Oral tranexamic acid and thrombosis risk in women.
Ontology highlight
ABSTRACT: Background
Oral tranexamic acid is effective for heavy menstrual bleeding, but the thrombosis risk with this treatment is largely not studied.Methods
Using nationwide registries, we assessed associations between use of oral tranexamic acid and risk of deep-vein thrombosis or pulmonary embolism and arterial thrombosis in heart or brain in a nationwide historical prospective cohort of Danish women aged 15 to 49 years in the period 1996-2017. Exclusion criteria included potential confounding factors such as history of thromboembolism, anticoagulation therapy, thrombophilia, and cancer.Findings
Among 2·0 million women followed for 13·8 million person-years, 3,392 venous thromboembolisms and 4,198 arterial thromboses occurred. A total of 63,896 women (3·2%) filled 146,729 prescriptions of oral tranexamic acid during follow-up with median filled prescription per user being one of 15 g. The age-standardised incidence rate of venous thromboembolism was 11·8 (95% CI 4·6 to 30·2) per 10,000 person-years in oral tranexamic acid use compared to 2·5 (2·4 to 2·6) per 10,000 person-years in non-use. For arterial thrombosis, the age-standardised incidence rate per 10,000 person-years was 3·4 (1·1 to 10·7) among exposed compared to 3·0 (2·9 to 3·1) in non-exposed. Comparing oral tranexamic acid use with non-use, the adjusted incidence rate ratio was 4·0 (1·8 to 8·8) for venous thromboembolism and 1·3 (0·4 to 4·2) for arterial thrombosis.Number needed to harm per five days of treatment was 78,549 women for venous thromboembolism.Interpretation
We found use of oral tranexamic acid to be positively associated with venous thromboembolism. However, number needed to harm per five days of treatment was high.
SUBMITTER: Meaidi A
PROVIDER: S-EPMC8176123 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Tranexamic acid (TA) emerged as a promising agent for melasma. However, due to its hydrophilic structure, topical TA should be combined with a penetration-enhancing strategy to augment efficacy. To evaluate the efficacy of fractional erbium:YAG laser-assisted delivery (LAD) of topical TA 5% either with or without oral TA treatment in recalcitrant melasma patients. The authors retrospectively assessed the treatment outcomes of melasma patients treated by fractional erbium:YAG LAD of topical TA 5%. Patients receiving a standard protocol including four biweekly laser sessions were eligible. The study included two groups: group 1 patients received oral TA and LAD of topical TA 5%, and group 2 patients received only LAD of topical TA 5%. Two blinded dermatologists reported pre-treatment and post-treatment modified MASI (mMASI) scores. Mean mMASI scores in both group 1 (n = 15) and group 2 (n = 19) were significantly lower at the end of the treatment than baseline values (p = 0.001; p = 0.022, respectively). The decrease of mMASI scores were higher in group 1 (median = 2.1) (64.7%) than in group 2 (median = 1.2) (41.8%) (p = 0.027). Fractional erbium:YAG LAD of topical TA 5% is an efficient treatment regimen for melasma patients recalcitrant to conventional treatment approaches. The implementation of oral TA to this regimen improves the therapeutic outcomes.
| S-EPMC8960089 | biostudies-literature
Project description:IntroductionThe CRASH-2 trial demonstrated that tranexamic acid (TXA) reduced mortality with no increase in adverse events in severely injured adults. TXA has since been widely used in injured adults worldwide. Our objective was to estimate mortality and adverse events in adults with trauma receiving TXA in studies published after the CRASH-2 trial.MethodsWe systematically searched PubMed, Embase, MicroMedex, and ClinicalTrials.gov for studies that included injured adults who received TXA and reported mortality and/or adverse events. Two reviewers independently assessed study eligibility, abstracted data, and assessed the risk of bias. We conducted meta-analyses using random effects models to estimate the incidence of mortality at 28 or 30 days and in-hospital thrombotic events.ResultsWe included 19 studies and 13 studies in the systematic review and meta-analyses, respectively. The pooled incidence of mortality at 28 or 30 days (five studies, 1538 patients) was 10.1% (95% confidence interval [CI], 7.8-12.4%) (vs 14.5% [95% CI, 13.9-15.2%] in the CRASH-2 trial), and the pooled incidence of in-hospital thrombotic events (nine studies, 1656 patients) was 5.9% (95% CI, 3.3-8.5%) (vs 2.0% [95% CI, 1.8-2.3%] in the CRASH-2 trial).ConclusionCompared to the CRASH-2 trial, adult trauma patients receiving TXA identified in our systematic review had a lower incidence of mortality at 28 or 30 days, but a higher incidence of in-hospital thrombotic events. Our findings neither support nor refute the findings of the CRASH-2 trial but suggest that incidence rates in adults with trauma in settings outside of the CRASH-2 trial may be different than those observed in the CRASH-2 trial.
| S-EPMC6526890 | biostudies-literature
Project description:Background:The use of tranexamic acid (TXA) has become increasingly prevalent for hemorrhage prevention in military trauma patients due to its known survival benefits. There is concern of increased venous thromboembolism (VTE) subsequent to receiving TXA. The purpose of this retrospective study was to determine the rate of VTE in severely injured military personnel during Operation Enduring Freedom (2009-2014). Methods:An analysis of 859 military trauma patients from the 2009-2014 Department of Defense Trauma Registry included subjects with an injury severity score (ISS) >10?and a massive transfusion (MT) (>10 units of blood products in the first 24?hours). Outcomes included a documented VTE (eg, deep vein thrombosis (DVT) or pulmonary embolism (PE)) during the patient's hospital course. Comparison between those who did/did not receive TXA was analyzed using three separate multiple regression analyses using listwise deletion, systematic replacement and multiple imputation. Results:Subjects (n=620) met inclusion criteria with 27% (n=169) having a documented VTE. A total of 30% that received TXA had a documented VTE, 26% that did not receive TXA had a documented VTE and 43% (n=264, n=620) of the sample did not have TXA documented as either given or not given. Multiple regression analyses using listwise deletion and systematic replacement of the TXA variable demonstrated no difference in odds of VTE, whereas the multiple imputation analysis demonstrated a 3% increased odds of VTE, a9.4% increased odds of PE and 8.1% decreased odds of DVT with TXA administration. Discussion:TXA use with an ISS >10?and MT resuscitation had a 3% increased odds of VTE and an increased odds of PE, whereas the odds of DVT were found to be decreased after multiple imputation analysis. Further research on the long-term risks and benefits of TXA usage in the military population is recommended. Level of evidence:IV-therapeutic.
| S-EPMC6996783 | biostudies-literature
Project description:AimsThe population pharmacokinetics (PK) and pharmacodynamics (PD) of tranexamic acid (TXA) have not been studied to prevent postpartum haemorrhage (PPH) in pregnant women. It is unclear which TXA dose assures sufficient PPH prevention. This study investigated population PK/PD of TXA in pregnant women who underwent caesarean delivery to determine the optimal prophylactic doses of TXA for future studies.MethodsWe analysed concentration (PK) and maximum lysis (PD) data from 30 pregnant women scheduled for caesarean delivery who received 5, 10 or 15 mg/kg of TXA intravenously using population approach.ResultsTXA PK was best described by a two-compartment model with first-order elimination and the following parameters: clearance (between-subject variability) of 9.4 L/h (27.7%), central volume of 10.1 L (47.4%), intercompartmental clearance of 22.4 L/h (66.7%), peripheral volume of 14.0 L (13.1%) and additive error of 1.4 mg/L. The relationship between TXA concentration and maximum lysis was characterized by a sigmoid Emax model with baseline lysis of 97%, maximum inhibition of 89%, IC50 of 6.0 mg/L (65.3%), hill factor of 8.5 (86.3%) and additive error of 7.3%. Simulations demonstrated that 500 and 650 mg of TXA maintained therapeutic targets for 30 minutes and 1 hour, respectively, in 90% of patients.ConclusionThis is the first population PK and PD study of TXA in pregnant women undergoing caesarean delivery. Our analysis suggests that a 650 mg dose provides adequate PPH prophylaxis up to 1 hour, which is less than the currently used 1000 mg of TXA in pregnant women.
| S-EPMC8355246 | biostudies-literature
Project description:BackgroundEvery 2 minutes, there is a pregnancy-related death worldwide, with one-third caused by severe postpartum hemorrhage. Although international trials demonstrated the efficacy of 1000 mg tranexamic acid in treating postpartum hemorrhage, to the best of our knowledge, there are no dose-finding studies of tranexamic acid on pregnant women for postpartum hemorrhage prevention.ObjectiveThis study aimed to determine the optimal tranexamic acid dose needed to prevent postpartum hemorrhage.Study designWe enrolled 30 pregnant women undergoing scheduled cesarean delivery in an open-label, dose ranging study. Subjects were divided into 3 cohorts receiving 5, 10, or 15 mg/kg (maximum, 1000 mg) of intravenous tranexamic acid at umbilical cord clamping. The inclusion criteria were ≥34 week's gestation and normal renal function. The primary endpoints were pharmacokinetic and pharmacodynamic profiles. Tranexamic acid plasma concentration of >10 μg/mL and maximum lysis of <17% were defined as therapeutic targets independent to the current study. Rotational thromboelastometry of tissue plasminogen activator-spiked samples was used to evaluate pharmacodynamic profiles at time points up to 24 hours after tranexamic acid administration. Safety was assessed by plasma thrombin generation, D-dimer, and tranexamic acid concentrations in breast milk.ResultsThere were no serious adverse events including venous thromboembolism. Plasma concentrations of tranexamic acid increased in a dose-proportional manner. The lowest dose cohort received an average of 448±87 mg tranexamic acid. Plasma tranexamic acid exceeded 10 μg/mL and maximum lysis was <17% at >1 hour after administration for all tranexamic acid doses tested. Median estimated blood loss for cohorts receiving 5, 10, or 15 mg/kg tranexamic acid was 750, 750, and 700 mL, respectively. Plasma thrombin generation did not increase with higher tranexamic acid concentrations. D-dimer changes from baseline were not different among the cohorts. Breast milk tranexamic acid concentrations were 1% or less than maternal plasma concentrations.ConclusionAlthough large randomized trials are necessary to support the clinical efficacy of tranexamic acid for prophylaxis, we propose an optimal dose of 600 mg in future tranexamic acid efficacy studies to prevent postpartum hemorrhage.
| S-EPMC8149481 | biostudies-literature
Project description:ObjectiveThis study compares the effectiveness of administering sublingual misoprostol combined with oxytocin to that of IV tranexamic acid combined with oxytocin to reduce intra and post-operative blood loss in high-risk women for postpartum haemorrhage (PPH) following cesarean section (CS).MethodsAbout 315 high-risk pregnant women undergoing CS participated in this trial. They were randomly assigned into three groups; tranexamic group, misoprostol group, and control group, according to the medication given in the operative theatre. All patients received oxytocin intraoperatively. They were assessed regarding intraoperative blood loss, the incidence of PPH, and the reduction in haemoglobin and hematocrit values.ResultsBoth tranexamic and misoprostol groups had similar results in reducing intra and post-operative blood loss. However, the reduction in haemoglobin and hematocrit were significantly lower in tranexamic and misoprostol groups compared to the control group (-0.78 ± 0.57 vs. -0.83 ± 0.52 vs. -1.32 ± 0.57 gm/dl, P < 0.001 and - 3.05 ± 1.28 vs. -3.06 ± 1.13 vs. -4.94 ± 1.82%, P < 0.001 respectively). In addition, the estimated blood loss was significantly lower in the tranexamic and misoprostol groups compared to the control group (641.6 ± 271.9 vs. 617.9 ± 207.4 vs. 1002.4 ± 340.7 ml, P < 0.001).ConclusionBoth tranexamic acid and misoprostol are equally capable of reducing blood loss, but the results were significantly better compared to using oxytocin alone in high-risk patients.Clinical trial registrationRegistered at www.Clinicaltrialsgovon07/10/2019 with registration number NCT04117243.
| S-EPMC10463445 | biostudies-literature
Project description:Background:Tranexamic acid (TXA) is widely used in orthopedic surgery to reduce perioperative bleeding. Since TXA inhibits fibrinolysis, there is concern that it may increase the risk of thromboembolic events. Objectives:To verify the prevalence of deep venous thrombosis (DVT) in patients receiving TXA during total knee arthroplasty and to compare topical with intravenous administration of the drug. Methods:All patients admitted for total knee arthroplasty due to primary arthrosis between June and November of 2014 were recruited consecutively. Thirty patients were randomized to a "topical group" (1.5 g TXA diluted in 50ml saline sprayed over the area operated, before tourniquet release), 30 to an "intravenous group" (20mg/kg TXA in 100 ml of saline, given at the same time as anesthesia), and 30 to a control group (100 ml of saline, given at the same time as anesthesia). All patients had duplex ultrasound scans of the legs on the 15th postoperative day. Results:Deep venous thrombosis events occurred in five of the 90 patients operated (one out of 30 in the topical group [3.3%], four out of 30 in the control group [13.3%], and zero in the intravenous group). All were confirmed by duplex ultrasound scans and all were asymptomatic. Prevalence rates of DVT were similar between groups (p = 0.112 for control vs. intravenous; p = 0.353 for control vs. topical; and p =1.000 for intravenous vs. topical, according to two-sided exact tests). Conclusions:Both topical and intravenous administration of TXA are safe with regard to occurrence of DVT, since the number of DVT cases in patients given TXA was not different to the number in those given placebo.
| S-EPMC5829705 | biostudies-literature
Project description:BackgroundGlanzmann thrombasthenia is a rare bleeding disorder due to defects in the glycoprotein Ilb/IIIa complex present on the platelet membrane. The most common mode of treatment for this disorder is platelet transfusion. However, scientific evidence does state that repeated transfusions could lead to auto immunization making transfusions ineffective.Aim and objectiveTo describe the use of a novel technique of soft splint with tranexamic acid paste to stop oral bleeding in a patient with Glanzmann thrombasthenia (GT).Case descriptionA 7-year-old female patient with a known history of GT was referred to the pediatric department. The chief complaint of the patient revealed a history of spontaneous bleeding from the oral cavity. The patient required multiple teeth extractions due to severely carious teeth. History revealed that the patient was admitted to the hospital (casualty) three times within 1 month due to a similar complaint leading to hypovolemic shock. Several transfusion procedures were done to stop the spontaneous bleeding. To stop the intraoral bleeding without transfusions, a novel method of using a soft splint with tranexamic acid paste (500 mg tablet crushed and mixed with saline) in the area of spontaneous bleeding was employed with a successful follow-up of 7 months.ConclusionSoft splint with the tranexamic acid paste can serve as an effective method of treatment for patients with spontaneous oral bleeding due to medical conditions like GT.Clinical relevanceThis case report highlights the need for awareness among all the healthcare providers about the importance of regular dental visits. The healthcare providers also need to emphasize the same to all patients with medical conditions to avoid such life-threatening situations.How to cite this articleBhavyaa R, Vignesh KC, Muthu MS, et al. Glanzmann Thrombasthenia: Use of the Soft Splint with Tranexamic Acid Paste to Reduce Spontaneous Oral Bleeding. Int J Clin Pediatr Dent 2021;14(4):580-585.
| S-EPMC8585906 | biostudies-literature
Project description:Venous thromboembolism (VTE) is a complex multifactorial disease influenced by genetic and environmental risk factors. An example for the latter is the regular use of combined oral contraceptives (CC), which increases the risk to develop VTE by 3 to 7 fold, depending on estrogen dosage and the type of progestin present in the pill. One out of 1'000 women using CC develops thrombosis, often with life-long consequences; a risk assessment is therefore necessary prior to such treatment. Currently known clinical risk factors associated with VTE development in general are routinely checked by medical doctors, however they are far from being sufficient for risk prediction, even when combined with genetic tests for Factor V Leiden and Factor II G20210A variants. Thus, clinical and notably genetic risk factors specific to the development of thrombosis associated with the use of CC in particular should be identified.Step-wise (logistic) model selection was applied to a population of 1622 women using CC, half of whom (794) had developed a thromboembolic event while using contraceptives. 46 polymorphisms and clinical parameters were tested in the model selection and a specific combination of 4 clinical risk factors and 9 polymorphisms were identified. Among the 9 polymorphisms, there are two novel genetic polymorphisms (rs1799853 and rs4379368) that had not been previously associated with the development of thromboembolic event. This new prediction model outperforms (AUC 0.71, 95% CI 0.69-0.74) previously published models for general thromboembolic events in a cross-validation setting. Further validation in independent populations should be envisaged.We identified two new genetic variants associated to VTE development, as well as a robust prediction model to assess the risk of thrombosis for women using combined oral contraceptives. This model outperforms current medical practice as well as previously published models and is the first model specific to CC use.
| S-EPMC5531518 | biostudies-literature
Project description:BackgroundVenous thromboembolism (VTE) affects nearly 1 million Americans annually, and many benefit from continued anticoagulation after the initial 3- to 6-month treatment period (secondary prevention).ObjectivesTo determine whether warfarin, apixaban, or rivaroxaban is associated with reduced recurrent VTE hospitalization in the secondary prevention of VTE.Patients/methodsWe performed a retrospective cohort study of participants enrolled in the MarketScan Insurance Database between 2013 and 2017 in those with an incident VTE. In those individuals who continued oral anticoagulation (warfarin, apixaban, or rivaroxaban) beyond 6 months, we determined the relative rate of recurrent VTE hospitalization.ResultsAmong 119 964 individuals with VTE, 25 419 remained on anticoagulation after 6 months and were matched successfully by age, sex, and date. After adjusting for a propensity score, apixaban versus rivaroxaban (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.45-0.94) and apixaban versus warfarin (HR, 0.68; 95% CI, 0.47-1.00) had a reduced risk of recurrent VTE hospitalization, and rivaroxaban versus warfarin (HR, 1.12; 95% CI, 0.94-1.33) had equivalent rates. For the rivaroxaban versus warfarin comparison there was a significant interaction by renal function (P < .01) where rivaroxaban was associated with a lower risk of recurrent VTE hospitalization (HR, 0.65; 95% CI, 0.41-1.03) in those with kidney disease and increased risk in those without kidney disease (HR, 1.24; 95% CI, 1.02-1.50).ConclusionsThese data suggest that apixaban has a lower recurrent VTE hospitalization rate than rivaroxaban during the secondary prevention of VTE, and further study of diverse patient populations, especially by kidney function, is warranted.
| S-EPMC8371351 | biostudies-literature