Combined Tranexamic Acid Research Articles

LOCAL APPLICATION OF TRANEXAMIC ACID IN KNEE REPLACEMENT

The purpose of the study – assessment of the efficacy of local application of tranexamic acid in TKA and the choice of the optimal dosage. Materials and methods. 48 patients were included in open-prospective study and were randomized to one of four groups. In the first group tranexamic acid was used as intravenous bolus at the beginning of the operation at a dose of 15 mg/kg. Additionally, after the installation of the prosthetic components, the surgeon performed periarticular infiltration of soft tissue by tranexamic acid solution at a dose of 15 mg/kg. In the second group of patients tranexamic acid was used as 500 mg intravenous bolus before surgery, and 500 mg locally after installation of the prosthesis components. In the third group of patients received tranexamic acid once at the beginning of the operation at a dose of 15 mg/kg iv bolus. In the fourth group tranexam was used after surgery once at a dose of 10 mg/kg. Results. In the first group of patients were achieved statistically significant, 5-6 times, reduction of blood loss on drainage in comparison with other groups, where the volume of postoperative blood loss was not significantly different between groups. Also in the first group recorded the smallest decrease in hemoglobin at the 5th postoperative day compared to the third and fourth groups. Complications associated with the use of tranexamic acid were not revealed. Conclusion. The method of periarticular infiltration by tranexamic acid in combination with its intravenous use in knee joint replacement is an effective and safe method for reduction of post-operative blood loss.

Is combined topical with intravenous tranexamic acid superior than topical, intravenous tranexamic acid alone and control groups for blood loss controlling after total knee arthroplasty: A meta-analysis.

Background:The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to evaluate the efficacy and safety of combined topical with intravenous tranexamic acid (TXA) versus topical, intravenous TXA alone or control for reducing blood loss after a total knee arthroplasty (TKA).Methods:In May 2016, a systematic computer-based search was conducted in the PubMed, Embase, Cochrane Library, Web of Science, and Chinese Wanfang database. This systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement criteria. Only patients prepared for primary TKA that administration combined topical with intravenous TXA with topical TXA, intravenous (IV) TXA, or control group for reducing blood loss were included. Eligible criteria were published RCTs about combined topical with intravenous TXA with topical alone or intravenous alone. The primary endpoint was the total blood loss and need for transfusion. The complications of deep venous thrombosis (DVT) were also compiled to assess the safety of combined topical TXA with intravenous TXA. Relative risks (RRs) with 95% CIs were estimated for dichotomous outcomes, and mean differences (MDs) with 95% CIs for continuous outcomes. The Cochrane risk of bias tool was used to appraise a risk of bias. Stata 12.0 software was used for meta-analysis.Results:Fifteen studies involving 1495 patients met the inclusion criteria. The pooled meta-analysis indicated that combined topical TXA with intravenous TXA can reduce the total blood loss compared with placebo with a mean of 458.66 mL and the difference is statistically significant (MD = −458.66, 95% CI: −655.40 to 261.91, P < 0.001). Compared with intravenous TXA, combined administrated TXA can decrease the total blood loss, and the difference is statistically significant (MD = −554.03, 95% CI: −1066.21 to −41.85, P = 0.034). Compared with the topical administration TXA, the pooled meta-analysis indicated that combined TXA can decrease the amount of total blood loss with mean 107.65 mL with statistically significant(MD = −107.65, 95% CI: −525.55 to −239.9141.85, P = 0.001). The pooled results indicated that combined topical with intravenous TXA can decrease the need for transfusion (RR = 0.34, 95% CI: 0.23–0.50, P < 0.001). There is no significant difference between combined topical with intravenous TXA with topical or intravenous TXA (P > 0.05) in terms of need for transfusion and the occurrence of DVT.Conclusion:Compared with topical, intravenous TXA alone or control group, combined topical with TXA, can decrease the total blood loss and subsequent need for transfusion without increasing the occurrence of DVT. The dose and timing to administration TXA is different, and more randomized controlled trials are warranted to clarify the optimal dosing and time to administration TXA.

Abnormal uterine bleeding

The article describes a clinical case of severe uterine bleeding in a patient with III degree of mitral valve insufficiency after mitral valve replacement, which was placed a clinical diagnosis of abnormal uterine bleeding (AUB). Given the categorical refusal of the patient and her relatives from holding hysteroscopy the conservative haemostatic therapy was appointed.In view of the congenital heart disease and the risks of thrombotic complications the oral contraceptive for patient was contraindicated. Therefore, for the treatment was selected the drug of tranexamic acid Vidanol at dose of 1.5 g every 8 hours for 5 days, as well as non-steroidal anti-inflammatory drug diclofenac sodium in rectal suppositories of 100 mg over 5 days. Considering the moderate secondary anemia and the severity of clinical symptoms, for patient was also appointed anti-anemia drug Ferinzhekt at a dose of 1000 mg intravenously once, followed by the appointment after 1 week Maltofer on 1 tablet 3 times a day for a month.During the first 12 hours of treatment with the combination Vidanol +diclofenac sodium was observed a decrease in the volume of blood loss of patient, the decrease of intensity of pain, and improvement in overall condition. Against the background stabilization of the general condition of the patient under ultrasound was performed the dissection and separation of intrauterine adhesions, which were detected during diagnostic hysteroscopy. In order to prevent recurrence of occurrence of this disease was introduced anti-adhesion gel Defensal in the uterus. Postoperatively, the patient also received antibiotic prophylaxis and complex of anti-inflammatory therapy.In the next two menstrual cycles in order to prevent of AUB the patient took from 1 to 5 day of menstruation on 500 mg of Vidanol 3 times a day, as well as suppositories diclofenac sodium one day before the onset of menstruation and within 5 days of the cycle. After 2 months at the time of the next menstruation for woman was set intrauterine system (IUS), which releasing daily 13.5 mg of levonorgestrel. At the control examination 3 months after IUS installation the patient was no complaints, no bleedings and pain, and her general condition was improved.This clinical case is an example of an effective and safe treatment for severe AUB for patient of reproductive age with severe somatic pathology. Appointment of tranexamic acid in combination with nonsteroidal anti-inflammatory drugs and anti-anemia therapy is effective in the treatment of AUB and can be used for the prevention of uterine bleeding.

The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: Combined tranexamic acid for TKA.

ObjectivesTranexamic acid (TXA) is an antifibrinolytic agent used as a blood-sparing technique in total knee arthroplasty (TKA), and is routinely administered by intravenous (IV) or intra-articular (IA) injection. Recently, a novel method of TXA administration, the combined IV and IA application of TXA, has been applied in TKA. However, the scientific evidence of combined administration of TXA in TKA is still meagre. This meta-analysis aimed to investigate the efficacy and safety of combined IV and IA TXA in patients undergoing TKA.Materials and MethodsA systematic search was carried out in PubMed, the Cochrane Clinical Trial Register (Issue12 2015), Embase, Web of Science and the Chinese Biomedical Database. Only randomised controlled trials (RCT) evaluating the efficacy and safety of combined use TXA in TKA were identified. Two authors independently identified the eligible studies, extracted data and assessed the methodological quality of included studies. Meta-analysis was conducted using Review Manager 5.3 software.ResultsA total of ten RCTs (1143 patients) were included in this study. All the included studies were randomised and the quality of included studies still needed improvement. The results indicated that, compared with either placebo or the single-dose TXA (IV or IA) group, the combination of IV and IA TXA group had significantly less total blood loss, hidden blood loss, total drain output, a lower transfusion rate and a lower drop in haemoglobin level. There were no statistically significant differences in complications such as wound infection and deep vein thrombosis between the combination group and the placebo or single-dose TXA group.ConclusionsCompared with placebo or the single-dose TXA, the combined use of IV and IA TXA provided significantly better results with respect to all outcomes related to post-operative blood loss without increasing the risk of thromboembolic complications in TKA.Cite this article: Z. F. Yuan, H. Yin, W. P. Ma, D. L. Xing. The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: combined tranexamic acid for TKA. Bone Joint Res 2016;5:353–361. DOI: 10.1302/2046-3758.58.BJR-2016-0001.R2.

Combination Intravenous and Intra-Articular Tranexamic Acid Compared with Intravenous Only Administration and No Therapy in Total Knee Arthroplasty: A Case Series Study

IntroductionExcessive perioperative bleeding requiring transfusion remains a potential complication of Total Knee Arthroplasty (TKA). There is overwhelming evidence supporting the efficacy of intravenous Tranexamic acid to reduce bleeding and the need for transfusion in TKA. There is still some question regarding the efficacy of other methods of Tranexamic acid administration. This case series study evaluated the effects of the use of intravenous Tranexamic acid administered alone, or in combination with intra-articular tranexamic acid on transfusion rate and other clinical outcomes; and compared this to a group of patients who received neither treatment.MethodWe conducted a case review of 150 patients who had undergone TKA from 2012-2015. 50 patients underwent TKA with IV Tranexamic acid (Group A). A further 50 patients underwent TKA with IV Tranexamic acid in combination with intra-articular administration of 2grams of Tranexamic acid in 20ml saline (Group B). A final 50 patients underwent TKA without the use of Tranexamic acid (non-treatment group). Outcome measures were transfusion rate, change in haemoglobin and haematocrit, medical review events, patient mortality and changes in knee flexion and extension measurements at six weeks after surgery.ResultsThere were no significant differences in red blood cell transfusion rates between the non-treatment group and the two treatment groups, however an absolute reduction in transfusion rate from 8% to 0% (p=0.134) was observed. The mean change of haemoglobin level in the non-treatment group was 29 while in treatment groups A and B, this was 23 and 19 respectively (p=0.0001). No significant difference was observed between treatment group A and B. There was a significant difference in post-operative haemoglobin level, where mean haemoglobin concentrations in non-treatment, Group A and B were 110 vs 115 vs 123 respectively (P= 0.0001). Pairwise comparison showed that Group B was significantly different when compared to both non treatment (p=0.0001) and treatment group A (p=0.020). There were no significant differences observed in other outcomes.ConclusionThis study supports the existing literature and suggests that the use of IV Tranexamic acid alone or in combination with intra-articular dose in TKA may reduce the requirement for transfusion (Level IV evidence). Furthermore, this study suggests that the use of tranexamic acid as a combination of Intravenous and intra-articular administration has no effect on range of motion, or medical complications during hospital stay. Although it was not a statistically significant finding, our study suggested a trend towards a greater reduction in haemoglobin and haematocrit fall in the combination therapy group when compared to IV Tranexamic acid alone

Combination of erythropoietin and tranexamic acid in bilateral simultaneous total hip arthroplasty: a randomised, controlled trial.

This study aimed to evaluate whether the combination of erythropoietin (EPO) and tranexamic acid (TXA) exerted any additional benefits on the number of blood transfusions required and haematological parameters compared with TXA alone following primary bilateral simultaneous total hip arthroplasty. We conducted a single-centre, prospective, randomised, and controlled trial at our hospital. Group EPO + TXA (n = 30) received daily subcutaneous injections EPO (10,000 IU) on preoperative days 1-4 and postoperative days 1-3. Additionally, these patients were administered TXA (15 mg/kg) 10 min prior to the incision. Group TXA (n = 32) received only TXA (15 mg/kg) 10 min prior to the incision. The primary outcomes were the haematological parameters and number of blood transfusions required. The secondary outcomes were total blood loss, drainage volume, and postoperative complications. The total amount of blood transfusion and mean blood transfusion per patient was lower in group EPO + TXA than in group TXA (p = 0.039, p = 0.023; respectively). In the postoperative period, patients in group EPO + TXA had higher haematological parameters (haemoglobin, haematocrit, and reticulocyte count) than patients in group TXA. No significant differences were found in total blood loss, drainage volume, and DVT or PE between the 2 groups. This study showed that administrating EPO + TXA in combination can increase haematological parameters and reduce the need for blood transfusion without increasing the risk of DVT or PE compared with TXA alone.

Efficacy of Tranexamic Acid in Combination With Conventional Therapy for Treatment of Pph

Haemorrhage is the leading cause of maternal mortality, accounting for about 35% of all maternal deaths. About 14 million women around the world suffer from Post Partum Hemorrhage (PPH) every year. Of them, about 2% die with an average interval of 2-4 hrs from onset of bleeding. Tranexamic Acid (TXA) is the most effective of the available anti-fibrinolytics, which has been shown to be very useful in reducing blood loss and incidence of blood transfusion in different surgeries. The study was done to see the efficacy of injectable tranexamic acid in addition to conventional treatment in control of atonic PPH. In this study, women having atonic PPH following vaginal delivery were grouped into two, A &amp; B. Group A received 2 amp inj.TXA (Tranexamic acid) i.v immediately after diagnosis of PPH and Group B received 10ml distilled water i.v. Both groups received all other necessary measures for control of PPH and outcomes were recorded in a preformed data collection sheet. All data were analyzed by computer based software Statistical Packages for Social Science (SPSS) version 15.The results showed that tranexamic acid significantly reduced the volume of blood loss in atonic PPH, 1141.23±489.91 ml in study group versus 1365.25±428.22 ml in control group.PPH control within 2 hr with medical therapies occurred more in TXA group (88.09%) than in control group (57.14%). Invasive procedures were less required in TXA group than in control group ,condom catheter in 4 pt. (9.52%) compared to 11(26.19%) in control group. Hysterectomy was done in 1 case of TXA group compared to 7 cases of control group. TXA also significantly reduced the necessity of blood transfusion in PPH, 26.19% in TXA group compared to 54.76% in control group. So one gm i.v. tranexamic acid given along with other conventional measures at the diagnosis of atonic PPH significantly reduces the amount of blood loss, requirement of blood transfusion, necessity of invasive procedures. JCMCTA 2015 ; 26 (2) : 34 - 39

Combined use of intravenous and topical tranexamic acid following cementless total hip arthroplasty: a randomised clinical trial.

This study was designed to compare the efficacy and safety of the combined use of tranexamic acid (TXA) with the intravenous (IV) or local use alone in total hip arthroplasty (THA). 210 patients were randomised to a IV group, a local group or a combined group. Participants received 1.5 g IV-TXA in the IV group, 3 g local TXA in the local group, or 1 g IV-TXA combined with 2 g local TXA in the combined group. The primary outcomes were total blood loss (TBL), maximum haemoglobin drop, and the incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE). TBL was (776.75 ± 188.95) ml in the combined group, which was significantly lower than in the IV group or the local group (p = 0.015, p = 0.001 respectively). Likewise, the mean values of maximum hemoglobin drop in the combined, IV, and local groups were 2.98 ± 0.78, 3.36 ± 0.78, and 3.89 ± 0.72 g/dL, respectively, with a significant intergroup difference (p&lt;0.001 for all). Asymptomatic DVT was detected in 1 patient of the IV group, and 2 patients of the combined group with the use of ultrasound. There were no episodes of PE, and no significant differences were seen between groups in terms of complications. Combined use of intravenous TXA and local TXA in primary unilateral THA can effectively decrease total blood loss and increase postoperative haemoglobin levels without influencing complication rates. It is suggested that this combined TXA regimen is more effective in decreasing blood loss in cementeless THA than intravenous or local administration alone.

Using a combination of tranexamic acid and rivaroxaban in total knee replacements reduces transfusion requirements: A prospective cohort study

IntroductionThe risk of venous thromboembolism (VTE) is high in orthopaedics. Oral direct factor Xa inhibitors have been introduced to help reduce the incidence of VTE. To reduce post-operative bleeding antifibrinolytics are used. AimWe aimed to ascertain the effect of two drugs on post-operative bleeding and transfusion requirements. MethodsWe prospectively recorded patient demographics, operative details, complications, transfusion incidence and VTE incidence in TKR patients. We also sent out a questionnaire to patients asking about wound bleeding and VTE. All patients were given 10 mg rivaroxaban 8 h post-operatively and then once a day for 14 days. Patients given tranexamic acid were given 500 mg IV, 5 min prior to wound closure at the discretion of the surgeon. VTE was confirmed by Doppler or CTPA as Deep Vein Thrombus or Pulmonary Embolism. Minor bleed was categorised as dressing soakage or reported wound leakage, major bleed as haematoma requiring revision within 30 days. Results509 patients underwent TKR: 200 (39%) only received rivaroxaban (Group 1), 296 (58%) also received tranexamic acid (Group 2). 13 (3%) of patients had no data available. 5 patients had a VTE: 4 (2%) Group 1, 1 (0.3%) Group 2 (P < 0.05). 39 patients had a minor bleed: 17 (8.5%) Group 1, 22 (7.4%) Group 2 (P = 0.5). 2 patients had major bleeds: 1 (0.5%) Group 1, 1 (0.33%) Group 2 (P = 0.69). Blood transfusions 21 (10.5%) Group 1, 9 (3%) Group 2 (P < 0.0001). ConclusionsWe have demonstrated a reduced requirement for blood transfusions in the tranexamic acid group. However our results whilst they show a trend towards decrease bleeding rates in both the minor and major bleeds are not significant, requiring larger studies looking at wound bleeding and leakage.

Diagnosis and management of acquired coagulation inhibitors: a guideline from UKHCDO

A United Kingdom Haemophilia Centre Doctors’ Organization (UKHCDO) guideline approved by the British Committee for Standards in Haematology Peter W Collins, Elizabeth Chalmers, Daniel Hart, Ian Jennings, Ri Liesner, Savita Rangarajan, Kate Talks, Michael Williams and Charles R. M. Hay School of Medicine, Cardiff University, University Hospital of Wales, Cardiff, Royal Hospital for Sick Children, Glasgow, Royal London Hospital, Barts and The London School of Medicine and Dentistry, Queen Mary University London, London, UK NEQAS Blood Coagulation, Sheffield, Great Ormond Street NHS Trust, London, Hampshire Hospital NHS Foundation Trust, Basingstoke & North Hampshire Hospital, Basingstoke, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle, Birmingham Children’s Hospital NHS Foundation Trust, Birmingham, and Manchester University Dept of Haematology, Manchester Royal Infirmary, Manchester, UK

Association of Cryoprecipitate and Tranexamic Acid With Improved Survival Following Wartime Injury

To quantify the impact of fibrinogen-containing cryoprecipitate in addition to the antifibrinolytic tranexamic acid on survival in combat injured. Retrospective observational study comparing the mortality of 4 groups: tranexamic acid only, cryoprecipitate only, tranexamic acid and cryoprecipitate, and neither tranexamic acid nor cryoprecipitate. To balance comparisons, propensity scores were developed and added as covariates to logistic regression models predicting mortality. A Role 3 Combat Surgical Hospital in southern Afghanistan. A total of 1332 patients were identified from prospectively collected U.K. and U.S. trauma registries who required 1 U or more of packed red blood cells and composed the following groups: tranexamic acid (n = 148), cryoprecipitate (n = 168), tranexamic acid/cryoprecipitate (n = 258), and no tranexamic acid/cryoprecipitate (n = 758). In-hospital mortality. Injury severity scores were highest in the cryoprecipitate (mean [SD], 28.3 [15.7]) and tranexamic acid/cryoprecipitate (mean [SD], 26 [14.9]) groups compared with the tranexamic acid (mean [SD], 23.0 [19.2]) and no tranexamic acid/cryoprecipitate (mean [SD], 21.2 [18.5]) (P < .001) groups. Despite greater Injury Severity Scores and packed red blood cell requirements, mortality was lowest in the tranexamic acid/cryoprecipitate (11.6%) and tranexamic acid (18.2%) groups compared with the cryoprecipitate (21.4%) and no tranexamic acid/cryoprecipitate (23.6%) groups. Tranexamic acid and cryoprecipitate were independently associated with a similarly reduced mortality (odds ratio, 0.61; 95% CI, 0.42-0.89; P = .01 and odds ratio, 0.61; 95% CI, 0.40-0.94; P = .02, respectively). The combined tranexamic acid and cryoprecipitate effect vs. neither in a synergy model had an odds ratio of 0.34 (95% CI, 0.20-0.58; P < .001), reflecting nonsignificant interaction (P = .21). Cryoprecipitate may independently add to the survival benefit of tranexamic acid in the seriously injured requiring transfusion. Additional study is necessary to define the role of fibrinogen in resuscitation from hemorrhagic shock.

Combined Treatment of Ulinastatin and Tranexamic Acid Provides Beneficial Effects by Inhibiting Inflammatory and Fibrinolytic Response in Patients Undergoing Heart Valve Replacement Surgery

To investigate the effect of ulinastatin and tranexamic acid administered alone or in combination on inflammatory cytokines and fibrinolytic system in patients undergoing heart valve replacement surgery during cardiopulmonary bypass (CPB). CPB-induced fibrinolytic hyperfunction and systemic inflammatory response syndrome (SIRS) are the leading causes responsible for the occurrence of postsurgical complications such as postsurgical cardiac insufficiency and lung injury, which may lead to an increase in postsurgical bleeding, prolongation of hospital stay, and increased costs. One hundred twenty patients undergoing heart valve replacement surgery during CPB were randomly assigned into 4 groups of 30 patients each: blank control group (Group C), tranexamic acid group (Group T), ulinastatin group (Group U), and tranexamic acid-ulinastatin combination group (Group D). Physiological saline, tranexamic acid, ulinastatin, and a combination of tranexamic acid and ulinastatin were given to each group, respectively. Arterial blood was collected from the radial artery at 4 time points: after induction of anesthesia (T1), unclamping the ascending aorta (T2), and at 1 hour (T3) and 24 hours (T4) after CPB. The levels of plasma tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), neutrophil elastase (NE), and the concentrations of tissue plasminogen activator (t-PA) and α2-antiplasmin (α2-AP) were detected. The changes in the volume of pericardial mediastinal drainage after surgery were observed and recorded. The plasma TNF-α, IL-6, and NE levels significantly increased in patients from all 4 groups at time points of T2, T3, and T4 in comparison to those before CPB (P < .05), and the plasma TNF-α and IL-6 levels in groups U and D were significantly lower than those in the other 2 groups (P < .05). The plasma t-PA, α2-AP, and D-dimer concentrations significantly increased in patients from all 4 groups at T2 and T3 compared with those before CPB (P < .05), and the plasma t-PA and D-dimer concentrations were significantly lower in groups T and D than those in groups U and C (P < .05) at T2 and T3. The plasma α2-AP concentrations in groups T and D were significantly higher than those in Group C at T3 (P < .05). The volumes of pericardial mediastinal drainage per body surface area were significantly lower in groups T and D than those in Group C 6 hours after the surgery (P < .05). Ulinastatin inhibits the release of inflammatory medium and reduces the inflammatory response during CPB. Tranexamic acid can effectively inhibit the fibrinolytic hyperfunction caused by CPB and thus decreases postsurgical bleeding. In addition, it exhibits a minor anti-inflammatory response. As a consequence, a combined treatment of ulinastatin and tranexamic acid reduces postsurgical bleeding and shortens postoperative hospital stay in patients undergoing heart valve replacement surgery.

A Retrospective Analysis of Blood Loss With Combined Topical and Intravenous Tranexamic Acid After Coronary Artery Bypass Graft Surgery

Intravenous antifibrinolytics are the gold standard for blood conservation during cardiac surgery. Recent evidence suggests that topical tranexamic acid administration also is effective, although the efficacy of combined topical and intravenous administration has never been reported. Combined administration may offer superior hemostasis while decreasing side effects. The current study explores the use of combined topical and intravenous tranexamic acid as a blood conservation strategy in cardiac surgery. Retrospective cohort. A single-center, academic, tertiary care hospital. One hundred sixty elective coronary artery bypass graft patients. A practice change allowed a retrospective comparison of postoperative chest tube drainage in patients with intravenous or combined (intravenous and topical) tranexamic acid. Chest tube drainage was decreased in the combined group at 3 (164.8 ± 102.2 v 242.7 ± 148.9 mL, p < 0.001), 6 (265.6 ± 163.7 v 358.8 ± 247.2 mL, p = 0.006), and 12 hours (374.3 ± 217.1 v 498.5 ± 336.6 mL, p = 0.006) postoperatively compared with the intravenous group. The tranexamic acid dose was higher in the combined group (5.1 ± 1.1 v 4.1 ± 1.3 g, p < 0.001), but less was administered intravenously (3.1 ± 1.1 v 4.1 ± 1.3 g, p < 0.001). No differences were observed in adverse events. This study suggested that combined tranexamic acid administration may be superior for blood conservation, but fully powered randomized controlled trials will be required to confirm these findings and determine the safety advantage and clinical relevance of adding topical tranexamic acid to existing blood conservation strategies.

Stabilization of fibrin clots by activated prothrombin complex concentrate and tranexamic acid in FVIII inhibitor plasma

Defective hemostasis in haemophilia patients with FVIII inhibitors results in a dramatic decrease in thrombin generation forming unstable fibrin clots that are susceptible to fibrinolyisis. In this study we tested whether the combination of plasma derived activated prothrombin complex concentrate (pd-aPCC) with tranexamic acid (TXA) may improve fibrin clot stability in FVIII inhibitor plasma. A microplate assay for clot lysis time was used to assess clot stability in FVIII inhibitor plasma. The effect of pd-aPCC on clot stability was first tested using the commercial FVIII inhibitor plasma. TXA (5 ~ 10 mg mL⁻¹) increased clot lysis time, but pd-aPCC (0.25 ~ 1.0 U mL⁻¹) had no effect on it. The combination of pd-aPCC and TXA significantly increased clot lysis time compared with TXA alone. The effect appeared to be limited to fibrin clot resistance to fibrinolysis, as TXA was found to have no effect on thrombin generation induced by pd-aPCC. The effect of pd-aPCC and TXA on clot stability was then tested and verified in plasma samples from ten patients with severe haemophilia A and inhibitors. The combination of TXA (10 mg mL⁻¹) and pd-aPCC (0.5 U mL⁻¹) significantly increased clot lysis time compared to TXA alone. Our results suggest that the combination of pd-aPCC with TXA improves clot stability in FVIII inhibitor plasma without additional increases in thrombin generation.

Tranexamic Acid Increases Clot Stability in Patients with Severe Hemophilia A.

Patients with severe Hemophilia A have a compromised clot formation. In addition, it is suggested that severe Hemophilia A is associated with reduced clot stability. Hence, during the recent years antifibrinolytics have been increasingly used as part of the prophylactic haemostatic treatment e.g. during surgical procedures. However, so far only limited evidence supports the systematic use of antifibrinolytics in these patients. In the present laboratory and clinical study we examined whether reduced clot stability in severe Hemophilia A could be improved by treatment with the antifibrinolytic drug tranexamic acid in combination with recombinant factor VIII (rFVIII). Eight patients with verified severe Hemophilia A (factor VIII:C <0.01 IU/mL) were included. None of the patients had previous or present inhibitor against factor VIII (Bethesda titre < 0.6 IU/mL), and all patients were abstinent to factor VIII substitution for at least 72 hours prior to blood sampling. A baseline blood sample was obtained. Subsequently, the patients received an i.v. bolus injection of rFVIII aiming at increasing the functional level of factor VIII to around 50%. Ten minutes later a second blood sample was obtained followed by i.v. injection of tranexamic acid (10 mg per kg). After another 10 minutes the third blood sample was obtained. In order to provide documentation on the haemostatic potential of tranexamic acid we adopted a thrombelastographic model of continuous whole blood coagulation using ROTEM Coagulation Analyzers (Pentapharm®, Munich, Germany). The whole blood clot formation was evaluated using activation with recombinant human tissue factor (TF - Innovin®, Dade Behring, final dilution 1:17000). The clot stability was evaluated using reaction mixture containing TF (final dilution 1:17000) and recombinant single chain tissue plasminogen activator (t-PA - American Diagnostics, final concentration t-PA 2 nM). Using the software DyCoDerivAn™ GOLD (AvordusoL, Risskov, Denmark) we obtained dynamic parameters of clot initiation (CT, s) and clot propagation such as the maximum velocity of clot formation (MaxVel, mm × 100/s) and the time until maximum velocity of clot propagation (t, MaxVel, s). Whole blood clot stability was analysed by evaluation of the maximum clot formation (MCF, mm × 100) and by the area under the elasticity curve (AUEC, mm × 100/s). Initially, ex vivo experiments were performed with buffer to record a baseline profile. Subsequently, rFVIII (final plasma concentration 0.5 IU/mL) and tranexamic acid (final plasma concentration 0.2 mg/mL) were added. Following the ex vivo experiments, analyses were performed 10 minutes after the patients had been administered rFVIII and tranexamic acid, respectively. We found almost total accordance between ex vivo and in vivo results both in the TF assay and the TF + t-PA assay. As expected, rFVIII increased clot formation indicated by a significantly shorter CT, higher MaxVel and shorter t, MaxVel. Tranexamic acid induced no further measurable improvements of the clot formation profile. Analyses of the clot stability using the TF + t-PA assay showed that rFVIII increased MCF three fold, whereas adding tranexamic acid revealed a four fold increase. The AUEC increased 5 fold after rFVIII and 24 fold after addition of tranexamic acid. In conclusion the study documents that treatment with tranexamic acid in combination with rFVIII significantly improves clot stability in patients with Hemophilia A.

A randomized trial of tranexamic acid in combination with cell salvage plus a meta-analysis of randomized trials evaluating tranexamic acid in off-pump coronary artery bypass grafting

We sought to evaluate the effectiveness of tranexamic acid in off-pump coronary artery bypass grafting surgery, either when used in combination with mechanical cell salvage or when used alone. One hundred patients were randomized to either 2 g of tranexamic acid as an intravenous bolus before sternotomy or to placebo. Intraoperative and postoperative cell salvage was used in all patients. The primary end point was early postoperative blood loss (within 4 hours). To evaluate the efficacy of tranexamic acid in isolation, we also performed a meta-analysis of 4 randomized trials identified from a systematic literature search. The primary end point of the meta-analysis was red cell transfusion. In our randomized trial patients in the tranexamic acid group had a significant reduction in early postoperative blood loss, (median difference, 50 mL; 95% confidence interval, 15-100 mL; P < .01); however, there was no reduction in the frequency of blood component transfusion. Patients in the placebo group received a significantly larger volume of autotransfused red cells (median difference, 120 mL; 95% confidence interval, 0-220 mL; P = .02). The meta-analysis demonstrated a significant reduction in red cell transfusions in patients receiving tranexamic acid compared with those receiving placebo (risk ratio, 0.48; 95% confidence interval, 0.24-0.97; P = .041). There was also a reduction in the frequency of any allogeneic blood component transfusion, as well as a highly significant reduction in postoperative blood loss, in patients receiving tranexamic acid (P < .001). Tranexamic acid reduces blood loss and transfusion requirements in off-pump coronary artery bypass grafting surgery. A reduction in allogeneic blood transfusion was not evident in the presence of perioperative cell salvage. These data support the routine use of tranexamic acid in off-pump coronary artery bypass grafting surgery.

Evaluation of hemorrhage depressors on blood loss during orthognathic surgery: a retrospective study

Purpose Correction of dentofacial deformities by orthognathic surgery may cause significant bleeding and therefore hypotensive anesthesia is often used to reduce the blood loss. The main objective of the present clinical study was to determine whether the addition of hemorrhage depressors to other medication during orthognathic surgery would further reduce the blood loss. Patients and methods Thirty patients, consecutively operated on with standardized Le Fort I osteotomies in 1998 (n = 15, control group) and 1999 (n = 15, treatment group), were included in the study. Both groups received hypotension anesthesia during surgery and the treatment group received additional hemorrhage depressors; tranexamic acid and desmopressin. Results The mean blood loss was 740 ± 410 mL (11.3 mL/kg) in the control group and 400 ± 210 mL (5.7 mL/kg) in the treatment group. The results showed a statistically significant reduction of blood loss in the treatment group ( P < .01). Conclusions This study shows that blood loss during orthognathic surgery under hypotensive anesthesia can be significantly reduced when a combination of tranexamic acid and desmopressin is added.

WHICH ANTIFIBRINOLYTIC THERAPY IS MOST EFFECTIVE IN PREVENTING BLEEDING IN HIGH RISK CARDIAC SURGERY PATIENTS

Introduction: Both aprotinin and tranexamic acid have been shown to be effective in reducing bleeding associated with cardiac surgery. [1,2] We determined the effectiveness of aprotinin, tranexamic acid, tranexamic acid and a platelet sparing maneuver compared to control for reduction of bleeding and transfusion requirements associated with cardiac surgery. Methods: Following IRB approval and written informed patient consent, 160 redo sternotomy or combination cardiac surgery patients were randomly assigned in a double blinded fashion to receive one of four treatment regiments: 1.a full Hamersmith aprotinin infusion, [1] 2.tranexamic acid infusion (10mg/kg load, 1mg/kg/hr infusion), [2] 3.tranexamic acid infusion (10mg/kg load, 1mg/kg/hr infusion) with a platelet sparing maneuver where 12.5% of the patients blood volume was withdrawn prior to cardiopulmonary bypass (CPB) and reinfused following CPB, or 4.a control group with a normal saline infusion. Blood loss and transfusion requirements in the operating room and in the first 24 hours in the intensive care platelet unit (ICU) were recorded. Bleeding time, thromboelastograph, and platelet count and mean volume were performed pre and postoperatively. Statistical significance p <or=to 0.05. Results: There was no difference between the groups in demographic or surgical variables, CPB duration, cross-clamp duration, and heparin concentrations. There also was no difference in laboratory tests between groups. The control groups had greater blood loss intraoperatively and in the first 4 hours in the ICU. The control group also received greater transfusions of red blood cells than the other groups (Figure 1 and Figure 2 Below). The combination of tranexamic acid with a platelet sparing maneuver had a similar reduction in blood loss and transfusion requirements as the aprotinin group.Figure 1: Total Operating Room TransfusionsFigure 2: Total ICU Transfusions over 24 hoursDiscussion: Aprotinin and tranexamic acid with a platelet sparing maneuver had the best reduction of blood loss and transfusion requirements.

Low-dose tranexamic acid combined with aprotinin in the pre-operative management of ruptured intracranial aneurysms

Among our patients with ruptured intracranial aneurysms 149 were managed pre-operatively with a combination of tranexamic acid (AMCA), 3 gm daily, and aprotinin at an average of 400,000 KIU (Kallikrein inactivating units) daily. Antifibrinolytics were started within three days of the last haemorrhage, and continued for at least six days. The first 91 cases, managed in the years 1971 to 1980, have been evaluated retrospectively. The remaining 58 patients were managed in the period 1981-1985 and carefully watched for possible complications of treatment. No significant differences were noted in the results of patients managed either before or after 1981. The rate of recurrent SAH (10%) was lower than the natural history of aneurysmal SAH. Satisfactory inhibition of fibrinolysis was documented in the CSF collected at the time of operation in 15 patients. This, as well as our previous suggestions that the combination of low-dose AMCA and aprotinin might carry a lesser risk of causing ischaemic complications and hydrocephalus than the conventional antifibrinolytic treatment, might stimulate future studies on fibrinolysis in SAH.