Antifibrinolytic Agents Research Articles

The many roles of tranexamic acid: An overview of the clinical indications for TXA in medical and surgical patients.

Clinically significant bleeding can occur as a consequence of surgery, trauma, obstetric complications, anticoagulation, and a wide variety of disorders of hemostasis. As the causes of bleeding are diverse and not always immediately apparent, the availability of a safe, effective, and non-specific hemostatic agent is vital in a wide range of clinical settings, with antifibrinolytic agents often utilized for this purpose. Tranexamic acid (TXA) is one of the most commonly used and widely researched antifibrinolytic agents; its role in postpartum hemorrhage, menorrhagia, trauma-associated hemorrhage, and surgical bleeding has been well defined. However, the utility of TXA goes beyond these common indications, with accumulating data suggesting its ability to reduce bleeding and improve clinical outcomes in the face of many different hemostatic challenges, without a clear increase in thrombotic risk. Herein, we review the literature and provide practical suggestions for clinical use of TXA across a broad spectrum of bleeding disorders.

TREATMENT OF ORAL BLEEDING IN A PATIENT WITH FANCONI ANEMIA: ASSOCIATION WITH LOCAL HEMOSTATIC AGENT AND MOUTHGUARD

Fanconi anemia (FA) is a rare autosomal recessive genetic disorder, characterized by congenital malformations of certain organs, thrombocytopenia, and chronic anemia due to the progressive failure of bone marrow, with an elevated risk of infections and bleeding. A 24-year-old male patient with FA was referred to our clinic with a chief complaint of cheek biting and resultant significant bleeding. During clinical evaluation, a traumatic ulcer in the left buccal mucosa was observed with a massive blood clot formed inappropriately along with continuous bleeding. The patient's platelet count was 4000/mm3, indicating the need of a platelet transfusion prior the procedure. Suture and topic antifibrinolytic agent dressing and an ethylene vinyl acetate (EVA) mouthguard was installed with the sole purpose of reduction of local trauma. After 7 postoperative days, the oral lesion was almost completely healed without secondary bleeding. Fanconi anemia (FA) is a rare autosomal recessive genetic disorder, characterized by congenital malformations of certain organs, thrombocytopenia, and chronic anemia due to the progressive failure of bone marrow, with an elevated risk of infections and bleeding. A 24-year-old male patient with FA was referred to our clinic with a chief complaint of cheek biting and resultant significant bleeding. During clinical evaluation, a traumatic ulcer in the left buccal mucosa was observed with a massive blood clot formed inappropriately along with continuous bleeding. The patient's platelet count was 4000/mm3, indicating the need of a platelet transfusion prior the procedure. Suture and topic antifibrinolytic agent dressing and an ethylene vinyl acetate (EVA) mouthguard was installed with the sole purpose of reduction of local trauma. After 7 postoperative days, the oral lesion was almost completely healed without secondary bleeding.

Effect of Intravenous Aminocaproid Acid on Blood Loss and Transfusion Requirements After Bilateral Varus Rotational Osteotomy: A Double-blind, Placebo-controlled Randomized Trial.

Background:ε-Aminocaproic acid (EACA) is an antifibrinolytic agent that has been shown to decrease blood loss and transfusion requirements in several populations undergoing various surgical procedures. However, the efficacy of EACA has not been assessed in pediatric patients with cerebral palsy undergoing bilateral varus rotational femoral osteotomies. The purpose of this study was to assess the efficacy of intravenous EACA in reducing calculated intraoperative blood loss and transfusions in this population.Methods:Patients aged 18 years or younger were eligible. Patients were randomized to receive EACA or placebo (saline), and randomization was stratified based on sex and whether or not additional soft tissue or osseous procedures were performed. On the basis of retrospective data, the calculated sample size was 12 patients per arm to detect a difference of 250-mL blood loss. The primary outcome was calculated intraoperative blood loss. Secondary outcomes included transfusion requirements, 24-hour drain output, length of stay, and incidence of complications.Results:The mean age of patients in this study was 8 years (SD: 2.4 y). There were no differences in age, sex, height, weight, type of anesthesia, operative time, and associated procedures between the EACA and placebo groups (P>0.05). Preoperative hematocrit was lower in the EACA group (37.1 vs. 40.0, P=0.04). Calculated intraoperative blood loss was 536 mL in the EACA group and 628 mL in the placebo group (P=0.45). Transfusions were required in 62% of patients in the EACA group and 67% of patients in the placebo group (P=0.68). Total 24-hour drain output was 72.5 mL in the EACA group and 103.3 mL in the placebo group (P=0.37). Length of stay was similar between both groups, and there were no drug or placebo-related complications in either group.Conclusions:There was no difference in blood loss or transfusion requirements associated with EACA compared with placebo; however, this study is underpowered to detect smaller differences in blood loss. Additional studies with larger sample sizes are needed to confirm these findings and further elucidate the indications for antifibrinolytic agents in pediatric patients.Level of EvidenceLevel I.

Nebulized Tranexamic Acid for the Use of Epistaxis: A Case Report.

Tranexamic acid is an antifibrinolytic agent and functions as a competitive inhibitor of plasminogen activation, promoting hemostasis. Topical application of tranexamic acid for the control of epistaxis has been described in the literature, mainly through administration with gauze and packing. There is limited evidence for the use of tranexamic acid via alternative routes of administration such as nebulization. We describe a patient who presented to the emergency department with epistaxis who was treated with nebulized tranexamic acid. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case provides an alternative treatment modality using nebulizing tranexamic acid to help manage epistaxis in patients that cannot be managed with topical antifibrinolytic therapy administered by other means.

Tranexamic Acid for Acute Hemorrhage: A Narrative Review of Landmark Studies and a Critical Reappraisal of Its Use Over the Last Decade.

The publication of the Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage-2 (CRASH-2) study and its intense dissemination prompted a renaissance for the use of the antifibrinolytic agent tranexamic acid (TXA) in acute trauma hemorrhage. Subsequent studies led to its widespread use as a therapeutic as well as prophylactic agent across different clinical scenarios involving bleeding, such as trauma, postpartum, and orthopedic surgery. However, results from the existing studies are confounded by methodological and statistical ambiguities and are open to varied interpretations. Substantial knowledge gaps remain on dosing, pharmacokinetics, mechanism of action, and clinical applications for TXA. The risk for potential thromboembolic complications with the use of TXA must be balanced against its clinical benefits. The present article aims to provide a critical reappraisal of TXA use over the last decade and a "thought exercise" in the potential downsides of TXA. A more selective and individualized use of TXA, guided by extended and functional coagulation assays, is advocated in the context of the evolving concept of precision medicine.

Bronchoscopic delivery of aminocaproic acid as a treatment for pulmonary bleeding: A case series

ObjectiveBronchoscopy is an essential therapeutic modality in the treatment of pulmonary bleeding. Although numerous endoscopic treatments exist, topical ε-aminocaproic acid has not been described in the literature. This study documents the use of this novel treatment for pulmonary bleeding and compares it to available evidence for tranexamic acid, a similar anti-fibrinolytic agent. DesignCase-series study. SettingICU and general inpatient floors of a tertiary medical center. PatientsForty-six patients receiving endobronchial ε-aminocaproic acid for the treatment or prevention of pulmonary bleeding. Measurements and main resultsOf the 46 patients included in the study, 41.6% and 13% presented with non-massive and massive hemoptysis, respectively. In patients with active pulmonary bleeding, endobronchial application of ε-aminocaproic acid and accompanying therapies resulted in cessation of bleeding in 94.7% of cases. A total of six patients received ε-aminocaproic acid monotherapy; in three patients with active bleeding, 100% achieved hemostasis after treatment. Of the 36 patients successfully treated for active pulmonary bleeding, 27.8% had recurrent bleeding within 30 days. Thirty-day adverse events were as follows: death (10 patients), deep vein thrombosis (2 patients), renal failure (2 patients), and stroke (2 patients). ConclusionsEndobronchial administration of ε-aminocaproic acid during bronchoscopy may be a safe and efficacious option in the treatment and prevention of pulmonary bleeding. Further studies are necessary to better define ε-aminocaproic acid's safety profile, optimal routes of administration, and comparative effectiveness to tranexamic acid.

Mitigation of Vascular Permeability Using Bradykinin Receptor Antagonist and Anti-Fibrinolytic Agent in Rats with Polytrauma and Hemorrhagic Shock

Introduction: Clinical studies suggest that one third of patients suffering major trauma develop acute traumatic coagulopathy (ATC), which is associated with increased morbidity and mortality. Recent evidence in both animal and clinical studies has shown that development of ATC is associated with an increase in fibrinolytic activity, initiated by an elevation in tissue plasminogen activator (tPA) immediately after trauma. Previous studies demonstrate that administration of the anti-fibrinolytic agent tranexamic acid (TXA) not only inhibits fibrinolytic activity in traumatized tissue but also attenuates lung edema after resuscitation in rats with polytrauma and hemorrhagic shock, suggesting a potential correlation between fibrinolysis and vascular permeability. One of the underlying mechanisms of acute elevation in vascular permeability after severe trauma is associated with an elevation of bradykinin activity due to activation of the tPA-plasmin-bradykinin pathway. This study will test the hypothesis that early intervention by administration of a bradykinin receptor antagonist with or without TXA prior to resuscitation attenuates edema in the tissues after resuscitation in rats with polytrauma/hemorrhagic shock. Method: Sprague-Dawley rats (350-450g) under anesthesia with isoflurane received polytrauma followed by hemorrhage (40% of blood volume). The rats either received vehicle (normal saline) or bradykinin receptor-2 antagonist (BR-2A (HOE140, 0.5mg/kg)), TXA (20mg/kg) or BR-2A/TXA via femoral vein at 45min after trauma (n=6-8/each group), followed by resuscitation with Lactated Ringer's solution (20% of blood volume) at 60min after trauma. Four normal rats, not undergoing surgical procedures were treated as normal control. At 2hr after trauma (1hr after resuscitation), the rats were euthanized and the tissues from internal organs were harvested and weighed for wet weight. The tissue samples were then transferred to a 600C oven for 10-14 days. The dry weight was determined when the weight of dried tissue was constant for three consecutive days. The wet-dry weight ratio was then calculated to represent the water content for each tissue. The wet-dry weight ratio was also measured in traumatized tissues collected from the injured sites of liver, intestine and skeletal muscle (at hindlimb). At 2hr after trauma, prothrombin time (PT) was measured for systemic hemostatic condition, and the resuscitation outcome was assessed by lactate levels. Results: The wet/dry weight ratio is different in organs due to underlying structure and water content. Trauma, hemorrhage and resuscitation led to a significant elevation of wet/dry weight ratio in a majority of the organs (except for heart, kidney, and stomach). The wet/dry weight ratio was significantly higher in traumatized tissues than non-traumatized tissues (at liver, intestine and skeletal muscle). BR-2A significantly decreased the wet/dry weight ratio of the brain (4.51±0.03 (BR-2A) vs 4.64±0.03 (Vehicle)), but had no effect on the other organs. TXA significantly reduces the wet/dry weight ratio of the lung and intestine (lung: 5.02±0.07 (BR-2A) vs 5.23±0.06 (Vehicle), p=0.003; Intestine: 4.16±0.10 (BR-2A) vs 4.45±0.07 (Vehicle), p=0.036) but not in the brain and other tissues. The combination of BR-2A with TXA significantly decreased elevation of wet/dry weight ratio of the brain, lung and intestine, but there was no synergistic effect on wet/dry weight ratio found in any organs. However, the rats treated with combination treatment of BR-2A and TXA had the lowest lactate level at 2hr after trauma as compared to rats treated with vehicle (1.85±0.15 vs 3.39±0.29 mmol/l, p=0.032) suggesting an overall improvement of resuscitation outcome. BR-2A, TXA or a combination of the two did not cause significant change in MAP and HR, and had no significant effect on systemic coagulopathy (elevation of prothrombin time) at 2hr after trauma and hemorrhage. Conclusions: This study suggests that BR-2A and TXA independently mitigate tissue-specific vascular permeability in trauma and hemorrhagic shock. Future studies are necessary to investigate the optimal dose and timing of administration of BR-2A or BR-2A with TXA in trauma and hemorrhagic shock to improve the outcome and efficacy of treatment. Disclosures No relevant conflicts of interest to declare.

Aprotinin in adults at high risk of major blood loss during isolated CABG with cardiopulmonary bypass: a profile of its use in the EU

Prophylactic treatment with aprotinin, a haemostatic antifibrinolytic agent, is indicated to reduce blood loss and blood transfusion in adults with a high risk of major bleeding undergoing primary or repeat isolated coronary artery bypass graft (CABG) with cardiopulmonary bypass. Overall, aprotinin was consistently more effective than tranexamic acid, e-aminocaproic acid, desmopressin and placebo in reducing massive blood loss, the need for transfusions of blood products, and the need for reoperation due to diffuse bleeding in trials in this patient population, and was generally well-tolerated. The approval of aprotinin in the EU was reinstated by the European Medicines Agency (EMA) in 2012, following subsequent analysis of the clinical data that led to its suspension in 2007. The EMA analysis concluded that the reduction in massive bleeding provided by aprotinin in patients undergoing isolated CABG is clinically relevant, as it reduces complications, the need for blood product transfusions and the length of hospital stay, without increasing mortality. The relaunch of aprotinin was accompanied by a risk management to assess the pattern of use and safety of aprotinin in clinical practice. Data from centres enrolled in the Nordic Aprotinin Patient Registry are being collected and will be assessed in the final report.

Effect of Coagulation Factor Concentrates on Markers of Endothelial Cell Damage in Experimental Hemorrhagic Shock.

Plasma-based resuscitation showed protective effects on the endothelial glycocalyx compared with crystalloid resuscitation. There is paucity of data regarding the effect of coagulation factor concentrates (CFC) on the glycocalyx in hemorrhagic shock (HS). We hypothesized that colloid-based resuscitation supplemented with CFCs offers a therapeutic value to treat endothelial damage following HS. Eighty-four rats were subjected to pressure-controlled (mean arterial pressure (MAP) 30-35 mm Hg) and lab-guided (targeted cutoff: lactate >2.2. mmol/L and base deficit > 5.5 mmol/L) HS. Animals were resuscitated with fresh frozen plasma (FFP), human albumin (HA) or Ringer's lactate (RL) and RL or HA supplemented with fibrinogen concentrate (FC) or prothrombin complex concentrate (PCC). Serum epinephrine and the following markers of endothelial damage were assessed at baseline and at the end-of-observation (120 min after shock was terminated): syndecan-1, heparan sulfate, and soluble vascular endothelial growth factor receptor 1 (sVEGFR 1). Resuscitation with FFP had no effect on sVEGFR1 compared with crystalloid-based resuscitation (FFP: 19.3 ng/mL vs. RL: 15.9 ng/mL; RL+FC: 19.7 ng/mL; RL+PCC: 18.9 ng/mL; n.s.). At the end-of-observation, syndecan-1 was similar among all groups. Interestingly, HA+FC treated animals displayed the highest syndecan-1 concentration (12.07 ng/mL). Resuscitation with FFP restored heparan sulfate back to baseline (baseline: 36 ng/mL vs. end-of-observation: 36 ng/mL). The current study revealed that plasma-based resuscitation normalized circulating heparan sulfate but not syndecan-1. Co-administration of CFC had no further effect on glycocalyx shedding suggesting a lack of its therapeutic potential. VExperimental in vivo study.

The emerging importance of tranexamic acid in dermatology.

Tranexamic acid (TA) is an antifibrinolytic agent, increasingly recognized as being of utility for a wide variety of skin diseases. We review the evidence supporting the use of TA for a range of dermatological indications, including (among others) melasma, postinflammatory hyperpigmentation, urticaria, angio-oedema and haemostasis, in addition to practical considerations of its use by dermatologists.

Fibrinolysis Inhibitors: Potential Drugs for the Treatment and Prevention of Bleeding.

Hyperfibrinolytic situations can lead to life-threatening bleeding, especially during cardiac surgery. The approved antifibrinolytic agents such as tranexamic acid, ε-aminocaproic acid, 4-aminomethylbenzoic acid, and aprotinin were developed in the 1960s without the structural insight of their respective targets. Crystal structures of the main antifibrinolytic targets, the lysine binding sites on plasminogen's kringle domains, and plasmin's serine protease domain greatly contributed to the structure-based drug design of novel inhibitor classes. Two series of ligands targeting the lysine binding sites have been recently described, which are more potent than the most-widely used antifibrinolytic agent, tranexamic acid. Furthermore, four types of promising active site inhibitors of plasmin have been developed: tranexamic acid conjugates targeting the S1 pocket and primed sites, substrate-analogue linear homopiperidylalanine-containing 4-amidinobenzylamide derivatives, macrocyclic inhibitors addressing nonprimed binding regions, and bicyclic 14-mer SFTI-1 analogues blocking both, primed and nonprimed binding sites of plasmin. Furthermore, several allosteric plasmin inhibitors based on heparin mimetics have been developed.

Comparison Effect of Tranexamic Acid (TA) and Tranexamic Acid Combined with Vitamin C (TXC) on Drainage Volume and Atrial Fibrillation Arrhythmia in Patients Undergoing Cardiac Bypass Surgery: Randomized Clinical Trial.

BackgroundTranexamic acid and vitamin C are potent antifibrinolytic and oxidative stress agents that reduce blood loss and transfusion blood in cardiopulmonary bypass (CPB).ObjectivesThe aim of this study was to evaluate the efficacy of tranexamic acid (TA) and tranexamic acid combined with vitamin C (TXC) on drainage volume (blood loss) and atrial fibrillation (AF) in patients undergoing cardiac bypass surgery in Gorgan, Shafa hospital, Iran.MethodsThis study is a double-blind randomized clinical trial. A sample size of 120 candidates of cardiac bypass surgery were included in this prospective study. Patients were randomly assigned to treatments in two groups. In both groups, 50 mg/kg tranexamic acid was administered intravenously directly before sternotomy: group A (N = 58) patients received tranexamic acid (TA) only and group B (N = 62) tranexamic acid with vitamin C (TXC) half an hour before surgery and 2 g vitamin C with 100 mL 0.9% saline were injected. Subsequently, during 4 days after surgery, 1000 mg of vitamin C and 100 cc 0.9% saline was infused every day. Intraoperative and postoperative blood loss (volume of blood in the drain) and atrial fibrillation complications were recorded for 24 hours after the operation.ResultsThe patients who received vitamin C had less bleeding during operation and in the early hours post-operation. Patients in (TA) group had mean drainage of 34.41 milliliter more than patients in (TXC) group (P < 0.001). Chi-square test showed that arrhythmia (AF) condition was the same in the two groups during 14 times of study (four times during operation and ten times up to 24 hours after the operation), and AF arrhythmia in the two groups was less than 5%.ConclusionsIn this study tranexamic acid with vitamin C have a positive effect on the amount of drainage (blood loss) and there was no significant difference in the incidence of AF between two groups.

Effect of tranexamic acid administration on acute traumatic coagulopathy in rats with polytrauma and hemorrhage.

Trauma and hemorrhagic shock can lead to acute traumatic coagulopathy (ATC) that is not fully reversed by prehospital resuscitation as simulated with a limited volume of fresh whole blood (FWB) in a rat model. Tranexamic Acid (TXA) is used as an anti-fibrinolytic agent to reduce surgical bleeding if administered prior to or during surgery, and to improve survival in trauma if given early after trauma. It is not clear from the existing clinical literature whether TXA has the same mechanism of action in both settings. This study sought to explore the molecular mechanisms of TXA activity in trauma and determine whether administration of TXA as a supplement to FWB resuscitation could attenuate the established ATC in a rat model simulating prehospital resuscitation of polytrauma and hemorrhagic shock. In a parallel in-vitro study, the effects on clotting assays of adding plasmin at varying doses along with either simultaneous addition of TXA or pre-incubation with TXA were measured, and the results suggested that maximum anti-fibrinolytic effect of TXA on plasmin-induced fibrinolysis required pre-incubation of TXA and plasmin prior to clot initiation. In the rat model, ATC was induced by polytrauma followed by 40% hemorrhage. One hour after trauma, the rats were resuscitated with FWB collected from donor rats. Vehicle or TXA (10mg/kg) was given as bolus either before trauma (TXA-BT), or 45min after trauma prior to resuscitation (TXA-AT). The TXA-BT group was included to contrast the coagulation effects of TXA when used as it is in elective surgery vs. what is actually feasible in real trauma patients (TXA-AT group). A single dose of TXA prior to trauma significantly delayed the onset of ATC from 30min to 120min after trauma as measured by a rise in prothrombin time (PT). The plasma d-dimer as well as plasminogen/fibrinogen ratio in traumatized liver of TXA-BT were significantly lower as compared to vehicle and TXA-AT. Wet/dry weight ratio and leukocytes infiltration of lungs were significantly decreased only if TXA was administrated later, prior to resuscitation (TXA-AT). In conclusion: Limited prehospital trauma resuscitation that includes FWB and TXA may not correct established systemic ATC, but rather may improve overall outcomes of resuscitation by attenuation of acute lung injury. By contrast, TXA given prior to trauma reduced levels of fibrinolysis at the site of tissue injury and circulatory d-dimer, and delayed development of coagulopathy independent of reduction of fibrinogen levels following trauma. These findings highlight the importance of early administration of TXA in trauma, and suggest that further optimization of dosing protocols in trauma to exploit TXA’s various sites and modes of action may further improve patient outcomes.

Topical tranexamic acid inhibits fibrinolysis more effectively when formulated with self‐propelling particles

BackgroundEndogenous fibrinolytic activation contributes to coagulopathy and mortality after trauma. Administering tranexamic acid (TXA), an antifibrinolytic agent, is one strategy to reduce bleeding; however, it must be given soon after injury to be effective and minimize adverse effects. Administering TXA topically to a wound site would decrease the time to treatment and could enable both local and systemic delivery if a suitable formulation existed to deliver the drug deep into wounds adequately. ObjectivesTo determine whether self‐propelling particles could increase the efficacy of TXA. MethodsUsing previously developed self‐propelling particles, which consist of calcium carbonate and generate CO2 gas, TXA was formulated to disperse in blood and wounds. The antifibrinolytic properties were assessed in vitro and in a murine tail bleeding assay. Self‐propelled TXA was also tested in a swine model of junctional hemorrhage consisting of femoral arteriotomy without compression. ResultsSelf‐propelled TXA was more effective than non‐propelled formulations in stabilizing clots from lysis in vitro and reducing blood loss in mice. It was well tolerated when administered subcutaneously in mice up to 300 to 1000 mg/kg. When it was incorporated in gauze, four of six pigs treated after a femoral arteriotomy and without compression survived, and systemic concentrations of TXA reached approximately 6 mg/L within the first hour. ConclusionsA formulation of TXA that disperses the drug in blood and wounds was effective in several models. It may have several advantages, including supporting local clot stabilization, reducing blood loss from wounds, and providing systemic delivery of TXA. This approach could both improve and simplify prehospital trauma care for penetrating injury.

Efficacy of intravenous tranexamic acid in reducing perioperative blood loss in patients undergoing hemiarthroplasty

Introduction: Femoral neck fractures are frequent injuries in a trauma centre and have a high incidence in the general population. Hip fracture surgeries are associated with substantial blood loss, exposing patients to postoperative anaemia. The severity of anaemia is related directly to post-operative functional recovery of the patients, which is related to long-term mortality. Blood transfusion related adverse effects also can directly influence the recovery. Tranexamic acid is a simple and inexpensive synthetic antifibrinolytic agent, which prevents the degradation of fibrin and delays the breakdown of haemostasis clots. Aim of this study is to assess the efficacy of intra-venous administration of Tranexamic acid in patients undergoing hemiarthroplasty with regards to blood loss at perioperative period. Materials and Methods: A prospective randomised control study was done in a tertiary care hospital in southern part of India during the period of January 2016 to June 2017. 40 consecutive fracture neck of femur patients were randomised into two group, each group consist of 20 patient, Group 1 patients received placebo of 50 ml of normal saline administered intravenously 10 minutes before starting the surgery. Group 2 patients received Tranexamic acid -1500Mg diluted in 50ml Normal Saline administered intravenously 10 minutes before the surgery. Intraoperative blood loss was assessed by collecting the number of fully soaked mopping pads, fully soaked gauze pieces and quantity of irrigation fluid form suction bottle after subtracting the amount of normal saline used for wash. Post operatively all patients were assessed by evaluating the haemoglobin, Packed cell volume values from patients and blood collected in the negative suction drain of day 1 and day 2. The study group and control group parameters were analysed and compared. Results: 45 patients were enrolled in our study and 5 patients were excluded from the study due to not giving consent for study. Demographic date like age, gender, side of fracture, type of fracture type of prosthesis were not influenced our study. Requirement of intra operative blood transfusion were significantly reduced in study group in comparison with control group which was statistically significant (p=0.027). In study group only 3 patient received blood transfusion, whereas control group 11 patents were received. Conclusion: In our study, there was significant reduction in the amount of blood loss in tranexamic acid administered group when compared to the placebo group. Tranexamic acid was cost effective and safer when compared to blood components. Tranexamic acid should be considered for routine use in Hemiarthroplasty surgery to decrease blood loss.

Perioperative Management and Factors Associated With Transfusion in Cranial Vault Reconstruction.

Bleeding is the most common adverse event in patients undergoing cranial vault reconstruction. The authors compare the transfusion rates against a national sample to determine whether the patients experience lower transfusion rates. The authors queried the Pediatric National Surgical Quality Improvement Program (Peds-NSQIP) for patients who underwent cranial vault reconstruction (CPT 61559) and compared them to patients who underwent cranial vault reconstruction for sagittal craniosynostosis at Children's Hospital and Medical Center (CHMC) in Omaha, Nebraska. Patients over the age of 24 months were excluded. Binary logistic regression analysis was performed using IBM-SPSS v24.0 to determine factors associated with transfusion at CHMC. Patient demographics, preoperative hematocrit and platelet counts, readmission rates, and reoperation rates did not differ between CHMC (N = 54) and Peds-NSQIP (N = 1320) cohorts. Patients in the CHMC cohort had shorter preincision anesthesia times (47 versus 80 minutes, P < 0.001), shorter operative times (108 versus 175 minutes, P < 0.001), lower transfusion rates (50% versus 73%, P < 0.001), and smaller mean transfusion volumes (16 versus 33 mL/kg, P < 0.001); however mean length of stay was longer (4.1 versus 3.6 days, P < 0.001). Factors independently associated with transfusion at CHMC included preoperative hematocrit (odds ratio [OR] 0.423, P = 0.002), administration of an antifibrinolytic agent (OR 0.004, P = 0.001) and temperature at the time of incision (OR 0.020, P = 0.043). Patients at CHMC require less transfused blood and experience low transfusion rates. Preoperative hematocrit, administration of antifibrinolytic agents, and temperature at the time of incision are all modifiable factors associated with perioperative transfusion.

Comparison of the Effects of Intravenous and Oral Tranexamic Acid on Perioperative Hemoglobin Levels During Total Knee Arthroplasty.

Background: Tranexamic acid (TXA) is an antifibrinolytic agent shown to reduce perioperative blood loss in patients undergoing total knee arthroplasty (TKA), but there are limited data regarding the efficacy of intravenous (IV) in comparison to oral (PO) TXA. Objective: The purpose of this research was to compare the effects of IV and PO TXA on perioperative hemoglobin (Hgb) levels in patients who have undergone TKA. Methods: In this single-center, retrospective chart review, patients at least 18 years of age who received IV or PO TXA following medical center protocol from 1 of 3 orthopedic surgeons were included. The primary outcome was the change in Hgb within 24 hours following TKA. Secondary outcomes included comparisons of postsurgical complications and hospital length of stay. Results: The IV TXA group contained 62 participants, and the PO TXA group contained 61 participants. Patients receiving PO therapy had a larger decrease in Hgb compared with the IV TXA group (-2.382 vs -1.908, P = 0.02), but there were no statistically significant differences in mean length of stay (3.13 vs 2.95, P = 0.27), venous thromboembolism (VTE) occurrence (0 vs 0, P = 1), or requirement for transfusions (6 vs 5, P = 0.76). Conclusions and Relevance: IV and PO TXA may not be equivalent in outcomes for patients undergoing TKA. This study found a statistically significant decrease in the mean change of Hgb in patients receiving PO TXA compared with IV TXA. However, the rate of transfusions, mean length of stay, and rate of VTE were similar between groups.

Single Low Dose of rFVIIa Combined with Antifibrinolytic Agent is a Simple and Safe Treatment for Factor XI-Deficient Patients undergoing Surgery.

Factor XI (FXI) deficiency is a rare autosomal bleeding disorder. The rarity of spontaneous bleeding and absence of optimal tools to predict the bleeding risk in FXI-deficient patients hamper the standardization of prophylactic treatment enabling them to undergo major surgeries without blood products. We explored the effectiveness of a single and very low dose of recombinant factor VIIa (rFVIIa) along with tranexamic acid (TXA) as prophylactic treatment for FXI-deficient patients undergoing various types of surgery at various sites of injury. We studied the potential use of thrombin generation (TG) as a surrogate tool for predicting thrombogenicity. Our cohort consisted of 10 patients with severe FXI deficiency undergoing 12 interventions. Patients received a single dose of 10 to 15 μg/kg rFVIIa at the end of surgery in addition to TXA initiated 2 hours before surgery at the dose of 4 g/day for 3 to 5 days. TG was tested before and 30 minutes after rFVIIa administration. All operations were uneventful and none of the patients bled excessively or required blood products. No thrombotic event was reported, and the postoperative hospitalization duration was comparable to that of patients without bleeding disorders. TG performed at the peak of rFVIIa was below the curve of healthy controls, thus confirming that the administered dose was not thrombogenic. A single very low dose of rFVIIa along with TXA is a simple and safe treatment to control hemostasis in severe FXI-deficient patients undergoing diverse type of surgical procedure at various sites.

Clinical impact of massive transfusion protocol implementation in non-traumatic patients

BackgroundMassive transfusion protocol (MTP) has been used to provide plasma and packed red blood cells (pRBCs) rapidly. MTP also has been adapted for non-traumatic patients. The effects of hospital-wide MTP implementation on clinical outcomes were reviewed. MethodsThis was a retrospective study of patients who received massive transfusion before and after MTP implementation, between August 2010 and May 2018. Massive transfusion was defined as 10 or more units of pRBCs within 24 h. Recipients of massive transfusion were divided into periods before and after MTP implementation. The 24 -h death rate, thirty-day death rate and several laboratory findings were investigated. ResultsEighty patients whose massive transfusion occurred before MTP implementation and 63 patients whose massive transfusion occurred after MTP implementation were compared. No statistically significant difference was found in 24 -h death rate (15.0% vs. 23.8%, p = 0.181), or 30-day death rate (43.8% vs. 36.5%, p = 0.381). Use of an anti-fibrinolytic agent was more frequent in patients after the MTP implementation (31.3% vs. 55.6%, p = 0.003). A statistically significant difference was found in the lowest body temperature of the two groups during the 24 -h period (34.7 °C vs. 35.6 °C, p < 0.001). Transfusion ratio of plasma to pRBC was numerically improved after the MTP implementation (1:1.91 vs. 1:1.58, p = 0.173). Earlier initiation of pRBC transfusion was achieved after implementation (51 min vs. 40 min, p = 0.042). ConclusionsMTP implementation showed improved coagulation profiles, but did not show a statistically significant death-rate reduction in non-traumatic patients.

Tranexamic acid in cardiac surgery: a systematic review and meta-analysis (protocol)

IntroductionBleeding during cardiac surgery is associated with increased morbidity and mortality. Tranexamic acid is an antifibrinolytic with proven efficacy in major surgeries. Current clinical practice guidelines recommend intraoperative use in...