Clinical use of tranexamic acid: evidences and controversies

Abstract Tranexamic acid (TXA) significantly reduces blood loss in a wide range of surgical procedures and improves survival rates in obstetric and trauma patients with severe bleeding. Although it mainly acts as a fibrinolysis inhibitor, it also has an anti-inflammatory effect, and may help attenuate the systemic inflammatory response syndrome found in some cardiac surgery patients. However, the administration of high doses of TXA has been associated with seizures and other adverse effects that increase the cost of care, and the administration of TXA to reduce perioperative bleeding needs to be standardized. Tranexamic acid is generally well tolerated, and most adverse reactions are considered mild or moderate. Severe events are rare in clinical trials, and literature reviews have shown tranexamic acid to be safe in several different surgical procedures. However, after many years of experience with TXA in various fields, such as orthopedic surgery, clinicians are now querying whether the dosage, route and interval of administration currently used and the methods used to control and analyze the antifibrinolytic mechanism of TXA are really optimal. These issues need to be evaluated and reviewed using the latest evidence to improve the safety and effectiveness of TXA in treating intracranial hemorrhage and bleeding in procedures such as liver transplantation, and cardiac, trauma and obstetric surgery.

Management of Perioperative Anticoagulation in a Patient with Antiphospholipid Antibody Syndrome Undergoing Cardiac Surgery: A Case Report

Patients with Antiphospholipid syndrome (APLS) are at high risk for both bleeding and thrombotic complications during cardiac surgery involving cardiopulmonary bypass (CPB). In this case we present a patient with APLS and Immune Thrombocytopenic Purpura who successfully underwent aortic valve replacement (AVR) with CPB despite recent craniotomy for subdural hematoma evacuation. Anticoagulation for CPB was monitored by targeting an Activated Clotting Time (ACT) that was 2× the upper limit of normal. A multidisciplinary approach was essential in ensuring a safe and successful operation.

The Efficacy of Tranexamic Acid in Cardiac Surgery Requiring Cardio-Pulmonary Bypass (CPB) to Reduce Post-Operative Blood Loss and Requirement of Allogenic Blood Transfusion

Introduction: Cardiac surgery, owing to its invasiveness,need of anticoagulation, exposure to extracorporeal circulation(CPB) and relatively longer duration, is known to be associatedwith an increased risk of perioperative blood loss and allogeneicblood transfusions. Excessive bleeding requiring allogenicblood and blood components transfusion after cardiopulmonarybypass (CPB) is a common complication of cardiac surgeryimparting detrimental health and economic consequences.Many techniques like preoperative autologous blood collection(PAC), Acute normovolumic hemodilution (ANH), use ofminiaturized CPB circuit and use of ultrafiltration duringconduct of cardiopulmonary bypass (CPB) have been appliedin the past to conserve the blood during perioperative periodin cardiac surgery. Current study aimed to observe the efficacyof Tranexamic acid used during intraoperative period onpost-operative blood loss and requirement of allogenic bloodand blood products transfusion in cardiac surgical patientsrequiring cardiopulmonary bypass (CPB).Material and methods: 120 adult patients undergoingcardiac surgery requiring elective cardiopulmonary bypass(CPB) were categorized into 2 groups. Study (“TXA”) groupwas subjected to administration of tranexamic acid (20 mg/kg in divided doses). The 1st dose (10 mg/kg) was givenbefore initiation of CPB, 2nd dose (5 mg/kg) was given duringrewarming on CPB and 3rd dose (5 mg/kg) was given afterweaning off CPB along with protamine. The control (“NS”)group patients received normal saline as a placebo. Statisticalanalysis was done using “z test”.Results: “TXA” group had significantly lower post-operativebleeding and lesser requirement of allogenic blood and bloodproducts transfusion. The mean post-operative blood lossin “TXA” group was 427.42+/- 225.18 ml vs. 728.67+/-301.33ml in “NS” group. The mean PCV units transfused postoperatively in 72 hours in “TXA” group was 0.20+/-0.44 unitsvs. 0.67+/-0.60 in “NS” group. Patients in “TXA” group didnot require any FFP or platelets unit in contrast to “NS” groupwhere few patients required these products.Conclusion: The use of Tranexamic acid during intraoperative period in patient undergoing cardiac surgeryrequiring cardiopulmonary bypass circuit significantly reducesthe post-operative bleeding and requirement of allogenicblood and blood products transfusion.

Effectiveness and Safety of Tranexamic Acid in Spinal Deformity Surgery

OBJECTIVE: Spinal deformity surgery has the potential risk of massive blood loss. To reduce surgical bleeding, the use of tranexamic acid (TXA) became popular in spinal surgery, recently. The purpose of this study was to determine the effectiveness of intra-operative TXA use to reduce surgical bleeding and transfusion requirements in spinal deformity surgery. METHODS: A total of 132 consecutive patients undergoing multi-level posterior spinal segmental instrumented fusion (≥5 levels) were analyzed retrospectively. Primary outcome measures included intraoperative estimated blood loss (EBL), transfusion amount and rate of transfusion. Secondary outcome measures included postoperative transfusion amount, rate of transfusion, and complications associated with TXA or allogeneic blood transfusions. RESULTS: The number of patients was 89 in TXA group and 43 in non-TXA group. There were no significant differences in demographic or surgical traits between the groups except hypertension. The EBL was significantly lower in TXA group than non-TXA group (841 vs. 1336 mL, p=0.002). TXA group also showed less intra-operative and postoperative transfusion requirements (544 vs. 812 mL, p=0.012; 193 vs. 359 mL, p=0.034). Based on multiple regression analysis, TXA use could reduce surgical bleeding by 371 mL (37 % of mean EBL). Complication rate was not different between the groups. CONCLUSION: TXA use can effectively reduce the amount of intra-operative bleeding and transfusion requirements in spinal deformity surgery. Future randomized controlled study could confirm the routine use of TXA in major spinal surgery.

Antifibrinolytics in cardiac surgery.

Cardiac surgery exerts a significant strain on the blood bank services and is a model example in which a multi-modal blood-conservation strategy is recommended. Significant bleeding during cardiac surgery, enough to cause re-exploration and/or blood transfusion, increases morbidity and mortality. Hyper-fibrinolysis is one of the important contributors to increased bleeding. This knowledge has led to the use of anti-fibrinolytic agents especially in procedures performed under cardiopulmonary bypass. Nothing has been more controversial in recent times than the aprotinin controversy. Since the withdrawal of aprotinin from the world market, the choice of antifibrinolytic agents has been limited to lysine analogues either tranexamic acid (TA) or epsilon amino caproic acid (EACA). While proponents of aprotinin still argue against its non-availability. Health Canada has approved its use, albeit under very strict regulations. Antifibrinolytic agents are not without side effects and act like double-edged swords, the stronger the anti-fibrinolytic activity, the more serious the side effects. Aprotinin is the strongest in reducing blood loss, blood transfusion, and possibly, return to the operating room after cardiac surgery. EACA is the least effective, while TA is somewhere in between. Additionally, aprotinin has been implicated in increased mortality and maximum side effects. TA has been shown to increase seizure activity, whereas, EACA seems to have the least side effects. Apparently, these agents do not differentiate between pathological and physiological fibrinolysis and prevent all forms of fibrinolysis leading to possible thrombotic side effects. It would seem prudent to select the right agent knowing its risk-benefit profile for a given patient, under the given circumstances.

Manejo de la enfermedad de von Willebrand en ginecología y obstetricia: revisión cualitativa de la literatura / A qualitative review of the literature regarding managing Von willebrand disease in obstetrics and gynaecology

Introducción: la enfermedad de Von Willebrand es el trastorno de la coagulación con mayor prevalencia de mujeres en edad fértil y, por lo tanto, es el trastorno genético de la hemostasia más frecuente en la práctica ginecológica y obstétrica. Objetivo: hacer una revisión de la enfermedad de Von Willebrand en pacientes de ginecología y obstetricia con especial énfasis en la fisiopatología, el diagnóstico y el tratamiento. Metodología: se realizó una búsqueda bibliográfica en las bases de datos electrónicas MEDLINE/Pubmed, Elsevier, Interscience, EBSCO, Scopus, SciELO de 1980 al 2009, Cochrane Pregnancy and Childbirth Group (septiembre 30 del 2009) y libros de texto impresos. Resultados: el diagnóstico se basa en una cuidadosa anamnesis y pruebas de laboratorio de detección y confirmatorias. La correcta identificación de los diferentes tipos y subtipos es importante desde el punto de vista terapéutico. El tratamiento requiere medicaciones específicas como la desmopresina, concentrados de factor VIII y terapias coadyuvantes. No existe evidencia para contraindicar la vía vaginal del parto, sin embargo, se debe individualizar cada caso en particular. Conclusión: las mujeres con trastornos de la coagulación presentan durante la menarquia, la gestación, el parto y el puerperio un riesgo mayor de sangrado lo que hace obligatoria una adecuada evaluación y un manejo multidisciplinario durante el embarazo.

Introduction: Von Willebrand disease (vWD) is a disorder of the coagulation, being more prevalent in fertile females and is thus the most frequently occurring genetic haemostasis disorder in obstetric and gynaecological practice. Objective: reviewing the literature concerning vWD in obstetric and gynaecology patients, placing special emphasis on the disease’s physiopathology, diagnosis and treatment. Methodology: a bibliographic search was made of MEDLINE electronic databases via pubmed, Elsevier, Interscience, EBSCO, Scopus and SciELO from 1980 to 2009. The Cochrane Pregnancy and Childbirth Group (September 30th 2009) and printed texts and books were also consulted. Results: diagnosis was based on careful anamnesis and detection and confirmatory laboratory tests. Correct identification of different types and subtypes is important from a therapeutic point of view. Treatment requires specific medication such as desmopressin, factor VIII concentrates and coadjuvant therapies. No evidence was found to contraindicate vaginal birth route; however, each particular case must be taken individually. Conclusion: females suffering from coagulation disorders present a greater risk of bleeding during menarche, pregnancy, giving birth and the puerperium. This means that suitable evaluation and multidisciplinary management must be mandatory during pregnancy.

Tranexamic Acid Versus a Placebo in Decreasing Blood Loss in Patients Undergoing Spine Surgery / 대한마취과학회지

BACKGROUND: Major spine surgery can be associated with dramatic blood loss, thereby requiring a high-volume transfusion. Tranexamic acid inhibits fibrinolysis and it has been used in general surgery. The effect of tranexamic acid on blood loss and transfusion requirements during spine surgery was prospectively studied. METHODS: Twenty-two patients scheduled for orthopaedic surgery for spinal stenosis under general anesthesia were randomly selected to receive, either tranexamic acid administered as a bolus of 15 mg/kg, or the equivalent volume of saline, during the operation and postoperatively. The anesthetic and perioperative management were standardized. The total blood loss of each patient and transfusion requirements were noted. Hematocrit, PT, PTT, and platelet count measure were performed before and after surgery. RESULTS: The tranexamic acid group demonstrated a significantly less amount of blood loss (859.5 +/- 280.0 ml) compared to the placebo group (1366.0 +/- 333.7 ml). In addition the fluid and homologous transfusion requirements in the placebo group were greater than in the tranexamic acid group. CONCLSIONS: Tranexamic acid during major spine surgery significantly reduces both blood loss and consequent blood transfusion requirements.