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.

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.

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.
OBJECTIVE: The use of intraoperative (Local and Intravenous) tranexamic acid reduces blood loss during femoral telescoping nail application in O.I.
METHODS:
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 %).
CONCLUSIONS: 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.
METHODS: II; Randomized Controlled Trial (RCT).

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OBJECTIVE: Our aim was to compare the effects of intraarticular and intravenous (IV) tranexemic acid (TXA) application on bleeding and complication rates in patients who underwent total knee arthroplasty (TKA).
METHODS: Between 2017 and 2021, 406 patients who underwent TKA with 2 g of IV TXA and retrograde 1.5 g of TXA applied through the drain were included in the study. Of the patients, 206 were in the IV TXA group. Preoperative and postoperative hemoglobin levels, drain output, BMI, ASA score, blood loss, and the number of transfused patients were recorded. Complications such as symptomatic venous thromboembolism were also recorded.
RESULTS: There was no significant difference between the two groups in terms of age, sex, American Society of Anesthesiologists (ASA) score, or BMI (p = 0.68, 0.54, 0.28, 0.45). Total drain output and blood loss were significantly higher in the IV TXA group than in the intraarticular TXA group (p < 0.0001, p < 0.0001). Eighteen patients in the IV TXA group and 1 patient in the intraarticular TXA group received a blood transfusion (p < 0.0001). There was no difference between the two groups in terms of preoperative hemoglobin or platelet count (p = 0.24). However, postoperative hemoglobin level was higher in the patients who received intraarticular TXA (p=0.0005). More thromboembolism events were seen in the IV TXA group (p < 0.0001).
CONCLUSIONS: Intraarticular TXA application reduces blood loss more than IV application, reduces the blood transfusion rate, and causes fewer complications.
BACKGROUND: tranexemic acid, total knee arthroplasty, intraarticular injection, blood loss, blood transfusion.

OBJECTIVE: To derive systematic-review informed, modified Delphi consensus regarding antifibrinolytic and adjunct hemostatic agents in neonates and children supported with extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE consensus conference.
METHODS: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.
METHODS: Use of antifibrinolytics (epsilon-aminocaproic acid [EACA] or tranexamic acid), recombinant factor VII activated (rFVIIa), or topical hemostatic agents (THAs).
METHODS: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Eleven references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form.
RESULTS: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. One weak recommendation and three consensus statements are presented.
CONCLUSIONS: Evidence supporting recommendations for administration of antifibrinolytics (EACA or tranexamic acid), rFVIIa, and THAs were sparse and inconclusive. Much work remains to determine effective and safe usage strategies.

BACKGROUND: Melasma is a chronic pigmentary disorder. In this study, an innovative cream combining cysteamine and tranexamic acid (TXA) was assessed.
OBJECTIVE: To evaluate the safety, efficacy, and patient satisfaction of a novel nano-formulated cysteamine and TXA combination cream in treating subjects with epidermal melasma.
METHODS:   Fifty (50) randomized subjects participated and received cysteamine and TXA combination cream. The cream was applied for 30 minutes daily for a 3-month duration. Treatment effectiveness, safety, patient satisfaction, and adherence were evaluated.
RESULTS: A continuous improvement in melasma was observed, with modified Melasma Area and Severity Index (mMASI) scores improving by 40%, 57%, and 63% at 30, 60, and 90 days, respectively. The primary endpoint of a decrease in mMASI scores was met, with 91% of participants experiencing melasma improvement. Patient Satisfaction and Patient Adherence scores indicated satisfaction. Convenience exhibited the strongest correlation with patient adherence.  Conclusion: Nano-formulated cysteamine and TXA combination cream showed significant efficacy in decreasing mMASI score while demonstrating a strong safety profile and patient satisfaction.  J Drugs Dermatol. 2024;23(7):529-537.     doi:10.36849/JDD.7765R1.