MARS and Hemostasis in Patients at High Risk of Bleeding
MARS and Hemostasis in Patients at High Risk of Bleeding
Introduction: Liver failure is associated with reduced synthesis of clotting factors, consumptive coagulopathy, and platelet dysfunction. The aim of the study was to evaluate the effects of liver support using a molecular adsorbent recirculating system (MARS) on the coagulation system in patients at high risk of bleeding.
Methods: We studied 61 MARS treatments in 33 patients with acute liver failure (n = 15), acute-on-chronic liver failure (n = 8), sepsis (n = 5), liver graft dysfunction (n = 3), and cholestasis (n = 2). Standard coagulation tests, standard thromboelastography (TEG), and heparinase-modified and abciximab-fab-modified TEG were performed immediately before and 30 minutes after commencement of MARS, and after the end of MARS treatment. Prostaglandin I2 was administered extracorporeally to all patients; 17 patients additionally received unfractioned heparin.
Results: Three moderate bleeding complications in three patients, requiring three to four units of packed red blood cells, were observed. All were sufficiently managed without interrupting MARS treatment. Although there was a significant decrease in platelet counts (median, 9 G/l; range, -40 to 145 G/ l) and fibrinogen concentration (median, 15 mg/dl; range, -119 to 185 mg/dl) with a consecutive increase in thrombin time, the platelet function, as assessed by abciximab-fab-modified TEG, remained stable. MARS did not enhance fibrinolysis.
Conclusion: MARS treatment appears to be well tolerated during marked coagulopathy due to liver failure. Although MARS leads to a further decrease in platelet count and fibrinogen concentration, platelet function, measured as the contribution of the platelets to the clot firmness in TEG, remains stable. According to TEG-based results, MARS does not enhance fibrinolysis.
The molecular adsorbent recirculating system (MARS) has been developed and successfully used in patients with liver failure to replace excretory liver function and detoxification. MARS is based on principles of albumin dialysis, and was shown to significantly improve hepatic encephalopathy, cerebral blood flow, renal function, and systemic hemodynamics. It has further been shown that plasma concentrations of ammonia and many albumin-bound molecules, such as bilirubin, decreased during MARS therapy. Nevertheless, improved outcome has been demonstrated in patients with hepatorenal syndrome and acute-on-chronic liver failure.
Patients with liver failure exhibit major disturbances of hemostasis and are thus at a very high risk of bleeding. Decreased synthesis of clotting and inhibitory factors, decreased clearance of activated factors, quantitative and qualitative platelet defects, hyperfibrinolysis, and accelerated intravascular coagulation may all be present together in these patients. Therefore, extracorporeal detoxification circuits, such as MARS, must be highly biocompatible and anticoagulatory measures to avoid clotting within the system must be tested for safety in such patients. On the basis of pathophysiological processes occurring after contact of blood with artificial surfaces, platelets are predominant in the genesis of extracorporeal thrombosis. Therefore, attempts to run extracorporeal circulation without anticoagulation may result in frequent circuit clotting, except in severely thrombocytopenic patients, but with the risk of a further platelet loss. Under these circumstances, extracorporeal inhibition of platelet function by prostaglandins combined with heparin has been shown to increase the biocompatibility of extracorporeal circulation.
The effects of extracorporeal support on hemostasis must be closely monitored in patients with liver failure to avoid major coagulation disbalances. The battery of traditional coagulation tests, which include prothrombin time, partial thromboplastin time, thrombin time, factor assays, and platelet function studies are based on isolated, static end points of standard laboratory tests. They do not take into account the interaction of the clotting cascade and platelets in whole blood. Thromboelastography (TEG) allows assessment of haemostatic function, documenting the interaction of platelets with the protein coagulation cascade from the time of the initial platelet-fibrin interaction, through platelet aggregation, clot strengthening, and fibrin cross linkage to eventual clot lysis. Moreover, different modified TEG methods allow the specific evaluation of platelet function and the effect of endogenous and/or exogenous heparinoids on plasmatic coagulation. Using a TEG-guided algorithm, a reduction of blood and fluid requirements during liver transplantation has been demonstrated.
In the present study, we evaluated the effects of anticoagulation regimens on the coagulation system and bleeding events in patients with liver failure undergoing MARS therapy. Traditional coagulation tests, standard TEG, and modified TEG were used to comprehensively monitor coagulation.
Abstract and Introduction
Abstract
Introduction: Liver failure is associated with reduced synthesis of clotting factors, consumptive coagulopathy, and platelet dysfunction. The aim of the study was to evaluate the effects of liver support using a molecular adsorbent recirculating system (MARS) on the coagulation system in patients at high risk of bleeding.
Methods: We studied 61 MARS treatments in 33 patients with acute liver failure (n = 15), acute-on-chronic liver failure (n = 8), sepsis (n = 5), liver graft dysfunction (n = 3), and cholestasis (n = 2). Standard coagulation tests, standard thromboelastography (TEG), and heparinase-modified and abciximab-fab-modified TEG were performed immediately before and 30 minutes after commencement of MARS, and after the end of MARS treatment. Prostaglandin I2 was administered extracorporeally to all patients; 17 patients additionally received unfractioned heparin.
Results: Three moderate bleeding complications in three patients, requiring three to four units of packed red blood cells, were observed. All were sufficiently managed without interrupting MARS treatment. Although there was a significant decrease in platelet counts (median, 9 G/l; range, -40 to 145 G/ l) and fibrinogen concentration (median, 15 mg/dl; range, -119 to 185 mg/dl) with a consecutive increase in thrombin time, the platelet function, as assessed by abciximab-fab-modified TEG, remained stable. MARS did not enhance fibrinolysis.
Conclusion: MARS treatment appears to be well tolerated during marked coagulopathy due to liver failure. Although MARS leads to a further decrease in platelet count and fibrinogen concentration, platelet function, measured as the contribution of the platelets to the clot firmness in TEG, remains stable. According to TEG-based results, MARS does not enhance fibrinolysis.
Introduction
The molecular adsorbent recirculating system (MARS) has been developed and successfully used in patients with liver failure to replace excretory liver function and detoxification. MARS is based on principles of albumin dialysis, and was shown to significantly improve hepatic encephalopathy, cerebral blood flow, renal function, and systemic hemodynamics. It has further been shown that plasma concentrations of ammonia and many albumin-bound molecules, such as bilirubin, decreased during MARS therapy. Nevertheless, improved outcome has been demonstrated in patients with hepatorenal syndrome and acute-on-chronic liver failure.
Patients with liver failure exhibit major disturbances of hemostasis and are thus at a very high risk of bleeding. Decreased synthesis of clotting and inhibitory factors, decreased clearance of activated factors, quantitative and qualitative platelet defects, hyperfibrinolysis, and accelerated intravascular coagulation may all be present together in these patients. Therefore, extracorporeal detoxification circuits, such as MARS, must be highly biocompatible and anticoagulatory measures to avoid clotting within the system must be tested for safety in such patients. On the basis of pathophysiological processes occurring after contact of blood with artificial surfaces, platelets are predominant in the genesis of extracorporeal thrombosis. Therefore, attempts to run extracorporeal circulation without anticoagulation may result in frequent circuit clotting, except in severely thrombocytopenic patients, but with the risk of a further platelet loss. Under these circumstances, extracorporeal inhibition of platelet function by prostaglandins combined with heparin has been shown to increase the biocompatibility of extracorporeal circulation.
The effects of extracorporeal support on hemostasis must be closely monitored in patients with liver failure to avoid major coagulation disbalances. The battery of traditional coagulation tests, which include prothrombin time, partial thromboplastin time, thrombin time, factor assays, and platelet function studies are based on isolated, static end points of standard laboratory tests. They do not take into account the interaction of the clotting cascade and platelets in whole blood. Thromboelastography (TEG) allows assessment of haemostatic function, documenting the interaction of platelets with the protein coagulation cascade from the time of the initial platelet-fibrin interaction, through platelet aggregation, clot strengthening, and fibrin cross linkage to eventual clot lysis. Moreover, different modified TEG methods allow the specific evaluation of platelet function and the effect of endogenous and/or exogenous heparinoids on plasmatic coagulation. Using a TEG-guided algorithm, a reduction of blood and fluid requirements during liver transplantation has been demonstrated.
In the present study, we evaluated the effects of anticoagulation regimens on the coagulation system and bleeding events in patients with liver failure undergoing MARS therapy. Traditional coagulation tests, standard TEG, and modified TEG were used to comprehensively monitor coagulation.