Coagulation management in trauma patients

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 in compensating the blood loss further aggravates the situation. 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, platelet concentrations, clotting factors and probably antifibrinolytic agents is essential in restoring the impaired coagulation system in trauma patients.     

Gerinnungsmanagement bei schweren operativen Blutungen

Severe intraoperative bleeding may endanger the patient's life, necessitate additional human resources and increase perioperative costs. The aetiology of perioperative coagulopathy is complex and consists of depletion, consumption and dilution of clotting factors and thrombocytes. Cofactors like hypothermia, acidosis and severe anaemia may aggravate coagulopathy. Previously healthy patients often show hypofibrinogenaemia as the primary trigger of coagulopathy, whereas thrombocytopenia rather is a late event during massive bleeding. Early and differentiated diagnosis is essential for initiating targeted therapy. Evaluation of the clinical bleeding situation and coagulation tests, in particular point-of-care testing like thrombelastography, should be used to guide and control the therapeutic strategy. Fresh frozen plasma, concentrates of clotting factors, platelet concentrates and antifibrinolytic drugs are available for therapy of perioperative coagulopathy. To obtain optimal benefit for the patient, these products should be applied based on a therapeutic algorithm.     

Fresh plasma and concentrates of clotting factors for therapy of perioperative coagulopathy: what is known?

Acquired, perioperative coagulopathy often develops due to acute bleeding. In the case of primarily healthy patients with normal bone marrow and liver functions, a lack of coagulation factors initiates coagulopathy before secondary thrombopenia arises. Replacement of coagulation factors can be performed by infusion of fresh plasma (single donor or pooled plasma) or concentrates of clotting factors. Fresh plasma as well as concentrates of clotting factors available in German-speaking countries are of high quality and fulfil all safety standards. Undesirable side-effects due to transmission of infections and immunological reactions are--in all probability--more uncommon for virus-inactivated plasma and clotting factors than for single donor plasma. In contrast, thromboembolic complications are unlikely when using fresh frozen plasma, because it contains a balanced ratio of pro-coagulatory and anti-coagulatory factors. For virus-inactivated pooled plasma and concentrates of clotting factors, sporadic reports of thromboembolic events have been published. Concentrates of clotting factors can be stored easily and are rapidly prepared for use. In contrast, fresh frozen plasma has to be thawed before application leading to a significant delay in the schedule. During activated hemostasis, the half-life of clotting factors is significantly reduced in comparison to a stable physiological situation. In the case of perioperative coagulopathy higher dosages of fresh plasma and clotting factors than those recommended in published guidelines are often necessary for successful treatment. When using fresh plasma for coagulation therapy the resulting volume load must be considered. In conclusion, a modern concept of perioperative coagulation management should include fresh plasma as well as concentrates of clotting factors. The anesthetist should be familiar with the available components and be able to consider and adapt them to the individual situation.     

Frischplasma und Faktorenkonzentrate zur Therapie der perioperativen Koagulopathie

Acquired, perioperative coagulopathy often develops due to acute bleeding. In the case of primarily healthy patients with normal bone marrow and liver functions, a lack of coagulation factors initiates coagulopathy before secondary thrombopenia arises. Replacement of coagulation factors can be performed by infusion of fresh plasma (single donor or pooled plasma) or concentrates of clotting factors. Fresh plasma as well as concentrates of clotting factors available in German-speaking countries are of high quality and fulfil all safety standards. Undesirable side-effects due to transmission of infections and immunological reactions are – in all probability – more uncommon for virus-inactivated plasma and clotting factors than for single donor plasma. In contrast, thromboembolic complications are unlikely when using fresh frozen plasma, because it contains a balanced ratio of pro-coagulatory and anti-coagulatory factors. For virus-inactivated pooled plasma and concentrates of clotting factors, sporadic reports of thromboembolic events have been published. Concentrates of clotting factors can be stored easily and are rapidly prepared for use. In contrast, fresh frozen plasma has to be thawed before application leading to a significant delay in the schedule. During activated hemostasis, the half-life of clotting factors is significantly reduced in comparison to a stable physiological situation. In the case of perioperative coagulopathy higher dosages of fresh plasma and clotting factors than those recommended in published guidelines are often necessary for successful treatment. When using fresh plasma for coagulation therapy the resulting volume load must be considered. In conclusion, a modern concept of perioperative coagulation management should include fresh plasma as well as concentrates of clotting factors. The anesthetist should be familiar with the available components and be able to consider and adapt them to the individual situation.     

Dilutional coagulopathy, an underestimated problem?

When no fresh frozen plasma is available, acute major blood loss is compensated above all with crystalloids, colloids and erythrocyte concentrates, meaning that all plasma clotting factors are diluted. Consumption coagulopathy is almost always accompanied by dilutional coagulopathy. Formulas for calculating critical blood loss and standard coagulation tests are often not helpful in the case of massive transfusion. On the other hand, systems suitable for point of care, such as thrombelastography, have important advantages. In the case of consumption and dilutional coagulopathy plasma coagulation is disturbed and critical values are first seen for fibrinogen. Not only is fibrin polymerization impaired by the bleeding-induced loss and dilution of fibrinogen, but also by interaction with artificial colloids, particularly hydroxyethyl starch preparations. Therapy of consumption and dilutional coagulopathy calls for fresh frozen plasma. If this is not available in sufficient quantity or within a reasonable time, coagulation factor concentrates must be used. Neither fresh frozen plasma therapy nor treatment with coagulation factor concentrates has been the subject of detailed clinical study. Further studies are needed to work out guidelines for coagulation management in the case of massive blood loss.     

Gerinnungstherapie beim Polytrauma ohne Point-of-care-Testung

Analysis of blood coagulation with thrombelastometry (ROTEM?) and thrombelastography (TEG?) and analysis of thrombocyte function by a Multiplate? assay is possible in only a few hospitals in Germany. Recently, the grade of recommendation (GoR) for point-of-care (POC) testing in official guidelines was increased and is now classified as GoR 1C. If a POC-based option is not available alternatives must be used. Besides blood products (RBC, FFP, TC), coagulation factor concentrates are used to treat trauma-induced coagulopathy. The benefits of therapy with factor concentrates are fewer immunological and infection side effects as well as faster effects after administration of specific coagulation factors. A good outcome in patients with multiple trauma is only possible by an adequate transfusion regime and administration of coagulation factors.     

Pathophysiologie des Schocks unter besonderer Berücksichtigung der schockspezifischen Hämostasestörung

Circulatory shock is defined as a syndrome of hemodynamic and metabolic disturbances. Impairment of macro-and microcirculation initiated by different causes is followed by a reversible and later on by an irreversible disturbance of cell metabolism. Breakdown of organ function may be the consequence. The shock specific discomposure of the hemostatic system is characterized by an acitivation of blood coagulation. This leads first to hypercoagulability accompanied by a tendency to thrombosis; later on the impairment of the hemostatic balance is followed by the consumption of coagulation factors and by hypocoagulability with a more or less pronounced bleeding tendency. Treatment of shock is the main prerequisite to avoid and overcome shock induced coagulation disorder. Heparin administration, fresh blood and fresh plasma are adjuvant measures. Substitution of concentrates of clotting factors are indicated only in states of total consumption of the coagulation system.     

PPSB as first choice treatment in the reversal of oral anticoagulant therapy

In the treatment of reversal of oral anticoagulant therapy, a number of treatment modalities is available and depends on the severity of the clinical situation and the degree of the coagulopathy. FFP and PPSB (PCC) are commonly used in the treatment and/or in combination with cessation of oral anticoagulant therapy and administration of Vitamin K. The double viral inactivated plasma product PPSB-SD is the first choice treatment in this indication because of the relatively constant, high concentrated level of the Vitamin K dependent coagulation factors II, VII, IX and X, compared to FFP.     

Neue (Querschnitt-)Leitlinien der Bundesärztekammer für die Hämotherapie mit gefrorenem Frischplasma

Some new blood products and plasma derivatives have extended the possibilities in hemotherapy to such an extent that the therapeutic and evidence-based therapy options can only really be managed with the aid of guidelines. Four approved plasma preparations are available in Germany: fresh frozen plasma, lyophilized plasma, solvent-detergent (SD) pool plasma and methylene blue-light-treated plasma. Evidence of the clinical efficacy of plasma is mainly based on uncontrolled observational studies, case reports or expert opinion. Plasma is indicated for complex coagulopathy associated with manifest or imminent bleeding, particularly with massive transfusion, disseminated intravascular coagulation and liver disease. With the exception of emergency situations when clotting assay results are not available in time, a clinically relevant coagulopathy must be verified before plasma is administered. The rapid infusion of at least 10 ml of plasma per kg body weight is required to significantly increase the respective clotting factor or inhibitor levels. Prothrombin complex concentrates (PPSB) should be preferred to plasma for the rapid reversal of oral anticoagulation. Side effects of plasma are rare but have to be considered.     

An overview about elbow instability

Coagulopathy is common in orthopedic surgery patients either due to acquired factors, such as surgery, trauma, medications, or hemorrhage. Perioperative monitoring of blood coagulation is critical to diagnose the causes of hemorrhage, guide hemostatic therapies, predict the risk of bleeding during surgical procedures, and reduce risk of postoperative cardiac and thromboembolic events. In contrast to previous interventions that measure specific portions of the clotting cascade (such as intrinsic or extrinsic pathways or platelet aggregation), “Point-of-care” coagulation monitoring devices assess the viscoelastic properties of whole blood. These techniques have the potential to measure the entire clotting process, starting with fibrin formation, clot retraction, and fibrinolysis. Furthermore, the coagulation status of patients is assessed in whole blood, allowing the plasmatic coagulation system to interact with platelets and red cells, and thereby providing useful additional information on platelet function. Improved monitoring of coagulopathy is particularly important as new anticoagulant drugs emerge that affect the clotting cascade in novel ways, including the inhibition of intrinsic and extrinsic pathways and platelet function. It is important for orthopedic surgeons to understand the pharmacology and reversal of these drugs in the perioperative setting. The purpose of this review is to review the current techniques to monitoring perioperative coagulopathy and to identify the manner in which novel anticoagulant medications affect the clotting cascade with particular interest in trauma and spine surgery.     

Autotransfusion and plasmapheresis in preparation for surgery. Behavior of coagulation

With the current day implementation of methods of autotransfusion one retransfuses if possible only washed red cell concentrates and eliminates the plasma. In the case of operations where patients undergo large blood loss, one must effect a substitution for the lost plasma volume and the lost clotting factors. In addition to electrolyte and colloidal solutions one can use a substitution of homologous and also autologous fresh frozen plasma (FFP). The effects of different substitutes on the clotting reaction has been investigated in 47 patients on whom extensive orthopaedic and also traumatologic surgical operations have been performed. By the combination of homologous blood and homologous FFP as also with autologous red cells and homologous FFP the clotting reactions remain the same. This determines the advantages of autotransfusion as compared with conventional techniques but, in addition, there is a saving in the usage of homologous blood. Where an operation can be planned in advance, the necessary FFP can be obtained from the patient. By utilisation of autologous FFP the operative and post- operative blood losses are reduced. As a result it is possible e.g. in total hip prosthesis, in approximately 90% of all cases, to operate without using homologous blood or plasma. The determined stability of AT III in autologous plasma--without AT III prophylaxis of thrombosis by Heparin is ineffective--and all other clotting factors leads to an expectancy of a not activated clotting mechanism and at the same time to low thrombosis risks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Current concepts of hemostasis: implications for therapy

The revised model of coagulation has implications for therapy of both hemorrhagic and thrombotic disorders. Of particular interest to anesthesiologists is the management of clotting abnormalities before, during, and after surgery. Most hereditary and acquired coagulation factor deficiencies can be managed by specific replacement therapy using clotting factor concentrates. Specific guidelines have also been developed for perioperative management of patients using anticoagulant agents that inhibit platelet or coagulation factor functions. Finally, recombinant factor VIIa has been used off-label as a hemostatic agent in some surgical situations associated with excessive bleeding that is not responsive to conventional therapy.     

Gerinnungsmanagement bei Eingriffen mit extrakorporaler Zirkulation

After cardiac surgery with extracorporeal circulation, approximately 20% of patients show significant bleeding tendencies and 5% require re-intervention. In 50% of patients undergoing re-operation, no surgical cause can be determined, suggesting coagulopathy after cardiopulmonary bypass (CPB). For perioperative management of transfusion of blood products and coagulation factor concentrates, a clinical algorithm for the perioperative hemostatic therapy in patients undergoing cardiac surgery with CPB has been developed. The currently available evidence and the point of care methods routinely accessible in our institution (blood gas analysis, ACT, point of care Quick value, aPTT and platelet count) were used. The intervention with plasma products, coagulation factor concentrates and hemostatic drugs after extracorporeal circulation are described. Extensive bleeding history as well as the efficacy and side effects of antifibrinolytic treatment are discussed.     

Pathophysiology and treatment of coagulopathy in massive hemorrhage and hemodilution

Fluid resuscitation after massive hemorrhage in major surgery and trauma may result in extensive hemodilution and coagulopathy, which is of a multifactorial nature. Although coagulopathy is often perceived as hemorrhagic, extensive hemodilution affects procoagulants as well as anticoagulant, profibrinolytic, and antifibrinolytic elements, leading to a complex coagulation disorder. Reduced thrombin activation is partially compensated by lower inhibitory activities of antithrombin and other protease inhibitors, whereas plasma fibrinogen is rapidly decreased proportional to the extent of hemodilution. Adequate fibrinogen levels are essential in managing dilutional coagulopathy. After extensive hemodilution, fibrin clots are more prone to fibrinolysis because major antifibrinolytic proteins are decreased.Fresh frozen plasma, platelet concentrate, and cryoprecipitate are considered the mainstay hemostatic therapies. Purified factor concentrates of plasma origin and from recombinant synthesis are increasingly used for a rapid restoration of targeted factors. Future clinical studies are necessary to establish the specific indication, dosing, and safety of novel hemostatic interventions.     

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.     

Coagulopathy and placental abruption: changing management with ROTEM-guided fibrinogen concentrate therapy

Placental abruption may cause significant haemorrhage and coagulopathy that can progress rapidly due to simultaneous consumption and depletion of clotting factors. Plasma fibrinogen levels are predictive of further haemorrhage. Rapid detection and treatment of hypofibrinogenaemia is essential in the evolving clinical and haematological situation. The use of near-patient testing of coagulation using rotational thromboelastometry (ROTEM) allows dynamic monitoring of coagulopathy. Following the introduction of fibrinogen concentrate into our unit, a ROTEM-guided algorithm was developed for use in obstetric haemorrhage. We describe four cases of placental abruption, haemorrhage and severe coagulopathy that span the introduction of the algorithm. Three cases were associated with intrauterine death and the fourth with delivery of an extremely premature neonate. Rotational thromboelastometry was used in all cases but methods of fibrinogen replacement differ, illustrating evolving management of the condition in our unit.     

A mathematical model for fresh frozen plasma transfusion strategies during major trauma resuscitation with ongoing hemorrhage.

BACKGROUND: Randomized controlled trials of how best to administer fresh frozen plasma (FFP) in the presence of ongoing severe traumatic hemorrhage are difficult to execute and have not been published. Meanwhile, coagulopathy remains a common occurrence during major trauma resuscitation and hemorrhage remains a major cause of traumatic deaths, suggesting that current coagulation factor replacement practices may be inadequate. METHODS: We used a pharmacokinetic model to simulate the dilutional component of coagulopathy during hemorrhage and compared different FFP transfusion strategies for the prevention or correction, or both, of dilutional coagulopathy. Assuming the rates of volume replacement and loss are roughly equal, we derived the hematocrit and plasma coagulation factor concentration over time based on the rate of blood loss and replacement, the hematocrit and coagulation factor concentration of the transfusate, and the hematocrit and plasma factor concentration at the time when FFP transfusion begins. RESULTS: Once excessive deficiency of factors has developed and bleeding is unabated, 1-1.5 units of FFP must be given for every unit of packed red blood cells (PRBC) transfused. If FFP transfusion should start before plasma factor concentration drops below 50% of normal, an FFP:PRBC transfusion ratio of 1:1 would prevent further dilution. CONCLUSION: During resuscitation of a patient who has undergone major trauma, the equivalent of whole-blood transfusion is required to correct or prevent dilutional coagulopathy.     

The impact of fresh frozen plasma vs coagulation factor concentrates on morbidity and mortality in trauma-associated haemorrhage and massive transfusion

Introduction

Clinical observations together with recent research highlighted the role of coagulopathy in acute trauma care and early aggressive treatment has been shown to reduce mortality.

Methods

Datasets from severely injured and bleeding patients with established coagulopathy upon emergency room (ER) arrival from two retrospective trauma databases, (i) TR-DGU (Germany) and (ii) Innsbruck Trauma Databank/ITB (Austria), that had received two different strategies of coagulopathy management during initial resuscitation, (i) fresh frozen plasma (FFP) without coagulation factor concentrates, and (ii) coagulation factor concentrates (fibrinogen and/or prothrombin complex concentrates) without FFP, were compared for morbidity, mortality and transfusion requirements using a matched-pair analysis approach.

Results

There were no major differences in basic characteristics and physiological variables upon ER admission between the two cohorts that were matched. ITB patients had received substantially less packed red blood cell (pRBC) concentrates within the first 6 h after admission (median 1.0 (IQR_25-75 0-3) vs 7.5 (IQR_25-75 4-12) units; p < 0.005) and the first 24 h as compared to TR-DGU patients (median 3 (IQR_25-75 0-5) vs 12.5 (8-20) units; p < 0.005). Overall mortality was comparable between both groups whilst the frequency for multi organ failure was significantly lower within the group that had received coagulation factor concentrates exclusively and no FFP during initial resuscitation (n = 3 vs n = 15; p = 0.015). This translated into trends towards reduced days on ventilator whilst on ICU and shorter overall in-hospital length of stays (LOS).

Conclusion

Although there was no difference in overall mortality between both groups, significant differences with regard to morbidity and need for allogenic transfusion provide a signal supporting the management of acute post-traumatic coagulopathy with coagulation factor concentrates rather than with traditional FFP transfusions. Prospective and randomised clinical trials with sufficient patient numbers based upon this strategy are advocated.     

Homologous fresh frozen plasma in heart surgery. Myth or necessity

Routine administration of homologous fresh frozen plasma (FFP) is widely carried out in cardiac surgery although the risks of blood transfusion can never be excluded. The effect of two units of FFP (430 +/- 11 ml) given after the end of extracorporeal circulation (ECC) (group 1, n = 20) was compared to a control group (n = 20) without FFP in elective aorto coronary bypass patients. Various laboratory parameters, including coagulation data, were measured before and after the end of ECC up to the 1st postoperative day. The patients were comparable with regard to biometric data, anesthesia, and surgical procedure. The major result of this study shows, that routine administration of FFP has no beneficial effect with respect to hemostatic balance. In comparison to a control group, the increase in elastase and decrease in paO2 was even more pronounced in the FFP group. Both blood loss and the need for blood transfusion did not differ between the groups. It can be concluded that a bleeding tendency in cardiac surgery may be caused by ECC itself and by perioperative plasma loss. The routine administration of a relatively small amount of FFP has no positive influence on hemostasis. Substitution therapy in this situation should be guided by the results of coagulation studies.     

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创伤性凝血病的发病机制十分复杂,具有多源性,涉及凝血系统的多个方面,其具体发生机制尚未完全明确。已知的发病机制主要有:稀释性凝血病、低温性凝血病、酸中毒性凝血病和消耗性凝血病等。对发病机制的新认识为临床创伤后凝血功能障碍的检测及治疗带来了新的改变。除常规实施"小容量复苏"和"允许性低血压"复苏的损伤控制性复苏策略外,近年来研究发现:对创伤低凝病人给予1:1的新鲜冰冻血浆(FFP)与红细胞(RBC)大比例血浆输注,可大幅度降低出血病死率和总病死率;抗纤溶治疗是近年来创伤止血治疗的重要进展。