Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates.
TL;DR: It is concluded that deficiency of fibrinogen develops earlier than any other hemostatic abnormality when plasma-poor RCCs are used for the replacement of major blood loss.
Abstract: The purpose of this study was to assess the change of platelet and fibrinogen concentrations and the change of activities of prothrombin and factors V and VII when major surgical blood loss was replaced with plasma-poor red cell concentrates (RCCs) and colloid plasma substitutes. Sixty patients were studied. The average blood loss was 65% +/- 41% of the calculated blood volume (CBV). Blood loss was monitored carefully and replaced without delay to ensure stable blood volume. Blood samples were obtained at the induction of anesthesia and at the end of the recovery room period, or before the patient was given fresh frozen plasma. In addition, a platelet count was determined after each 20% blood loss. The results were converted to relative values, and simple linear regression with logarithmic transformation was applied. The initial platelet concentration was 257 +/- 89 x 10(3)/mm3 and the extrapolation of the regression line intercepted the critical level of 50 x 10(3)/mm3 at 230% (confidence interval 169%-294%) blood loss. The initial fibrinogen concentration was 3.7 +/- 1.1 g/L and the hemostatically significant level of 1.0 g/L was already reached at 142% (117%-169%) blood loss (r2 = 0.90). Activities of prothrombin and coagulation factors V and VII reached their critical levels at 201% (160%-244%), 229% (167%-300%), and 236% (198%-277%) blood loss, respectively. We conclude that deficiency of fibrinogen develops earlier than any other hemostatic abnormality when plasma-poor RCCs are used for the replacement of major blood loss.
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TL;DR: The guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation, and may also serve as a basis for local implementation.
Abstract: Severe trauma continues to represent a global public health issue and mortality and morbidity in trauma patients remains substantial. A number of initiatives have aimed to provide guidance on the management of trauma patients. This document focuses on the management of major bleeding and coagulopathy following trauma and encourages adaptation of the guiding principles to each local situation and implementation within each institution. The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004 and included representatives of six relevant European professional societies. The group used a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were reconsidered and revised based on new scientific evidence and observed shifts in clinical practice; new recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. This guideline represents the fourth edition of a document first published in 2007 and updated in 2010 and 2013. The guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation. Best-practice use of blood products during further resuscitation continues to evolve and should be guided by a goal-directed strategy. The identification and management of patients pre-treated with anticoagulant agents continues to pose a real challenge, despite accumulating experience and awareness. The present guideline should be viewed as an educational aid to improve and standardise the care of the bleeding trauma patients across Europe and beyond. This document may also serve as a basis for local implementation. Furthermore, local quality and safety management systems need to be established to specifically assess key measures of bleeding control and outcome. A multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. The implementation of locally adapted treatment algorithms should strive to achieve measureable improvements in patient outcome.
1,247 citations
Cites background from "Hemostatic factors and replacement ..."
...A platelet count of 50 × 10(9)/l may be anticipated when 28 approximately two blood volumes have been replaced by fluid or red cell components [421]....
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...Fibrinogen levels decrease early in many patients who sustain severe 20 trauma, and low fibrinogen levels are associated with higher transfusion requirements and 21 increased mortality [421]....
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University of Copenhagen1, Centre Hospitalier Universitaire de Grenoble2, University of Valladolid3, University of Naples Federico II4, Innsbruck Medical University5, Ludwig Maximilian University of Munich6, Maastricht University7, University of Valencia8, Royal Lancaster Infirmary9, University of Salzburg10
TL;DR: These guidelines are intended to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible.
Abstract: The aims of severe perioperative bleeding management are three-fold. First, preoperative identification by anamesis and laboratory testing of those patients for whom the perioperative bleeding risk may be increased. Second, implementation of strategies for correcting preoperative anaemia and stabilisation of the macro- and microcirculations in order to optimise the patient’s tolerance to bleeding. Third, targeted procoagulant interventions to reduce the amount of bleeding, morbidity, mortality and costs. The purpose of these guidelines is to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible. The Guidelines Committee of the European Society of Anaesthesiology (ESA) formed a task force with members of scientific subcommittees and individual expert members of the ESA. Electronic databases were searched without language restrictions from the year 2000 until 2012. These searches produced 20 664 abstracts. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. At the suggestion of the ESA Guideline Committee, the Scottish Intercollegiate Guidelines Network (SIGN) grading system was initially used to assess the level of evidence and to grade recommendations. During the process of guideline development, the official position of the ESA changed to favour the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This report includes general recommendations as well as specific recommendations in various fields of surgical interventions. The final draft guideline was posted on the ESA website for four weeks and the link was sent to all ESA members. Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.
883 citations
TL;DR: Key changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants.
Abstract: Introduction: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved. Methods: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature. Results: Key changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies. Conclusions: A comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.
800 citations
Cites background from "Hemostatic factors and replacement ..."
...In initial acute loss, the bone marrow and spleen variably release platelets, and a platelet count of 50 × 10(9)/l may be anticipated when approximately two blood volumes have been replaced by fluid or red cell components [370]....
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01 Jan 2010
TL;DR: In this article, the authors presented an updated version of the guideline published by the Task Force for Advanced Bleeding Care in Trauma and updated in 2010, which included new recommendations on the appropriate use of vasopressors and inotropic agents.
Abstract: IntroductionEvidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved.MethodsThe multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature.ResultsKey changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies.ConclusionsA comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.http://ccforum.com/content/17/4/442
797 citations
TL;DR: Fresh‐frozen plasma (FFP), cryoprecipitate and cryosupernatant plasma are very limited and should not be used to reverse warfarin anticoagulation in the absence of severe bleeding, and PRP may be used as an alternative to FFP.
Abstract: The indications for transfusing fresh-frozen plasma (FFP), cryoprecipitate and cryosupernatant plasma are very limited. When transfused they can have unpredictable adverse effects. The risks of transmitting infection are similar to those of other blood components unless a pathogen-reduced plasma (PRP) is used. Of particular concern are allergic reactions and anaphylaxis, transfusion-related acute lung injury, and haemolysis from transfused antibodies to blood group antigens, especially A and B. FFP is not indicated in disseminated intravascular coagulation without bleeding, is only recommended as a plasma exchange medium for thrombotic thrombocytopenic purpura (for which cryosupernatant is a possible alternative), should never be used to reverse warfarin anticoagulation in the absence of severe bleeding, and has only a very limited place in prophylaxis prior to liver biopsy. When used for surgical or traumatic bleeding, FFP and cryoprecipitate doses should be guided by coagulation studies, which may include near-patient testing. FFP is not indicated to reverse vitamin K deficiency for neonates or patients in intensive care units. PRP may be used as an alternative to FFP. In the UK, PRP from countries with a low bovine spongiform encephalopathy incidence is recommended by the Departments of Health for children born after 1 January 1996. Arrangements for limited supplies of single donor PRP of non-UK origin are expected to be completed in 2004. Batched pooled commercially prepared PRP from donors in the USA (Octaplas) is licensed and available in the UK. FFP must be thawed using a technique that avoids risk of bacterial contamination. Plastic packs containing any of these plasma products are brittle in the frozen state and must be handled with care.
786 citations
Cites background from "Hemostatic factors and replacement ..."
...More recently Hiippala et al (1995) found that clinically significant fibrinogen deficiency develops after a loss of about 150% of the blood volume – earlier than any other haemostatic abnormality – when plasma-poor red cell concentrates are used in replacing major blood loss; and Stainsby and…...
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...They also stated that platelet counts correlate highly with microvascular bleeding and recommend platelet transfusion if this falls below 50 · 109/l. More recently Hiippala et al (1995)...
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References
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1,786 citations
TL;DR: It is recommended that any patient receiving massive transfusions who develops diffuse microvascular bleeding be given platelet concentrates, and the most useful laboratory test for predicting abnormal bleeding was the platelet count.
Abstract: Twenty-seven patients requiring massive transfusions were studied prospectively to determine whether administration of stored, modified whole blood induced a primary disorder of hemostasis evidenced by generalized microvascular oozing. Platelet counts fell in proportion to the number of units of blood transfused. In contrast, the levels of factors V and VIII correlated poorly with the units of blood transfused, 85% of the total variation in the levels being due to influences other than transfused blood. Levels of all other clotting factors were unrelated to the number of units of blood given. Eight patients developed abnormal bleeding. The cause appeared to be dilutional thrombocytopenia in five patients, and DIC in three. In six of the eight, bleeding was controlled with platelet concentrates alone. Two patients were given cryoprecipitate also. The most useful laboratory test for predicting abnormal bleeding was the platelet count. Fibrinogen levels should be followed as an aid in the diagnosis of DIC. The BT, PT, and PTT were not helpful in assessing the cause of bleeding, unless they were greater than 1.5 times the control value. We recommend that any patient receiving massive transfusions who develops diffuse microvascular bleeding be given platelet concentrates. Platelet counts as high as 100,000 may be required to control bleeding from surgical wounds. It is not necessary to supplement transfusions of stored, modified whole blood with fresh blood or fresh frozen plasma.
322 citations
TL;DR: Clotting factor activities and coagulation screening tests in 36 massively transfused patients were measured after every 12 units of blood and whenever diffuse microvascular bleeding (MVB) developed.
Abstract: Clotting factor activities and coagulation screening tests in 36 massively transfused patients were measured after every 12 units of blood and whenever diffuse microvascular bleeding (MVB) developed. Moderate deficiencies in clotting factors were common, but they were not associated with MVB. MVB was associated with severe abnormalities of coagulation, i.e. a fibrinogen level less than 0.5 g/l or clotting factor levels less than 20%. The quantitative relationship between the prothrombin (PT) and partial thromboplastin (PTT) times and underlying clotting factor levels was explored by multiple linear regression. Clotting factor levels accounted for only 65-85% of the variability in these tests. However, clotting factor activities less than 20% were reliably reflected by marked prolongations of the PT and PTT (values greater than 1.8 times control). Our data suggest that commonly used replacement formulas are not likely to prevent MVB, since consumption of platelets and/or clotting factors, rather than simple dilution, is a major cause of the deficiencies leading to MVB. Modified whole blood alone was sufficient replacement therapy for most patients. Guidelines for transfusion of supplemental components during massive transfusion are given.
292 citations
198 citations
TL;DR: This study studied 32 ASA physical status I or II patients who lost more than 50% of their blood volume during elective posterior spinal stabilization and found that elective surgical patients who receive packed red cells experience a coagulation factor deficit as the initial abnormality in clinical hemostasis.
Abstract: The purpose of this study was: 1) to define coagulation abnormalities in patients who receive red cell concentrates rather than whole blood for large volume blood loss (greater than 0.5 blood volume); and 2) to determine when coagulation abnormalities lead to increased bleeding in the massively transfused surgical patient. We studied 32 ASA physical status I or II patients (mean age 15.6 +/- 2.3 yr) who lost more than 50% of their blood volume during elective posterior spinal stabilization. Crystalloid solutions and packed red cell concentrates were used to replace blood and fluid losses. Invasive hemodynamic measures, urinary output, and serial hematocrit determinations were used to help maintain a constant intravascular volume and confirm the estimates of blood loss. The quality of hemostasis was assessed during operation. In 15 of the 32 patients, surgical hemostasis remained effective throughout posterior spinal fusion. A coagulation profile (prothrombin time [PT] and activated partial thromboplastin time [aPTT], platelet count, and fibrinogen) was measured at the conclusion of operation in these patients. In 17 patients, increased surgical bleeding as a result of decreased clot formation and increased bleeding from the wound was present. In these 17 patients at the time increased bleeding was diagnosed, hemostatic tests (PT, aPTT, fibrinogen, platelet count, and coagulation factor assays V, VIII, and IX) were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)
175 citations