Treatment Of Hyperfibrinolysis Research Articles

Hyperfibrinolysis; A Serious and Mortal Complication After Cardiopulmonary Bypasses: Case Report

Hemorrhage is one of the major complications of cardiac surgery when using cardiopulmonary bypass (CPB). Despite all kinds of medical and surgical treatment, post bypass bleeding is still a serious problem. Hypothermia, acidosis, hypovolemia, and hypoperfusion lead to disruption of the coagulation process in severe trauma as well as in CPB. Hyperfibrinolysis (HF) is a life-threatening bleeding disorder in major trauma patients. The incidence of HF has been estimated in the range of 15% to 20%. The gold standard for the detection of HF is thrombelastography or thromboelastometry. Blood products and tranexamic acid are used in the treatment of hyperfibrinolysis. The agents that can be used as an alternative to tranexamic acid in HF treatment are aprotinin and epsilon aminocaproic acid. Early diagnosis and treatment of HF are life-saving. For this purpose, we wanted to share this rare pathology.

Diagnosis and Treatment of Hyperfibrinolysis in Trauma (A European Perspective).

Fibrinolysis activation occurs almost universally after severe trauma. Systemic hyperfibrinolysis is a key component of acute traumatic coagulopathy and associated with poor clinical outcomes, although controversy exists over optimal treatment strategies. The mechanistic drivers and dynamics of fibrinolytic activation in response to injury and trauma resuscitation are currently unclear. Furthermore, therapeutic triggers are compounded by the lack of a sensitive and rapid diagnostic tool, with discrepancy between hyperfibrinolysis diagnosed by viscoelastic hemostatic assays versus biomarkers for fibrinolysis. Rotational thromboelastometry and thromboelastography appear capable of detecting the severest forms of hyperfibrinolysis but are relatively insensitive to moderate, yet clinically significant fibrinolytic activation. Rapid evaluation of the current status of the fibrinolytic system remains a challenge and therefore the decision whether to administer an antifibrinolytic agent should be based on available evidence from clinical trials. In line with current European guidelines, we recommend that all bleeding trauma patients, and in particular, severely injured patients with evidence of hemorrhagic shock, should receive early empiric tranexamic acid. This review explains our current knowledge of the pathophysiological pathways which induce hyperfibrinolysis in trauma hemorrhage, evaluates the available diagnostic modalities, and describes current treatment strategies.

Behandlung der traumainduzierten Koagulopathie - Was ist die Evidenz?

The increasing understanding of trauma-induced coagulopathy has led to an expansion of treatment strategies in the acute management of trauma patients. The aim of this manuscript is to give a summary of current recommendations for the treatment of trauma-induced coagulopathy based on current literature and valid guidelines. Thetrauma-induced coagulopathyis an independentacutemultifactorial diseasewith significantimpact on the mortalityof severelyinjured patients. Largely responsible for the occurrence and severity of trauma-induced coagulopathy seems to be tissue trauma and shock-induced hypoperfusion. Coagulopathy is amplified by accompanying factors such as hypothermia or dilution. Diagnosis and therapy of deranged coagulation should start as soon as possible. Routinely tested coagulation parameters are of limited use to confirm diagnosis. Therapy follows the concept of "damage control resuscitation". Infusion of large volumes should be avoided and a mean arterial pressure of 65mmHg (in consideration of contraindications!) may be aimed.A specific protocol for massive transfusion should be introduced and continued.Acidaemia should be prevented and treated by appropriate shock therapy.Loss of body temperature should be prevented and treated. Hypocalcaemia <0.9 mmol/l should be avoided and may be treated. For actively bleeding patients, packed red blood cells (pRBC) may be given at haemoglobin<10g/dl(0,62mmol/l). If massive transfusion is performed using fresh frozen plasma (FFP), a ratio of FFP to pRBC of 1:2 to 1:1 should be achieved.For treatment of hyperfibrinolysis after severe trauma the use of tranexamic acid should be considered at an early stage. Fibrinogen should be substituted at levels <1,5g/l (4,41μmol/l). Prothrombin complex concentrates may be helpfull for treatment of diffuse bleeding or anticoagulativemedikation. In acute bleeding, platelets may be transfused at a platet count <100000/μl. For diffuse bleeding or thrombocytopathic patients desmopressin might be a therapeutic option.If a factor XIII (FXIII) measurement is not promptly available, a factor XIII blind-dose should be considered in severe ongoing bleeding. The use of recombinant activated coagulation factor VII (rFVIIa) be considered if major bleeding persists despite standard attempts to control bleeding and best practice use of blood components.

Hyperfibrinolysis and Point-of-Care Thromboelastography: Rapid Detection of Hyperfibrinolysis without Immediate Antifibrinolysis Confers Worse Survival Results Than Prophylaxis, In Liver Transplantation

AbstractAbstract 1420 Background and Aims:Bleeding during orthotopic liver transplantation (OLT) can be due to pre-existing conditions associated with the primary disease, peri-operatory complications or systemic disease (such as sepsis or disseminated intravascular coagulation); the procedure itself is associated with pro-hemorrhagic states (reflecting the liver's importance in hemostasis), the most relevant of which is hyperfibrinolysis (HF) –starting in the anhepatic stage after the removal of the host liver, and worsening during reperfusion of the donor organ. Specific prophylaxis minimizes bleeding due to uncontrolled HF; aprotinin was used successfully for prophylaxis until its approval was discontinued. Patients with severe hemorrhages can be stabilized through blood product (BP) transfusion, which is associated with non-negligible morbidity and mortality, and may contribute to decreased survival. Therefore, when HF is identified as a cause of bleeding, it should be addressed and specifically treated with antifibrinolytics; point-of-care (POC) rotational thromboelastography (ROTEG) can quickly evaluate the cumulative function of platelets, coagulation and fibrinolysis, and help identify bleeding due to HF. We have previously found that in our center the use of BP in patients undergoing HF-prophylaxis with aprotinin was identical to those who spontaneously never developed HF, and significantly lower than in those with POC ROTEG-identified HF treated with antifibrinolytics after bleeding had started. We proposed that antifibrinolysis should be instituted as soon as ROTEG-evidence of HF was found, regardless of bleeding status, to decrease the amount of BP transfused. This study aims to determine whether there was a survival difference between the use of prophylaxis and POC ROTEG, as could be suggested by the differences in BP consumption. Methods:We reviewed 293 OLTs performed in our center from January 2004 to December 2009; we excluded 64 transplants which involved pediatric patients (defined as being under 18 years of age), 10 cases with incomplete charts, 30 re-transplants and 14 emergency OLTs for acute toxic hepatic failure. We thus included 175 patients in our survival analysis (Kaplan-Meier). Results:We found that patients undergoing prophylaxis for HF showed no difference in survival (p=0.810) compared to those who did not undergo prophylaxis and in whom ROTEG demonstrated an absence of spontaneous HF. We also found that those patients who were not subjected to prophylaxis - excluding those transplanted for familial amyloid polyneuropathy (FAP) - and in whom (due to logistic reasons) ROTEG was not available to guide treatment, had no difference in survival (p=0.928) compared to those who had ROTEG-confirmed HF (in whom antifibrinolytic treatment was usually not immediately started). In our series of patients we identified three distinct survival curves. Patients transplanted for FAP (a condition which does not affect liver structure or function, but in which OLT can replace a defective metabolic function), who did not undergo prophylaxis or ROTEG, had an overall survival (OS) of 95.1% at 78.0 months of follow-up; patients without HF (either confirmed by ROTEG or as a result of prophylaxis) had an OS of 87.0%; patients with ROTEG-confirmed HF and those without prophylaxis or ROTEG had an OS of 76.5% (p=0.028). Discussion and Conclusions:We conclude that prophylaxis with aprotinin was effective and abolished HF, conferring identical survival results to the subset of patients who spontaneously do not develop HF (as confirmed by ROTEG), while late treatment of confirmed HF with antifibrinolytics produces identical survival results to blind ROTEG-unguided empiricism. Considering patient OS, ROTEG-guided treatment of HF, when not consistently instituted as soon as HF is identified (regardless of bleeding status), confers worse survival results than those previously obtained when HF-prophylaxis was possible using aprotinin. These findings add support to the hypothesis that antifibrinolysis should be started immediately upon recognition of HF on POC ROTEG, to improve overall survival (and, as we previously found, to decrease the consumption of BP). We suggest that operating room protocols should be developed by the surgical and clinical and laboratorial hematology teams, to optimize the choice and dose of antifibrinolytic drugs, and the timing of ROTEG analysis during OLT. Disclosures:No relevant conflicts of interest to declare.

How useful is ε-aminocaproic acid for the treatment of hyperfibrinolysis in patients with cirrhosis?

How useful is e-aminocaproic acid for the treatment of hyperfibrinolysis in patients with cirrhosis?