Antithrombin effect on coagulation and fibrinolytic profiles after living donor liver transplantation: a pilot study

Abstract

Early after liver transplantation, patients are in a hypercoagulable state because of an imbalance between coagulation and fibrinolysis because of the slow recovery of depleted anticoagulant proteins. Antithrombin (AT) is used in anticoagulant protocols to prevent thrombosis. The subjects of the present study were 17 men and eight women that underwent living donor liver transplantation. The initial 15 cases were administered AT concentrate (1500 U/day) on postoperative days (POD) 1 through 3 (AT group) and the following 10 consecutive cases were not administered AT (control). AT, thrombin-AT complex, plasmin-alpha2 plasmin inhibitor complex, thrombomodulin, fibrin degradation product D-dimer (FDP-DD) level, prothrombin time international normalized ratio, activated partial thromboplastin time, and platelet counts were measured. In the AT group, AT activity was maintained at levels >80% for 5 days after transplantation. In the control group, AT activity did not return to normal during the first 2 weeks after the operation. FDP-DD levels were significantly higher in the control group than in the AT group (P < 0.05). Six patients in the control group and three patients in the AT group required transfusions with platelet concentrate (P < 0.05). AT supplementation might reduce FDP-DD levels and prevent decreased platelet counts in the early stages after liver transplantation.

Effects of plasma transfusions on antithrombin levels after paediatric liver transplantation

“…As plasma transfusions only marginally increase AT levels, some authors have evaluated the effect of AT concentrates. They have shown that AT concentrates can efficiently increase AT levels as they cause less hemodilution . This has mostly been evaluated in extracorporeal membrane oxygenation (ECMO), another clinical situation with a potential imbalance between pro‐ and anticoagulant factors, in which there is possibly some value in correcting low AT levels .…”

Pharmacokinetics of human antithrombin III concentrate in the immediate postoperative period after liver transplantation

“…Therefore the recovery of endogenous AT‐III activity was modelled independent of the administration of exogenous dose of AT‐III in this study. The recovery of endogenous AT‐III activity level after liver transplantation was modelled using an E max model as follows; where the AT3 max is the maximum recovered AT‐III activity level during PODs and the T 50 is the time to recover half of AT3 max level . Every subject had a predose AT‐III activity level, so the observed value was used for the model.…”

“…Risk factors of thrombotic complications include hypercoagulability, poor surgical technique, and anatomical variation . A hypercoagulable state due to the imbalance between stimulated coagulation activity and impaired fibrinolysis activity is often observed in the early postoperative period after liver transplantation . Preoperative prolonged hepatic dysfunction and delayed recovery of the transplanted graft may lead to depletion of anticoagulation factors.…”

“…Preoperative prolonged hepatic dysfunction and delayed recovery of the transplanted graft may lead to depletion of anticoagulation factors. Plasma AT‐III activity levels have been reported to decrease to as low as 80% of the preoperative level in the early post‐transplant period and gradually normalize in the first 2 weeks after transplantation . Since lower plasma activity levels of AT‐III might be associated with hepatic artery thrombosis, AT‐III supplementation has been widely considered.…”

“…Intensive anticoagulation therapy including AT‐III was reported to markedly decrease the incidence of HAT after paediatric liver transplantation . Kaneko et al advocated AT‐III administration early after liver transplantation based on their results of a pilot study that it might reduce fibrin degradation product D‐dimer (FDP‐DD) levels . Another study showed that lower AT‐III activity was associated with portal vein thrombosis after splenectomy in patients with liver cirrhosis .…”