Prophylactic tranexamic acid in patients with hematologic malignancy: a placebo controlled, randomized clinical trial
Evidence of effectiveness of prophylactic use of tranexamic acid (TXA) in thrombocytopenia is lacking. To determine whether TXA safely reduces bleeding incidence in patients undergoing treatment for hematologic malignancies, a randomized double blind clinical trial was conducted June 2016 through June 2020. Of 3120 screened adults 356 patients were eligible and enrolled, and 337 patients (mean age, 53.9; 141 (41.8%) women), randomized to 1,300mg TXA orally or 1,000mg TXA intravenously (n=168) versus placebo (n=169) thrice daily for maximum 30 days. 330 patients were activated when their platelet counts fell below 30,000/µl; 279 (83%) had complete outcome ascertainment. WHO grade 2 or higher bleeding was observed in the 30 days following activation in 50.3% (73/145) and 54.2% (78/144) of patients in the TXA and placebo groups, adjusted odds ratio: 0.83 (95%CI:0.50,1.34; p=0.44). There was no statistically significant difference in mean number of platelet transfusions (0.1;95%CI:-1.9,2.0), mean days alive without grade 2 or higher bleeding (0.8;95%CI:-0.4,2.0), thrombotic events (6/163 (3.7%) TXA, 9/163 (5.5%) placebo), or deaths due to serious bleeding. Most common adverse events were: diarrhea [(116/164 (70.7%) TXA and 114/163 (69.9%) placebo)]; febrile neutropenia [111/164 (67.7%) TXA, 105/163 (64.4%) placebo]; fatigue [106/164 (64.6%) TXA, 109/163 (66.9%) placebo]; and nausea [104/164 (63.4%) TXA, 97/163 (59.5%) placebo]. Among patients with hematologic malignancy undergoing chemotherapy or hematopoietic stem cell transplantation, prophylactic treatment with tranexamic acid compared with placebo did not significantly reduce the risk of WHO grade 2 or higher bleeding. Trial Registration: Clinicaltrials.gov Identifier: NCT02578901.
Patients who were thrombocytopenic due to primary bone marrow disorders or chemotherapy, immunotherapy, and/or radiation therapy (n= 337).
Tranexamic acid (TXA) orally or intravenously (n= 168).
Placebo (n= 169).
The primary outcome of WHO grade 2 or higher bleeding during the first 30 days after activation was observed for 73 out of 145 (50.3%) and 78 out of 144 (54.2%) patients in the TXA and placebo groups, respectively. There was no statistically significant difference in mean number of platelet transfusions (0.1), mean days alive without grade 2 or higher bleeding (0.8), thrombotic events (6/163 (3.7%) TXA, 9/163 (5.5%) placebo), or deaths due to serious bleeding.
Intra-articular versus intravenous administration of tranexamic acid in lower limb total arthroplasty: a systematic review and meta-analysis of randomised clinical trials
European journal of orthopaedic surgery & traumatology : orthopedie traumatologie. 2022
AIM: The ideal route of tranexamic acid (TXA) administration in total hip arthroplasty (THA) or total knee arthroplasty (TKA) remains controversial. This study aims to identify the optima route of TXA administration in THA or TKA. METHODS PUBMED, EMBASE, MEDLINE and CENTRAL database were systematically searched until 4 August 2021 for randomised studies that compared intravenous (IV) or intra-articular (IA) administration of TXA in THA or TKA. RESULTS Sixty-seven studies enrolling 8335 patients (IA: 4162; IV: 4173) were eligible for quantitative and qualitative analysis. Comparable results were demonstrated in the incidence of venous thromboembolisation (OR:0.96, p = 0.84), total blood loss (MD: - 9.05, p = 0.36), drain output (MD: - 7.36, p = 0.54), hidden blood loss (MD: - 6.85, p = 0.47), postoperative haemoglobin level (MD: 0.01, p = 0.91), haemoglobin drop (MD: - 0.10, p = 0.22), blood transfusion rate (OR: 0.99, p = 0.87), total adverse events (OR: 1.12, p = 0.28), postoperative range of motion (MD: 1.08, p = 0.36), postoperative VAS pain score (MD: 0.13, p = 0.24) and postoperative D-dimer level (MD: 0.61, p = 0.64). IV route of TXA administration was associated with significantly longer length of hospital stay compared to IA route of administration (MD: - 0.22, p = 0.01). CONCLUSION In this meta-analysis, both IV and IA route of TXA administration were equally effective in managing blood loss and postoperative outcomes in lower limb joints arthroplasty. LEVEL OF EVIDENCE Level 1. PROSPERO Registration CRD42021271355.
Peri-articular administration of tranexamic acid is an alternative route in total knee arthroplasty: a systematic review and meta-analysis
Journal of orthopaedic surgery and research. 2022;17(1):211
BACKGROUND As an antifibrinolytic agent, tranexamic acid (TXA) is increasingly used in total knee arthroplasty (TKA) to reduce blood loss. The administration of intravenous and intra-articular TXA has been well explored, but the most efficient way to administer TXA remains in question. Peri-articular injection (PAI) of TXA is a recently mentioned method. A meta-analysis of the efficacy of PAI TXA in patients after TKA should be performed. METHODS A systematic search was performed within PubMed, Embase, and the Cochrane Library up to November 8, 2021. Two authors independently screened studies for eligibility and extracted data for analysis. The primary outcome was haemoglobin change. The secondary outcomes were haematocrit change, total drainage volume, thromboembolic events, and blood transfusion. RESULTS A total of ten studies were included in this meta-analysis. The results indicated that there was a significant decrease in haemoglobin change when using PAI TXA compared with no TXA (mean difference - 1.05; 95% CI - 1.28 to - 0.81; P < 0.00001; I(2) = 0%), but it had no significant differences compared with IA and IV (mean difference - 0.01; 95% CI - 0.17 to - 0.14; P = 0.85; I(2) = 39%). There were no significant differences between the TXA < 1.5 g subgroup (0.10, 95% CI - 0.27 to 0.46; P = 0.60; I(2) = 0%) and the TXA ≥ 1.5 g subgroup (0.18, 95% CI - 0.12 to 0.48; P = 0.24; I(2) = 74%). In addition, the combined group (PAI plus IV or IA) was superior to the IV or IA group in terms of haemoglobin change (mean difference - 0.51; 95% CI - 0.76 to - 0.27; P < 0.0001; I(2) = 19%). Regarding haematocrit change, the pooled result showed it was significantly less in the PAI group than the non-TXA group. Similarly, comparing it against the IV subgroup, the result revealed a difference in favour of the PAI group, with a mean difference of - 1.89 g/dL (95% CI - 2.82 to - 0.95; P < 0.0001; I(2) = 67%). For total drainage volume, the pooled result was in favour of PAI TXA over no TXA (297 ml, 95% CI - 497.26 to - 97.23; P = 0.004; I(2) = 87%), but it had no significant difference compared with IA and IV (mean difference - 37.98; 95% CI - 115.68 to 39.71; P = 0.34; I(2) = 95%). There was no significant difference in thromboembolic events (OR 0.74; 95% CI 0.25 to 2.21; P = 0.59; I(2) = 0%). Blood transfusion was not significantly different between the PAI group and the non-TXA group (OR 0.50; 95% CI 0.23 to 1.06; P = 0.07; I(2) = 21%), and there was no significant difference between PAI and the other two TXA injection methods (OR 0.72; 95% CI 0.41 to 1.25; P = 0.24; I(2) = 19%). CONCLUSION PAI has comparable effects to IV and IA injections. PAI is an alternative injection route of TXA for patients who have undergone TKA.
Comparison of Tranexamic acid, Remifentanil, and Hydralazine on the bleeding volume during Dacryocystorhinostomy surgery
International journal of physiology, pathophysiology and pharmacology. 2022;14(3):177-186
BACKGROUND Bleeding in Dacryocystorhinostomy (DRC) limits the surgeon's sight and access. Tranexamic acid, Remifentanil, and Hydralazine reduce intraoperative blood loss. However, no study has been carried out to compare the efficacy of the latter drugs during DCR surgery. METHODS Ninety healthy candidates for DCR surgery with chronic Dacryocystitis (aging 20-80) were randomly assigned in groups of 30 to receive low doses of Tranexamic acid (TXA) (10 mg/kg with a maximum dose of 1000 mg), Remifentanil (0.1 µ/kg), or Hydralazine (0.1 mg/kg). All drugs were infused over 15 minutes before the initiation of surgery. The primary outcome was the bleeding volume during the surgery and until 2 hours in recovery. This study was approved by the Iranian Registry of Clinical Trials with the code of IRCT20210614051574N10 (https://en.irct.ir/trial/62759). RESULTS Thirty patients (mean age ± SD: 50.48±13.4) were investigated. Mean blood loss volume was lower in Remifentanil and Hydralazine groups compared with the TXA group (P<0.05); there was no significant difference (P>0.05) in bleeding volume between Remifentanil and Hydralazine groups (Tranexamic acid group: 146.83±91 ml, Remifentanil group: 77.6±52.1 ml, Hydralazine group: 80.0±48.7 ml, 95% confidence interval, P<0.05). CONCLUSION Our results show that Remifentanil and Hydralazine are more effective than Tranexamic acid in bleeding control.
Effect of Tranexamic Acid on Blood Loss and the Quality of Surgical Field in Transsphenoidal Pituitary Surgeries: Double-Blind Placebo-Controlled Randomized Control Trial
Neurology India. 2022;70(3):960-964
BACKGROUND AND AIMS Pituitary adenomas are common intracranial neoplasms and several cases require surgery, radiotherapy or radiosurgery. Transsphenoidal access to the pituitary gland is the commonest surgical approach. In microscopic or endoscopic approach to the pituitary, even modest bleeding can significantly worsen the surgical field for the neurosurgeon, lengthen intra-operative time and lead to potentially catastrophic complications. METHODS The investigators hypothesized that administration of tranexamic acid (TXA) would improve the quality of the surgical field and reduce bleeding during transsphenoidal surgery (TSS) of pituitary tumors. Fifty American Society of Anesthesiologists (ASA) physical-status 1 or 2 patients undergoing TSS were randomized into two groups: T and P. Patients in Group T received 25 mg/kg bolus of TXA followed by intraoperative infusion of 1 mg/kg/hour, while those in Group P received a matching saline infusion. The operating neurosurgeon, and the anesthesiologist, who managed the patient and collected data, were blinded to the test drug. Surgical field quality was assessed using the Boezaart scale. A single neurosurgeon performed all the surgeries to ensure consistency in estimating the quality of the surgical field. RESULTS The median Boezaart score (interquartile range) was 3 (1.0) in Group T and 3.0 (1.5) in Group P (P = 0.03). There was an absolute blood loss reduction of nearly 32% with TXA use. Blood loss in Group T was 334 ± 101 mL, compared to 495 ± 226 mL in Group P (P = 0.002). CONCLUSION The administration of TXA significantly improved the quality of surgical field and reduced blood loss in patients undergoing TSS.
The effect of tranexamic acid on myocardial injury in cardiac surgical patients: a systematic review and meta-analysis
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 2022
Tranexamic acid (TXA) is one of the most commonly used antifibrinolytic agents for surgical patients. However, the effect of TXA on myocardial injury remains controversial. We systemically reviewed literature regarding the effectiveness of TXA on myocardial injury in patients who have undergone a cardiac surgery. We included all randomized controlled trials (RCTs) comparing TXA and control (saline) in cardiac surgical patients. Relevant studies were identified by a comprehensive electronic literature search from database inception to 15 August 2021. A standardized data extraction form was used to collect methodological and outcome variables from each eligible study. We conducted a meta-analysis to estimate the pooled effect size of TXA administration on myocardial injury. In total, eight RCTs were identified, with 292 patients in the TXA group, and 241 patients in saline or control group. The meta-analysis demonstrated that patients in the TXA group had lower levels of CK-MB and cTnI within 24 h postoperatively (CK-MB: P = 0.005; cTnI: P = 0.01), compared with the saline group. No significant difference was found with respect to AST level (P = 0.71) between TXA and saline groups within 24 h postoperatively. TXA administration was found to be associated with less myocardial injury among patients who have undergone cardiac surgery. High-quality randomized controlled trials are warranted to further examine the cardioprotective effects of TXA.
Intravenous Tranexamic acid versus placebo during Caesarian section: A comparative study
Pakistan journal of medical sciences. 2022;38(5):1183-1187
OBJECTIVES To evaluate the effectiveness of Tranexamic Acid in preventing postpartum hemorrhage against placebo in high-risk women undergoing cesarean section. METHODS A double-blinded placebo-controlled comparative trial was conducted at the Obstetrics and Gynecology Department of Nishtar Hospital for one year, from 15(th) June 2020 to 15(th) June 2021. A total of 60 women who were at high risk of postpartum hemorrhage and had to undergo elective cesarean sections were included in the study. Among them, initial 30 patients were administered Tranexamic Acid before skin incision whereas later 30 were treated as the placebo group. These women were then observed for blood loss during surgery and within 24 hrs. after surgery and any postoperative complications such as thromboembolic events, the need for additional uterotonic agents, and blood transfusions. RESULTS Out of 60 women, 30 were placed in each group. The groups had no significant difference in terms of baseline data and post-partum hemorrhage-associated risk factors (p>0.05). However, the occurrence rate of primary post-partum hemorrhage (blood loss greater than 1000 ml) was significantly less in a tranexamic acid group than the placebo group (16.6% vs 60%, respectively, p<0.01). Similarly, the requirement of additional uterotonic agents (13.3% vs 43.3%, respectively) and the need for blood transfusion (6.0% vs 23.3%, respectively) was lower in a tranexamic group than in the placebo group. CONCLUSION The study highlighted the significance of tranexamic acid in controlling post-partum hemorrhages, the requirement of additional uterotonic agents, improving post-partum hemoglobin, and the need for blood transfusion.
Tranexamic acid is not inferior to placebo with respect to adverse events in supected tbi patients not in shock with a normal head ct: A retrospective study of a randomized trial
The journal of trauma and acute care surgery. 2022
BACKGROUND A 2-gram bolus of tranexamic acid (TXA) has been shown to reduce 28-day mortality in a RCT. This study investigates whether out-of-hospital TXA use is associated with adverse events or unfavorable outcomes in suspected TBI when intracranial hemorrhage (ICH) is absent on initial CT. METHODS This study utilized data from a 2015-2017, multicenter, randomized trial studying the effect of the following TXA doses on moderate to severe TBI: 2-gram bolus, 1-gram bolus plus 1-gram infusion over 8 hours, and a placebo bolus with placebo infusion. Of the 966 participants enrolled, 395 with an initial CT negative for ICH were included in this analysis. Fifteen adverse events (28-day incidence) were studied: MI, DVT, seizure, pulmonary embolism, ARDS, cardiac failure, liver failure, renal failure, CVA, cardiac arrest, cerebral vasospasm, "any thromboembolism", hypernatremia, AKI, and infection. Other unfavorable outcomes analyzed include mortality at 28 days & 6 months, GOSE ≤4 at discharge & 6 months, ICU-free days, ventilator-free days, hospital-free days, and combined unfavorable outcomes. In both study drug groups the incidence of dichotomous outcomes and quantity of ordinal outcomes were compared to placebo. RESULTS No statistically significant increase in adverse events or unfavorable outcomes was found between either TXA dosing regimen and placebo. Demographics and injury scores were not statistically different other than two methods of injury which were overrepresented in the 1-gram TXA bolus +1-gram TXA infusion. CONCLUSIONS Administration of either a 2-gram TXA bolus or a 1-gram TXA bolus plus 1-gram TXA 8-hour infusion in suspected-TBIs without ICH is not associated with increased adverse events or unfavorable outcomes. Because the out-of-hospital 2-gram bolus is associated with a mortality benefit it should be administered in suspected-TBI. LEVELS OF EVIDENCE Level II, Therapeutic.
Topical Application of Tranexamic Acid Can Reduce Postoperative Blood Loss in Calcaneal Fractures: A Randomized Controlled Trial
The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons. 2022
The traditional lateral "L" approach is common for managing calcaneal fractures with a drawback of significant blood loss. Yet there are no prospective studies on the hemostatic effect of the topical use of tranexamic acid (TXA) in calcaneal fracture surgeries. The purpose of this study was to evaluate the role of topical administration of TXA in reducing postoperative blood loss in calcaneal fractures. Forty participants were randomly distributed into the TXA group (n = 20) and the control group (n = 20). All participants underwent the same surgery via the lateral "L" approach. At the end of the operation, the surgical wound was irrigated with 80 mL 0.5 g/L TXA in the TXA group and 80 mL 0.9% sodium chloride in the control group, followed by the routine use of a drainage tube when closing the incision. Then, 20 mL 0.5 g/L TXA (TXA group) or 20 mL 0.9% sodium chloride solution (control group) was injected retrogradely into the wound through the drainage tube, which was clipped for 30 minutes thereafter. There were no significant differences in the baseline data between the 2 groups (p > .05). There was significantly less blood loss in the first 24 hours and total blood loss postoperation in the TXA group (p < .01). The surgical wounds healed well after surgery in both groups with no complication. We concluded that topical application of TXA in calcaneal fracture surgeries is a safe and useful method that can reduce postoperative blood loss.
Combined and intravenous administration of TXA reduces blood loss more than topical administration in primary total knee arthroplasty: A randomized clinical trial
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2022;166(1):68-76
AIM: To determine the most effective administration of tranexamic acid (TXA) in patients with primary total knee arthroplasty (TKA). MATERIAL AND METHOD We enrolled a total of 400 patients (154 men and 346 women) in this randomized trial (4 groups, each of 100 patients). The first group (IV1) had a single intravenous dose (15 mg TXA/kg) prior to skin incision. Group 2 (IV2) had TXA in 2 intravenous doses (15 mg TXA/kg): prior to skin incision and 6 hours after the first dose. Group 3 (TOP) had 2 g TXA in 50 mL of saline irrigated topically at the end of the surgery. The fourth group (COMB) combined IV1 and TOP regimens. We monitored the amount of total blood loss (TBL), haemoglobin drop, use of blood transfusions (BTs), and complications in each patient. RESULTS The amount of TBL was significantly lower in IV1, IV2 and COMB regimens compared to the TOP (P<0.0001). The lowest decrease in haemoglobin within 12 hours after surgery was observed in intravenous regimens (P=0.045). A significant difference in haemoglobin decrease on day 1 after the surgery was demonstrated in the COMB and intravenous regimens (P=0.011). CONCLUSION In primary TKA, it is preferable to administer TXA intravenously in two doses or in a combined regimen. Simple topical administration of TXA was not as effective and is indicated only in cases where systemic administration of TXA is contraindicated. No substantial complications occurred in either group of patients.