Antifibrinolytic Tranexamic Acid Research Articles

Synergism of red blood cells and tranexamic acid in the inhibition of fibrinolysis

BackgroundPostpartum hemorrhage (PPH) is the leading cause of maternal death worldwide. The World Maternal Antifibrinolytic trial showed that antifibrinolytic tranexamic acid (TXA) reduces PPH deaths. Maternal anemia increases the risk of PPH. The World Maternal Antifibrinolytic-2 trial is now assessing whether TXA can prevent PPH in women with anemia. Low red blood cell (RBC) counts promote fibrinolysis by altering fibrin structure and plasminogen activation. ObjectivesWe explored interactions between RBCs and TXA in inhibiting fibrinolysis. MethodsWe used global fibrinolytic assays (ball sedimentation and viscoelasticity) to monitor the lysis of fibrin containing plasminogen and tissue-type plasminogen activator. We applied a fluorogenic kinetic assay to measure plasmin generation in fibrin clots and scanning electron microscopy to study fibrin structure. ResultsAccording to parallel-line bioassay analysis of the fibrin lysis-time data, the antifibrinolytic potency of 4-128 μM TXA was increased in the presence of 10% to 40% (v/v) RBCs. Global fibrinolysis assays showed that the joint effect of RBCs and TXA was about 15% larger than the sum of their individual effects in the inhibition of fibrinolysis. In plasminogen activation, TXA added the same increment of inhibition to the effect of RBCs at any cell count in the fibrin clot. Regarding fibrin structure, TXA thickened fibrin fibers, which impaired plasminogen activation, whereas RBCs promoted fine fibers that were more resistant to plasmin. ConclusionsThe antifibrinolytic potency of TXA is enhanced in fibrin formed in the presence of RBCs through inhibition of plasminogen activation and fibrin lysis, which correlates with modifications of fibrin structures.

An integrative analytical approach designed for feasible tranexamic acid assay using o-phthalaldehyde as a fluorogenic probe: applications to tablets, ampoules, and urine.

Antifibrinolytic tranexamic acid (TRX) suppresses plasminogen activation to plasmin in a competitive way. TRX is approved for the management of heavy menstrual periods, hereditary angioedema, hemophilia, postpartum hemorrhage, surgery, tooth extraction, and severe blood loss after acute trauma. Here, the practical use of an isoindole derivative was established for a novel, easy-to-use, and affordable TRX assay. In the presence of a molecule containing a sulfhydryl group (2-mercaptoethanol) 0.02% v/v, the primary amine moiety in TRX allows its combination with o-phthalaldehyde to produce a luminous product. Excitation (338.8nm) and emission (433.9nm) wavelengths were used to monitor the isoindole fluorophore yield, and each operational variable was carefully examined and adjusted. The calibration graph was constructed with fluorescence intensity versus TRX concentration, excellent linearity was observed at concentrations between 40 and 950 ng/ml, and limit of detection and limit of quantitation were 41.3 and 13.6ng/ml, respectively. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines were used to validate the method. The developed method for TRX assay in various dosage forms and urine was successfully implemented and was shown to be an effective, simple, and quick replacement for the TRX assay in clinical trials and quality control.

Thromboembolic Complications Following Perioperative Tranexamic Acid Administration

IntroductionThe antifibrinolytic tranexamic acid (TXA) may reduce death in trauma; however, outcomes associated with TXA use in patients without proven hyperfibrinolysis remain unclear. We analyzed the associations of empirically administered TXA, hypothesizing that TXA use would correlate to lower transfusion totals but increased thromboembolic complications. MethodsThis retrospective cohort study compared trauma patients started on massive transfusion protocol at a Level I trauma center from 2016 to 2021 who either did or did not receive TXA. Our primary outcome was in-hospital mortality. Venous thromboembolism (VTE; pulmonary embolism or deep vein thrombosis), transfusion volumes, and coagulation measures were considered secondarily. Descriptive statistics, univariate analyses, and multivariable logistic regression were used to evaluate differences in outcomes. ResultsTXA patients presented with lower systolic blood pressure (100 versus 119.5 mmHg, P = 0.009), trended toward higher injury severity (ISS of 25 versus 20, P = 0.057), and were likelier to have undergone thoracotomy or laparotomy (89 versus 71%, P = 0.002). After adjusting for age, mechanism, presenting vitals, and operation, TXA was not significantly associated with mortality or VTE. TXA patients had larger volumes of packed red blood cells, platelets, and plasma transfused within 4- and 24-h (P ≤ 0.002). No differences in clot stability, captured via thromboelastography, were noted. ConclusionsDespite no differences in mortality or VTE between patients who did and did not receive TXA, there were significant differences in transfusion totals. TXA patients had worse presenting physiology and likely had more severe bleeding. This absence of adverse outcomes supports TXA's safety. Nevertheless, further inquiry into the precise mechanism of TXA may help guide its empiric use, allowing for more targeted application.

Hyperfibrinolysis drives mechanical instabilities in a simulated model of trauma induced coagulopathy

IntroductionTrauma induced coagulopathy (TIC) is common after severe trauma, increasing transfusion requirements and mortality among patients. TIC has several phenotypes, with primary hyperfibrinolysis being among the most lethal. We aimed to investigate the contribution of hypercoagulation, hemodilution, and fibrinolytic activation to the hyperfibrinolytic phenotype of TIC, by examining fibrin formation in a plasma-based model of TIC. We hypothesized that instabilities arising from TIC will be due primarily to increased fibrinolytic activation rather than hemodilution or tissue factor (TF) induced hypercoagulation. MethodsThe influence of TF, hemodilution, fibrinogen consumption, tissue plasminogen activator (tPA), and the antifibrinolytic tranexamic acid (TXA) on plasma clot formation and structure were examined using rheometry, optical properties, and confocal microscopy. These were then compared to plasma samples from trauma patients at risk of developing TIC. ResultsCombining TF-induced clot formation, 15 % hemodilution, fibrinogen consumption, and tPA-induced fibrinolysis, the clot characteristics and hyperfibrinolysis were consistent with primary hyperfibrinolysis. TF primarily increased fibrin polymerization rates and reduced fiber length. Hemodilution decreased clot optical density but had no significant effect on mechanical clot stiffness. TPA addition induced primary clot lysis as observed mechanically and optically. TXA restored mechanical clot formation but did not restore clot structure to control levels. Patients at risk of TIC showed increased clot formation, and lysis like that of our simulated model. ConclusionsThis simulated TIC plasma model demonstrated that fibrinolytic activation is a primary driver of instability during TIC and that clot mechanics can be restored, but clot structure remains altered with TXA treatment.

Epsilon Aminocaproic Acid's Safety and Efficacy in Pediatric Surgeries Including Craniosynostosis Repair: A Review of the Literature.

Craniosynostosis, the premature fusion of skull sutures in children, requires surgical correction. This procedure routinely requires allogeneic blood transfusions, which are associated with multiple risks of their own. Since 2008, antifibrinolytics tranexamic acid (TXA) and epsilon aminocaproic acid (EACA or Amicar) have been widely used. There is literature comparing the two agents in scoliosis and cardiothoracic surgery, but the literature comparing the two agents in pediatric craniofacial surgery (CF) is limited. Tranexamic acid use is more common in pediatric CF surgery and has been thoroughly studied; however, it costs about three times as much as EACA and has been associated with seizures. This study compiles the literature assessing the safety and efficacy of EACA in reducing blood loss and transfusion volumes in children and explores its potential use in pediatric CF surgery.Papers from 2000 to 2021 regarding the effectiveness and safety of EACA in Pediatric scoliosis, cardiothoracic, and craniosynostosis surgery were reviewed and compiled. Papers were found via searching PubMed and Cochrane databases with the key terms: Epsilon aminocaproic acid, EACA, Amicar, Tranexamic acid, TXA, craniosynostosis, scoliosis, cardiothoracic, and pediatric. Prospective studies, retrospective studies, and meta-analyses were included.Twenty-nine papers were identified as pertinent from the literature searched. Four were meta-analyses, 14 were retrospective, and 11 were prospective. Of these papers, seven were of cardiac surgery, 12 were of scoliosis, and nine were of craniosynostosis. During our search, EACA has been shown to consistently reduce blood transfusion volumes compared to control. However, it is not as effective when compared to TXA. EACA has a similar safety profile to TXA but has a reduced risk of seizures. There are not many studies of EACA in craniosynostosis repair, but the existing literature shows promising results for EACA's efficacy and safety, warranting more studies.

Prehospital Tranexamic Acid (TXA) in Patients with Traumatic Brain Injury (TBI).

Traumatic brain injury (TBI) remains a significant medical and socioeconomic challenge. The initial injury may be complicated by haemostatic derangements leading to exacerbation of lesions and haemorrhagic progression. The results from the CRASH-3 trial have promoted the implementation of the antifibrinolytic tranexamic acid (TXA) into prehospital Emergency Medical Services (EMS) protocols. Very recently, the efficacy and safety of early out-of-hospital TXA compared to placebo was assessed in patients with moderate or severe TBI in a prospective, multicenter phase II trial, e.g. "The Prehospital TXA for TBI"-trial. Simultaneously, the results from a retrospective analysis of prospectively collected observational data into the Dutch pre-hospital TBI database were published which had assessed whether prehospital administration of TXA may be associated with mortality and functional outcomes in patients with severe TBI. Both studies are reviewed against their limitations and windows of opportunity are highlighted.

Impact of intravenous tranexamic acid on patients undergoing shoulder arthroplasty surgery.

Shoulder arthroplasty surgery carries the risk of blood loss. The antifibrinolytic tranexamic acid (TXA) is effective in reducing blood loss in lower limb arthroplasty. The purpose of this study was to assess blood loss and associated complications following shoulder arthroplasty performed with and without TXA for both elective and trauma indications. A cohort study was performed to assess blood loss, transfusion requirements and post-operative venous thromboembolic events (VTE) following shoulder arthroplasty undertaken with and without the use of intravenous TXA. The study consisted of 67 patients (n = 36 with TXA; n = 31 without TXA). Type of arthroplasty included reverse-shoulder arthroplasty, total-shoulder arthroplasty and hemiarthroplasty. There was no significant difference between TXA and non-TXA groups regarding blood loss (TXA group haemoglobin drop 20.6 mg/dL; non-TXA group haemoglobin drop 20.5 mg/dL; p = 0.978). There was no significant difference in measured outcomes with or without TXA use for elective or trauma indications, nor regarding type of arthroplasty. The use of intravenous TXA in shoulder arthroplasty was not associated with a significant reduction in blood loss or post-operative transfusion rates, nor did it impact on VTE. This result was not affected by the indication being elective or trauma nor the type of arthroplasty surgery performed.

Bleeding is increased in amyloid precursor protein knockout mouse

BackgroundAmyloid precursor protein (APP) is highly expressed in platelets. APP is the precursor to amyloid beta (Aβ) peptides that accumulate in cerebral amyloid angiopathy and plaques in Alzheimer disease. APP and its metabolites interact with many components of the coagulation system, and have both anticoagulant and procoagulant properties, but it is unclear if APP contributes to hemostasis in vivo. ObjectivesTo determine whether APP contributes to hemostasis in mice, including when inhibitors of coagulation are administered. MethodsBlood loss in APP knockout (KO) mice was measured in liver laceration and tail transection models of hemorrhage. Blood loss was also measured following tail transection in mice given an inhibitor of coagulation factor Xa (apixaban), platelet inhibitors (aspirin + clopidogrel), tissue‐type plasminogen activator (t‐PA), or the antifibrinolytic tranexamic acid (TXA). Results and DiscussionBlood loss from liver lacerations was similar between APP KO mice and wild‐type (WT) mice, but APP KO mice bled more from tail transections. When mice were challenged with aspirin + clopidogrel, the difference in bleeding between APP KO and WT mice was abrogated. In contrast, a difference in bleeding between the strains persisted when mice were treated with apixaban, t‐PA, or TXA. Blood collected from APP KO mice and analyzed with thromboelastography had longer clotting times, and the clots were less stiff and more susceptible to fibrinolysis compared to blood from WT mice. ConclusionsThe absence of APP measurably increases bleeding in mice, which is consistent with a role for platelet‐derived APP and Aβ peptides in hemostasis.

18. Safety and efficacy of tranexamic acid use in posterior cervical decompression and fusion surgery

BACKGROUND CONTEXT Posterior cervical decompression and fusion (PCDF) involves substantial blood loss, resulting in blood transfusions and associated complications, such as infections, hypotension and organ damage. The antifibrinolytic tranexamic acid (TXA), an inhibitor of the activation of plasminogen, has been shown to be beneficial in multiple surgical procedures without any apparent increase in postoperative complications. However, only a few studies report on TXA utilization in cervical spine surgery and there is currently no literature detailing the short-term safety of its use in this setting. PURPOSE To evaluate the short-term safety and efficacy of tranexamic acid use in multilevel posterior cervical decompression and fusion surgery. STUDY DESIGN/SETTING Retrospective case-control study from a single academic institution. PATIENT SAMPLE Forty-seven patients were identified to have undergone PCDF at our institution by one surgeon, 19 with the utilization of a TXA protocol and 28 patients without. Inclusion criteria were adults (age ≥18 years) with cervical stenosis and/or spondylosis who underwent cervical posterior spinal fusion surgery of at least 2 levels. OUTCOME MEASURES Intraoperative and postoperative blood loss and incidence of adverse events, including myocardial infarction (MI), acute renal failure, stroke, seizure, deep vein thrombosis (DVT) and pulmonary embolism (PE) were evaluated in the perioperative period and at 1-month follow-up. METHODS From January 2015 to April 2018, 47 patients were identified to have undergone PCDF, 19 with the utilization of a TXA protocol at our institution. Inclusion criteria were adults (age ≥18 years) with cervical stenosis and/or spondylosis who underwent cervical posterior spinal fusion surgery of at least 2 levels. The incidence of adverse events, including myocardial infarction (MI), acute renal failure, stroke, seizure, deep vein thrombosis (DVT) and pulmonary embolism (PE) were evaluated in the perioperative period and at 1-month follow-up. RESULTS Based on the inclusion criteria, 39 patients were selected. Nineteen (49%) received TXA as per our instructional protocol and 20 (51%) did not. Postoperative blood was significantly reduced (453ml vs 701ml; p = 0.03) in the group that received TXA. There was also a significant reduction in duration of surgery associated with TXA use (269 min vs 328 min; p = 0.05). There were no cardiac or thromboembolic complications on the first 30 days after surgical intervention on the TXA group, but there was a transient atrial fibrillation on the standard group. There were no infections, seizure activity, epidural hematomas or renal complications reported in either group. CONCLUSIONS TXA use during PCDF is a safe, effective method to reduce postoperative blood loss. Considering the limited number of patients in this study, these results should be validated on a larger group of patients. FDA DEVICE/DRUG STATUS Unavailable from authors at time of publication.

Short-term safety of tranexamic acid use in posterior cervical decompression and fusion surgery

Posterior cervical decompression and fusion (PCDF) can result in substantial blood loss, leading to blood transfusions and associated complications, such as infections, hypotension and organ damage. The antifibrinolytic tranexamic acid (TXA), an inhibitor of the activation of plasminogen, has been shown to be beneficial in multiple surgical procedures without any apparent increase in postoperative complications. However, there are only few studies reporting TXA utilization in cervical spine surgery and there is currently no literature detailing the short-term safety of its use in this setting. The purpose of our study is to determine the safety profile of TXA in posterior cervical decompression and fusion. From January 2015 to April 2018, 47 patients were identified to have undergone PCDF, 19 with the utilization of a TXA protocol at our institution. The incidence of adverse events was evaluated in the perioperative period and at 1 month follow-up. Of 39 patients, Nineteen (49%) received TXA as per our instructional protocol and 20 (51%) did not. Post-operative blood was significantly reduced (453 ml vs 701 ml; p = 0.03) in the group that received TXA. There was also a significant reduction in duration of surgery associated with TXA use (269 min vs 328 min; p = 0.05). There were no complications on the first 30 days after surgical intervention on the TXA group. TXA use during PCDF is a safe, effective method to reduce postoperative blood loss. Considering the limited number of patients in this study, these results should be validated on a larger group of patients.

Urinary proteome analysis of acute hypercoagulable state in rat model induced by ε-aminocaproic acid

The hypercoagulable state occurs in a group of prothrombotic disorders associated with an increased risk for thromboembolic events, but it is difficult to diagnose due to the lack of available biomarkers. This study aimed to investigate systematic changes of urinary proteome in acute hypercoagulable state induced by certain antifibrinolytics. To reduce the effects of both genetic and environmental factors on the urinary proteome, we used a rat model of acute hypercoagulable state induced by an antifibrinolytic agent ε-aminocaproic acid, resembling human hypercoagulable state. Urine samples were collected during acute hypercoagulable state for analysis by liquid chromatography-tandem mass spectrometry (LCMS/MS). Of 65 significantly changed proteins in acute hypercoagulable state, 38 proteins had human orthologs, and 18 proteins were identified as stable in normal human urine. None of the identified proteins have been found to be clotting factors, but 4 proteins are known to be involved in the regulation of blood coagulation factors. Two proteins were verified as the markers associated with acute hypercoagulable state by Western blot analysis. In addition, four common differential urinary proteins have been found in acute hypercoagulable state induced by another antifibrinolytics tranexamic acid. These four proteins are potential biomarkers for early diagnosis of hypercoagulable state to prevent the development of thrombotic diseases.

Antifibrinolytics for heavy menstrual bleeding.

Antifibrinolytics for heavy menstrual bleeding.

Abstract 521: A Pilot Study Comparing Anti-Inflammatory Effects of Tranexamic Acid and Epsilon Aminocaproic Acid in Pediatric Congenital Heart Surgery

Background: Antifibrinolytic agents are frequently used during pediatric heart surgery with cardiopulmonary bypass (CPB) to reduce transfusions. There are no studies comparing anti-inflammatory effects of antifibrinolytic agents, tranexamic acid (TXA) and Epsilon Aminocaproic acid (EACA). We compared the two agents in pediatric patients undergoing redo sternotomy with CPB. Aim: To compare anti-inflammatory effects of tranexamic acid versus aminocaproic acid in pediatric patients undergoing redo sternotomy and cardiopulmonary bypass. Methods: We conducted a randomized, double blind pilot study, comparing 10 subjects in each group receiving EACA and TXA. A cytokine panel was used to measure 13 inflammatory markers in pre, immediate post and 24 hours post-CPB period. Between group comparisons were tested with Mann-Whitney U tests and within group comparisons with Friedman tests. Results: Sample characteristics were comparable in both groups. Post CPB, plasma levels of 7 markers increased significantly (p<0.05) in both groups, including MCP-1; 3 increased significantly (p<0.03) in the EACA group alone, including GM-CSF; and 3 did not change over time (Table 1). No difference was found between groups for markers except for IL-10, which was significantly higher in EACA group post CPB. While absolute values of markers, chest tube output and volume of blood product needs were lower in TXA group, the differences were not statistically significant. Conclusion: There was no significant difference in anti-inflammatory profiles between EACA and TXA in this pilot study. GM-CSF and MCP-1 were increased in our study post CBP which has not been described in previous studies.

THE CORRELATION OF TRANEXAMIC ACID USED AS ANTIFIBRINOLYTIC THERAPY TO GLASGOW COMA SCALE FOR THE FIRST 7 DAYS IN HAEMORRHAGIC STROKE PATIENTS

Objective: Treatment of haemorrhagic stroke using tranexamic acid is still used in some hospitals, to prevent the occurrence of the complication called rebleeding. Rebleeding is an important cause of bad outcomes that result loss of consciousness and even death. The administration of the antifibrinolytic tranexamic acid in patients with haemorrhagic stroke can reduce the occurrence of rebleeding but it also can increase poor outcome caused by cerebral ischemia that can worsen the patient's condition.Methods: This study used observational study design, cohort, prospective, and multicenter. The purpose of this study was to determine the effectiveness of the use of tranexamic acid in patients with haemorrhagic stroke. Statistical testing is done by analyzing the Glasgow Coma Scale (GCS) score on day 1st, day 3rd, and day 7th between the treatment groups haemorrhagic stroke patients who received tranexamic acid therapy as antifibrinolytic therapy in Bethesda Hospital for 23 patients compared with a control group of patients haemorrhagic stroke who did not receive therapy as tranexamic acid antifibrinolytic therapy in the Dr. Sardjito Hospital for 23 patients.Results: The statistical analysis of the independent t-test showed that there was no significant difference between the average GCS score of day 1st (P=262), day 3rd (P=0.293), and day 7th (P=0.648) between treatment group and control group. The statistical analysis of the Mann-Whitney showed that there was not significant difference comparing the difference between the pre and post GCS score at treatment group and control group (P=0.158).Conclusion: Administration of tranexamic acid in patients with haemorrhagic stroke (treatment group) gives the same clinical response compared to the patients who did not receive tranexamic acid therapy (control group) based on assessment of the Glasgow Coma Scale (GCS) score.

Prehospital administration of tranexamic acid in trauma patients.

BackgroundEvidence on prehospital administration of the antifibrinolytic tranexamic acid (TXA) in civilian trauma populations is scarce. The aim was to study whether prehospital TXA use in trauma patients was associated with improved outcomes.MethodsThe prehospital database of the ADAC (General German Automobile Club) Air Rescue Service was linked with the TraumaRegister of the German Trauma Society to reidentify patients documented in both registries. Primarily admitted trauma patients (2012 until 2014) who were treated with TXA during the prehospital phase were matched with patients who had not received prehospital TXA, applying propensity score-based matching.ResultsThe matching yielded two identical cohorts (n = 258 in each group), since there were no significant differences in demographics or injury characteristics (mean Injury Severity Score 24 ± 14 [TXA] vs. 24 ± 16 [control]; p = 0.46). The majority had sustained blunt injury (90.3 % vs. 93.0 %; p = 0.34). There were no differences with respect to prehospital therapy, including rates of intubation, chest tube insertion or both administration of i.v. fluids and catecholamines. During ER treatment, the TXA cohort received fewer numbers of red blood cells and plasma units, but without reaching statistical significance. Incidences of organ failure, sepsis or thromboembolism showed no significant differences as well, although data were incomplete for these parameters. Early mortality was significantly lower in the TXA group (e.g., 24-h mortality 5.8 % [TXA] vs. 12.4 % [control]; p = 0.01), and mean time to death was 8.8 ± 13.4 days vs. 3.6 ± 4.9 days, respectively (p = 0.001). Overall hospital mortality was similar in both groups (14.7 % vs. 16.3 %; p = 0.72). The most pronounced mortality difference was observed in patients with a high propensity score, reflecting severe injury load.ConclusionsThis is the first civilian study, to our knowledge, in which the effect of prehospital TXA use in trauma patients has been examined. TXA was associated with prolonged time to death and significantly improved early survival. Until further evidence emerges, the results of this study support the use of TXA during prehospital treatment of severely injured patients.

Coagulation factor concentrate-based therapy for remote damage control resuscitation (RDCR): a reasonable alternative?

The concept of remote damage control resuscitation (RDCR) is still in its infancy and there is significant work to be done to improve outcomes for patients with life-threatening bleeding secondary to injury. The prehospital phase of resuscitation is critical and if shock and coagulopathy can be rapidly minimized before hospital admission this will very likely reduce morbidity and mortality. The optimum transfusion strategy for these patients is still highly debated and the potential implications of the recently published pragmatic, randomize, optimal platelet, and plasma ratios trial (PROPPR) for RDCR have been reviewed. Identifying the appropriate transfusion strategy is mandatory before adopting prehospital hemostatic resuscitation strategies. An alternative approach is based on the early administration of coagulation factor concentrates combined with the antifibrinolytic tranexamic acid (TXA). The three major components to this approach in the context of RDCR target the following steps to achieve hemostasis: 1) stop (hyper)fibrinolysis; 2) support clot formation; and 3) increase thrombin generation. Strong evidence exists for the use of TXA. The data from the prospective fibrinogen in trauma induced coagulopathy (FIinTIC) study will inform on the prehospital use of fibrinogen in bleeding trauma patients. Deficits in thrombin generation may be addressed by the administration of prothrombin complex concentrates. Handheld point-of-care devices may be able to support and guide the prehospital and remote use of intravenous hemostatic agents including coagulation factor concentrates along with clinical presentation, assessment, and the extent of bleeding. Combinations may even be more effective for bleeding control. More studies are urgently needed.

Is tranexamic acid effective for acute upper gastrointestinal bleeding?

Upper gastrointestinal bleeding constitutes a medical-surgical emergency given its important associated morbidity and mortality. The antifibrinolytic tranexamic acid might help stopping bleeding, but controversy remains about its role in this setting. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified five systematic reviews including eight randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded tranexamic acid probably decreases rebleeding and mortality, without increasing thromboembolic adverse effects in patients with upper gastrointestinal bleeding.

Von Willebrand Factor for Menorrhagia: A Survey and Literature Review

Von Willebrand Factor for Menorrhagia: A Survey and Literature Review

Antifibrinolytics Reduce Blood Loss in Adult Spinal Deformity Surgery

This is a prospective, randomized, double-blinded comparison of tranexamic acid (TXA), epsilon aminocaproic acid (EACA), and placebo used intraoperatively in patients with adult spinal deformity. The purpose of this study was to provide high-quality evidence regarding the comparative efficacies of TXA, EACA, and placebo in reducing blood loss and transfusion requirements in patients undergoing posterior spinal fusion surgery. Spine deformity surgery usually involves substantial blood loss. The antifibrinolytics TXA and EACA have been shown to improve hemostasis in large blood loss surgical procedures. Fifty-one patients undergoing posterior spinal fusion of at least 5 levels for correction of adult spinal deformity were randomized to 1 of 3 treatment groups. Primary outcome measures included intraoperative estimated blood loss, total loss, (estimated blood loss + postoperative blood loss), and transfusion rates. Patients received TXA (n = 19), EACA (n = 19), or placebo (n = 13) in the operating room (mean ages: 60, 47, and 43 yr, respectively); TXA patients were significantly older and had larger estimated blood volumes than both other groups. Total losses were significantly reduced for EACA versus control, and there was a demonstrable but nonsignificant trend toward reduced intraoperative blood loss in both antifibrinolytic arms versus control. EACA had significant reductions in postoperative blood transfusions versus TXA. The findings in this study support the use of antifibrinolytics to reduce blood loss in posterior adult spinal deformity surgery. 1.

Population Pharmacokinetics of Tranexamic Acid in Adults Undergoing Cardiac Surgery With Cardiopulmonary Bypass

Background Interest in antifibrinolytic tranexamic acid (TA) has grown since the widespread removal of aprotinin, but its dosing during cardiac surgery is still debated. The objectives of this study were to investigate the population pharmacokinetics (PK) of TA given with either low- or high-dose continuous infusion schemes in adult cardiac surgery patients during cardiopulmonary bypass (CPB). Methods Patients were randomized to receive either low-dose (10 mg kg–1 followed by an infusion of 1 mg kg−1 h−1 throughout the operation, and 1 mg kg−1 into the CPB) or high-dose (30 mg kg−1, then 16 mg kg−1 h−1, and 2 mg kg−1 into the CPB) TA. Serum TA concentrations were measured in 61 patients and the data were modelled using Monolix. Results TA concentrations were 28–55 µg ml−1 in the low-dose group and 114–209 µg ml−1 in the high-dose group throughout surgery. TA PK was best described by a two-compartment open model. The main covariate effect was bodyweight, whereas the CPB did not influence the PK. Assuming a bodyweight of 70 kg, the population estimates were 4.8 litre h−1 for clearance, 6.6 litre for the volume of the central compartment, 32.2 litre h−1 for the diffusional clearance, and the peripheral volume of distribution was 10.8 litre. Conclusions The PK of TA was satisfactorily described by an open two-compartmental model, which was used to propose a dosing scheme suitable for obtaining and maintaining the desired plasma concentration in a stable and narrow range in cardiac surgery patients. Clinical trial registration ClinicalTrials.gov , NCT00809393.