Anticoagulation and Bleeding during Veno-Venous Extracorporeal Membrane Oxygenation: Insights from the PROTECMO Study.

Rationale: Definitive guidelines for anticoagulation management during veno-venous extracorporeal membrane oxygenation (VV ECMO) are lacking, whereas bleeding complications continue to pose major challenges. Objectives: To describe anticoagulation modalities and bleeding events in adults receiving VV ECMO. Methods: This was an international prospective observational study in 41 centers, from December 2018 to February 2021. Anticoagulation was recorded daily in terms of type, dosage, and monitoring strategy. Bleeding events were reported according to site, severity, and impact on mortality. Measurements and Main Results: The study cohort included 652 patients, and 8,471 days on ECMO were analyzed. Unfractionated heparin was the initial anticoagulant in 77% of patients, and the most frequently used anticoagulant during the ECMO course (6,221 d; 73%). Activated partial thromboplastin time (aPTT) was the most common test for monitoring coagulation (86% of days): the median value was 52 seconds (interquartile range, 39 to 61 s) but dropped by 5.3 seconds after the first bleeding event (95% confidence interval, -7.4 to -3.2; P < 0.01). Bleeding occurred on 1,202 days (16.5%). Overall, 342 patients (52.5%) experienced at least one bleeding event (one episode every 215 h on ECMO), of which 10 (1.6%) were fatal. In a multiple penalized Cox proportional hazard model, higher aPTT was a potentially modifiable risk factor for the first episode of bleeding (for 20-s increase; hazard ratio, 1.07). Conclusions: Anticoagulation during VV ECMO was a dynamic process, with frequent stopping in cases of bleeding and restart according to the clinical picture. Future studies might explore lower aPTT targets to reduce the risk of bleeding.

Melatonin partially rescues defects induced by tranexamic acid exposure during oocyte maturation in mice.

Tranexamic acid (TXA) is widely used among young women because of its ability to whiten skin and treat menorrhagia. Nevertheless, its potential effects on oocyte maturation and quality have not yet been clearly clarified. Melatonin (MT) is an endogenous hormone released by the pineal gland and believed to protect cells from oxidative stress injury. In the present study, we used in vitro maturation model to investigate the toxicity of TXA and the protective role of MT in mouse oocyte. Compared with the control group, TXA-exposed group had significantly lower nuclear maturation (57.72% vs. 94.08%, P < 0.001) and early embryo cleavage rates (38.18% vs. 87.66%, P < 0.001). Further study showed that spindle organization (52.56% vs. 18.77%, P < 0.01) and chromosome alignment (33.23% vs. 16.66%, P < 0.01) were also disrupted after TXA treatment. Mechanistically, we have demonstrated that TXA induced early apoptosis of oocytes (P < 0.001) by raising the level of ROS (P < 0.001), which was consistent with an increase in mitochondrial damage (P < 0.01). Fortunately, all these effects except the spindle defect were successfully rescued by an appropriate level of MT. Collectively, our findings indicate that MT could partially reverse TXA-induced oocyte quality deterioration in mouse by effectively improving mitochondrial function and reducing oxidative stress-mediated apoptosis.

Tranexamic acid in trauma: After 3 hours from injury, when is it safe and effective to use again?

Tranexamic acid (TXA) has proven mortality benefit if used early after traumatic injury, likely related to a combination of bleeding reduction and other non-bleeding effects. If TXA is given more than 3 h after traumatic injury, there is a significant and paradoxical increased risk of death due to bleeding. TXA has level 1 evidence for use as a bleeding reduction agent in isolated orthopedic operations, but in polytrauma patients undergoing orthopedic operations, it is not clear if and when TXA is safe or effective once outside the 3-h window of proven trauma efficacy.

Use of crushed tranexamic acid tablets in water for paediatric patients with bleeding disorders.

BACKGROUND: Ε-Aminocaproic acid oral solution (EACA OS) is the only commercially available antifibrinolytic for patients who cannot swallow tablets. Insurance denials and high costs remain barriers to its use. OBJECTIVES: To determine the safety and efficacy of crushed tranexamic acid tablets in water (cTXAw) for children with bleeding disorders. METHODS: We retrospectively reviewed records of children (<10 years) with bleeding disorders who received cTXAw or EACA OS from 1 December 2018, through 31 July 2022, at Mayo Clinic (Rochester, Minnesota). Bleeding outcomes were defined according to ISTH criteria. RESULTS: Thirty-two patients were included (median age, 3 years; male, n = 23). Diagnoses were VWD (n = 17), haemophilia (n = 5), FVII deficiency (n = 3), inherited platelet disorder (n = 4), ITP (n = 2), and combined FV and FVII deficiencies (n = 1). Thirty-two courses of cTXAw (monotherapy 24/32; mean duration 6 days) and fifteen courses of EACA (monotherapy 12/15; mean duration 5 days) were administered. No surgical procedures (n = 28) were complicated by bleeding. Of the 19 bleeding events, 16 had effective haemostasis, two had no reported outcome, and one had no response. cTXAw and EACA were equally effective in preventing and treating bleeding (p value > .1). No patients had adverse effects. Eight of 19 patients (42%) who were initially prescribed EACA OS did not receive it because of cost or insurance denial. The estimated average wholesale price of one treatment was $94 for cTXAw and $905 for EACA OS. CONCLUSIONS: CTXAw appears to be an effective, safe, and low-cost alternative option to EACA OS for young children with bleeding disorders.

Cesarean hysterectomy for placenta accreta spectrum: Surgeon specialty-specific assessment.

OBJECTIVE: To assess (i) clinical and pregnancy characteristics, (ii) patterns of surgical procedures, and (iii) surgical morbidity associated with cesarean hysterectomy for placenta accreta spectrum based on the specialty of the attending surgeon. METHODS: The Premier Healthcare Database was queried retrospectively to study patients with placenta accreta spectrum who underwent cesarean delivery and concurrent hysterectomy from 2016 to 2020. Surgical morbidity was assessed with propensity score inverse probability of treatment weighting based on surgeon specialty for hysterectomy: general obstetrician-gynecologists, maternal-fetal medicine specialists, and gynecologic oncologists. RESULTS: A total of 2240 cesarean hysterectomies were studies. The most common surgeon type was general obstetrician-gynecologist (n = 1534, 68.5%), followed by gynecologic oncologist (n = 532, 23.8%) and maternal-fetal medicine specialist (n = 174, 7.8%). Patients in the gynecologic oncologist group had the highest rate of placenta increta or percreta, followed by the maternal-fetal medicine specialist and general obstetrician-gynecologist groups (43.4%, 39.6%, and 30.6%, P < .001). In a propensity score-weighted model, measured surgical morbidity was similar across the three subspecialty groups, including hemorrhage / blood transfusion (59.4-63.7%), bladder injury (18.3-24.0%), ureteral injury (2.2-4.3%), shock (8.6-10.5%), and coagulopathy (3.3-7.4%) (all, P > .05). Among the cesarean hysterectomy performed by gynecologic oncologist, hemorrhage / transfusion rates remained substantial despite additional surgical procedures: tranexamic acid / ureteral stent (60.4%), tranexamic acid / endo-arterial procedure (76.2%), ureteral stent / endo-arterial procedure (51.6%), and all three procedures (55.4%). Tranexamic acid administration with ureteral stent placement was associated with decreased bladder injury (12.8% vs 23.8-32.2%, P < .001). CONCLUSION: These data suggest that patient characteristics and surgical procedures related to cesarean hysterectomy for placenta accreta spectrum differ based on surgeon specialty. Gynecologic oncologists appear to manage more severe forms of placenta accreta spectrum. Regardless of surgeon's specialty, surgical morbidity of cesarean hysterectomy for placenta accreta spectrum is significant.

Third stage of labor: evidence-based practice for prevention of adverse maternal and neonatal outcomes.

The third stage of labor is defined as the time period between delivery of the fetus through delivery of the placenta. During a normal third stage, uterine contractions lead to separation and expulsion of the placenta from the uterus. Postpartum hemorrhage is a relatively common complication of the third stage of labor. Strategies have been studied to mitigate the risk of postpartum hemorrhage, leading to the widespread implementation of active management of the third stage of labor. Initially, active management of the third stage of labor consisted of a bundle of interventions including administration of a uterotonic agent, early cord clamping, controlled cord traction, and external uterine massage. However, the effectiveness of these interventions as a bundle has been questioned, leading to abandonment of some components in recent years. Despite this, upon review of selected international guidelines, we found that the term "active management of the third stage of labor" was still used, but recommendations for and against individual interventions were variable and not necessarily supported by current evidence. In this review, we: (1) examine the physiology of the third stage of labor, (2) present evidence related to interventions that prevent postpartum hemorrhage and promote maternal and neonatal health, (3) review current global guidelines and recommendations for practice, and (4) propose future areas of investigation. The interventions in this review include pharmacologic agents to prevent postpartum hemorrhage, cord clamping, cord milking, cord traction, cord drainage, early skin-to-skin contact, and nipple stimulation. Treatment of complications of the third stage of labor is outside of the scope of this review. We conclude that current evidence supports the use of effective pharmacologic postpartum hemorrhage prophylaxis, delayed cord clamping, early skin-to-skin contact, and controlled cord traction at delivery when feasible. The most effective uterotonic regimens for preventing postpartum hemorrhage after vaginal delivery include oxytocin plus ergometrine; oxytocin plus misoprostol; or carbetocin. After cesarean delivery, carbetocin or oxytocin as a bolus are the most effective regimens. There is inconsistent evidence regarding the use of tranexamic acid in addition to a uterotonic compared with a uterotonic alone for postpartum hemorrhage prevention after all deliveries. Because of differences in patient comorbidities, costs, and availability of resources and staff, decisions to use specific prevention strategies are dependent on patient- and system-level factors. We recommend that the term "active management of the third stage of labor" as a combined intervention no longer be used. Instead, we recommend that "third stage care" be adopted, which promotes the implementation of evidence-based interventions that incorporate practices that are safe and beneficial for both the woman and neonate.

Tranexamic acid for percutaneous nephrolithotomy: an abridged Cochrane review.

OBJECTIVE: To assess the effects of tranexamic acid (TXA) in individuals with kidney stones undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: We performed a literature search of Cochrane Library, PubMed (including MEDLINE), Embase, Scopus, Global Index Medicus, trials registries, grey literature, and conference proceedings. We included randomised controlled trials (RCTs) that compared treatment with PCNL with administration of TXA to placebo (or no TXA) for patients aged ≥18 years. Two review authors independently classified studies and abstracted data. Primary outcomes were blood transfusion, stone-free rate (SFR), thromboembolic events (TEE). We rated the certainty of evidence (CoE) according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach using a minimally contextualised approach with pre-defined thresholds for minimally clinically important differences (MCID). RESULTS: We included 10 RCTs assessing the effect of systemic TXA in PCNL vs placebo (or no TXA). Eight studies were published as full text. Based on an adjusted baseline risk of blood transfusion of 5.7%, systemic TXA may reduce blood transfusions (risk ratio [RR] 0.45, 95% confidence interval [CI] 0.27-0.76). Based on an adjusted baseline SFR of 75.7%, systemic TXA may increase SFR (RR 1.11, 95% CI 0.98-1.27). There is probably no difference in TEEs (risk difference 0.001, 95% CI -0.01 to 0.01). Systemic TXA may increase adverse events (AEs) (RR 5.22, 95% CI 0.52-52.72). Systemic TXA may have little to no effect on secondary interventions (RR 1.15, 95% CI 0.84-1.57). The CoE for most outcomes was assessed as low or very low. CONCLUSIONS: Based on a body of evidence of 10 RCTs, we found that systemic TXA in PCNL may reduce blood transfusions, major surgical complications, and hospital length of stay, as well as improve the SFR; however, it may increase AEs. These findings should inform urologists and their patients in making informed decisions about the use of TXA in the setting of PCNL.

Tranexamic acid reduces perioperative blood transfusions following open radical cystectomy - a propensity-score matched analysis.

PURPOSE: Radical cystectomy is associated with bleeding and high transfusion rates, presenting challenges in patient management. This study investigated the prophylactic use of tranexamic acid during radical cystectomy. METHODS: All consecutive patients treated with radical cystectomy at a tertiary care university center were included from a prospectively maintained database. After an institutional change in the cystectomy protocol patients received 1 g of intravenous bolus of tranexamic acid as prophylaxis. To prevent bias, propensity score matching was applied, accounting for differences in preoperative hemoglobin, neoadjuvant chemotherapy, tumor stage, and surgeon experience. Key outcomes included transfusion rates, complications, and occurrence of venous thromboembolism. RESULTS: In total, 420 patients were included in the analysis, of whom 35 received tranexamic acid. After propensity score matching, 32 patients and 32 controls were matched with regard to clinicopathologic characteristics. Tranexamic acid significantly reduced the number of patients who received transfusions compared to controls (19% [95%-Confidence interval = 8.3; 37.1] vs. 47% [29.8; 64.8]; p = 0.033). Intraoperative and postoperative transfusion rates were lower with tranexamic acid, though not statistically significant (6% [1.5; 23.2] vs. 19% [8.3; 37.1], and 16% [6.3; 33.7] vs. 38% [21.9; 56.1]; p = 0.257 and p = 0.089, respectively). The occurrence of venous thromboembolism did not differ significantly between the groups (9% [2.9; 26.7] vs. 3% [0.4; 20.9]; p = 0.606). CONCLUSION: Prophylactic tranexamic administration, using a simplified preoperative dosing regimen of 1 g as a bolus, significantly lowered the rate of blood transfusion after cystectomy. This exploratory study indicates the potential of tranexamic acid in enhancing outcomes of open radical cystectomy.

Use of platelet transfusions and tranexamic acid in patients with myelodysplastic syndromes: A clinical practice survey.

AIM: Thrombocytopenia and bleeding are common in myelodysplastic syndromes (MDS), but optimal management is unknown. We conducted a survey to identify current clinical practice regarding platelet transfusion (PLT-T) and tranexamic acid (TXA) to inform future trial design. METHOD: A 25-question survey was distributed to members of the ALLG from December 2020 to July 2021. RESULTS: Sixty-four clinicians across Australia, New Zealand and Singapore responded. Clinicians treated a median of 15 MDS patients annually. Twenty-nine (45%) reported having institutional guidelines regarding prophylactic PLT-T. Although 60 (94%) said they would consider using TXA, most (58/64; 91%) did not have institutional guidelines. Clinical scenarios showed prophylactic PLT-T was more likely administered for patients on disease-modifying therapy (49/64; 76%, commonest threshold <10 × 109 /L) or with minor bleeding (32/64 [50%] transfusing at threshold <20 × 109 /L, 23/64 [35%] at <10 × 109 /L). For stable untreated patients, 29/64 (45%) would not give PLT-T and 32/64 (50%) would. Most respondents (46/64; 72%) were interested in participating in trials in this area. Potential barriers included resource limitations, funding and patient/clinician acceptance. CONCLUSION: Real-world management of MDS-related thrombocytopenia varies and there is a need for clinical trials to inform practice.

The Association Between Tranexamic Acid and Seizures in Moderate or Severe Traumatic Brain Injury.

INTRODUCTION: Tranexamic acid (TXA) administered within 2 h of injury reduces mortality in traumatic brain injury (TBI) with intracranial hemorrhage. TXA also reduces the seizure threshold in a dose-dependent manner. We examined whether a 2-g bolus of prehospital TXA administered in moderate or severe TBI is associated with seizure activity within 72 h of injury. METHODS: Patients from the prehospital TXA for TBI trial with Glasgow Coma Scale < 13, blunt head injury, and time-of-seizure data were included in this analysis. The original trial randomized patients with suspected TBI to placebo, 1-g TXA bolus + 1-g 8-h TXA infusion, or 2-g TXA bolus within 2 h of injury. In this secondary analysis, multivariable logistic regression was performed to examine the association of treatment group with seizure incidence. The model controlled for age, Glasgow Coma Scale, Injury Severity Score, intracranial hemorrhage, Abbreviated Injury Scale-head, and home antiseizure medication use. RESULTS: Of the 786 patients who met the inclusion criteria, 19 had seizures within 72 h (five in placebo, two in 1-g bolus/1-g infusion, and 12 in 2-g bolus). The 2-g TXA bolus was not associated with increased seizures compared to placebo (odds ratio 0.41, 95% confidence interval 0.12-1.18, P = 0.12). Home antiseizure medication use was associated with increased seizures (odds ratio 15.95, 95% confidence interval 3.79-60.57, P < 0.001). CONCLUSIONS: A prehospital 2-g TXA bolus in moderate or severe TBI was not associated with increased seizure activity during the first 72 h after injury; however, limited power, limited use of continuous electroencephalography, and unavailable seizure prophylaxis data highlight the need for further study.

Tranexamic Acid Use in the Surgical Arena: A Narrative Review.

INTRODUCTION: Tranexamic acid (TXA) is a potent antifibrinolytic drug that inhibits the activation of plasmin by plasminogen. While not a new medication, TXA has quickly gained traction across a variety of surgical subspecialties to prevent and treat bleeding. Knowledge on the use of this drug is essential for the modern surgeon to continue to provide excellent care to their patients. METHODS: A comprehensive review of the PubMed database was conducted of articles published within the last 10 y (2014-2024) relating to TXA and its use in various surgical subspecialties. Seminal studies regarding the use of TXA older than 10 y were included from the author's archives. RESULTS: Indications for TXA are not limited to trauma alone, and TXA is utilized across a variety of surgical subspecialties from neurosurgery to hepatic surgery to control hemorrhage. Overall, TXA is well tolerated with common dose-dependent adverse effects, including headache, nasal symptoms, dizziness, nausea, diarrhea, and fatigue. More severe adverse events are rare and easily mitigated by not exceeding a dose of 50 mg/kg. CONCLUSIONS: The administration of TXA as an adjunct to treat trauma saves lives. The ability of TXA to induce seizures is dose dependent with identifiable risk factors, making this serious adverse effect predictable. As for the potential for TXA to cause thrombotic events, uncertainty remains. If this association is proven to be real, the risk will likely be small, since the use of TXA is still advantageous in most situations because of its efficacy for a more common concern, bleeding.

Tranexamic Acid Administration Does Not Alter Inflammation After Traumatic Brain Injury, Regardless of Timing.

INTRODUCTION: Tranexamic acid (TXA) administered early after traumatic brain injury (TBI) can decrease morbidity and mortality. The purpose of this study is to determine if the timing of TXA administration after TBI affects postinjury inflammatory markers or phosphorylated tau (p-tau) levels within the hippocampus. METHODS: Male mice (9-11 wk) were split into six groups based on injury and timing of TXA administration (n = 5 per group): Sham, TBI-only, 100 mg/kg TXA-only, TBI + TXA 10 min, TBI + TXA 1 h, and TBI + TXA 6 h. Moderate concussive TBI was induced via weight drop. Serum and brain homogenates were collected at 6 and 24 h postinjury and analyzed for 14 inflammatory cytokines via multiplex enzyme-linked immunosorbent assay. Serum was analyzed for glial fibrillary acidic protein levels. Additional cohorts were survived to 30 d for hippocampal p-tau quantification using immunohistochemistry. RESULTS: Serum levels of interleukin (IL) 1ß (IL-1ß), IL-3, IL-12, IL-17, monocyte chemoattractant protein-1, granulocyte-macrophage colony-stimulating factor, and regulated on activation, normal T-cell expressed and secreted were elevated in TBI mice compared to sham mice at 24 h. Levels of IL-1ß and monocyte chemoattractant protein-1 were lower in 6-h TXA-treated mice than 1-h TXA-treated mice following TBI. IL-12 and macrophage inflammatory protein-1α levels were decreased in 6-h TXA-treated mice compared to 10-min TXA-treated mice. Administration of TXA at 10 min and 6 h but not 1 h postTBI reduced serum glial fibrillary acidic protein levels compared to TBI-only mice. Hippocampal p-tau accumulation was increased after TBI but not reduced by TXA administration. CONCLUSIONS: Our results demonstrate that neither early nor delayed administration of TXA conveyed significant systemic or cerebral benefit in cytokine levels following TBI. Further research should be conducted to assess blood brain barrier integrity and neurobehavioral recovery following TXA administration postTBI.

Tranexamic acid use in sarcoma surgery patients: A systematic review and meta-analysis.

INTRODUCTION: Perioperative bleeding increases morbidity and mortality in sarcoma patients. Tranexamic acid (TXA), an antifibrinolytic, is widely utilized in non-sarcoma orthopaedic surgeries, but its adoption in sarcoma surgery is hindered by concerns about thrombotic events. METHODS: Searches in Ovid MEDLINE, EMBASE, and CENTRAL were performed without date restrictions. Inclusion criteria encompassed sarcoma patients undergoing surgery with TXA intervention. Two authors independently screened studies, resolved conflicts, and assessed biases. RESULTS: Eight studies met inclusion criteria, comprising 2142 patients. TXA administration varied in dose and timing across studies. Meta-analysis revealed significantly reduced mean blood loss with TXA of -462.5 mL ([95% confidence interval [CI: -596.7, -328.31], p < 0.001) but no difference in transfusion rates (odds ratio [OR] = 0.51 [95% CI: 0.14-1.89]) or venous thromboembolism events (OR = 0.93 [95% CI: 0.40, 2.16]). Study biases were predominantly moderate to high due to retrospective designs and lack of control for confounders. Quality of reporting varied, with limitations identified in outcome reporting and effect size estimation. CONCLUSIONS: Despite evidence of reduced blood loss, the absence of prospective studies limits conclusive recommendations on TXA use in sarcoma surgery. Further research is warranted to determine optimal TXA regimens and assess safety concerns regarding thrombotic events in this patient population.

Best practices in the treatment of melasma with a focus on patients with skin of color.

BACKGROUND: Melasma is a chronic hypermelanosis of the skin that affects approximately 1% of the global population, predominantly affects women, and is more prevalent in skin of color. Melasma is a common driver for patients with skin of color to seek out a dermatologist for treatment, and ensuring the right approach for these patients is important because some treatments may be associated with adverse side effects. Because of the chronicity of the disease and established psychosocial and emotional impacts, there is a large need to ensure care follows the best available evidence on the treatment of patients with melasma. OBJECTIVE: Here, we summarized current available topical treatments for melasma with considerations dermatologists should have for their patients with skin of color. METHODS: Steering committee consensus on clinical best practices. RESULTS: We describe a flexible and focused treatment algorithm that reflects both treatment and maintenance periods that is a consensus of our extensive clinical experience. LIMITATIONS: Use of real-world evidence and potential for individual practice bias. CONCLUSION: Melasma can be challenging to treat, particularly in patients with skin of color, and our recommendations for best practices for patients in the United States are an important step toward standardizing care.

Association between tranexamic acid administration and mortality based on the trauma phenotype: a retrospective analysis of a nationwide trauma registry in Japan.

BACKGROUND: In trauma systems, criteria for individualised and optimised administration of tranexamic acid (TXA), an antifibrinolytic, are yet to be established. This study used nationwide cohort data from Japan to evaluate the association between TXA and in-hospital mortality among all patients with blunt trauma based on clinical phenotypes (trauma phenotypes). METHODS: A retrospective analysis was conducted using data from the Japan Trauma Data Bank (JTDB) spanning 2019 to 2021. RESULTS: Of 80,463 patients with trauma registered in the JTDB, 53,703 met the inclusion criteria, and 8046 (15.0%) received TXA treatment. The patients were categorised into eight trauma phenotypes. After adjusting with inverse probability treatment weighting, in-hospital mortality of the following trauma phenotypes significantly reduced with TXA administration: trauma phenotype 1 (odds ratio [OR] 0.68 [95% confidence interval [CI] 0.57-0.81]), trauma phenotype 2 (OR 0.73 [0.66-0.81]), trauma phenotype 6 (OR 0.52 [0.39-0.70]), and trauma phenotype 8 (OR 0.67 [0.60-0.75]). Conversely, trauma phenotypes 3 (OR 2.62 [1.98-3.47]) and 4 (OR 1.39 [1.11-1.74]) exhibited a significant increase in in-hospital mortality. CONCLUSIONS: This is the first study to evaluate the association between TXA administration and survival outcomes based on clinical phenotypes. We found an association between trauma phenotypes and in-hospital mortality, indicating that treatment with TXA could potentially influence this relationship. Further studies are needed to assess the usefulness of these phenotypes.

Concentration-effect relationship for tranexamic acid inhibition of tissue plasminogen activator-induced fibrinolysis in vitro using the viscoelastic ClotPro® TPA-test.

BACKGROUND: Tranexamic acid is an antifibrinolytic drug that is commonly administered for obstetric haemorrhage. Conventional viscoelastic tests are not sensitive to tranexamic acid, but the novel ClotPro® TPA-test can measure tranexamic acid-induced inhibition of fibrinolysis. We aimed to evaluate the TPA-test in pregnant and non-pregnant women. METHODS: We performed an in vitro study of whole blood samples spiked with tranexamic acid from pregnant women in the first, second, and third trimester (n=20 per group) and from non-pregnant women (n=20). We performed ClotPro TPA-tests of whole blood sample and ClotPro EX-tests, FIB-tests, and TPA-tests. RESULTS: Clot lysis was inhibited in a concentration-dependent manner up to a tranexamic acid concentration of 6.25 mg L-1. At tranexamic acid concentrations of 12.5 mg L-1 and above, clot lysis was completely inhibited. The concentration-effect relationship of tranexamic acid did not differ in a clinically important manner in blood from pregnant women across all three trimesters or from non-pregnant controls. A median maximum lysis cut-off value of at9 least 16% (25-75th percentiles 15-18), a median clot lysis time of 3600 s (25-75th percentiles 3600-3600), or both was associated with a tranexamic acid concentration of least 12.5 mg L-1. CONCLUSIONS: The ClotPro® TPA-test is sensitive in detecting inhibition of fibrinolysis by tranexamic acid in whole blood samples of pregnant and non-pregnant women. The concentration-effect relationship of tranexamic acid to inhibit fibrinolysis in whole blood did not differ for women in the first, second, and third trimester or for non-pregnant women.

Improved outcome with individualised antifibrinolytic therapy: what is the evidence?

Viscoelastic haemostatic testing (VHT) has been used to determine hyperfibrinolysis and hypofibrinolysis. When modified by addition of tissue plasminogen activator (tPA), VHT has been suggested to assess responses to antifibrinolytic therapy and to estimate the concentration of tranexamic acid in patients undergoing cardiac surgery. Despite some evidence that tPA-modified VHT might allow individualisation of antifibrinolytic therapy, further studies are warranted to prove its clinical benefit for postsurgical bleeding, transfusion of blood products, and thromboembolic events.

Viscoelastic coagulation monitoring for tranexamic acid: personalised antifibrinolytic dosing?

Ex vivo viscoelastic testing can be used to assess the concentration responses to tranexamic acid in blood samples obtained from pregnant women across the three trimesters and in non-pregnant controls. Minor variations in fibrinolysis across pregnancy suggest a target tranexamic acid blood concentration of 12.5 mg L-1 for complete inhibition of fibrinolysis. Although the data support the potential utility of viscoelastic testing using the ClotPro® TPA test in maintaining therapeutic tranexamic acid concentrations during postpartum haemorrhage, it might obscure potentially crucial endogenous fibrinolysis inhibitor interactions essential to the microcirculation.

Point-of-care testing for tranexamic acid efficacy: a proof-of-concept study in cardiac surgical patients.

BACKGROUND: Low-dose tranexamic acid (TXA) has been recently recommended for cardiopulmonary bypass (CPB) to reduce associated complications. Although point-of-care laboratory tests for TXA concentrations are unavailable, a novel TPA-test on the ClotPro® system can measure TXA-induced inhibition of fibrinolysis. We evaluated the performance of the TPA-test in vitro and in patients undergoing surgery requiring CPB. METHODS: Blood samples were obtained from six volunteers for in vitro evaluation of tissue plasminogen activator (tPA)-triggered fibrinolysis and the effects of TXA. This was followed by an observational study in 20 cardiac surgery patients to assess clinical effects of TXA on the TPA-test. RESULTS: Hyperfibrinolysis induced by tPA was inhibited by TXA ≥2 mg L-1 in a concentration-dependent manner, and was completely inhibited at TXA ≥10 mg L-1. In patients undergoing CPB, antifibrinolytic effect was detectable on TPA-test parameters after a 0.1 g bolus of TXA at the end of CPB, and complete inhibition of fibrinolysis was obtained with TXA ≥0.5 g. The antifibrinolytic effects of 1 g TXA on TPA-test parameters were gradually attenuated over 18 h after surgery. However, the fibrinolytic inhibition continued in four patients with estimated glomerular filtration rate (eGFR) ≤30 ml min-1 1.73 m-2. The eGFR had strong correlations with TPA-test parameters at 18 h after surgery (r=0.86-0.92; P<0.0001). CONCLUSIONS: The TPA-test is sensitive to low concentrations of TXA and serves as a practical monitoring tool for postoperative fibrinolytic activity in cardiac surgery patients. This test might be particularly useful in patients with severe renal impairment.

Efficacy of perioperative systemic tranexamic acid along with topical hemocoagulase in decreasing axillary drain output in breast cancer patients undergoing axillary lymph node dissection: A randomized, double-blind, placebo-controlled, superiority trial.

BACKGROUND: Excess and prolonged axillary drainage is a frequent nuisance following axillary lymph node dissection (ALND) in breast cancer patients. No consensus exists about the best method to prevent this consistently and reliably. Tranexamic acid (TA) has been found to reduce the amount and duration of drainage, but the reduction is not optimal. We hypothesized that systemic administration of TA along with the topical application of hemocoagulase (H) to the axillary dissection bed may decrease the cumulative axillary drain output and shorten the requirement of drainage after ALND as compared to placebo. PATIENT AND METHODS: Seventy women undergoing ALND for breast carcinoma were randomized into two groups, the intervention (TA + H) group and the control (C) group. The cumulative drain output (primary objective), duration of drainage, incidence of seroma formation after drain removal, number of seroma aspirations required, volume of seroma aspirated, and incidence of surgical site infection (SSI) were compared. RESULTS: The mean cumulative output in the TA + H group was significantly lower than the C group (290 ± 200 mL vs. 552 ± 369 mL, p < 0.001). Axillary drains were removed significantly earlier in the TA + H group (6.6 ± 2.2 vs. 11.7 ± 6.0 days, p < 0.001), but the incidence of seroma formation (p = 0.34), number of aspirations required (p = 0.33), volume of seroma aspirated (p = 0.47), and the incidence of SSI (p = 0.07) were similar. CONCLUSIONS: Perioperative systemic administration of tranexamic acid along with topical application of H to the axillary dissection bed is effective in reducing cumulative axillary drain output after ALND. This strategy may also facilitate earlier removal of suction drains.