Recent findings in the pathophysiology and monitoring of hemostasis in patients with end stage liver disease have major impact on coagulation management during liver transplantation. There is increasing evidence, that...Recent findings in the pathophysiology and monitoring of hemostasis in patients with end stage liver disease have major impact on coagulation management during liver transplantation. There is increasing evidence, that the changes in both coagulation factors and platelet count regularly observed in patients with liver cirrhosis cannot be interpreted as a reliable indicator of diffuse bleeding risk. Instead, a differentiated view on hemostasis has led to the concept of a rebalanced coagulation system: While it is important to recognize that procoagulant factors are reduced in liver cirrhosis, it is also evident that synthesis of anticoagulant factors and fibrinolytic proteins produced in the liver is also diminished. Similarly, the decreased platelet count may be counterbalanced by increased platelet aggregability caused by highly active von Willebrand multimeres. The coagulation system is therefor stated to be rebalanced. While under normal "unstressed" conditions diffuse bleeding is rarely observed, however both diffuse bleeding or thrombus formation may occur when compensation mechanisms are exhausted. While most patients presenting for liver transplantation have severe cirrhosis, liver function and thus production of pro- and anticoagulant factors can be preserved especially in cholestatic liver disease. During liver transplantation, profound changes in the hemostasis system can occur. Surgical bleeding can lead to diffuse bleeding as coagulation factors and platelets are already reduced. Ischemia and tissue trauma can lead to alterations of hemostasis comparable to trauma induced coagulopathy. A further common disturbance often starting with the reperfusion of the transplanted organ is hyperfibrinolysis which can eventually precipitate complete consumption of fibrinogen and an endogenous heparinization by glycocalyx shedding. Moreover, thrombotic events inliver transplantations are not uncommon and contribute to increased mortality. Besides conventional laboratory methods, bed-side monitoring of hemostasis(e.g., thrombelastography, thrombelastometry) is often used during liver transplantation to rapidly diagnose decreases in fibrinogen and platelet count as well as hyperfibrinolysis and to guide treatment with blood products, factor concentrates, and antifibrinolytics. There is also evidence which suggests when algorithms based on bed-side hemostasis monitoring are used a reduction of blood loss, blood product use, and eventual mortality are possible. Notably, the bed-side monitoring of anticoagulant pathways and the thrombotic risk is not possible at time and thus a cautious and restrictive use of blood products is recommended.展开更多
BACKGROUND Hemostasis of patients suffering from liver cirrhosis is challenging due to both,pro-and anticoagulatory disorders leading to hemostatic alterations with distinct abnormalities of coagulation.Pathological c...BACKGROUND Hemostasis of patients suffering from liver cirrhosis is challenging due to both,pro-and anticoagulatory disorders leading to hemostatic alterations with distinct abnormalities of coagulation.Pathological changes in conventional coagulation analysis and platelet count are common manifestations of decreased liver synthesis of coagulation factors and reduced platelet count in these patients.However,conventional coagulation analysis and platelet count do not reflect invivo coagulation status or platelet function.The purpose of this present observational study was therefore to assess the haemostatic profile including plasmatic coagulation using thrombelastometry and impedance aggregometry for platelet function in patients suffering from liver cirrhosis.AIM To assess the hemostatic profile of cirrhotic patients according to model for endstage liver disease(MELD)score.METHODS Our study included both in-and outpatients suffering from liver cirrhosis attending the out-and inpatient care of the department of hepatology.Demographic and biochemical data as well as medical history including cause of liver cirrhosis,end stage kidney failure and medication with anticoagulants were recorded.To assess the hemostatic profile,platelet function was analyzed by multiple electrode aggregometry(MEA)using Multiplate^■(ADP-,ASPI-and TRAP-test)and thrombelastometry using ROTEM^■(EXTEM,INTEM,FIBTEM).Data were compared using Mann-Whitney U-or χ^2-test.Spearman correlation was performed to analyze the association between MELD Score and results of thrombelastometry and MEA.RESULTS A total of 68 patients attending the out-and inpatient care suffering from liver cirrhosis were screened.Of these,50 patients were included and assigned to groups according to MELD score 6 to 11(n=25)or≥17(n=25).Baseline patient characteristics revealed significant differences for MELD score(8 vs 22,P<0.0001)and underlying laboratory parameters(international normalized ratio,bilirubine,creatinine)as well as fibrinogen level(275 mg/dL vs 209 mg/dL,P=0.006)and aPTT(30 s vs 35 s,P=0.047).MEA showed a moderately impaired platelet function(medians:AUCADP=43U,AUCASPI=71U,AUCTRAP=92U)but no significant differences between both groups.Thrombelastometry using ROTEM?(EXTEM,INTEM,FIBTEM)revealed values within normal range in both groups.No significant correlation was observed between MELD score and results of MEA/thrombelastometry.CONCLUSION Our data demonstrate a partially impaired hemostatic profile in liver cirrhosis patients unrelated to MELD score.An individual assessment of a potential coagulopathy should therefore be considered.展开更多
BACKGROUND Conventional coagulation tests are widely used in chronic liver disease to assess haemostasis and to guide blood product transfusion.This is despite the fact that conventional tests do not reliably separate...BACKGROUND Conventional coagulation tests are widely used in chronic liver disease to assess haemostasis and to guide blood product transfusion.This is despite the fact that conventional tests do not reliably separate those with a clinically significant coagulopathy from those who do not.Viscoelastic testing such as thromboelastography(TEG)correlate with bleeding risk and are more accurate in identifying those who will benefit from blood product transfusion.Despite this,viscoelastic tests have not been widely used in patients with chronic liver disease outside the transplant setting.AIM To assess the utility of Viscoelastic Testing guided transfusion in chronic liver disease patients presenting with bleeding or who require an invasive procedure.METHODS PubMed and Google Scholar searches were performed using the key words“thromboelastography”,“TEG”or“viscoelastic”and“liver transplantation”,“cirrhosis”or“liver disease”and“transfusion”,“haemostasis”,“blood management”or“haemorrhage”.A full text review was undertaken and data was extracted from randomised control trials that evaluated the outcomes of viscoelastic test guided transfusion in those with liver disease.The study subjects,inclusion and exclusion criteria,methods,outcomes and length of follow up were examined.Data was extracted by two independent individuals using a standardized collection form.The risk of bias was assessed in the included studies.RESULTS A total of five randomised control trials included in the analysis examined the use of TEG guided blood product transfusion in cirrhosis prior to invasive procedures(n=118),non-variceal haemorrhage(n=96),variceal haemorrhage(n=60)and liver transplantation(n=28).TEG guided transfusion was effective in all five studies with a statistically significant reduction in overall blood product transfusion compared to standard of care.Four of the five studies reported a significant reduction in transfusion of fresh frozen plasma and platelets.Two studies showed a significant reduction in cryoprecipitate transfusion.No increased risk of bleeding was reported in the three trials where TEG was used perioperatively or prior to an invasive procedure.Two trials in the setting of cirrhotic variceal and non-variceal bleeding showed no difference in control of initial bleeding.In those with variceal bleeding,there was a statistically significant reduction in rate of re-bleeding at 42 d in the TEG arm 10%(vs 26.7%in the standard of care arm P=0.012).Mortality data reported at various time points for all five trials from 6 wk up to 3 years was not statistically different between each arm.One trial in the setting of non-variceal bleeding demonstrated a significant reduction in adverse transfusion events in the TEG arm 30.6%(vs 74.5%in the control arm P<0.01).In this study there was no significant difference in total hospital stay although length of stay in intensive care unit was reduced by an average of 2 d in the TEG arm(P=0.012).CONCLUSION Viscoelastic testing has been shown to reduce blood product usage in chronic liver disease without compromising safety and may enable guidelines to be developed to ensure patients with liver disease are optimally managed.展开更多
文摘Recent findings in the pathophysiology and monitoring of hemostasis in patients with end stage liver disease have major impact on coagulation management during liver transplantation. There is increasing evidence, that the changes in both coagulation factors and platelet count regularly observed in patients with liver cirrhosis cannot be interpreted as a reliable indicator of diffuse bleeding risk. Instead, a differentiated view on hemostasis has led to the concept of a rebalanced coagulation system: While it is important to recognize that procoagulant factors are reduced in liver cirrhosis, it is also evident that synthesis of anticoagulant factors and fibrinolytic proteins produced in the liver is also diminished. Similarly, the decreased platelet count may be counterbalanced by increased platelet aggregability caused by highly active von Willebrand multimeres. The coagulation system is therefor stated to be rebalanced. While under normal "unstressed" conditions diffuse bleeding is rarely observed, however both diffuse bleeding or thrombus formation may occur when compensation mechanisms are exhausted. While most patients presenting for liver transplantation have severe cirrhosis, liver function and thus production of pro- and anticoagulant factors can be preserved especially in cholestatic liver disease. During liver transplantation, profound changes in the hemostasis system can occur. Surgical bleeding can lead to diffuse bleeding as coagulation factors and platelets are already reduced. Ischemia and tissue trauma can lead to alterations of hemostasis comparable to trauma induced coagulopathy. A further common disturbance often starting with the reperfusion of the transplanted organ is hyperfibrinolysis which can eventually precipitate complete consumption of fibrinogen and an endogenous heparinization by glycocalyx shedding. Moreover, thrombotic events inliver transplantations are not uncommon and contribute to increased mortality. Besides conventional laboratory methods, bed-side monitoring of hemostasis(e.g., thrombelastography, thrombelastometry) is often used during liver transplantation to rapidly diagnose decreases in fibrinogen and platelet count as well as hyperfibrinolysis and to guide treatment with blood products, factor concentrates, and antifibrinolytics. There is also evidence which suggests when algorithms based on bed-side hemostasis monitoring are used a reduction of blood loss, blood product use, and eventual mortality are possible. Notably, the bed-side monitoring of anticoagulant pathways and the thrombotic risk is not possible at time and thus a cautious and restrictive use of blood products is recommended.
文摘BACKGROUND Hemostasis of patients suffering from liver cirrhosis is challenging due to both,pro-and anticoagulatory disorders leading to hemostatic alterations with distinct abnormalities of coagulation.Pathological changes in conventional coagulation analysis and platelet count are common manifestations of decreased liver synthesis of coagulation factors and reduced platelet count in these patients.However,conventional coagulation analysis and platelet count do not reflect invivo coagulation status or platelet function.The purpose of this present observational study was therefore to assess the haemostatic profile including plasmatic coagulation using thrombelastometry and impedance aggregometry for platelet function in patients suffering from liver cirrhosis.AIM To assess the hemostatic profile of cirrhotic patients according to model for endstage liver disease(MELD)score.METHODS Our study included both in-and outpatients suffering from liver cirrhosis attending the out-and inpatient care of the department of hepatology.Demographic and biochemical data as well as medical history including cause of liver cirrhosis,end stage kidney failure and medication with anticoagulants were recorded.To assess the hemostatic profile,platelet function was analyzed by multiple electrode aggregometry(MEA)using Multiplate^■(ADP-,ASPI-and TRAP-test)and thrombelastometry using ROTEM^■(EXTEM,INTEM,FIBTEM).Data were compared using Mann-Whitney U-or χ^2-test.Spearman correlation was performed to analyze the association between MELD Score and results of thrombelastometry and MEA.RESULTS A total of 68 patients attending the out-and inpatient care suffering from liver cirrhosis were screened.Of these,50 patients were included and assigned to groups according to MELD score 6 to 11(n=25)or≥17(n=25).Baseline patient characteristics revealed significant differences for MELD score(8 vs 22,P<0.0001)and underlying laboratory parameters(international normalized ratio,bilirubine,creatinine)as well as fibrinogen level(275 mg/dL vs 209 mg/dL,P=0.006)and aPTT(30 s vs 35 s,P=0.047).MEA showed a moderately impaired platelet function(medians:AUCADP=43U,AUCASPI=71U,AUCTRAP=92U)but no significant differences between both groups.Thrombelastometry using ROTEM?(EXTEM,INTEM,FIBTEM)revealed values within normal range in both groups.No significant correlation was observed between MELD score and results of MEA/thrombelastometry.CONCLUSION Our data demonstrate a partially impaired hemostatic profile in liver cirrhosis patients unrelated to MELD score.An individual assessment of a potential coagulopathy should therefore be considered.
文摘BACKGROUND Conventional coagulation tests are widely used in chronic liver disease to assess haemostasis and to guide blood product transfusion.This is despite the fact that conventional tests do not reliably separate those with a clinically significant coagulopathy from those who do not.Viscoelastic testing such as thromboelastography(TEG)correlate with bleeding risk and are more accurate in identifying those who will benefit from blood product transfusion.Despite this,viscoelastic tests have not been widely used in patients with chronic liver disease outside the transplant setting.AIM To assess the utility of Viscoelastic Testing guided transfusion in chronic liver disease patients presenting with bleeding or who require an invasive procedure.METHODS PubMed and Google Scholar searches were performed using the key words“thromboelastography”,“TEG”or“viscoelastic”and“liver transplantation”,“cirrhosis”or“liver disease”and“transfusion”,“haemostasis”,“blood management”or“haemorrhage”.A full text review was undertaken and data was extracted from randomised control trials that evaluated the outcomes of viscoelastic test guided transfusion in those with liver disease.The study subjects,inclusion and exclusion criteria,methods,outcomes and length of follow up were examined.Data was extracted by two independent individuals using a standardized collection form.The risk of bias was assessed in the included studies.RESULTS A total of five randomised control trials included in the analysis examined the use of TEG guided blood product transfusion in cirrhosis prior to invasive procedures(n=118),non-variceal haemorrhage(n=96),variceal haemorrhage(n=60)and liver transplantation(n=28).TEG guided transfusion was effective in all five studies with a statistically significant reduction in overall blood product transfusion compared to standard of care.Four of the five studies reported a significant reduction in transfusion of fresh frozen plasma and platelets.Two studies showed a significant reduction in cryoprecipitate transfusion.No increased risk of bleeding was reported in the three trials where TEG was used perioperatively or prior to an invasive procedure.Two trials in the setting of cirrhotic variceal and non-variceal bleeding showed no difference in control of initial bleeding.In those with variceal bleeding,there was a statistically significant reduction in rate of re-bleeding at 42 d in the TEG arm 10%(vs 26.7%in the standard of care arm P=0.012).Mortality data reported at various time points for all five trials from 6 wk up to 3 years was not statistically different between each arm.One trial in the setting of non-variceal bleeding demonstrated a significant reduction in adverse transfusion events in the TEG arm 30.6%(vs 74.5%in the control arm P<0.01).In this study there was no significant difference in total hospital stay although length of stay in intensive care unit was reduced by an average of 2 d in the TEG arm(P=0.012).CONCLUSION Viscoelastic testing has been shown to reduce blood product usage in chronic liver disease without compromising safety and may enable guidelines to be developed to ensure patients with liver disease are optimally managed.