and transmitted securely. In hip surgery TXA (15 mg/kg BW as either a single or double bolus at the start of the intervention and 3 h thereafter) resulted in a reduction of allogeneic blood transfusions but increased the risk of hypercoagulability [84–86]. Steinmetz H, Berkefeld J, Forsting M, et al. Pathologically excessive and/or prolonged uterine bleeding is one of the most frequent symptoms in women suffering from coagulation abnormalities [59]. Viscoelastic tests such as thromboelastometry or thrombelastography (ROTEM and TEG, respectively), on the other hand, can detect HF but only if plasmin-antiplasmin levels are high or α2-antiplasmin levels are very low [20]. Doch gerade bei Schwerverletzten hat das Antifibrinolytikum womöglich auch unerwünschte Wirkungen. mit dem Ziel, die Versorgung von Polytrauma-Patienten bzw. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. Recognized indications of tranexamic acid in pediatrics (expert opinion), aTopical use: TXA (solution for injection) is locally applied without dilution or diluted with NaCl 0.9%; when applied in the mouth the swallowed amount should be added to the total dosage. A comprehensive retrospective cohort study (n = 872,416) has furthermore shown that TXA results in a significant reduction of the probability of transfusion in patients undergoing total hip or knee replacement (OR 0.31–0.38; p < 0.001) without increasing the risk of thromboembolism, kidney failure or combined complications [79]. Since it is located on the European Watershed between Rhine and Danube, the municipal territory is the site of the remains of Fossa Carolina, an early Medieval attempt to bridge the watershed. Morrison JJ, Ross JD, Dubose JJ, Jansen JO, Midwinter MJ, Rasmussen TE. 9. sharing sensitive information, make sure you’re on a federal Dosages need not be modified in patients with impaired liver function and elderly patients with no kidney dysfunction (Table 4). Germans MR, Post R, Coert BA, Rinkel GJ, Vandertop WP, Verbaan D. Ultra-early tranexamic acid after subarachnoid hemorrhage (ULTRA): study protocol for a randomized controlled trial. TXA is of utmost importance in the prevention and treatment of traumatic and perioperative bleeding due to the resulting reduction in perioperative blood loss and blood transfusion requirements. Polytrauma occurs when a person experiences injuries to multiple body parts and organ systems often, but not always, as a result of blast-related events. Several studies revealed that HF exceeding 3% was associated with a dramatic increase in mortality [5, 6, 30–32]. Myles PS, Smith JA, Kasza J, Silbert B, Jayarajah M, Painter T, et al. Benign gynecological interventions (e. g. myomectomy), In combination with activated factor concentrate (FEIBA, factor VIII inhibitor bypass activity; 1 ml = 25 E* factor VIII inhibitor bypass activity; see footnote 3), Fibrinolysis due to disseminated intravascular coagulation without any significant bleeding. Tranexamic acid and blood loss during and after cesarean section: a meta-analysis. Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: the spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy. Shahid A, Khan A. Tranexamic acid in decreasing blood loss during and after caesarean section. The risk of mortality increases with the severity of HF. Meretoja A, Churilov L, Campbell BC, Aviv RI, Yassi N, et al. Leitlinien für Diagnostik und Therapie in der Neurologie. Zahed R, Moharamzadeh P, Alizadeharasi S, Ghasemi A, Saeedi M. A new and rapid method for epistaxis treatment using injectable form of tranexamic acid topically: a randomized controlled trial. Tranexamsäure wirkt antihämorrhagisch, indem es die fibrinolytische Eigenschaft von Plasmin hemmt. Treuchtlingen is situated on the river Altmühl, 9 km southwest of Weißenburg in Bayern, and 45 km northeast of Donauwörth . Maddali MM, Rajakumar MC. Ives C, Inaba K, Branco BC, Okoye O, Schochl H, et al. The CRASH-2 study published in Lancet in 2010, which comprised 20,211 patients, showed that the use of TXA (loading dose of 1 g TXA for 10 min + 1 g infusion over 8 h) compared to matching placebo resulted in a significant reduction of overall (14.5% vs. 16%, respectively) and hemorrhage-induced (4.9% vs. 5.6%, respectively) mortality in trauma patients without increasing the rate of thromboembolism [10]; however, the CRASH-2 data should be viewed with caution as it was performed mostly in developing and threshold countries and no influence on transfusion rates by TXA was documented. In a subsequent study (n = 1332) it was shown that patients exclusively treated with cryoprecipitates (n = 168) exhibited the same survival rates as patients treated only with TXA (n = 148); the survival rate was highest in patients administered both TXA and cryoprecipitate (n = 258) [13]. Association of cryoprecipitate and tranexamic acid with improved survival following wartime injury: findings from the MATTERs II Study. Before Chauhan S, Bisoi A, Kumar N, et al. Tranexamic acid for epistaxis in hereditary hemorrhagic telangiectasia patients: a European cross-over controlled trial in a rare disease. TXA is of utmost importance in the prevention and treatment of traumatic and perioperative bleeding due to the resulting reduction in perioperative blood loss and blood transfusion requirements. The site is secure. This is also confirmed by a meta-analysis of 46 randomized controlled studies on 2925 orthopedic surgery patients, which also pointed to a reduction of total intraoperative and postoperative blood loss [80]. (Da die AWMF Website momentan nicht stabil erreichbar ist, könnt ihr die Leitlinie auch bei ITLS herunterladen ). Dewan Y, Komolafe EO, Mejía-Mantilla JH, Perel P, Roberts I, Shakur H, CRASH-3 Collaborators CRASH-3 – tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial. Demographics, care patterns, and outcomes of patients admitted to cardiac intensive care units: The critical care cardiology trials network prospective north American multicenter registry of cardiac critical illness. In beiden Gruppen sind die Hälfte der Patienten NYHA-Klasse 2, während eine ASA-Klassifizierung nicht angegeben ist. It focuses on five different topics, 1. Die europäischen Leitlinien zum Management der schweren Blutung und Koagulopathie nach Trauma empfehlen seit dem Jahr 2013 die frühestmögliche Gabe von Tranexamsäure (TXA) zur Inhibierung der Hyperfibrinolyse, die im Zuge der traumaassoziierten Koagulopathie (TIK) bereits bei Klinikaufnahme bestehen kann. Schöchl H, Voelckel W, Grassetto A, Schlimp CJ. CRASH-2 Collaborators, Intracranial Bleeding Study Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study). D. Fries: Astra Zeneca, AOP Orphan, Baxter, Bayer, BBraun, Biotest, CSL Behring, Delta Select, Dade Behring, Edwards, Fresenius, Glaxo, Haemoscope, Hemogem, Lilly, LFB, Mitsubishi Pharma, NovoNordisk, Octapharm, Pfizer, Tem-Innovation. In trauma patients with partly excessive bleeding TXA can also reduce mortality, in particular if administered within a narrow time frame after injury. Tranexamic acid in trauma: How should we use it? Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis. Soweit aus dem Supplement hervorgeht, hat kein Patient ein bleibendes neurologisches Defizit, jedoch muss kritisch hinterfragt werden, ob die hochdosierte Gabe von TXA, die auf Grundlage dieser Studie nur wenige EK-Transfusion einspart, die Inkaufnahme einer höheren Inzidenz von Krampfanfällen rechtfertigt. Stibbe J, Kluft C, Brommer EJP. Moore HB, Moore EE, Gonzalez E, Chapman MP, Chin TL, et al. In patients suffering from hemophilia, von Willebrand disease or congenital platelet dysfunctions, topical3 (in the form of mouthwashes), buccal or intravenous administration of TXA will help reduce hemorrhage and blood loss, particularly mucosal bleeding. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Pharmacological interventions to decrease blood loss and blood transfusion requirements for liver resection. Beide Gruppen unterschieden sich in den sekundären Endpunkten nicht. Accessibility Die Patienten in beiden Gruppen sind vergleichbar. Kritisch anzumerken ist, dass die Prozentangaben in den Tabellen 1 und 2 rechnerisch nicht immer nachzuvollziehen sind und somit nicht immer klar ist, auf welchen Teil sich die Prozentangabe bezieht. By definition, HF is a state of increased clot resolution that may be associated with severe, potentially life-threatening hemorrhage. Morimoto Y, Yoshioka A, Sugimoto M, Imai Y, Kirita T. Haemostatic management of intraoral bleeding in patients with von Willebrand disease. Similar results were obtained in a meta-analysis of 25 RCTs (n = 5411) and large-scale observational studies (n = 5977), which confirmed the efficacy of TXA, as compared with placebo, in reducing blood loss, allogeneic blood transfusion needs and the reoperation rate due to postoperative hemorrhage [91]. 2014 I 37. Moreover, a Cochrane review concluded that antifibrinolytic therapy helps reduce blood loss and perioperative transfusion needs [94], with TXA and EACA being equally effective. ), Primary and adjuvant in hereditary thrombopathies/thrombopenia [. National Library of Medicine Sentürk MB, Cakmak Y, Yildiz G, Yildiz P. Tranexamic acid for cesarean section: a double-blind, placebo-controlled, randomized clinical trial. Movafegh A, Eslamian L, Dorabadi A. Lethhaby A, Farquhar C, Cook I. Antifibrinolytics for heavy menstrual bleeding. Menorrhagia in adolescents with inherited bleeding disorders. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Caglar GS, Tasci Y, Kayikcioglu F, Haberal A. http://creativecommons.org/licenses/by/4.0/, http://www.who.int/selection_medicines/committees/expert/18/applications/tranexamic/en/, Prophylaxis and treatment of bleeding due to a local or systemic hyperfibrinolysis in adults and children over the age of 1 year, Ears, nose and throat (ENT) surgery (adenoidectomy, tonsillectomy, dental extractions), Gynecological surgery or obstetric hemorrhage, Abdominal and thoracic surgery and other major surgery, e. g. cardiac surgery, As antidote in bleeding requiring immediate treatment while on fibrinolytic treatment, Prophylaxis of recurrent bleeding in traumatic hyphema, Dental extraction and other interventions in ENT area in patients with hereditary coagulopathies, Mucosal bleeding in patients with coagulopathies, Gastrointestinal disturbances (nausea, vomiting, diarrhea), Drop of blood pressure/dizziness following a too fast intravenous administration, Early pregnancy, in late pregnancy only when vitally indicated, Massive bleeding in the upper urinary tract (risk of ureter obstruction due to clot), Intrathecal and intraventricular injection, intracerebral administration (risk of cerebral edema and convulsions), Diseminated intravascular coagulation (DIC) without severe hemorrhage, Retrospective single centre analysis of policy before and after use of high dose TXA 10 g, RCT (multi centre, prospective, randomized controlled), RCT (prospective, randomized, double-blind), RCT (prospective, double-blind, randomized, controlled), RCT (prospective, double-blind, placebo controlled), Randomized, prospective case-control study, 15–25 mg/kg on preceding evening or 1.5–2× dosage on day of surgery, 1.0–1.5 g on preceding evening or 1.5–2× dosage on day of surgery, Excessive fibrinolysis (e. g. liver transplantation, medication induced), Adjuvant as hemostatic agent, in hemophilia and von Willebrand disease (e. g. dentistry, not in renal bleeding! Gungorduk K, Asıcıoğlu O, Yıldırım G, Ark C, Tekirdağ Aİ, Besımoglu B. Abdel-Aleem H, Alhusaini TK, Abdel-Aleem MA, Menoufy M, Gülmezoglu AM. Ihr Kommentar zur Studie. Bidolegui F, Arce G, Lugones A, Pereira S, Vindver G. Tranexamic acid reduces blood loss and transfusion in patients undergoing total knee arthroplasty without tourniquet: a prospective randomized controlled trial. J. Grabert und M. Velten geben an, dass kein Interessenkonflikt besteht. In a double-blind, randomized, placebo controlled trial (n = 222) TXA (preoperative bolus followed by intraoperative permanent infusion) reduced drainage volume and transfusion needs in elective coronary artery bypass graft (CABG) [90]. Postpartum hemorrhage (PPH) is among the leading causes of maternal mortality worldwide [38, 39]. Polytrauma is a medical term used to describe someone who has been subjected to multiple traumatic injuries. TXA also inhibits plasmin activity directly, although only at higher doses [24]. Military application of tranexamic acid in trauma emergency resuscitation (MATTERs) study. Improved point-of-care identification of hyperfibrinolysis is needed. HHS Vulnerability Disclosure, Help Bethesda, MD 20894, Web Policies On the other hand, combined administration of activated factor concentrate (Anti-Inhibitor Coagulant Complex, FEIBA/Baxter) and TXA is not recommended in view of the rather unpredictable increase in coagulability (hypercoagulability). International Consortium for Evidence Based Perfusion. In patients undergoing total knee replacement, oral TXA (1 g preoperatively followed by 1 g every 6 h over a period of 18 h postoperatively) proved effective in reducing postoperative fibrinolysis [82, 83]. 8600 Rockville Pike As a library, NLM provides access to scientific literature. HHS Vulnerability Disclosure, Help Unlike elective surgery patients, 25–35% of all patients with severe physical injuries already show some form of coagulopathy when admitted to the shock room. Also, topical (see footnote 3) application of TXA in the thoracic cavity is recommended to reduce postoperative blood loss after CABG (1C). In recent years the focus has increasingly been on severe trauma with subsequent tissue hypoxia. In the course of neurosurgical interventions TXA (1 g immediately after diagnosis of an aneurysmal subarachnoid hemorrhage [aSAH], followed by 1 g every 6 h up to the time the aneurysm has been corrected) reduced the mortality risk due to early rebleeding by 80% [113]. Therapie hereditärer Thrombozytopathien Interdisziplinäre S2K-Leitlinie der Ständigen Kommission Pädiatrie der Gesellschaft für Thrombose- und Hämostaseforschung e. V. Leitlinie Thrombozytopathien Therapie AWMF Register Nr. However, once the LY30 extended to more than 3%, mortality increased to 20%. Sie blockiert die Aktivierung von Plasminogen zu Plasmin. Hess JR, Brohi K, Dutton RP, Hauser CJ, Holcomb JB, et al. TBI frequently occurs in polytrauma in combination with other disabling conditions, such as amputation, burns, spinal cord injury, auditory and visual damage , spinal cord injury (SCI), post-traumatic stress disorder (PTSD . Dieses "Pro & Kontra" fasst die aktuelle Diskussion über die präklinische Gabe von TXA kritisch zusammen. Leitlinie Polytrauma. Reproduced with permission from [6]. In der Einzelanalyse war statistisch lediglich für Krampfanfälle eine signifikante Häufung in der Hochdosisgruppe (1,0 % vs. 0,4 %, p = 0,05) zu detektieren. Zusammenfassend ist der OPTIMAL-Trial eine groß angelegte und für die Frage nach der optimalen TXA-Dosierung gut angelegte Studie, die schlussendlich aber kein überzeugendes Ergebnis liefern kann. Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. TXA reduces both the incidence of secondary hemorrhage after cervical conisation [100] (B) and the incidence of perioperative bleeding during gynecologic oncologic surgery [101] (C) [3]. Polytrauma occurs when a person experiences injuries to multiple body parts and organ systems often, but not always, as a result of blast-related events. Bouet PE, Ruiz V, Legendre G, Gillard P, Descamps P, Sentilhes L. Policy of high-dose tranexamic acid for treating postpartum hemorrhage after vaginal delivery. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology. Shakur H, Roberts I, Bautista R, Caballero J, Coats T, et al. In acute bleeding in the upper gastrointestinal tract TXA reduces mortality [3, 72, 73], with a recent Cochrane analysis reporting a relative mortality risk of 0.60 and a relative after-bleeding risk of 0.72 [74]. Das tatsächlich transfundierte EK-Volumen beträgt im Median in beiden Gruppen 0 ml. Intraoperative use of tranexamic acid to reduce transfusion rate in patients undergoing radical retropubic prostatectomy: double blind, randomised, placebo controlled trial. Guideline on antiplatelet and anticoagulation management in cardiac surgery. Hyperfibrinolysis at admission is an uncommon but highly lethal event associated with shock and prehospital fluid administration. http://creativecommons.org/licenses/by/4.0/deed.de. Molenaar IQ, Warnaar N, Groen H, Tenvergert EM, Slooff MJ, Porte RJ. Novikova N, Hofmeyr GJ. In a pharmacokinetic study of heart operations the recommended TXA dosage plan for children was a loading dose of 6.4 mg/kg BW with weight-adapted infusion rates ranging from 3.1 mg/kg BW/h to 2.0 mg/kg BW/h (BW 5–40 kg) [107]. Dose comparison of tranexamic acid in pediatric cardiac surgery. Ngaage DL, Bland JM. In pediatrics TXA has a wide field of application (Table 6). 5 - 7, 91781 Weissenburg in Bayern, Bavaria, Germany. Patienten mit penetrierendem Thoraxtrauma, massivem Hämatothorax und/oder schweren Verletzungen von Lunge und Herz werden notfallmäßig thorakotomiert und bei Zeichen einer Hohlorganperforation. Polytrauma can be caused by motor vehicle accidents, falls from heights, bullet injuries, blast injuries caused by explosive devices, etc. Es ist Spekulation, ob ältere Patienten mit einem vermutlich niedrigeren Hb von der Hochdosistherapie mit TXA profitieren könnten, oder sich bei wahrscheinlich schon vorbestehenden Organschäden die TXA-Nebenwirkungen deutlicher ausprägen würden. Accordingly, in 2011 the World Health Organization (WHO) added TXA to its list of essential medicines.1 In addition, the reduction of perioperative blood loss and the resulting decline in the demand for transfusions have induced European societies (Task Force for Advanced Bleeding Care in Trauma and the European Society of Anesthesiology) to publish in recent guidelines a 1A recommendation for the use of TXA in the case of traumatic and perioperative bleeding [2, 3]. According to expert opinion, administration of TXA is not recommended in the following cases: If TXA were still to be administered, this should only be done in patients in whom an activation of the fibrinolytic system preponderates and in the presence of severe bleeding. Brohi K, Cohen MJ, Davenport RA. Zufferey PJ, Miquet M, Quenet S, Martin P, Adam P, et al. The organization and running of meetings as well as the subsequent coordinating process and publication of the present review article were financed through an unrestricted grant by Pfizer Corp. Austria. In cases of moderate and mild hemophilia, von Willebrand disease type 1 (mild deficiency) and storage pool disease (thrombocyte granular defect) it is recommended to use desmopressin jointly with TXA [62, 70, 71]. Die Hochdosistherapie mit TXA bestand aus einem Bolus nach Anästhesieinduktion (30 mg/kgKG), Erhaltungsdosis (16 mg/kgKG und h) und einem Bolus zum Beginn der EKZ (2 mg/kgKG). 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery. Background: Polytrauma patients are expected to have a higher risk of mortality than that obtained by the summation of expected mortality owing to their individual injuries. Hotel Garni Am Ellinger Tor. The role of antifibrinolytic agents in gynecologic cancer surgery. In the course of major surgical interventions (especially cardiac surgery, orthopedic surgery and liver transplantations) TXA reduces perioperative blood loss and the need for transfusions. So far there have been no reports suggesting the presence of serious side effects, not even with high dosages and long-term administration (Table 2; [28]). The effect of aprotinin, tranexamic acid, and aminocaproic acid on blood loss and use of blood products in major pediatric surgery: a meta-analysis. #9 Best Value of 2,415 places to stay in Gunzenhausen. The hemostatic effect of tranexamic acid in conisatio colli uteri. 1Clinical Department of Hematology and Hemostaseology, Medical University Vienna, Vienna, Austria, 2Department of General and Surgical Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria, 3Department of Anesthesiology and Intensive Care Medicine, AUVA Accident Hospital Salzburg, Salzburg, Austria, 4Academic Teaching Hospital, Paracelsus Private Medical University Salzburg, Salzburg, Austria, 5Department of Children and Adolescents Medicine, Medical University Innsbruck, Innsbruck, Austria, 6Department of Anesthesiology and Intensive Care Medicine, Medical University Graz, Graz, Austria. PPH: results of clinical studies with tranexamic acid in obstetrics, CS cesarean section, RCT randomized clinical trial, PPH postpartum hemorrhage, PAMBA para-aminomethylbenzoic acid, TXA tranexamic acid. Zufferey P, Merquiol F, Laporte S, Decousus H, Mismetti P, et al. Meta-analysis of randomised and large matched observational studies. Sekhavat L, Tabatabaii A, Dalili M, Farajkhoda T, Tafti AD. Alle anderen analysierten Parameter einschließlich der maximalen Lyse änderten sich nach Verabreichung von Tranexamsäure nicht. Blanié A, Bellamy L, Rhayem Y, Flaujac C, Samama CM, Fontenay M, Rosencher N. Duration of postoperative fibrinolysis after total hip or knee replacement: a laboratory follow-up study. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. 68 reviews. Huang F, Wu D, Ma G, Yin Z, Wang Q. Tranexamsäure bindet an Plasminogen und hemmt dessen Aktivierung zu Plasmin. Trauma-associated hemorrhagic shock is the most frequent cause of avoidable deaths, with hyperfibrinolysis (HF) at the time of hospitalization having been identified as an independent predictor of mortality [4–6]. Cotton BA, Harvin JA, Kostousouv V, Minei KM, Radwan ZA, et al. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. 3Topical administration is not mentioned in the prescribing information. Es bildet sich ein Komplex aus Tranexamsäure und Plasminogen. Abdul-Kadir R, McLintock C, Ducloy AS, El-Refaey H, England A, et al. in der vorliegenden OPTIMAL-Studie. Bouwmeester FW, Bolte AC, van Geijn HP. Ellinger Str. Aprotinin was, however, withdrawn from the market in 2007, since massive side effects had been observed in the course of complex cardiovascular surgery [9]. The joint guidelines of the Austrian Neurological Society (Österreichische Gesellschaft für Neurologie, ÖGN) and the German Neurological Society (Deutsche Gesellschaft für Neurologie, DGN) published in 2008 explicitly do not recommend a prophylactic administration of antifibrinolytics for SAH (↓↓) [117], a position that was repeated in the updated version of 2012 [118].