Coagulopaty in associated with massive transfusion

Massive hemorrhage is a formidable challenge for anesthesia care providers in the elective setting and poses even greater potential challenges in the trauma setting. In all this cases, the anesthesia care providers are faced with large-volume resuscitations that typically start with crystalloid and colloid and rapidly progress to blood and blood products. These large-volume replacement may cause coagulopathy, which can be difficult to manage in the setting of ongoing blood loss. Coagulopathy associated with massive transfusion is multifactorial event that results from hemodilution, hypothermia, the use of fractionated blood products and disseminated intravascular coagulation. Maintaining a normal body temperature is a first-line, effective strategy to improve hemostasis during massive transfusion. Treatment strategies include the maintenance of adequate tissue perfusion, the corection of anemia, and the use of hemostatic blood products.     

Massive transfusion and coagulopathy: pathophysiology and implications for clinical management

Purpose

To review the pathophysiology of coagulopathy in massively transfused, adult and previously hemostatically competent patients in both elective surgical and trauma settings, and to recommend the most appropriate treatment strategies.

Methods

Medline was searched for articles on “massive transfusion,” “transfusion,” “trauma,” “surgery,” “coagulopathy” and “hemostatic defects.” A group of experts reviewed the findings.

Principal findings

Coagulopathy will result from hemodilution, hypothermia, the use of fractionated blood products and disseminated intravascular coagulation. The clinical significance of the effects of hydroxyethyl starch solutions on hemostasis remains unclear. Maintaining a normal body temperature is a first-line, effective strategy to improve hemostasis during massive transfusion. Red cells play an important role in coagulation and hematocrits higher than 30% may be required to sustain hemostasis. In elective surgery patients, a decrease in fibrinogen concentration is observed initially while thrombocytopenia is a late occurrence. In trauma patients, tissue trauma, shock, tissue anoxia and hypothermia contribute to the development of disseminated intravascular coagulation and microvascular bleeding. The use of platelets and/or fresh frozen plasma should depend on clinical judgment as well as the results of coagulation testing and should be used mainly to treat a clinical coagulopathy.

Conclusions

Coagulopathy associated with massive transfusion remains an important clinical problem. It is an intricate, multifactorial and multicellular event. Treatment strategies include the maintenance of adequate tissue perfusion, the correction of hypothermia and anemia, and the use of hemostatic blood products to correct microvascular bleeding.

Objectif

Revoir la physiopathologie de la coagulopathie chez les adultes transfusés massivement et auparavant compétents sur le plan hémostatique, à la fois dans le contexte ďune intervention chirurgicale réglée ou à la suite ďun traumatisme. Recommander les stratégies thérapeutiques les plus appropriées.

Méthode

Dans Medline, nous avons cherché les articles traitant de “massive transfusion,” “transfusion,” “trauma,” “surgery,”“coagulopathy” et “hemostatic defects.” Un groupe ďexperts a examiné les résultats.

Constatations principales

La coagulopathie résulte de ľhémodilution, ľhypothermie, ľusage de produits sanguins fractionnés et la coagulation intravasculaire disséminée. La portée clinique des effets des solutions ďhydroxyéthyl-amidon sur ľhémostase n’est toujours pas claire. Le maintien ďune température corporelle normale est une stratégie de première intention efficace pour améliorer ľhémostase pendant la transfusion massive. Les globules rouges sont importants dans la coagulation et des hématocrites supérieurs è 30 % pourraient être nécessaires à une hémostase adéquate. Chez les patients en chirurgie réglée, une baisse de la concentration de fibrinogène est observée précocement tandis que la thrombocytopénie est plus tardive. Chez les traumatisés, le trauma tissulaire, le choc, ľanoxie et ľhypothermie tissulaires contribuent au développement ďune coagulation intravasculaire disséminée et du saignement microvasculaire. Ľutilisation de plaquettes et/ou de plasma frais congelé dépendra du jugement du clinicien ainsi que des résultats des tests de coagulation. La transfusion devra surtout viser le traitement ďune coagulopathie clinique (saignement microvasculaire).

Conclusion

La coagulopathie associée à la transfusion massive demeure un important problème clinique. C’est un événement complexe, multifactoriel et multicellulaire. Le traitement comprend le maintien ďune perfusion tissulaire adéquate, la correction de ľhypothermie et de ľanémie et ľusage de produits sanguins hémo-statiques pour corriger le saignement microvasculaire.

     

Trauma, shock, and disseminated intravascular coagulation: lessons from the classical literature

A trauma patient's survival depends on the ability to control 2 opposing conditions, bleeding at the early phase and thrombosis at a late phase of trauma. The mixed existence of physiological responses for hemostasis and wound healing and pathological hemostatic responses makes it difficult to understand the mechanisms of the 2 stages of coagulopathy after trauma. Traumatic coagulopathy is multifactorial but disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype is the predominant and initiative pathogenesis of coagulopathy at the early stage of trauma. High levels of inflammatory cytokines and severe tissue injuries activate the tissue-factor-dependent coagulation pathway followed by massive thrombin generation and its activation. Low levels of protein C and antithrombin induce insufficient coagulation control and the inhibition of the anticoagulation pathway. Primary and secondary fibrin(ogen)olysis is highly activated by the shock-induced tissue hypoxia and disseminated fibrin formation, respectively. Consumption coagulopathy and severe bleeding are subsequently observed in trauma patients. Persistently high levels of plasminogen activator inhibitor-1 expressed in the platelets and endothelium then change the DIC with the fibrinolytic phenotype into the thrombotic phenotype at approximately 24 to 48 hours after the onset of trauma. All of these changes coincide with the definition of DIC, which can be clearly distinguished from normal responses for hemostasis and wound healing by using sensitive molecular markers and DIC diagnostic criteria such as those outlined by the Japanese Association for Acute Medicine and the International Society on Thrombosis and Haemostasis. Treatments of DIC with the fibrinolytic phenotype involve the surgical repair of the trauma, improvement of shock, and the rapid and sufficient replacement of platelet concentrate, fresh frozen plasma, and depleted coagulation factors. The administration of an antifibrinolytic agent (tranexamic acid) may reduce the risk of death in bleeding trauma patients associated with this type of DIC.     

Are we giving enough coagulation factors during major trauma resuscitation?

Hemorrhage is a major cause of trauma deaths. Coagulopathy exacerbates hemorrhage and is commonly seen during major trauma resuscitation, suggesting that current practice of coagulation factor transfusion is inadequate. Reversal of coagulopathy involves normalization of body temperature, elimination of the causes of disseminated intravascular coagulation (DIC), and transfusion with fresh-frozen plasma (FFP), platelets, and cryoprecipitate. Transfusion should be guided by clinical factors and laboratory results. However, in major trauma, clinical signs may be obscured and various factors conspire to make it difficult to provide the best transfusion therapy. Existing empiric transfusion strategies for, and prevailing teachings on, FFP transfusion appear to be based on old studies involving elective patients transfused with whole blood and may not be applicable to trauma patients in the era of transfusion with packed red blood cells (PRBCs). Perpetuation of such concepts is in part responsible for the common finding of refractory coagulopathy in major trauma patients today. In this review, we argue that coagulopathy can best be avoided or reversed when severe trauma victims are transfused with at least the equivalent of whole blood in a timely fashion.     

Monitoring of Perioperative Dilutional Coagulopathy Using the ROTEM Analyzer: Basic Principles and Clinical Examples

Recent changes in quality of transfusion supply, transfusion triggers as well as fluid therapy promote the development of dilutional coagulopathy. Nevertheless, up to now guidelines generally assume presence of hypocoagulability when more than one individual circulating blood volume is lost. This might be true for some patients under some conditions but is not necessarily true for every patient. Routine coagulation tests are insufficient in predicting increased bleeding and, moreover, available after an unacceptable time delay. Therefore the occurrence of diffuse microvascular bleeding is often used as clinical sign to start hemostatic therapy. However, such severe derangement of hemostasis might lead to the development of secondary tissue damage and frequently is unresponsive to conventional treatment. Coagulopathy occurring during extensive surgery or after polytrauma can be detected and treated early when using the ROTEM monitoring. Recent data showing a direct beneficial effect of hemostatic therapy on blood loss and final outcome are scarce. However, evidence exists that the amount of blood loss, presence of coagulopathy and number of transfusions needed are associated with poor outcome in bleeding patients. Although manifold articles have been published already using thrombelastography for various indications (medline research "thrombelastography", 2022 articles), further data are needed to confirm the clinical experience that this technique is an excellent tool for safe patient management.     

Massive hemorrhage and mechanisms of coagulopathy in trauma

Trauma is disease of the young, mainly affecting people between 15-40 years of age. Uncontrolled massive bleeding is the leading cause of early in-hospital mortality, within 48h of admission, and the second leading cause of prehospital death in victims of both military and civilian trauma, accounting for 40-45% of the total fatalities. Coagulopathy develops early after injury and is present in 25-36% of trauma victims upon admission to the emergency department. Coagulopathy correlates to the severity of trauma and is associated with an increased risk of mortality. The aim of this paper is to explain pathophysiology of developing coagulopathy in trauma. The coagulopathy in the trauma patient is complex and multifactorial. It includes: dilutional coagulopathy, hypothermia, acidosis, hyperfibrinolysis, anemia and consumption coagulopathy. When the patient develops the so called "lethal triad" of hypothermia, acidosis and coagulopathy, surgical restoration of vascular integrity may be insufficient to achieve a deffinitive control of blood loss and non-mechanical bleeding from small vessels, usually terminated by spontaneous coagulation, becomes a life-threatening condition.     

Massive transfusion in the trauma patient: Continuing Professional Development

Purpose

Massive transfusion has recently been given a dynamic definition, namely, the replacement of more than four red cell concentrates within an hour. The purpose of this continuing professional development module is to review the pathophysiology of hemorrhagic shock in the trauma patient and the current management strategies of the massively bleeding trauma patient.

Principal findings

The massively bleeding trauma patient requires concurrent hemorrhage control and blood replacement therapy. Although there are many complications of massive transfusions, such as acid-base disturbances, electrolyte abnormalities, and hypothermia, perhaps the most difficult aspect to manage is acute trauma coagulopathy. Historically, coagulopathy was attributed to dilution of coagulation factors; however, recent accumulated evidence indicates that it is a multifactorial process associated with hypoperfusion, factor consumption, and hyperfibrinolysis. In an attempt to minimize acute trauma coagulopathy, massive transfusion protocols with equal ratios of red cell concentrates, frozen plasma, and platelets have been proposed. This type of hemostatic resuscitation, with near equal ratios of blood and blood products, has improved survival, but it is not without risk. In addition to the rapid and effective restoration of blood volume, the specific goal of transfusion management should be to maintain the patient??s oxygen carrying capacity, hemostasis, and biochemistry.

Conclusion

The current literature does not permit firm conclusions to be drawn regarding optimal transfusion ratios. It remains appropriate, however, to devise a massive transfusion protocol at the institutional level that provides treating physicians with rapid delivery of a reasonable initial ratio of products. This would permit patient-centred management with an emphasis on surgical control of bleeding, maintenance of normothermia, avoidance of electrolyte abnormalities, acid-base balance, and the timely delivery of blood products.

Objectives

After reading this module, the reader should be able to:

1. Enumerate the complications associated with massive transfusion in the trauma context;
2. Understand how the coagulopathy present in the trauma patient differs from that seen in the elective setting;
3. Identify the modifications suggested by the recent literature for the management of massive transfusion in the trauma setting;
4. Appreciate the evidence for the institution of massive transfusion protocols.

     

A novel hemostatic agent: the potential role of recombinant activated factor VII (rFVIIa) in anesthetic practice.

PURPOSE: To review the role of recombinant factor VIIa in anesthetic practice. SOURCE: A review of the published literature. MAIN FINDINGS: The mechanism of action of rFVIIa suggests enhancement of hemostasis limited to the site of injury without systemic activation of the coagulation cascade. In addition to its indication for use in patients with hemophilia, use of rFVIIa for treatment of uncontrolled massive hemorrhage in various peroperative settings appears to be rational, safe, and effective. Published results suggest that in trauma patients rFVIIa may play a role as an adjunctive hemostatic measure in addition to surgical hemostatic techniques There is preliminary evidence that hemorrhagic complications (eg. epistaxis, vaginal bleeding) associated with profound thrombocytopenia can be reversed with rFVIIa even at platelet counts below 10,000 per microL. Various case reports outlining the successful treatment with recombinant factor VIIa of patents experiencing intractable bleeding after valve replacement surgery, and with severe hemorrhage during therapy with left ventricular assist device, indicate the potential therapeutic efficacy of this agent in cardiac surgical procedures. Additionally, rFVIIa has been used successfully for treatment of massive postoperative bleeding following general surgery. CONCLUSIONS: rFVIIa is a novel hemostatic agent that shows promise in non-hemophiliac patents of a significant therapeutic role in variety of coagulopathic and hemorrhagic conditions in clinical situations ranging from thrombocytopenia, disseminated intravascular coagulation and transfusion-related coagulopathy, as well as in patients experiencing massive blood loss undergoing orthotopic liver transplantation, cardiac, orthopedic and genitourinary surgery.     

Management of massive operative blood loss

Coagulopathy associated with massive operative blood loss is an intricate, multicellular and multifactorial event. Massive bleeding can either be anticipated (during major surgery with high risk of bleeding) or unexpected. Management requires preoperative risk evaluation and preoperative optimization (discontinuation or modification of anticoagulant drugs, prophylactic coagulation therapy). Intraoperatively, the causal diagnosis of the complex pathophysiology of massive bleeding requiring rapid and specific coagulation management is critical for the patient's outcome. Treatment and transfusion algorithms, based on repeated and timely point-of-care coagulation testing and on the clinical judgment, are to be encouraged. The time lapse for reporting results and insufficient identification of the hemostatic defect are obstacles for conventional laboratory coagulation tests. The evidence is growing that rotational thrombelastometry or modified thrombelastography are superior to routine laboratory tests in guiding intraoperative coagulation management. Specific platelet function tests may be of value in platelet-dependent bleeding associated e.g. with extracorporeal circulation, antiplatelet therapy, inherited or acquired platelet defects. Therapeutic approaches include the use of blood products (red cell concentrates, platelets, plasma), coagulation factor concentrates (fibrinogen, prothrombin complex, von Willebrand factor), pharmacological agents (antifibrinolytic drugs, desmopressin), and local factors (fibrin glue). The importance of normothermia, normovolemia, and homeostasis for hemostasis must not be overlooked. The present article reviews pathomechanisms of coagulopathy in massive bleeding, as well as routine laboratory tests and viscoelastic point-of-care hemostasis monitoring as the diagnostic basis for therapeutic interventions.     

Koagulopathie

Coagulopathy after trauma is a major cause for uncontrolled hemorrhage in trauma vicitims. Approximately 40% of trauma related deaths are attributed to or caused by exsanguination. Therefore the prevention of coagulopathy is regarded as the leading cause of avoidable death in these patients. Massive hemorrhage after trauma is usually caused by a combination of surgical and coagulopathic bleeding. Coagulopathic bleeding is multifactorial, including dilution and consumption of both platelets and coagulation factors, as well as dysfunction of the coagulation system. Because of the high mortality associated with hypothermia, acidosis and progressive coagulopathy, this vicious circle is often referred to as the lethal triad, potentially leading to exsanguination. To overcome this coagulopahty-related bleeding an empiric therapy is often instituted by replacing blood components. However, the use of transfusion of red blood cells has been shown to be associated with post-injury infection and multiple organ failure. In the management of mass bleeding it is therefore crucial to have a clear strategy to prevent coagulopathy and to minimize the need for blood transfusion.     

Coagulopathy in multiple trauma: new aspects of therapy

Coagulopathy after trauma is a major cause for uncontrolled hemorrhage in trauma victims. Approximately 40% of trauma related deaths are attributed to or caused by exsanguination. Therefore the prevention of coagulopathy is regarded as the leading cause of avoidable death in these patients. Massive hemorrhage after trauma is usually caused by a combination of surgical and coagulopathic bleeding. Coagulopathic bleeding is multifactorial, including dilution and consumption of both platelets and coagulation factors, as well as dysfunction of the coagulation system. Because of the high mortality associated with hypothermia, acidosis and progressive coagulopathy, this vicious circle is often referred to as the lethal triad, potentially leading to exsanguination. To overcome this coagulopahty-related bleeding an empiric therapy is often instituted by replacing blood components. However, the use of transfusion of red blood cells has been shown to be associated with post-injury infection and multiple organ failure. In the management of mass bleeding it is therefore crucial to have a clear strategy to prevent coagulopathy and to minimize the need for blood transfusion.     

Gerinnungsmanagement beim Polytrauma

Hemorrhage after traumatic injury results in coagulopathy which only worsens the situation. This coagulopathy is caused by depletion and dilution of clotting factors and platelets, increased fibrinolytic activity, hypothermia, metabolic changes and anemia. The effect of synthetic colloids used for compensating the blood loss, further aggravates the situation through their specific action on the hemostatic system. Bedside coagulation monitoring permits relevant impairment of the coagulation system to be detected very early and the efficacy of the hemostatic therapy to be controlled directly. Administration of fresh frozen plasma (FFP), platelet concentrates and antifibrinolytic agents is essential for restoring the impaired coagulation system in trauma patients. Clotting factor concentrates should be administered if coagulopathy is based on diagnosed depletion of clotting factors, if FFP is not available and if transfusion of FFP is insufficient to treat the coagulopathy. Recombined FVIIa is frequently employed during severe bleeding which could not be treated by conventional methods but the results of on-going clinical trials are not yet available.     

Hypothermie und die tödliche Triade

Hemorrhage is the second leading cause of death of trauma victims. The coagulopathy of trauma is characterized by non-surgical diffuse bleeding from serosal surfaces, mucosal lesions, wounds and vascular access sites which occur in combination with serious injury, acidosis, hypothermia, dilution/consumption and disseminated intravascular coagulation. Acidosis and hypothermia decisively impair the function of platelets and coagulation factors, as well as fibrin and thrombin generation. However, single coagulation factors are affected differently. As prophylaxis is easier than therapy, it should start as soon as possible and best at the scene of the accident. Active and passive (re-)warming to normothermia, at least above 35°C, limited crystalloid and colloidal volume replacement to reach a mean arterial pressure of ≥65 mmHg (hypotensive resuscitation), prevention and correction of acidosis to reach a pH above 7.2 or a BE less negative than -12.5, as well as early and sufficient administration of hemostatic drugs, first of all plasma, fibrinogen, and platelets will improve patients survival chances.     

Recombinant activated factor VII used in a man with refractory bleeding from a stab wound injuring the liver and kidney

A 30-year-old man bled massively from a stab wound that injured his liver and right kidney and entered a life-threatening cycle of transfusion, hypothermia, coagulopathy, and rebleeding in spite of surgery and aggressive resuscitation. He was given a single dose of recombinant activated factor VII (rVIIa; NovoSeven, Novo Nordisk, Denmark) in a final attempt to save his life. The patient responded favorably, as bleeding stopped almost immediately and coagulation markers became normal. Clinical course following rVIIa administration was good. Severe bleeding in the trauma patient needing massive transfusion can become complicated by dilutional coagulopathy and hypothermia. Therapy with rVIIa is a promising aid to controlling bleeding in the repeatedly transfused patient who does not respond to standard replacement of blood products.     

The acute coagulopathy of trauma shock: Clinical relevance

Recent observational studies have identified an acute coagulopathy in trauma victims that is present on arrival in the emergency room. It has been associated with a four-fold increase in mortality and increased incidence of organ failure. Conventional trauma resuscitation and transfusion protocols are designed for dilutional coagulopathy and appear inadequate in the management of acute traumatic coagulopathy and massive transfusion.Acute Coagulopathy of Trauma Shock (ACoTS) is caused by a combination of tissue injury and shock, and may occur without significant fluid administration, clotting factor depletion or hypothermia. The mechanism through which acute coagulopathy develops is unclear but activation of the protein C pathway has been implicated.Standard coagulation tests do not identify cases in a timely fashion and ACoTS should be suspected in any trauma patient with a significant magnitude of injury and shock, as evidenced by an abnormal admission base deficit on blood gas. Development of point of care coagulometers and whole blood coagulation analysers, such as rotational thromboelastometry, may enable earlier laboratory identification of this group. Retrospective studies performed by the American military indicate that resuscitation of severely injured patients with higher ratios of plasma given early may improve outcome and reduce overall blood product use. The place of adjunctive pharmaceutical agents within this strategy remains unclear.There is an acute coagulopathy associated with trauma and shock that is an independent predictor of outcomes. Delineation of this entity, with directed management protocols should lead to a reduction in avoidable deaths from haemorrhage after trauma.     

Utility of whole blood hemostatometry using the clot signature analyzer for assessment of hemostasis in cardiac surgery

BACKGROUND: A hemostatic monitor capable of rapid, accurate detection of clinical coagulopathy within the operating room could improve management of bleeding after cardiopulmonary bypass (CPB). The Clot Signature Analyzer is a hemostatometer that measures global hemostasis in whole blood. The authors hypothesized that point-of-care hemostatometry could detect a clinical coagulopathic state in cardiac surgical patients. METHODS: Fifty-seven adult patients scheduled for a variety of elective cardiac surgical procedures were studied. Anesthesia, CPB, heparin anticoagulation, protamine reversal, and transfusion for post-CPB bleeding were all managed by standardized protocol. Clinical coagulopathy was defined by the need for platelet or fresh frozen plasma transfusion. The Clot Signature Analyzer collagen-induced thrombus formation (CITF) assay measured platelet-mediated hemostasis in vitro. The activated clotting time, platelet count, prothrombin time, activated partial thromboplastin time, and fibrinogen concentration were also measured. RESULTS: The postprotamine CITF was greater in patients who required hemostatic transfusion than in those who did not (17.6 +/- 8.0 min vs. 10.5 +/- 5.7 min, respectively; P < 0.01). Postprotamine CITF values were highly correlated with platelet and fresh frozen plasma transfusion (Spearman r = 0.50, P < 0.001 and r = 0.40, P < 0.005, respectively). Receiver operator characteristic curves showed a highly significant relation between the postprotamine CITF and intraoperative platelet and fresh frozen plasma transfusion (area under the curve, 0.78-0.81, P < 0.005) with 60-80% sensitivity, specificity, positive and negative predictive values at cutoffs of 12-14 min. Logistic regression demonstrated that the CITF was independently predictive of post-CPB hemostatic transfusion, but standard hemostatic assays were not. CONCLUSIONS: The Clot Signature Analyzer CITF detects a clinical coagulopathic state after CPB and is independently predictive of the need for hemostatic transfusion. Hemostatometry has potential utility for monitoring hemostasis in cardiac surgery.     

Platelets, hemostasis, and thromboembolism during treatment of acute respiratory insufficiency with extracorporeal membrane oxygenation.

Twenty-eight patients were supported with long-term extracorporeal membrane oxygenation as a treatment for acute respiratory insufficiency. Clinical, laboratory, and autopsy data concerning platelets, hemostasis, and thromboembolic disease are presented for the periods during and after bypass. During bypass, a "foreign-surface coagulopathy" was encountered which consisted of abnormal bleeding plus frequent, generalized, small and large vessel thromboembolic events. The abnormal bleeding is attributed to heparin, thrombocytopenia, and a qualitative platelet defect. Possible causes of the thromboembolic events including disseminated intravascular coagulation are also discussed, and speculations are offered concerning clinical management and directions for future investigation.     

The roles of activated protein C in experimental trauma models

Trauma-induced coagulopathy is classified into primary and secondary coagulopathy, with the former elicited by trauma and traumatic shock itself and the latter being acquired coagulopathy induced by anemia, hypothermia, acidosis, and dilution. Primary coagulopathy consists of disseminated intravascular coagulation and acute coagulopathy of trauma shock (ACOTS). The pathophysiology of ACOTS is the suppression of thrombin generation and neutralization of plasminogen activator inhibitor-1 mediated by activated protein C that leads to hypocoagulation and hyperfibrinolysis in the circulation. This review tried to clarify the validity of activated protein C hypothesis that constitutes the main pathophysiology of the ACOTS in experimental trauma models.     

Utility of Whole Blood Hemostatometry Using the Clot Signature Analyzer® for Assessment of Hemostasis in Cardiac Surgery

Background: A hemostatic monitor capable of rapid, accurate detection of clinical coagulopathy within the operating room could improve management of bleeding after cardiopulmonary bypass (CPB). The Clot Signature Analyzer(R) is a hemostatometer that measures global hemostasis in whole blood. The authors hypothesized that point-of-care hemostatometry could detect a clinical coagulopathic state in cardiac surgical patients.

Methods: Fifty-seven adult patients scheduled for a variety of elective cardiac surgical procedures were studied. Anesthesia, CPB, heparin anticoagulation, protamine reversal, and transfusion for post-CPB bleeding were all managed by standardized protocol. Clinical coagulopathy was defined by the need for platelet or fresh frozen plasma transfusion. The Clot Signature Analyzer(R) collagen-induced thrombus formation (CITF) assay measured platelet-mediated hemostasis in vitro. The activated clotting time, platelet count, prothrombin time, activated partial thromboplastin time, and fibrinogen concentration were also measured.

Results: The postprotamine CITF was greater in patients who required hemostatic transfusion than in those who did not (17.6 +/- 8.0 min vs. 10.5 +/- 5.7 min, respectively;P < 0.01). Postprotamine CITF values were highly correlated with platelet and fresh frozen plasma transfusion (Spearman r = 0.50, P < 0.001 and r = 0.40, P < 0.005, respectively). Receiver operator characteristic curves showed a highly significant relation between the postprotamine CITF and intraoperative platelet and fresh frozen plasma transfusion (area under the curve, 0.78-0.81, P < 0.005) with 60-80% sensitivity, specificity, positive and negative predictive values at cutoffs of 12-14 min. Logistic regression demonstrated that the CITF was independently predictive of post-CPB hemostatic transfusion, but standard hemostatic assays were not.