Antifibrinolytic drugs for acute traumatic injury. Millions of people die from injuries worldwide every year and the Cochrane Injuries Group looks at the evidence on ways to reduce this. Mike Clarke, Podcast Editor for The Cochrane Library spoke with Ian Roberts, Coordinating Editor of the Group who is based at the London School of Hygiene and Tropical Medicine in England about their new review of tranexamic acid.
CRASH- 2 Trial collaborators. Antifibrinolytic drugs for acute traumatic injury. Page 1. Antifibrinolytic drugs for acute traumatic injury (Review)Roberts I, Shakur H, Ker K, Coats T, on behalf of the CRASH- 2 Trial collaborators. Thisisareprintof a. Cochrane review, preparedandmaintained by. The Cochrane Collaboration andpublishedin The.
- . To quantify the effects of antifibrinolytic drugs on. surgical intervention and receipt of blood transfusion after acute traumatic injury. SEARCH.
- . transfusion requirement and mortality after acute traumatic injury. Epistemonikos ID. Antifibrinolytic drugs for acute traumatic injury.
- Antifibrinolytic drugs for acute traumatic injury. Antifibrinolytic drugs for acute traumatic injury. Some examples of antifibrinolytic drugs are aprotinin.
OBJECTIVES: To quantify the effect of antifibrinolytic drugs in reducing blood loss, transfusion requirement and mortality after acute traumatic injury. Antifibrinolytic drugs for acute traumatic injury. Antifibrinolytic drugs for acute traumatic. the main comparison Antifibrinolytic drugs for bleeding. Podcast: Antifibrinolytic drugs for acute traumatic injury. Podcast: Antifibrinolytic drugs for acute traumatic injury. Antifibrinolytic drugs for acute traumatic injury. To assess the effect of antifibrinolytic drugs in patients with acute. We searched the Cochrane Injuries. Antifibrinolytic drugs for acute traumatic injury. Antifibrinolytic. surgical intervention and receipt of blood transfusion after acute traumatic injury. . CRASH-2 Trial collaborators. Antifibrinolytic drugs for. CRASH-2 Trial collaborators. Antifibrinolytic drugs for. drugs for acute traumatic injury.
. Antifibrinolytic drugs for acute traumatic. To quantify the effects of antifibrinolytic drugs on. Antifibrinolytic drugs for acute traumatic injury.
Cochrane Library. Issue 1http: //www. Antifibrinolytic drugs for acute traumatic injury (Review)Copyright © 2. The Cochrane Collaboration.
Published by John Wiley & Sons, Ltd. Page 2. T A B L E O F C O N T E N T S1.
HEADER . . . . . . ABSTRACT. . . . . PLAIN LANGUAGE SUMMARY . BACKGROUND. . . . OBJECTIVES. . . . METHODS. . . . . . RESULTS . . . . .
DISCUSSION. . . . AUTHORS’ CONCLUSIONS . ACKNOWLEDGEMENTS .
REFERENCES . . . . CHARACTERISTICS OF STUDIES . DATA AND ANALYSES . Analysis 1. 1. Comparison 1 Tranexamic acid versus placebo, Outcome 1 Death. Analysis 1. 2. Comparison 1 Tranexamic acid versus placebo, Outcome 2 Proportion undergoing surgical intervention. Analysis 1. 3. Comparison 1 Tranexamic acid versus placebo, Outcome 3 Proportion receiving blood transfusion.
Analysis 1. 4. Comparison 1 Tranexamic acid versus placebo, Outcome 4 Volume of blood transfused. Analysis 2. 1. Comparison 2 Aprotinin versus none, Outcome 1 Death.
Analysis 2. 2. Comparison 2 Aprotinin versus none, Outcome 2 Proportion undergoing surgical intervention. Analysis 2. 3. Comparison 2 Aprotinin versus none, Outcome 3 Volume of blood transfused. APPENDICES . . . . WHAT’S NEW . . . . HISTORY . . . . . CONTRIBUTIONS OF AUTHORS . DECLARATIONS OF INTEREST .
SOURCES OF SUPPORT. DIFFERENCES BETWEEN PROTOCOL AND REVIEWINDEX TERMS . Antifibrinolytic drugs for acute traumatic injury (Review)Copyright © 2. The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 3[Intervention Review]Antifibrinolytic drugs for acute traumatic injury. Ian Roberts. 1, Haleema Shakur. Katharine Ker. 1, Tim Coats.
CRASH- 2 Trial collaborators. Cochrane Injuries Group, London School of Hygiene & Tropical Medicine, London, UK. Department of Emergency Medicine,Leicester Royal Infirmary, Leicester, UK. Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, UKContact address: Ian Roberts, Cochrane Injuries Group, London School of Hygiene & Tropical Medicine, North Courtyard, Keppel.
Street, London, WC1. E 7. HT, UK. Ian. Roberts@Lshtm. ac.
Editorial group: Cochrane Injuries Group. Publication status and date: Edited (conclusions changed), published in Issue 1, 2. Review content assessed as up- to- date: 1. July 2. 01. 0. Citation: Roberts. I,Shakur. H,Ker. K,Coats. T,onbehalfofthe. CRASH- 2.
Trialcollaborators. Antifibrinolytic drugsforacutetraumaticinjury.
Cochrane Database of Systematic Reviews 2. Issue 1. Art. No.: CD0. DOI: 1. 0. 1. 00. CD0. 04. 89. 6. pub. Copyright © 2. 01. The Cochrane Collaboration.
Published by John Wiley & Sons, Ltd. A B S T R A C TBackground. Uncontrolled bleeding is an important cause of death in trauma victims. Antifibrinolytic treatment has been shown to reduce bloodloss following surgery and may also be effective in reducing blood loss following trauma. Objectives. To quantify the effect of antifibrinolytic drugs in reducing blood loss, transfusion requirement and mortality after acute traumaticinjury.
Search strategy. Wesearchedthe. Cochrane Injuries Group’s Specialised. Register, CENTRAL, MEDLINE, Pub. Med, EMBASE,Science Citation Index,National Research Register, Zetoc, SIGLE, Global Health, LILACS, and Current Controlled Trials. The Cochrane Injuries Group. Specialised Register, CENTRAL, MEDLINE and EMBASE searches were updated in July 2.
Selection criteria. We included all randomised controlled trials of antifibrinolytic agents (aprotinin, tranexamic acid [TXA] and epsilon- aminocaproicacid) following acute traumatic injury. Data collection and analysis. The titles and abstracts identified in the electronic searches were screened by two independent authors to identify studies that had thepotential to meet the inclusion criteria. The full reports of all such studies were obtained. From the results of the screened electronicsearches, bibliographic searches, and contacts with experts, two authors independently selected trials meeting the inclusion criteria,with any disagreements resolved by consensus.
Main results. Four trialsmetthe inclusion criteria. Two trialswith acombined total of 2. TXA on mortality; TXAreduced the risk of death by 1. RR=0. 9. 0, 9. 5% CI 0. Data from one trial involving 2. TXA reduced the risk of death due to bleeding by 1.
RR=0. 8. 5, 9. 5% CI 0. There was no evidence that. TXA increased the risk of vascular occlusive events or need for surgical intervention.
There was no substantial difference in the receiptof blood transfusion between the TXA and placebo groups. The two trials of aprotinin provided no reliable data. Antifibrinolytic drugs for acute traumatic injury (Review)Copyright © 2.
The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Page 4. Authors’ conclusions. TXA safely reduces mortality in bleeding trauma patients without increasing the risk of adverse events. Further trials are needed todetermine the effects of TXA in patients with isolated traumatic brain injury. P L A I N L A N G U A G E S U M M A R YBlood- clot promoting drugs for acute traumatic injury. Injury is the second leading cause of death for people aged five to 4.
Over three million people worldwide die of injuries, usuallybecause of extensive blood loss. Antifibrinolytic drugs promote blood clotting by preventing blood clots from breaking down. Someexamples of antifibrinolytic drugs are aprotinin, tranexamic acid (TXA) and epsilon- aminocaproic acid (EACA). Doctors sometimesgive these drugs to patients having surgery to prevent blood loss. They appear to have few complications. These drugs might also stopblood loss in seriously injured patients and, as a result, save lives. The authors of this review searched for randomised trials assessing the effects of antifibrinolytics in trauma patients.
When the reviewwas first done in 2. Since then, two new trials of TXA, one involving over 2. The results of this new research show that TXA reduces the risk of death compared to patients whoreceive no treatment without increasing the risk of adverse events. Two small trials of aprotinin were also found although they provided no reliable data. Furthermore, since May 2.
The authors conclude that TXA can safely reduce death in bleeding trauma patients. They suggest that future trials should explore theeffects of TXA in patients with traumatic brain injury with no other trauma. B A C K G R O U N DDescription of the condition. For people aged five to 4. HIV/AIDS as a cause of death. Each year, worldwide, about three mil- lion people die as a result of trauma (Murray 1.
Amongtraumapatientswhodosurvivetoreachhospital, exsanguination is a common cause of death, accountingfornearlyhalfofin- hospitaltraumadeathsinsomesettings(Sauaia. Central nervous system injury and multi- organ failure ac- countformostoftheremainder,bothofwhichcanbeexacerbatedby severe bleeding (BTF 2. Clotting helps to maintain the integrity of the circulatory sys- tem after vascular injury, whether traumatic or surgical in origin(Lawson 2. Major surgery and trauma trigger similar haemo- static responses and the consequent massive blood loss presentsanextreme challenge to the coagulation system. Part of the responseto surgery and trauma in any patient, is stimulation of clot break- down (fibrinolysis) which may become pathological (hyper- fibri- nolysis) in some cases.
Antifibrinolytic agents have been shown toreduce blood loss in patients with both normal and exaggeratedfibrinolyticresponsestosurgery,withoutapparentlyincreasingtherisk of post- operative complications. Description of the intervention. Antifibrinolytic agents arewidely usedinmajor surgery topreventfibrinolysis and reduce surgical blood loss. A recent systematic re- view (Henry 2. TXA]) in electivesurgical patients showed that antifibrinolytics reduced the num- bersneeding transfusion by one third,reducedthevolume neededpertransfusionbyoneunit,andhalvedtheneedforfurthersurgeryto control bleeding. These differences were all statistically signif- icant at the P< 0. Specifically, aprotinin reduced the rateof blood transfusion by 3.
RR]=0. 6. 6; 9. 5% con- fidence interval [9. CI] 0. 6. 0 to 0. TXA by 3. 9% (RR=0. CI 0. 5. 3 to 0. 7. Aprotinin use saved 1.
RBCs) (9. 5% CI 0. TXA use saved 0. 8. CI 0. 5. 3 to. 1. There was a non- significant reduction in mortality withboth aprotinin (RR=0. CI 0. 6. 3 to 1. 0. TXA (RR=2 Antifibrinolytic drugs for acute traumatic injury (Review)Copyright © 2.
The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Page 5. 0. 6. 0; 9. CI 0. 3. 3 to 1. 1.
However, concerns regarding an ap- parent increased risk of death compared to other antifibrinolyticsleadtotheremovalof aprotinin fromworldmarketsin. May 2. 00. 8. How the intervention might work. Because the coagulation abnormalities that occur after injury aresimilar to those after surgery, it is possible that antifibrinolyticagents might also reduce blood loss, the need for transfusion, andmortality following trauma.
A simple and widely practicable in- tervention that reduced blood loss following trauma might pre- vent hundreds of thousands of premature deaths. A reduction inthe need for transfusion would also have important public healthimplications. Blood is a scarce and expensive resource and majorconcerns remain about the risk of transfusion- transmitted infec- tion. Trauma is particularly common in parts of the world wherethe safety of blood transfusion cannot be assured. A recent studyin Uganda estimated the population- attributable fraction of HIVacquisition as a result of blood transfusion to be around two per- cent (Kiwanuka 2. Heymann 1. 99. 2). O B J E C T I V E STo quantify the effect of antifibrinolytic drugs on mortality, vas- cular occlusive events, surgical intervention and receipt of bloodtransfusion after acute traumatic injury.