TP receptor activation and CTGF production/function in human CRSsNP nasal mucosa stromal fibroblasts. We found that TP agonists including U46619 and IBOP ([1S-[1α,2α(Z),3ß(1E,3 S*),4α]]-7-[3-[3-hydroxy-4-(4-iodophenoxy)-1-butenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid) could promote CTGF protein/messenger RNA expression and secretion. The pharmacological intervention and TP activation assay with U46619 identified the possible participation of PKCµ, PKCδ, nuclear factor-κB (NF-κB), and cyclic AMP response element-binding protein (CREB) phosphorylation/activation in the CTGF induction. Moreover, a phorbol ester-phorbol-12-myristate 13-acetate (PMA) exhibited a similar cellular signaling and CTGF production profile to that elicited by TP activation. However, further small interfering RNA interference analysis revealed that only NF-κB and PKCδ-CREB pathways were necessarily required for TP-mediated CTGF production, which could not be completely supported by those findings from PMA. Finally, in a functional assay, although CTGF did not affect fibroblast proliferation, TP-mediated CTGF could drive novel self-migration in fibroblasts both in the scratch/wound healing and transwell apparatus assays. Meanwhile, the overall staining for stress fibers and formation of the lamellipodia and filopodia-like structures was concomitantly increased in the treated migrating cells. Collectively, we provided here that novel TP mediates CTGF production and self-migration in human nasal fibroblasts through NF-κB and PKCδ-CREB signaling pathways. More importantly, we also demonstrated that thromboxane, TP receptor, CTGF, and stromal fibroblasts may act in concert in the tissue remodeling/repair process during CRSsNP development and progression.

Intravenous tranexamic acid reduces complications following surgical treatment of pathologic fractures of the lower extremity.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the postoperative complications associated with administering intravenous (IV) tranexamic acid (TXA) in patients undergoing surgical fixation for neoplastic pathologic fractures of the lower extremities. METHODS: Patients ≥18 years old who underwent surgical intervention for neoplastic pathologic lower extremity fractures from 2015 to 2021 were identified using the Premier Healthcare Database. This cohort was divided by TXA receipt on the index surgery day. Patient demographics, hospital factors, patient comorbidities, and 90-day complications were assessed and compared between the cohorts. RESULTS: From 2015 to 2021, 4497 patients met inclusion criteria (769 TXA[+] and 3728 TXA[-]). Following propensity score matching, patients who received TXA had a significantly shorter length of stay than those who did not (7.6 ± 7.3 days vs. 9.0 ± 15.2, p = 0.036). Between the two cohorts, there were no significant differences in comorbidities. Regarding differences in postoperative complications, TXA(+) patients had significantly decreased odds of deep vein thrombosis (DVT) (1.87% vs. 5.46%; odds ratio [OR]:0.33; 95% confidence interval: 0.17-0.62; p = 0.001). CONCLUSION: Administration of IV TXA may be associated with a decreased risk of postoperative DVT without an increased risk of other complications. Orthopedic surgeons should consider the utilization of IV TXA in patients treated surgically for neoplastic pathologic fractures of the lower extremity.

Prophylactic tranexamic acid for reducing blood loss in pregnant females undergoing cesarean section: A systematic review and meta-analysis.

OBJECTIVE: We aim to assess the efficacy of prophylactic tranexamic acid (TXA) in reducing blood loss after cesarean section (CS). METHODS: We systematically searched PubMed and Embase for randomized controlled trials published between 1990 and 2023 to conduct a meta-analysis on adult women undergoing CS and receiving prophylactic TXA. RESULTS: Twenty-four trials, comprising 19 584 participants, were included. Most studies included women with healthy, full-term, singleton pregnancies. The pooled estimate showed a reduction in mean blood loss in the TXA arm with a standardized mean difference (SMD) of -1.50 (-2.03, -0.98: p < 0.001). There was a high level of heterogeneity (I2 98.86%). A subgroup analysis demonstrated no statistical difference in the effect of TXA on blood loss at 2 h of follow-up with SMD of -2.24 (-3.23, -1.35) compared to -1.07 (-1.56, -0.58) and -1.10 (-2.62, -0.42) at 24 and 48 h, respectively (p = 0.11). The effect of TXA on blood loss was smaller in high-income countries with SMD -0.24 (-0.44, -0.04) (I2 63%) than in low-/middle-income countries -1.78 (-2.35, -1.21) with I2 98%. Only three studies had low risk of bias and the effect of TXA from two of them was SMD -0.31 (-0.54, -0.09) (I2 0%). CONCLUSIONS: Despite the apparent beneficial effect of TXA in reducing blood loss after CS for women with uncomplicated term pregnancies, heterogeneity remains a serious concern. The current body of knowledge consists predominantly of small, likely biased studies, and large unbiased studies show only limited effects of prophylactic TXA.

Definition of refractory melasma and its treatment: a review.

Although patients with refractory melasma have been treated using various methods, there is still no precise definition or summary of the therapies. To define refractory melasma and conduct a review of the treatments, we searched for relevant publications in PubMed, Web of Science, and the Cochrane Library, and a total of 35 references were obtained. Refractory melasma can be roughly defined as an ineffective treatment for melasma, including topical bleaching agents, chemical peels, laser therapy, microdermabrasion for more than six months, or chemical peels treated more than six times. Meanwhile, physicians should be careful when treating patients with darker skin and dermal or mixed types of melasma since these individuals do not respond well to treatment. Lasers combined with other methods, especially different types of lasers or topical agents, are considered more effective than monotherapy. Oral tranexamic acid (TXA) is a prospective cure for refractory melasma. Other methods include a combination of chemical peels, microneedling, or injections with additional therapies. In conclusion, we were able to provide a rough definition of refractory melasma and list the available therapies. According to the literature, the most prevalent treatment is laser combination therapy. However, laser treatment should be considered only after topical agents and chemical peeling have failed. Considering its side effects, efficacy, and safety, oral TXA may be a better option, but more research is needed to make a firm conclusion. Moreover, maintenance therapy is required after treatment.

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.

The Presence of TGFß3 in Human Ovarian Intrafollicular Fluid and Its Involvement in Thromboxane Generation in Follicular Granulosa Cells through a Canonical TGFßRI, Smad2/3 Signaling Pathway and COX-2 Induction.

Ovarian follicular fluid (FF) has a direct impact on oocyte quality, playing key roles in fertilization, implantation, and early embryo development. In our recent study, we found FF thromboxane (TX) to be a novel factor inversely correlated with oocyte maturation and identified thrombin, transforming growth factor ß (TGFß), TNF-α, and follicular granulosa cells (GCs) as possible contributors to FF TX production. Therefore, this study sought to investigate the role of TGFß3 in regulating TX generation in human ovarian follicular GCs. TGFß3 was differentially and significantly present in the FF of large and small follicles obtained from IVF patients with average concentrations of 68.58 ± 12.38 and 112.55 ± 14.82 pg/mL, respectively, and its levels were correlated with oocyte maturity. In an in vitro study, TGFß3 induced TX generation/secretion and the converting enzyme-COX-2 protein/mRNA expression both in human HO23 and primary cultured ovarian follicular GCs. While TGFßRI and Smad2/3 signaling was mainly required for COX-2 induction, ERK1/2 appeared to regulate TX secretion. The participation of Smad2/3 and COX-2 in TGFß3-induced TX generation/secretion could be further supported by the observations that Smad2/3 phosphorylation and nuclear translocation and siRNA knockdown of COX-2 expression compromised TX secretion in GCs challenged with TGFß3. Taken together, the results presented here first demonstrated that FF TGFß3 levels differ significantly in IVF patients' large preovulatory and small mid-antral follicles and are positively associated with oocyte maturation. TGFß3 can provoke TX generation by induction of COX-2 mRNA/protein via a TGFßR-related canonical Smad2/3 signaling pathway, and TX secretion possibly by ERK1/2. These imply that TGFß3 is one of the inducers for yielding FF TX in vivo, which may play a role in folliculogenesis and oocyte maturation.

Eugenol Suppresses Platelet Activation and Mitigates Pulmonary Thromboembolism in Humans and Murine Models.

Platelets assume a pivotal role in the pathogenesis of cardiovascular diseases (CVDs), emphasizing their significance in disease progression. Consequently, addressing CVDs necessitates a targeted approach focused on mitigating platelet activation. Eugenol, predominantly derived from clove oil, is recognized for its antibacterial, anticancer, and anti-inflammatory properties, rendering it a valuable medicinal agent. This investigation delves into the intricate mechanisms through which eugenol influences human platelets. At a low concentration of 2 µM, eugenol demonstrates inhibition of collagen and arachidonic acid (AA)-induced platelet aggregation. Notably, thrombin and U46619 remain unaffected by eugenol. Its modulatory effects extend to ATP release, P-selectin expression, and intracellular calcium levels ([Ca2+]i). Eugenol significantly inhibits various signaling cascades, including phospholipase Cγ2 (PLCγ2)/protein kinase C (PKC), phosphoinositide 3-kinase/Akt/glycogen synthase kinase-3ß, mitogen-activated protein kinases, and cytosolic phospholipase A2 (cPLA2)/thromboxane A2 (TxA2) formation induced by collagen. Eugenol selectively inhibited cPLA2/TxA2 phosphorylation induced by AA, not affecting p38 MAPK. In ADP-treated mice, eugenol reduced occluded lung vessels by platelet thrombi without extending bleeding time. In conclusion, eugenol exerts a potent inhibitory effect on platelet activation, achieved through the inhibition of the PLCγ2-PKC and cPLA2-TxA2 cascade, consequently suppressing platelet aggregation. These findings underscore the potential therapeutic applications of eugenol in CVDs.

The efficacy and safety of tranexamic acid utilization in total ankle arthroplasty: a systematic review and meta-analysis.

INTRODUCTION: There is still a lack of information on the role of Tranexamic acid (TXA) in total ankle arthroplasty (TAA). The purpose of this study is to comprehensively review, consolidate, and analyze findings from existing research on the effectiveness and safety of TXA in TAA. MATERIALS AND METHODS: The comprehensive literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) using PubMed, Embase, Web of Science, and Cochrane databases, for original, English-language studies investigating the efficacy and safety of TXA in TAA, through February 2023. Evaluated data for the meta-analysis included estimated blood loss (EBL), change in perioperative hemoglobin, need for transfusion, and complications including DVT/PE, and wound complications. RESULTS: A total of nine studies were included in this study. In total, 450 TAA were included, with 244 receiving TXA (54.2%) and 206 not receiving TXA (45.8%). TXA in TAA significantly decreased EBL. A significantly lower rate of wound complications in the TXA group with the relative risk (RR) of 0.51. We classified wound complications into wound infection and delayed wound healing/dehiscence. A significant decrease in the rate of wound infection and a tendency showing a decrease in the rate of delayed wound healing/dehiscence in the TXA group were noted: the RR of 0.29, and 0.63, respectively. TXA did not increase the incidence of DVT/PE following TAA. CONCLUSIONS: In conclusion, the utilization of TXA during TAA demonstrated a statistically significant reduction in EBL and relative risk for wound complications. However, further RCTs with larger sample sizes will be necessary to establish a more robust conclusion regarding the efficacy and safety of TXA in TAA. LEVEL OF EVIDENCE: Level III, systematic review and meta-analysis.

Tranexamic acid versus oxytocin for primary postpartum Haemorrhage in the out-of-hospital setting: A systematic review with implications for rural practice.

INTRODUCTION: Primary postpartum haemorrhage causes approximately 25% of global maternal deaths and accounts for significant maternal morbidity. While high certainty evidence demonstrates that tranexamic acid reduces comparative blood loss in postpartum haemorrhage in hospital settings, limited data exist on the specific pharmacological management of this condition in out-of-hospital settings, and the implications for rural communities. OBJECTIVE: To determine the efficacy of oxytocin compared to tranexamic acid in women suffering postpartum haemorrhage in the out-of-hospital environment. DESIGN: A systematic review comparing evidence containing patients with postpartum haemorrhage in the out-of-hospital and/or rural setting, in which oxytocin/tranexamic acid were used. Outcome measures were comparative blood loss/haemorrhagic shock, the need for further interventions and maternal/neonatal morbidity/mortality. FINDINGS: No randomised control trials have been conducted in an out-of-hospital environment in relation to oxytocin/tranexamic acid. In this setting, there is no difference in outcome measures when using oxytocin compared to no intervention, or oxytocin compared to standard care. Data are lacking on the effect of tranexamic acid on the same outcome measures. DISCUSSION: Rural and out-of-hospital management of postpartum haemorrhage is limited by resource availability and practitioner availability, capacity and experience. In-hospital evidence may lack transferability, therefore direct evidence on the efficacy of pharmacological management in these contexts is scant and requires redress. CONCLUSION: There is no difference in blood loss, neonatal or maternal mortality or morbidity, or need for further interventions, when using oxytocin or TXA compared to no intervention, or compared to standard care, for PPH. Further studies are needed on the efficacy of these drugs, and alternate or co-drug therapies, for PPH in the out-of-hospital environment and rural clinical practice.

Interaction of preoperative chemoprophylaxis and tranexamic acid use does not affect transfusion in acetabular fracture surgery.

PURPOSE: While the effects of tranexamic acid (TXA) use on transfusion rates after acetabular fracture surgery are unclear, previous evidence suggests that holding deep vein thrombosis (DVT) chemoprophylaxis may improve TXA efficacy. This study examines whether holding DVT chemoprophylaxis in patients receiving TXA affects intraoperative and postoperative transfusion rates in acetabular fracture surgery. METHODS: We reviewed electronic medical records (EMR) of 305 patients who underwent open reduction and internal fixation of acetabular fractures (AO/OTA 62) and stratified patients per the following perioperative treatment: (1) no intraoperative TXA (noTXA), (2) intraoperative TXA and no preoperative DVT prophylaxis (opTXA/noDVTP), or (3) intraoperative TXA and preoperative DVT prophylaxis (opTXA/opDVTP). The primary outcomes were need for intraoperative or postoperative transfusion. Risk factors for each primary outcome were assessed using multivariable regression. RESULTS: Intraoperative or postoperative transfusion rates did not significantly differ between opTXA/opDVTP and opTXA/noDVTP groups (46.2% vs. 36%, p = 0.463; 15.4% vs. 28%, p = 0.181). Median units transfused did not differ between groups (2 ± 1 vs. 2 ± 1, p = 0.515; 2 ± 1 vs. 2 ± 0, p = 0.099). There was no association between preoperative DVT chemoprophylaxis and TXA with intraoperative or postoperative transfusions. EBL, preoperative hematocrit, and IV fluids were associated with intraoperative transfusions; age and Charlson Comorbidity Index (CCI) were associated with postoperative transfusions. CONCLUSION: Our findings suggest holding DVT prophylaxis did not alter the effect of TXA on blood loss or need for transfusion.

Cost-effectiveness and budget impact of adding tranexamic acid for management of post-partum hemorrhage in the Indian public health system.

BACKGROUND: Postpartum hemorrhage (PPH) is the global leading cause of maternal mortality, affecting nearly 3 to 6 percent of all women giving birth in India. The World Health Organization (WHO) has updated its guidelines to recommend the early use of intravenous (IV) tranexamic acid (TXA) in addition to standard care for all diagnosed PPH cases. This study aimed to assess the cost-effectiveness of introducing TXA for PPH management in the Indian public health system. METHODS: A decision analytic model was built using a decision tree to determine the cost-effectiveness of administering IV TXA to women experiencing PPH within 3 h of birth to existing management with uterotonics and supportive care. Using a disaggregated societal perspective, the costs and consequences for a hypothetical cohort of women experiencing PPH in public health facilities was estimated. The model was populated using probabilities, clinical parameters, and utilities from published literature, while cost parameters were largely derived from a primary economic costing study. The primary outcome of interest was the incremental cost-utility ratio (ICUR). Associated clinical events and net benefits were estimated. One-way and probabilistic sensitivity analysis (PSA) was undertaken. The budget impact was estimated for a national-level introduction. RESULTS: For an estimated annual cohort of 510,915 PPH cases in India, the addition of IV TXA would result in a per-patient disaggregated societal cost of INR 6607 (USD 95.15) with a discounted gain of 20.25 QALYs, as compared to a cost of INR 6486 (USD 93.41) with a discounted gain of 20.17 QALYs with standard care PPH management. At an ICUR value of INR 1470 per QALY gained (USD 21), the addition of IV TXA is cost-effective in Indian public health settings. The intervention is likely to prevent 389 maternal deaths, 177 surgeries, and 128 ICU admissions per 100,000 PPH cases. The findings are robust under uncertainty, with 94.5% of PSA simulations remaining cost-effective. A cumulative increase of 2.3% financial allocation for PPH management over five years will be incurred for TXA introduction. CONCLUSIONS: Addition of tranexamic acid for primary PPH management, as recommended by WHO, is cost-effective in Indian public health settings. Policy guidelines, training manuals, and facility checklists should be updated to reflect this recommendation.

Systematic review and meta-analysis of topical tranexamic acid in spine surgery.

OBJECTIVE: Tranexamic acid (TXA) is an antifibrinolytic drug associated with reduced blood loss in a range of surgical specialties, including neurosurgery, orthopedic surgery, and cardiac surgery. Concerns about venous thromboembolism and seizures from intravenous (IV) TXA have led to increased use of topical TXA. Given the relative scarcity of the literature on topical TXA compared with that on IV TXA within neurosurgery, the authors aimed to conduct a systematic review and meta-analysis on the safety, efficacy, and optimal administration of topical TXA in a wide range of spinal procedures and pathologies. METHODS: The PRISMA guidelines, Cochrane risk of bias tool, and Newcastle-Ottawa Scale were used to extract randomized controlled trials and high-quality case-control and cross-sectional/cohort studies (adult studies only) from PubMed, Web of Science, Cochrane Library, and Embase published between 2016 and 2023. Studies were analyzed by two independent reviewers for variables including dosage, TXA administration route, type of spine procedure, blood loss, adverse events including thromboembolism and infection, postoperative hemoglobin level, and hospitalization length. Pooled analysis comparing intraoperative and postoperative blood loss, postoperative hemoglobin levels, and hospitalization length of stay on the basis of route of TXA administration was conducted. RESULTS: Four cohort studies, 1 cross-sectional study, 1 case-control study, and 12 randomized controlled trials, together involving 2045 patients, were included. The most common route of topical TXA administration was via TXA in saline solution. Other routes of topical TXA included retrograde injection and TXA-soaked Gelfoam. In pooled analysis, topical TXA significantly reduced visible blood loss (standardized mean difference [SMD] -0.22, 95% CI -0.45 to -0.00001), postoperative blood loss (SMD -1.63, 95% CI -2.03 to -1.22), and length of hospital stay (SMD -1.02, 95% CI -1.42 to -0.61), as well as higher postoperative hemoglobin (SMD 0.59, 95% CI 0.34-0.83), compared with non-TXA controls. No significant differences in outcomes were found between topical and IV TXA or between combined (topical and IV) and IV TXA. Thromboembolism and infection rates did not significantly differ between any TXA administration group and non-TXA controls. CONCLUSIONS: In pooled analyses, topical TXA was associated with decreased perioperative blood loss in a wide range of scenarios, including cervical spine surgery and thoracolumbar trauma, as well as in patients with a thromboembolic history.

Local Application of Tranexamic Acid in Plastic Surgery Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: According to recent evidence, the use of local tranexamic acid (TXA) during plastic surgery may lessen blood loss. OBJECTIVES: To comprehensively assess the use of local TXA during plastic surgery through a systematic review and meta-analysis of randomized controlled trials addressing these issues. METHODS: Four electronic databases, including PubMed, Web of Science, Embase and the Cochrane Library, were searched until December 12, 2022. Following meta-analyses, the mean difference (MD) or standardized mean difference (SMD) for blood loss volume (BLV), ΔHct, ΔHb and operation time were calculated when appropriate. RESULTS: Eleven randomized controlled trials were included in the qualitative synthesis, while 8 studies were included in the meta-analysis. Compared with the control group, the local TXA group showed a reduction in blood loss volume of -1.05 (p < 0.00001; 95% CI, -1.72 to -0.38). However, local TXA had a limited effect on reducing ΔHct, ΔHb and operation time. A meta-analysis was not performed because of heterogeneity in other outcomes; however, except for 1 study in which no significant difference was observed on POD 1, all studies showed significantly lower rates of postoperative ecchymosis after surgery, 2 studies showed statistically significant reductions in transfusion risk or volume, and 3 studies reported significantly better surgical field quality in operations with local TXA. In the 2 included studies, the researchers concluded that local treatment does not play a role in relieving postoperative pain. CONCLUSIONS: Local TXA is associated with less blood loss, less ecchymosis and better surgical field in plastic surgery patients. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Topical Fibrin Sealant (Tisseel@) Does Not Provide a Synergic Blood-Conservation Effect with Tranexamic Acid in Total Knee Arthroplasty-A Prospective Randomized Controlled Trial.

Background and Objectives: The efficacy of tranexamic acid (TXA) in reducing perioperative blood loss during total knee arthroplasty (TKA) is well established. However, the potential synergistic blood-conservation effect of topical fibrin sealant (Tisseel@) remains unclear. This study aims to assess the effectiveness of the combination of Tisseel and TXA during TKA. Materials and Methods: A single-blinded, prospective, randomized controlled trial was conducted with 100 patients (100 knees) undergoing primary TKA. Participants were randomly assigned to either the TXA group (n = 50), receiving intravenous (IV) TXA, or the Tisseel@ + TXA group (n = 50), receiving intra-articular Tisseel@ combined with IV TXA. The primary outcomes included blood transfusion rate, decrease in Hb level, calculated blood loss, and estimated total postoperative blood loss. Secondary outcomes involved assessing clinical differences between the groups. Results: The transfusion rate was zero in both groups. The average estimated blood loss in the Tisseel@ + TXA group was 0.463 ± 0.2422 L, which was similar to that of the TXA group at 0.455 ± 0.2522 L. The total calculated blood loss in the Tisseel@ + TXA group was 0.259 ± 0.1 L, compared with the TXA group's 0.268 ± 0.108 L. The mean hemoglobin reduction in the first 24 h postoperatively was 1.57 ± 0.83 g/dL for the Tisseel@ + TXA group and 1.46 ± 0.82 g/dL for the TXA-only group. The reduction in blood loss in the topical Tisseel@ + TXA group was not significantly different from that achieved in the TXA-only group. The clinical results of TKA up to the 6-week follow-up were comparable between the groups. Conclusions: The combination of the topical fibrin sealant Tisseel@ and perioperative IV TXA administration, following the described protocol, demonstrated no significant synergistic blood-conservation effect in patients undergoing TKR.

Update on the efficacy and safety of intravenous tranexamic acid in hip fracture surgery: a systematic review and meta-analysis.

AIM: The aim of this meta-analysis was to assess the safety and efficacy of tranexamic acid (TXA) in the management of hip fracture surgeries in comparison with placebo. METHODS: A systematic search was conducted from August 6, 2021. Eligible studies included randomized clinical trials and prospective studies comparing the use of intravenous TXA in patients treated for hip fractures, in comparison with placebo. Review Manager was used for the meta-analysis. RESULTS: Eighteen prospective studies including 14 RCTs met the eligibility criteria. The results favored the TXA group in the quantity of total blood loss (MD = - 196.91 mL, 95% CI - 247.59, - 146.23, I2 = 92%), intraoperative blood loss (MD = - 26.86 mL, 95% CI - 36.96, - 16.78, I2 = 62%), and rate of blood transfusion (OR 0.35, 95% CI 0.28, 0.42, I2 = 0%). TXA also exhibited higher hemoglobin level at day 1 (MD = 6.77 g/L, 95% CI 4.30, 9.24, I2 = 83%) and day 3 (MD = 7.02 g/L, 95% CI 3.30, 10.74, I2 = 82%) postoperatively. There was no significant difference found in the incidence of thromboembolic events from occurring between the two groups, such as deep vein thrombosis (OR 1.22, 95% CI 0.73, 2.02, I2 = 0%) and pulmonary embolism (OR 0.82, 95% CI 0.33, 2.05, I2 = 0%). CONCLUSION: Administration of intravenous TXA appears to reduce blood loss, rate of blood transfusions and pose no increased risk of thromboembolic events. Therefore, TXA should be considered by physicians when managing hip fracture patients.

The role of thromboxane prostanoid receptor signaling in gastric ulcer healing.

The process of gastric ulcer healing includes cell migration, proliferation, angiogenesis and re-epithelialization. Platelets contain angiogenesis stimulating factors that induce angiogenesis. Thromboxane A2 (TXA2 ) not only induces platelet activity but also angiogenesis. This study investigated the role of TXA2 in gastric ulcer healing using TXA2 receptor knockout (TPKO) mice. Gastric ulcer healing was suppressed by treatment with the TXA2 synthase inhibitor OKY-046 and the TXA2 receptor antagonist S-1452 compared with vehicle-treated mice. TPKO showed delayed gastric ulcer healing compared with wild-type mice (WT). The number of microvessels and CD31 expression were lower in TPKO than in WT mice, and TPKO suppressed the expression of transforming growth factor beta (TGF-ß) and vascular endothelial growth factor A (VEGF-A) in areas around gastric ulcers. Immunofluorescence assays showed that TGF-ß and VEGF-A co-localized with platelets. Gastric ulcer healing was significantly reduced in WT mice transplanted with TPKO compared with WT bone marrow. These results suggested that TP signalling on platelets facilitates gastric ulcer healing through TGF-ß and VEGF-A.

Correlation of platelet-derived growth factor and thromboxane A2 expression with platelet parameters and coagulation indices in chronic altitude sickness patients.

NEW FINDINGS: What is the central question of this study? Is the expression of platelet-derived growth factor (PDGF) and thromboxane A2 (TXA2) elevated in chronic altitude patients, and are they related to thrombosis in chronic mountain sickness? What is the main finding and its importance? The expression of PDGF and TXA2 in both the bone marrow and the peripheral blood of patients with chronic mountain sickness is elevated, and they are considered to be correlated in the mechanism of thrombosis in the chronic mountain sickness. ABSTRACT: The purpose of this study was to evaluate the expression of platelet-derived growth factor (PDGF) and thromboxane A2 (TXA2) along with platelet parameters and coagulation indices in chronic mountain sickness (CMS) patients and healthy individuals on the Qinghai-Tibet Plateau. The levels of PDGF and TXA2 were examined in 22 CMS patients (age, 52.77 ± 9.92 years, haemoglobin, 219 ± 13 g/l) and 25 healthy individuals (age, 47.80 ± 9.78 years, haemoglobin, 146 ± 18 g/l), and the association between platelet parameters and coagulation indices was investigated. Mean platelet volume and fibrinogen degradation product were higher in the CMS compared to the control group (10.58 ± 0.83 vs. 8.92 ± 1.61, 7.50 ± 2.15 vs. 4.40 ± 2.51), platelet count and plateletcrit were lower in the CMS compared to the control group (0.13 (0.80, 0.16) vs. 0.23 (0.18, 0.24), 109 ± 46 vs. 204 ± 86). The levels of PDGF and TXA2 in the bone marrow and peripheral blood of CMS patients were higher (P < 0.01) in comparison to the control group. The two factors had no statistically significant relationship with platelet parameters or coagulation indices (P > 0.159). According to the current findings, platelets in CMS patients were activated, resulting in aberrant coagulation and PDGF and TXA2 expression, which could be due to physiological adjustments to the plateau's high altitude. To summarize, PDGF and TXA2 levels in CMS patients were not correlated with coagulation or platelet parameters, implying that the mechanism behind their increased expression warrants additional investigation.

Effectiveness of prophylactic doses of tranexamic acid in reducing hemorrhagic events in sleeve gastrectomy.

PURPOSE: Laparoscopic sleeve gastrectomy (LSG) is currently the most common bariatric surgery in the world. Although it appears to be a safe treatment for obesity, it is still at risk of complications. The latest literature shows that postoperative bleeding occurs in 2-4% of cases, and up to 3% of cases requires reoperation for hemostasis. The aim of the study is to assess the effect of tranexamic acid (TXA) on hemorrhagic events and the reoperation rate in patients undergoing LSG. METHODS: The study was designed as a retrospective analysis of patients undergoing LSG. We investigate the patients 6 months before and 6 months after introducing the prophylaxis doses of TXA into our bariatric protocol (non-TXA group vs TXA group). RESULTS: Three hundred fourteen patients underwent LSG in a high-volume center from 2016 to 2017. After introducing TXA, a statistically significant reduction in the incidence of hemorrhage during surgery was observed (22.3% vs 10.8%, p = 0.006). There was a statistically significant reduction in the need for the staple line oversewing (10.2% vs 1.9%, p = 0.002). The mean operating time and the mean length of hospital stay were significantly higher in the non-TXA group than TXA group (63.1 vs 53.7 min, p < 000.1; 2.3 vs 2.1, p = 0.02). In both groups of patients, no venous thromboembolism or other complications occurred within 6 months after the surgery. CONCLUSIONS: The prophylactic doses of TXA may be useful in reducing the hemorrhagic events during LSG. It may also shorten the length of hospital stay and the operating time.

Efficacy of topical tranexamic acid in epistaxis: A systematic review and meta-analysis.

INTRODUCTION: Epistaxis is a very common presentation in the emergency department (ED), accounting for approximately 1 in 200 ED visits in the United States. Currently, standard practice includes the initial use of topical anesthetics and vasoconstrictors, followed by more invasive treatments such as nasal packing, cauterization or surgical ligation for refractory cases. Over the years several studies have investigated the potential use of topical Tranexamic Acid (TXA) in the management of epistaxis. We have conducted a meta-analysis to assess the efficacy of topical TXA versus other standard practices or placebo in the management of epistaxis. METHODS: PubMed and Scopus databases were searched from inception to April 2021. We included randomized controlled trials and observational studies investigating the efficacy of TXA in bleeding cessation in epistaxis in adults. The primary outcome measured was the prevalence of bleeding cessation after treatment at first assessment. Other outcomes were bleeding reoccurrence between 24 and 72 h and at 7-8 days. A random-effects model was used to estimate odds ratio (OR) for outcomes. RESULTS: A total of eight studies were included in the analysis, including seven randomized trials and one retrospective study. We included a total of 1299 patients, 596 (46%) received TXA while 703 (54%) received control treatment (placebo, lidocaine plus vasoconstrictors or local anesthetics). Patients who were treated with TXA were 3.5 times (OR 3.5, 95% CI 1.3-9.7) more likely to achieve bleeding cessation at the first assessment. Patients treated with TXA had 63% (OR 0.37, 95% CI 0.20-0.66) less likelihood of returning due to rebleeding at 24-72 h. CONCLUSION: Topical TXA is associated with better bleeding cessation rates after treatment compared to the standard practices.

Evaluation of the safety of tranexamic acid use in pediatric patients undergoing spinal fusion surgery: a retrospective comparative cohort study.

BACKGROUND: Pediatric spinal fusion may be associated with significant intraoperative blood loss, leading to complications from transfusion, hypoperfusion and coagulopathy. One emerging strategy to mediate these risks is by utilization of the anti-fibrinolytic agent tranexamic acid (TXA). However, concerns regarding potential adverse reactions, specifically postoperative seizures and thrombotic events, still exist. To assess these risks, we examined the perioperative morbidity of TXA use in a large national database. METHODS: Retrospective data from pediatric patients (age 18 years or younger), discharged between January 2013 to December 2015, who underwent primary or revision posterior spinal fusions, was collected from the Premier Perspective database (Premier, Charlotte, NC). Patients were stratified by TXA use and records were assessed for complications of new onset seizures, strokes, pulmonary embolisms (PE) or deep vein thromboses (DVT) occurring during the perioperative period. RESULTS: In this cohort of 2,633 pediatric patients undergoing posterior spinal fusions, most often to treat adolescent idiopathic scoliosis, 15% received TXA. Overall, adverse events were rare in this patient population. The incidence of seizure, stoke, PE, or DVT in the control group was 0.54% (95% CI, 0.31% to 0.94%) and not significantly different from the TXA group. There was no significant difference in the incidence of DVTs, and no incidences of stroke in either group. There were no new-onset seizures or PEs in patients who received TXA. CONCLUSIONS: The use of TXA was not associated with an increased risk of adverse events including seizure, stroke, PE, and DVT. Our findings support the safety of TXA use in pediatric patients undergoing spinal fusion surgery.