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.     

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.     

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.     

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.     

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.     

The disparity between hypothermic coagulopathy and clotting studies.

Hypothermic patients commonly develop coagulopathy, but the effects of hypothermia on coagulation remain unclear because clinical laboratories routinely perform clotting tests only at 37 degrees C. Measurements of activated partial thromboplastin times (APTT), prothrombin times (PT), and thrombin times (TT) were performed on plasma from normothermic and hypothermic rats at a range of temperatures (25 degrees-37 degrees C) to assess the effects of hypothermia on apparent clotting factor levels and clotting factor activities. In general, clotting times were more severely prolonged when test temperatures were hypothermic than when body temperatures were hypothermic. Indeed, little to no prolongation resulted from body hypothermia alone. These findings reveal the observed disparity between clinically evident hypothermic coagulopathy and near-normal clotting studies. Clotting studies performed at 37 degrees C will not confirm hypothermic coagulopathy. These results indicate that the appropriate treatment for hypothermia-induced coagulopathy is rewarming rather than administration of clotting factors.     

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.     

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.     

Venous malformations and coagulopathy

Activation of the coagulation process is frequently encountered in patients with venous vascular malformations and results in the local formation of clots and the consumption of components of the coagulation process (platelets, clotting factors). This activation accounts for multiple biological abnormalities such as the elevation of the D-dimers, reduction of fibrinogen and platelets count and less frequently a local intravascular coagulation (LIC). This process seems to be responsible for the local painful symptoms. In case of LIC, bleeding complications may be observed. Therapeutically, antithrombotic treatment with low-molecular weight heparin can improve the local coagulopathy with beneficial effects on blood tests disturbances, pain and bleeding tendency.     

A description of the coagulopathy characteristics in amniotic fluid embolism: a case report

Amniotic fluid embolism is frequently associated with coagulopathy. However, the exact nature and evolution of the bleeding disorder is incompletely understood. We report a case of clinically diagnosed amniotic fluid embolism associated with major haemorrhage and coagulopathy. We measured sequential levels of all individual clotting factors, thrombin generation, fibrinogen, and D-dimer levels over the course of the event, beginning shortly after the patient’s initial collapse and during the subsequent resuscitation, to identify the specific abnormalities of coagulation from stored blood samples. A better understanding of amniotic fluid embolism and the associated coagulopathy is an important area of research to inform targeted treatment of the coagulopathy and improve outcomes for patients.     

Coagulation defects in neonates during cardiopulmonary bypass.

We examined components of the coagulation system in 30 neonates (age, 1 to 30 days) undergoing deep hypothermic cardiopulmonary bypass (CPB). A coagulation profile consisting of activated clotting time; prothrombin time; partial thromboplastin time; factors II, V, VII, VIII, IX, X, and I (fibrinogen); antithrombin III; platelet count; and heparin levels was evaluated before bypass, at three intervals during bypass (1 minute after initiation of bypass, stable hypothermic CPB, warm CPB), after weaning from CPB and administration of protamine, and 2 to 3 hours after skin closure. The initiation of CPB resulted in a 50% decrease in circulating coagulation factors and antithrombin III levels. Platelet counts were reduced by 70% with CPB initiation. Neither deep hypothermic temperatures nor prolonged exposure to extracorporeal surfaces had any additional effect on the coagulation profiles. This suggests that the coagulation system of a neonate undergoing CPB is profoundly and globally effected by hemodilution. We believe that treatment of post-CPB coagulopathy in neonates must address these global deficits.     

Clinical aspects of coagulation and haemorrhage

Haemorrhage affects all patient groups. Coagulopathy (an abnormality of the clotting system) is closely interlinked with haemorrhage and can either place patients at risk of future bleeding or can exacerbate active ongoing bleeding. There are many causes of coagulopathy – both inherited and acquired. During major haemorrhage, the presence of an acquired coagulopathy increases the likelihood of a poor clinical outcome and a patient is more likely to require large transfusion volumes, critical care admission and is three to four times more likely to die. Other forms of coagulopathy, such as drug-induced coagulopathy (anticoagulant/anti-platelet use) or inherited bleeding disorders, both increase the severity of any active bleeding and place patients at higher risk for future bleeding when exposed to a haemostatic challenge, such as surgery. This risk must be recognized and mitigated. This review focuses on the clinical aspects of coagulation and haemorrhage in all these patient groups.     

Alterations in the Coagulation Profile in Renal Pig-to-Monkey Xenotransplantation

Five monkey recipients of a porcine renal xenograft were studied to determine the relationship between fibrin formation in acute humoral xenograft rejection (AHXR) and procoagulant and anticoagulant factor levels to establish whether changes in coagulation parameters could be used to predict AHXR and determine whether AHXR is associated with overt disseminated intravascular coagulopathy (DIC) in this model. Variable degrees of compensated consumptive coagulopathy were observed in each primate. Elevated thrombin-antithrombin (TAT), F1+2 and D-dimer levels consistent with thrombin generation and fibrin formation were recorded. There was no consumption of the main clotting inhibitors (including antithrombin) or a progressive, severe drop in fibrinogen levels and platelet counts, although grafts were left in situ. After transplantation, D-dimer levels remained persistently high, so they were of limited value in defining this coagulopathy. At post mortem, no cases of multiorgan involvement typical of overt DIC were observed. The lack of a rapid postoperative recovery of clotting inhibitor levels after transplantation was invariably associated with early poor outcome. This study shows that AHXR is associated with various degrees of compensated consumptive coagulopathy in our pig-to-primate model. No clear relationship was found between coagulation parameter levels and graft outcome.     

Progresses in understanding trauma-induced coagulopathy and the underlying mechanism

Trauma-induced coagulopathy (TIC) is a clinical syndrome caused by imbalance between clotting, anticoagulation and fibrinolysis resulting from multiple pathological factors such as hemorrhage and tissue injury in the early stage of trauma, and is closely related to the outcome of trauma patients. It is proved in growing evidence that the endogenous coagulation disturbance in trauma itself is the activating factor of TIC, rather than dilution or other acquired coagulopathy. Therefore, a thorough understanding of the molecular mechanisms in the pathogenesis and progression is crucial for effective prevention and treatment in patients with TIC. This review focuses on transitions in the concept of TIC and mechanical progress.     

Clinical aspects of coagulation and haemorrhage

Haemorrhage affects all patient groups. Coagulopathy (an abnormality of the clotting system) is closely interlinked with haemorrhage and can either place patients at risk of future bleeding or can exacerbate active ongoing bleeding. There are many causes of coagulopathy, both inherited and acquired. During major haemorrhage, the presence of an acquired coagulopathy increases the likelihood of a poor clinical outcome and a patient is more likely to require large transfusion volumes, critical care admission and is three to four times more likely to die. Other forms of coagulopathy, such as drug-induced coagulopathy (anticoagulant/anti-platelet use) or inherited bleeding disorders, both increase the severity of any active bleeding and also place patients at higher risk for future bleeding when exposed to a haemostatic challenge, such as surgery. This risk must be recognized and mitigated. This review focuses on the clinical aspects of coagulation and haemorrhage in all these patient groups.     

Chronic consumption coagulopathy accompanying abdominal aortic aneurysm.

Each of two patients harboring a stable abdominal aortic aneurysm manifested severe recurrent bleeding consequent to chronic consumption coagulopathy (CCC). Both underwent successful aneurysmectomy, but in only one patient did bleeding cease and depressed clotting factors return to normal activity. In the other patient, subsequent observations suggested that his coagulopathy actually resulted from occult pancreatic carcinoma. We propose here criteria for establishing stable aneurysm as the cause of CCC and demonstrate the efficacy of heparin in reversing the coagulation defect prior to surgical intervention. These cases also illustrate that the discovery of CCC accompanying stable aneurysm may signal the presence of another underlying disorder.     

Thrombocytopenia in severe bacterial infections.

Twenty-eight patients with bacterial infections and coagulation abnormalities were studied. Thrombocytopenia was seen in 26 (93%). The coagulopathy was related to vitamin K deficiency in four patients and massive transfusions of stored blood in two. Three patients showed transient FDP elevation without evidence of acute consumption of clotting factors, and in only one patient (3.5%) was D.I.C. diagnosed. Eighteen patients were thrombocytopenic without evidence of another coagulation abnormality. Thus D.I.C. seems relatively rare in bacterial infections, and other mechanisms are required to explain the associated thrombocytopenia.     

Ascites-induced LeVeen shunt coagulopathy.

Ten of 11 patients undergoing peritoneovenous (LeVeen) shunt placement for intractable ascites had disseminated intravascular coagulation (DIC) following the shunt procedure. Intraoperative ascitic fluid specimens revealed fibrin split products (FSP) in high titer (1:100-1:1600) in all patients. Endotoxin was found in 6 of 11 ascitic fluid samples but in no plasma samples. Activated clotting factors, clot inhibitors, excess protein, and fibrinolytic activity were not found in ascitic fluid. Clotting factor levels were much lower than in plasma. Bleeding occurred after operation in two patients; this appeared to be related to the severity of liver dysfunction as demonstrated by elevations of bilirubin, serum glutamic oxalocetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and preoperative DIC. It is concluded that the LeVeen shunt coagulopathy is DIC, and may be related to exposure of the systemic circulation to FSP-rich ascitic fluid that may activate the coagulation mechanism. Bleeding complications do not appear to be related to the severity of the post shunt coagulopathy, but rather to the severity of liver dysfunction and presence of preoperative DIC (probably caused by the liver disease).     

Drugs affecting coagulation

The clotting cascade is a complex process and is an important survival mechanism. Major haemorrhage and thromboembolic events remain major causes of increased morbidity and mortality. Drugs affecting coagulation have primarily been utilized to treat or reduce the risk of thromboembolic events. However, the recent progress in the management of major trauma and treating coagulopathy has resulted in further research and development of drugs that improve clotting function. Knowledge of drugs used for both clinical circumstances is now required when working in anaesthesia or intensive care.     

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.