Lectures
Text-slides plus audio track of the speaker are available free of charge after personalized login. The following topics are presented:
Trauma Induced Coagulopathy
7th Innsbruck Winter Symposium for Coagulation 5th-6th November 2010
Karim Brohi
Surgeon Trauma Clinical Academic Unit, The Royal London Hospital, London, UK
Fibrinogen and Prothrombin Complex Concentrate for the Management of Massive Bleeding
7th Innsbruck Winter Symposium for Coagulation 5th-6th November 2010
Petra Innerhofer
Department of Anesthesia and Critical Care Medicine, Medical University Innsbruck, Austria
Hemostyptic Wound Bandages: Are There Any Differences
7th Innsbruck Winter Symposium for Coagulation 5th-6th November 2010
Michael A. Dubick
US Army Institute of Surgical Research, Fort Sam Houston, USA
Standard coagulation tests versus viscoelastic POC monitoring
7th Innsbruck Winter Symposium for Coagulation 5th-6th November 2010
Paer I Jahonsson
Rigshospitalet, Copenhagen, Denmark
Sisse R OstrowskiRigshospitalet, Copenhagen, Denmark
Do we really need FFP in Austria?
7th Innsbruck Winter Symposium for Coagulation 5th-6th November 2010
Sibylle A. Kozek-Langenecker
Department of Anaesthesia and Intensive Care, Evangelisches Krankenhaus Vienna, Vienna Austria
European Guidelines for the management of the bleeding trauma patient
7th Innsbruck Winter Symposium for Coagulation 5th-6th November 2010
Detection and impact of Hyperfibrinolysis in trauma
7th Innsbruck Winter Symposium for Coagulation 5th-6th November 2010
Plasma for the Patient with Traumatic Hemorrhagic Shock
7th Innsbruck Winter Symposium for Coagulation 5th-6th November 2010
Philip C. Spinella
Blood Systems Research Institute, San Francisco, CA, USA
Prothrombin Complex Concentrates (PCC) Usage in Perioperative Bleeding
Budapest 2010
Carl-Erik Dempfle
I Department of Medicine, University Hospital of Mannheim, Mannheim, Germany
Perioperative bleeding has numerous sources:
anticoagulant therapy, side-effects of drugs, liver disease (causing
impaired hepatic synthesis of coagulation factors, or
thrombocytopenia), vitamin K deficiency, disseminated intravascular
coagulation, massive blood loss, dilution coagulopathy (leading to
reduced levels of all coagulation factors, thrombocytopaenia, low
haematocrit), and inherited coagulation defects. Fresh frozen
plasma (FFP) has been proved inefficacious in correcting abnormal
prothrombin time (PT) values in patients with mild coagulation
abnormalities. Prothrombin complex concentrate was shown to be more
effective than FFP in normalizing PT and the thrombin peak in
dilutional coagulopathy and in correcting the concentration of
coagulation factors like FVII and FX.
Pathogen Inactivation of Plasma - Experiences from Finland
Budapest 2010
Tom Krusius
Finnish Red Cross Blood Service, Finland
Clinical use of fresh frozen plasma (FFP) per 1000
population varies considerably between European
countries. Among different types of blood products,
use of FFP is associated with the highest incidence
of serious adverse events. Optimal FFP should have
uniform quality and coagulation factor content,
improved virus safety, and no risk of TRALI, serious
allergic reaction, alloimmunization, or
graft-versus-host disease. Among FFP alternatives,
Octaplas fulfills these conditions. Octaplas has
following disadvantages: pooled product (causing
more donor exposures than FFP transfusion),
potential risk of increased transmission of
non-enveloped viruses, slight inactivation/removal
of coagulation factors during production process,
and increased costs due to processing and virus
inactivation.
Clinical experience in usage of coagulation factor concentrates in perioperative bleeding
30th International Symposium on Intensive Care and Emergency Medicine (ISICEM), 9-12 March 2010 in Brussels, Begium
Klaus Goerlinger
Universitaetsklinikum Essen, Essen, Germany
Management of perioperative bleeding involves:
identification of the cause of
bleeding (surgical/coagulopathic), rapid
availability of coagulation test results,
goal-directed haemostatic therapy, and use of
point-of-care-based algorithms to closely bind
diagnostics and therapy. Such algorithms are
available for several clinical settings: liver
transplantation, trauma, and cardiovascular
surgery. Fibrinogen represents more than 90% of the
total amount of coagulation factors in plasma and is
necessary for building a stable clot. A small amount
of enzyme coagulation factors is necessary for
thrombin generation. Insufficient fibrin formation
or thrombin generation can be corrected in a
targeted manner by administering coagulation factor
concentrates like fibrinogen concentrate and
prothrombin complex concentrate, respectively.
Rational and timely haemostatic intervention in severely bleeding patients: mechanistic and practical considerations.
ESA 2010
Cristina Solomon
Department of Anaesthesiology and Intensive Care Medicine St. Johann Hospital, Salzburg, Austria
Benny SoerensenSkejby Hospital, Aarhus, Denmark
Trauma-induced coagulopathy occurs through several
mechanisms: tissue damage leading to release of
tissue factor, which causes excessive activation of
coagulation; hypoperfusion inducing endothelial
release of tissue plasminogen activator and
fibrinolysis; initial excessive thrombin generation
leading to activation of thrombomodulin and protein
C, followed by reduced thrombin generation and
inactivation of PAI-1; acidosis causing inhibition
of thrombin generation; and volume substitution,
inducing dilution coagulopathy. Rational and timely
haemostatic intervention implies following actions:
correct pH and temperature; initiate
antifibrinolytic therapy; explore source of
bleeding; minimize trauma; avoid excessive dilution
with colloids; assure sufficient levels of
fibrinogen; restore fibrin polymerization; and
facilitate thrombin generation.
Recombinant factor VIIa: The treatment of the future?
Euroanaesthesia 2009
Sibylle Kozek-Langenecker
Professor and Chairwoman, Department of Anaesthesia and Intensive Care, Evangelisches Krankenhaus Vienna, Vienna Austria
Recombinant activated factor VII has a
licensed indication in haemophilia with inhibiting antibodies and
Glanzmann's disease. Despite controversial study results, national and
international guidelines for trauma-related bleeding management
recommend off-label administration of recombinant activated factor VII
in persisting bleeding (grade 2C) only after preconditioning of the
patient with adequate fibrinogen, platelet concentrates and acidosis
correction. Thrombotic events are a potential complication of
recombinant activated factor VII.
Guidelines in bleeding management - do they help?
ESA 09: Industrial satellite symposium
Susan Mallett
Department of Anaesthesia, Royal Free Hospital, London - UK
The aim of guidelines is to ensure the appropriate use of blood and blood components in the management of the bleeding patient, to identify the most appropriate blood components to treat coagulopathy, and to provide an indication of when treatment is required. Transfusion triggers for red blood cells, platelet concentrates, fresh frozen plasma, coagulation factor concentrates, and antifibrinolytics vary between guidelines and there is large variation in their application. The long turnaround time of standard coagulation analyses may impair the application of guidelines. Much of current perioperative transfusion practice is empirical. Many transfusions are inappropriate and unnecessary. Failure to identify the nature of the coagulopathy leads to increased transfusion of blood products.
A role for concentrated coagulation factors in the management of perioperative bleeding?
ESA 09: Industrial satellite symposium
Benny Soerensen
Centre for Haemophilia and Thrombosis, Guy's and St. Thomas' NHS Foundation Trust and Kings College London School of Medicine, London, UK
The use of coagulation factors concentrate for haemostatic therapy is encouraged for several reasons: transfusion of allogeneic blood products is associated with a number of adverse events; allogeneic blood products such as FFP lack efficacy in the correction of coagulation abnormalities; in vivo haemodilution decreases the concentration of fibrinogen, FII, FVII, and FXIII more than predicted by the degree of haemodilution. Prothrombin complex concentrate represents the state of the art in the acute reversal of vitamin K antagonist therapy. Fibrinogen concentrate has been shown to correct reduced clot firmness induced by haemodilution and to reduce transfusion requirements. Intraoperative administration of FXIII has been shown to improve clot firmness and reduce blood loss.
Following Austrian guidelines: "FFP free" level one trauma centre - reality or fiction?
ESA 09: Industrial satellite symposium
Herbert Schöchl
UKH Salzburg, Salzburg - Austria
A large proportion of severely traumatized patients are coagulopathic on arrival in the emergency room. The ratio of FFP:RBC administered for the treatment of bleeding in trauma patients may have an impact on survival, but the optimal ratio is unknown. Fibrinogen plays an important role in the management of trauma coagulopathic bleeding, because severe tissue trauma leads to a substantial consumption of fibrinogen. It has been shown that a high ratio of fibrinogen:RBC improves the survival of trauma patients. Application of a ROTEM-based coagulation management concept using fibrinogen concentrate and prothrombin complex concentrate may reduce transfusion and may have a positive effect on survival.
Austrian guidelines: Coagulation management in trauma-related, massive bleeding
ESA 09: Industrial satellite symposium
Sibylle Kozek-Langenecker
Professor and Chairwoman, Department of Anaesthesia and Intensive Care, Evangelisches Krankenhaus Vienna, Vienna Austria
Objectives of the new Austrian
guidelines for trauma-related bleeding management include the
restriction of allogeneic blood products, consideration of the
cell-based model of haemostasis, the use of point-of-care coagulation
monitoring and of effective coagulation factor concentrates. E.g.,
measurement and correction of fibrinogen concentration < 1,5-2 g/l
and/or diminished fibrin polymerization in the thrombelastometric
FIBTEM assay is recommended in bleeding trauma patients. If FFP is
used in massive coagulopathic bleeding about 30 ml/kg BW is required.
External and internal quality assurance for Rotational Thrombelastometry: Establishing quality management for Rotational Thrombelastometry - the process and helpful documents
Landshut 2009 - Rotational Thrombelastometry Expert Meeting
Andrea Dick
Klinikum der Universität München, München - Germany
Thromboelastometry is a whole-blood point of care method of coagulation assessment with proven usefulness in the perioperative setting. Quality management for thromboelastometry includes: operational integrity of the instrument, internal quality assurance and external quality assurance. The following features contribute to operational integrity: measurement principle, very low inter-channel imprecision, automatic pipetting, constant verification, solid state temperature control, etc. The internal quality assurance depends on pre-analytical factors, regular functional check of the pipette, and regular use of internal control samples. External quality assurance is challenged by a lack of a standardized control material identical to the material used in clinical application (e.g. whole blood).
Reduction in blood transfusions and cost saving by ROTEM
Landshut 2009 - Rotational Thrombelastometry Expert Meeting
Klaus Görlinger
Universitaetsklinikum Essen, Essen - Germany
Massive haemorrhage is a leading cause of death in trauma patients after hospital admission. Algorithms implementing coagulation monitoring at the point of care and goal-directed coagulation therapy based on coagulation factor concentrates permit reductions in allogeneic blood transfusion requirements in patients with severe bleeding and significant cost savings. Dr. Goerlinger presents the perioperative bleeding management driven by physiology at the University Hospital Essen in Germany.
Thromboelastometry - Evidence based medicine, guidelines, consensus, current status and future perspectives
Landshut 2009 - Rotational Thrombelastometry Expert Meeting
Benny Soerensen
Centre for Haemophilia and Thrombosis, Guy's and St. Thomas' NHS Foundation Trust and Kings College London School of Medicine, London, UK
Guidelines for the application of thromboelastometry in the clinical context should be based on knowledge gained from evidence-based medicine. A strategy of coagulation management based on an array of specific thromboelastometric tests to identify and treat individual coagulation disturbances has shown a substantial reduction in the transfusion of allogeneic blood products, in contrast to a strategy based on a single thrombelastographic test, which resulted in an increase in transfusion. Application of any algorithm should aim at reducing mortality, reducing the unnecessary use of allogeneic blood products, supporting a rational haemostatic intervention, optimizing health economics, and improving medical practice. Specific algorithms for cardiac surgery, non-cardiac surgery, and trauma have been developed with these aims in mid.
Hyperfibrinolysis in clinical practice
Landshut 2009 - Rotational Thrombelastometry Expert Meeting
Herbert Schöchl
UKH Salzburg, Salzburg - Austria
The key molecule of fibrinolysis is plasmin, with plasminogen as the precursor. Plasmin has the following functions: it cleaves fibrin and fibrinogen, resulting in the release of their degradation products, and it reduces platelet adhesion and aggregation by degradation of GP Ib and GP IIbIIIa. The main fibrinolysis activators are t-PA (tissue plasminogen activator) and u-Pa (urokinase plasminogen activator). The main fibrinolysis inhibitors are TAFI (thrombin-activated fibrinolysis inhibitor), PAI-1, and alpha2-antiplasmin. The risk factors for hyperfibinolysis include: hypoxia, trauma or surgery of organs containing t-PA, liver transplantation, extracorporeal circulation, hypo/hyperthermia, and iatrogenic factors such as fibrinolytic therapy, and SD plasma.
Patient Blood Management: An urgent need for change
Landshut 2009 - Rotational Thrombelastometry Expert Meeting
Donat R. Spahn
Universitaetsspital Zuerich, Zuerich - Switzerland
In recent years, it has become evident that RBC, FFP, and platelet transfusions are associated with a major adverse outcome, including increased mortality, major morbidity, risk of infection, TRALI, TACO, and so on. These findings have been obtained in different settings, such as cardiac surgery, trauma, liver transplantation, intensive care medicine, and orthopaedic surgery. Also, the costs associated with transfusion are higher than expected, because there are hidden costs which can only be identified by means of thorough process cost analysis. Patient blood management is a concept that includes the correction of preoperative anaemia, reduction in perioperative blood loss, and the optimization of anaemia management.
ALI, TRALI or TACO?
NATA 10th annual symposium
Ognjen Gajic
Rochester, MN, USA
The current description of TRALI includes an ARDS-like picture within one to 2 hours of transfusion (90% of cases within two hours), cyanosis, cough, pulmonary whiteout, absence of left atrial hypertension and transient leucopenia. The principal differential diagnosis is TACO, in which signs of fluid overload and congestive heart failure are usually present before transfusion. In TACO, prompt volume reduction with diuresis usually results in rapid improvement of the clinical status. Several algorithms have been developed to ease the differential diagnosis between the two transfusion related complications. Furthermore, the diagnosis of "possible TRALI" has been introduced to define acute lung injury in the presence of other ARDS risk factors.
Implementing Transfusion Practice Guidelines - The Austrian Way
NATA 10th annual symposium
Hans Gombotz
Linz, Austria
Regarding the gap between best practice and actual clinical care, current scientific evidence suggests that patients often do not receive therapy or receive inadequate or even harmful therapy. The Austrian Benchmark Study aimed at finding measures to optimise the use of blood components in selected surgical procedures in Austrian hospitals. The study showed that more than 60% of blood units were ordered but not transfused and that the prevalence of anaemia in patients undergoing elective surgery was high. Furthermore, the study showed that there was high variability in transfusion practice between centres.
How to implement Practice Guidelines
NATA 10th annual symposium
Hub Wollersheim
Nijrnegen, the Netherlands
Regarding the application of practice guidelines, it has been observed that evidence, best (safe) practices and new innovations or technologies are sometimes not used at all, or only used after a long lag time. Numerous reasons have been put forward by clinicians to explain the lack of adherence to guidelines. The consequences of low/no adherence to guidelines may become manifest through unexplained variations in otherwise standardized interventions, suboptimal care, and harm to the patient. The response to the introduction of improvements of technology into practice has been statistically described: there are innovators, early adopters, early majority, late majority, and laggards. A series of implementation strategies have been developed to support guideline implementation.
Fresh Frozen Plasma: Should We Be Using More or Less?
NATA 10th annual symposium
Jean-Francois Hardy
Centre Hospitalier de l'Universite de Montreal, Montreal - Canada
Unlike in elective surgery, in trauma tissue damage is massive and uncontrolled, initiation of transfusion may be late, hypovolaemia, shock and acidosis are present, temperature is not controlled, monitoring of haemostasis is late, and very often microvascular bleeding occurs. Activated protein C, and hyperfibrinolysis are considered to be among the causes of microvascular bleeding. The basic theoretical management of the bleeding patient includes correction of hypothermia, transfusion of RBC to correct haematocrit, transfusion of FFP to correct prolonged PT/aPTT and low fibrinogen concentration, transfusion of platelets to correct platelet count and function; however, the optimal ratio and dose of allogeneic blood products is not clear so far.
Transfusion-Associated Immune Modulation
NATA 10th annual symposium
Hans Jorgen Nielsen
Hvidovre, Denmark
Transfusion-related immune modulation (TRIMM) often occurs in patients with major surgery or trauma. Occurrence of TRIMM must be analysed from three perspectives: bacterial load, environment (level of training of the surgeon), and host defence. Impaired immune competence may already be present preoperatively in patients with solid tumours, trauma, current infections, large bowel perforation, alcohol abuse, genetic polymorphism. Intra- and postoperative factors like major surgery and perioperative blood transfusion add to the impairment. The impaired immune response may be detrimental for patients undergoing operations with high risk of contamination (large bowel surgery, posttrauma surgery, surgery on open fractures), while it may have a minor impact in non-contaminated surgery (e.g. primary hip/knee replacement).
Emerging Transfusion-Transmitted Infections - Role of Pathogen Inactivation
NATA 10th annual symposium
Rainer Moog
Essen, Germany
Although the risks of blood transfusion have decreased in recent years, one must remember that there is no zero risk with biological products. Current acknowledged risks include: bacterial infection, limitations in routine screening, transmission of new and emerging pathogens, and transfusion of leukocytes. Among the transfusion-transmitted pathogens are, for instance, viruses (e.g. the Chikungunya virus, transmitted by the Aedes mosquito, the West Nile virus), protozoa (e.g Babesia), prions (e.g. variant Creutzfeld Jacob disease). The risk of bacterial contamination exists not only with platelet concentrates, but also with RBC and plasma products. Bacterial screening of platelet concentrates, and pathogen inactivation are among the measures that may be taken to avoid contamination.
Insights into the BART Trial
NATA 10th annual symposium
Dean A. Fergusson
University of Ottawa, Centre for Transfusion Research, Ottawa - Canada
The BART study investigated the effect of aprotinin in decreasing massive postoperative bleeding postoperatively in comparison with epsilon-aminocaproic acid or tranexamic acid. The study included cardiac surgical patients at high risk of death, massive haemorrhage and life-threatening complications. The study was terminated because an increase in all-cause mortality in the aprotinin group was observed. The BART study was the first in history to investigate additional parameters to massive bleeding: the secondary endpoints were represented by fatal/life-threatening events and serious morbidity. The findings appear consistent with data presented in the literature.
Fibrinogen and Prothrombin Complex Concentrate for the Management of Massive Bleeding
NATA 10th annual symposium
Petra Innerhofer
Innsbruck, Austria
Haemorrhage is a major cause of death in trauma patients, in which a "lethal triad" consisting of coagulopathy, hypothermia and acidosis may be observed. New coagulation monitoring devices like ROTEM have changed the coagulation management practice in trauma patients. The ROTEM device rapidly provides a graphical display of the coagulation process and enables differential diagnosis and immediate and targeted therapy. The main cause of trauma-induced coagulopathy is bleeding resulting in the loss of the main components of the coagulation system. FFP transfusion appears to have limited efficacy in correcting haemodilution. Fibrinogen concentrate administration improves clot firmness and corrects bleeding. For improvement of thrombin generation, PCC formulations can be considered.
Effects of Colloids on Bleeding in Major Surgery
NATA 10th annual symposium
Sibylle Kozek-Langenecker
Professor and Chairwoman, Department of Anaesthesia and Intensive Care, Evangelisches Krankenhaus Vienna, Vienna Austria
Fluid therapy is mandatory in severe bleeding in order to stabilize macro- and microcirculation but fluid-specific antithrombotic effects may aggravate perioperative blood loss. Dilutional coagulopathy is dependent upon the type of the fluid and its dose which, in turn, is determined by the initial volume expanding capacity. Hydroxyethylstarches (HES) are widely used for colloidal volume expansion. Mixed anticoagulant and anti-platelet effects of HES is lowest for 3rd generation tetrastarch due to its rapid degradability in vivo. Tetrastarch significantly reduced blood loss and red blood cell transfusion requirements compared to 2nd generation pentastarch.
Fresh frozen plasma vs prothrombin complex concentrates: where is the evidence?
ISICEM 2009: Perioperative bleeding management: new approaches - improving outcomes
Pratima Chowdary
The KD Haemophilia Centre & Thrombosis Unit, Royal Free Hospital, London, UK
Platelet diagnostic in perioperative bleeding
3rd International Coagulation Course 2008
Management in perioperative bleeding complications
Sibylle Kozek-Langenecker
Professor and Chairwoman, Department of Anaesthesia and Intensive Care, Evangelisches Krankenhaus Vienna, Vienna Austria
In the periperative setting, platelet
diagnostics has following indications: positive bleeding
history (inherited or acquired platelet defect; antiplatelet
medication); extracorporeal circulation; unclear
intra-/postoperative bleeding (after normal first-level tests; in
the presence of factors that affect platelet function,
e.g. colloids). New POC methods for platelet function assessment are
available: Multiplate® (sensitive to COX-1 inhibitors and
ADP-receptor antagonists; predictive of bleeding in cardiac
surgery); PFA-100TM and Ultegra (sensitive to COX-1 inhibitors and
GPIIbIIIa inhibitors); PlateletMapping Assay® (sensitive to COX-1
inhibitors and ADP-receptor antagonists). Following perioperative
haemostatic interventions may be considered for improving platelet
function: platelet concentrates, DDAVP, rFVIIa, fibrinogen
concentrate, and antifibrinolytics.
Allogeneic Blood Products
3rd International Coagulation Course 2008
Management in perioperative bleeding complications
Donat R. Spahn
Universitaetsspital Zuerich, Zuerich - Switzerland
Transfusion of allogeneic blood products is
associated with adverse effects, adverse outcome, questionable
efficacy and high costs. The main adverse effects include: acute
reactions, AB0 mistransfusions, transmission of infectious diseases,
immunosuppression resulting in increased cancer recurrence and
increased postoperative infections, transfusion-related acute lung
injury TRALI and transfusion-related circulatory overload
TACO. TRALI, defined as non-cardiogenic pulmonary edema, hypoxemia,
onset within 6h or transfusion and symptoms that include dyspnea,
fever, tachycardia and hypotension, represents the leading cause of
transfusion-associated mortality. The adverse effect on outcome is
represented by an increase in mortality and major morbidity,
observed in various settings like intensive care unit, cardiology
and cardiac surgery.
Hemostatic Therapy in Cardiac Surgery
3rd International Coagulation Course 2008
Management in perioperative bleeding complications
Kenichi Tanaka
Division of Cardiothoracic Anaesthesia, Emory University School of Medicine
For the therapy of major bleeding in cardiac
surgery, following aspects are of importance: haemostatic therapy is
performed at the end of cardio-pulmonary bypass (CPB); haemostasis
needs to occur fast; thromboembolic complications need to be
avoided. Efficacious haemostasis requires sufficient thrombin
generation and sufficient coagulation substrate, while the avoidance
of thrombotic complications requires sufficient antithrombin
activity. The fibrinogen deficit observed after long CPB may be
corrected by administration of fibrinogen concentrate. This
therapeutic approach has been shown to reduce transfusion of
allogeneic blood products in aortic surgery. Fibrin is known as
antithrombin I because it acts by sequestering thrombin in the clot;
therefore, sufficient fibrin formation may also help avoid
thrombotic complications.
Anamnesis/what predicts bleeding?
3rd International Coagulation Course 2008
Management in perioperative bleeding complications
Georg Pfanner
LKH Feldkirch, Feldkirch - Austria
Perioperative bleeding is a feared
complication of surgery. The golden standard of preoperative
coagulation screening includes prothrombin time PT, activated
partial thromboplastin time aPTT, and platelet count. As
preoperative PT and aPTT do not provide additional information to
the bleeding history, do not predict bleeding and do not appear
cost-effective, for surgical interventions like tonsillectomy the
bleeding history may be more relevant than the standard coagulation
screening. A practical concept for the preoperative identification
of patients with impaired primary haemostasis based mainly on a
standardized questionnaire has been developed. The concept ensured
the satisfactory detection of impaired haemostasis and was
associated with a significant costs reduction.
New coagulation models
3rd International Coagulation Course 2008
Management in perioperativebleeding complications
Fabio Barros
Hospital Portugues de Beneficencia em Pernambuco e Recife, Pernambuco - Brazil
In the recent years, the traditional
Y-shaped cascade coagulation model has been replaced by a cell-based
(C-based) coagulation model. The C-based model emphasizes the roles
played by tissue factor-bearing cells and by platelets. In this model,
initial formation of a small amount of thrombin is generated by the
binding of circulating activated FVII to tissue factor at the injury
site/on the surface of tissue factor bearing cells (initiation
phase). Thrombin activates FVIII, FV and circulating platelets
(amplification phase). Finally, the formation of a high amount of
thrombin occurs on the surface of the activated platelets (propagation
phase), and transformation of fibrinogen into fibrin occurs.
Thrombelastography / -metry: Risk assurance
3rd International Coagulation Course 2008
Management in perioperative bleeding complications
Michael Spannagl
Klinikum der Universität München, Munich - Germany
Since whole blood clot formation is not
quantified by the standard coagulation tests, methods like
thrombelastography/thromboelastometry have been developed for the
concomitant assessment of many aspects of coagulation, including the
effects of platelets, fibrinogen and FXIII, coagulation factors and
fibrinolysis. Thromboelastometry (ROTEM) measures coagulation by
registering the viscoelastic changes of the blood pipetted into a
fixed cup in which a rotating plastic pin is immersed. Use of
thrombelastography/thromboelastometry in various settings like ICU,
trauma surgery, and cardiac surgery has been associated with a
reduction of allogeneic blood products transfusion and of the
associated costs. For the adequate application of these methods, a
quality management system appears necessary.
Thrombin generation basics: different methods
3rd International Coagulation Course 2008
Management in perioperative bleeding complications
Benny Soerensen
Centre for Haemophilia and Thrombosis, Guy's and St. Thomas' NHS Foundation Trust and Kings College London School of Medicine, London, UK
Thrombin generation may be considered to
represent "the momentum" of the haemostatic system. Thrombin activates
FVIII to FVIIIa (component of the "intrinsic tenase"), FV to FVa
(component of the "prothrombinase") and circulating platelets. The lag
time of thrombin generation is primarily defined by levels of free
tissue factor, tissue factor pathway inhibitor, free protein S, FVII,
FIX and fibrinogen. Prothrombin appears to be one of the most
important determinants of the thrombin potential. Direct
quantification of thrombin generation is possible through continuous
fluorometry and through subsampling and measurement of
TAT-complexes. Furthermore, thromboelastometry may constitute a
surrogate measure of thrombin generation.
Diagnosis of hyperfibrinolysis in the peri-operative setting: which test(s) should we use?
3rd International Coagulation Course 2008
Management in perioperative bleeding complications
Cedric Hermans
St-Luc University Hospital, Hemophilia Clinic, Brussels - Belgium
Fibrinolysis results into the destruction
of the blood clot, but it also plays an important role in vessel
wound repair and remodeling and in angiogenesis. The main
fibrinolytic enzyme is represented by plasmin; its formation from
the precursor plasminogen is induced by t-PA and
pro-urokinase/urokinase. The fibrinolytic process is controlled by
PAI1 (t-PA inhibitor) and by alpha2-antiplasmin (plasmin inhibitor).
The presence of D-dimers in circulation reflects the formation of
the fibrin network and its degradation by plasmin. For the diagnosis
of hyperfibrinolisis, following main tests may be considered:
Eugobulin Lysis Time, D-Dimers, and thromboelastometry ROTEM (APTEM
test).
Hemostatic Drugs (DDAVP, rVIIa, Tranexamic acid, Aprotinin)
3rd International Coagulation Course 2008
Management in perioperative bleeding complications
Marcel Levi
Academic Medical Center Amsterdam, Amsterdam - The Netherlands
In the medical setting, surgery remains the
most common cause of major bleeding. The pro-haemostatic
interventions are aimed at correcting the coagulopathy while
avoiding the risk of thrombosis. The pro-haemostatic drugs may
intervene at different levels of the haemostatic system. Improvement
of primary haemostasis may be achieved by administering DDAVP that
causes release of von Willebrand factor multimers. Anti-fibrinolytic
agents like lysine analogues act on the precursor of plasmin and may
correct the hyperfibrinolytic tendency and consequently decrease
bleeding and transfusion requirements. Stimulation of thrombin
generation may be obtained with rFVIIa for congenital bleeding
disorders like haemophilia.
Update on TRALI
3rd International Coagulation Course 2008
Management in perioperativebleeding complications
Jonathan P. Wallis
Freeman Hospital, Newcastle upon Tyne - UK
TRALI was first described in 1950 as
severe illness with immediate faintness, chills, fever, hypotension,
severe tachypnoea and dyspnoea that followed the injection of 50ml of
plasma. The mechanism of TRALI involves donor antibodies reacting with
recipient leukocytes that aggregate in pulmonary capillaries, and
secrete cytokines and chemokines damaging the endothelial
cells. Alternative mechanism: anti-class I antibodies bind to
endothelial cells, and neutrophils bind to the antibodies via Fc
receptors. TRALI is an important cause of pulmonary injury or death in
transfused patients. Possible solutions to avoid/decrease TRALI
include: reduction of plasma, use of pooled viricidally-treated
plasma, antibody screening of donors, and transfusion of FFP obtained
only from male donors.
Emergency anticoagulant reversal
3rd International Coagulation Course 2008
Management in perioperative bleeding complications
Bernard Vigue
Centre hospitalier de Bicetre, Le Kremlin Bicetre cedex - France
Although anticoagulant therapy has become
very common, the management of anticoagulation is still
problematic. Adherence to the management guidelines is limited and
the therapy-related haemorrhagic events may be
underestimated. Vitamin K antagonists decrease the risk of
thrombotic events in patients with cardiac valves, auricular
fibrillation, phlebitis and pulmonary embolism. Anticoagulation
reversal is indicated in patients with life-threatening
bleeding. Once the diagnosis is confirmed, administration of
haemostatic agents that contain the four coagulation factors
affected by the vitamin K antagonists (FII, FVII, FIX and FX) is
necessary. Unlike fresh frozen plasma FFP, prothrombin complex
concentrate PCC has shown ease of use, improved efficacy and
promptness of anticoagulation reversal.
FFP vs. PCC - Where is the Evidence?
3rd International Coagulation Course 2008
Management in perioperative bleeding complications
Pratima Chowdary
Royal Free NHS Trust, London - UK
Administration of haemostatic medication
in congenital and acquired bleeding disorders aims at preventing
intra-operative and postoperative bleeding, and thus at promoting
wound healing. In vivo recovery is defined as the relation between the
increase in the concentration of individual coagulation factors after
the administration of haemostatic therapy and the dose
administered. Both FFP and PCC have been used to correct the
coagulopathy of critical illness and liver disease, as well as
prophylactically pre-procedures, and for treating bleeding in liver
transplantation. The peripheral indices of coagulation (PT, aPTT,
platelet count) may be unreliable for guiding bleeding therapy in this
setting.
PCC in the peri-operative setting
3rd International Coagulation Course 2008
Management in perioperative bleeding complications
Klaus Görlinger
Universitaetsklinikum Essen, Essen - Germany
Prothrombin complex concentrates (PCC) are
purified coagulation factor concentrates containing FII, FVII, FIX,
FX, as well as proteins C, S and Z, antithrombin and heparin. PCC is
effective in the rapid reversal of oral anticoagulation (Warfarin,
Phenprocoumon, Marcoumar). PCC can be used for acute bleeding
therapy in patients with severe liver damage or liver failure. In
contrast to fresh frozen plasma (FFP), PCC may quickly increase
coagulation factors concentration without the risk of volume
overload (TACO), TRALI, viral transmission, or mistransfusion.
Administration of PCC can be guided by coagulation measurements like
ACT, PT, INR, Quick time, and thromboelastometry (ROTEM).
Fibrinogen concentrate in thrombocytopenia
2nd International Coagulation Course 2007
Management in perioperative bleeding complications
Dietmar Fries
Medizinische Universität Innsbruck, Innsbruck - Austria
In cardiac surgery, platelets count is
influenced by CPB duration, re-do, transfused cell-saver blood,
etc. In other settings, haemodilution plays a major role, with
fibrinogen concentration being the first to reach a critical level,
while platelet count reaches a critical level much later
on. Platelet concentrates transfusion should be avoided because of
unpredictable efficacy, viral/bacterial infection, immunologic
reactions. High fibrinogen concentration has proven protective of
bleeding in obstetrics, cardiac/neurosurgery. In swine
thrombocytopaenia model, fibrinogen concentrate showed significantly
higher efficacy in improving clot quality that platelet
concentrates. Fibrinogen concentrate may compensate low platelet
count and help avoid platelet concentrates transfusion.
Dilutional coagulopathy
2nd International Coagulation Course 2007
Management in perioperative bleeding complications
Petra Innerhofer
Medizinische Universität Innsbruck, Innsbruck - Austria
Haemodilution is part of a vicious
circle initiated by blood loss that leads to hypovolemia requiring
volume replacement. Correction of the volume leads to a decrease in
haematocrit and to dilution coagulopathy. Haematocrit influences
significantly platelets' adhesion and has an important impact on the
bleeding time. Many in vitro studies showed that colloids
(DEX>HES>GEL>Albumin) impair the thromboelastometry/graphy parameters
more than crystalloids. Furthermore, with regard to HES, gelatin and
crystalloids, fibrin polymerization appears to be the main
problem. Clinical studies during blood loss have shown that the
routine coagulation tests are poor predictors of bleeding and that the
fibrinogen deficiency is the first to occur with ongoing bleeding.
New Aspects in Diagnosis of Perioperative Coagulopathy
2nd International Coagulation Course 2007
Management in perioperative bleeding complications
Thomas Lang
Werlhof-Institut, Hannover - Germany
The methods of assessment of coagulation
need to address following aspects: primary haemostasis, thrombin
generation, clot formation and clot lysis. Thromboelastometry ROTEM
is a whole blood method used to obtain information on most of these
aspects. It measures the changes in the amplitude of rotation of a
pin immersed in a plastic cup containing the blood sample. The
rotation is progressively impeded by the fibrin strands forming
between the cup and the pin. The method assesses the rapidity of
initiation of fibrin formation, the dynamic interaction between
platelets and fibrinogen, as well as the stability of the blood
clot.
What compromises coagulation in trauma: Basics and diagnostics
2nd International Coagulation Course 2007
Management in perioperative bleeding complications
Herbert Schöchl
UKH Salzburg, Salzburg - Austria
Uncontrolled haemorrhage is the leading
cause of death in trauma patients. Acute traumatic coagulopathy may
be detected upon admission in the ER. It reflects the severity of
the tissue damage, it is not related to fluid administration and it
has a prognostic value for the patient's survival. Acute traumatic
coagulopathy is the result of bleeding, dilution,
consumption, (hyper)fibrinolysis, acidosis and hypothermia. Standard
coagulation tests do not appear advantageous for coagulation
monitoring in trauma patients because they are too time consuming
and reflect too little of the trauma coagulopathy. In contrast,
viscoelastic methods like thromboelastometry ROTEM provide fast
clinically relevant information on this complex blood clotting
disorder.
Thromboelastometry/Thromboelastography vs. standard laboratory tests in the perioperative setting
2nd International Coagulation Course 2007
Management in perioperative bleeding complications
Benny Soerensen
Centre for Haemophilia and Thrombosis, Guy's and St. Thomas' NHS Foundation Trust and Kings College London School of Medicine, London, UK
In the management of perioperative
bleeding specific challenges are raised: identifying whether the
source of bleeding is surgical or coagulopathic, using the correct
coagulation tests to identify fast and correctly the coagulation
disturbance, tailoring the optimal haemostatic intervention according
to the patient's acute needs. The standard coagulation analyses
include ACT, APTT, INR, fibrinogen, and platelet count. Continuous
thrombin generation analyses include measurement of thrombin
generation in plasma and in platelet-rich plasma, while
thrombelastography is used for continuous whole blood coagulation
measurement. For all these methods, the advantages and the
disadvantages need to be weighed separately.
