A novel anticoagulation protocol increased levels of antithrombin III, protein C and S after liver transplantation in children and resulted in a reduced incidence of hepatic artery thrombosis
Aimee Dai1, Gordon Thomas3, Michael Stormon4, Albert Shun3, Juliana Teo5, Juliana Puppi4, Elena Cavazzoni2.
1Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; 2Pediatric Intensive Care Unit, Children's Hospital at Westmead, Sydney, Australia; 3Department of Surgery, Children's Hospital at Westmead, Sydney, Australia; 4Department of Gastroenterology, Children's Hospital at Westmead, Sydney, Australia; 5Department of Haematology, Children's Hospital at Westmead, Sydney, Australia
Introduction: Hepatic artery thrombosis (HAT) is an uncommon but highly morbid complication after liver transplantation in children. This study aims to justify an anticoagulation protocol for the prevention of HAT.
Methods: Paediatric liver transplants performed between January 2008 and December 2018 were reviewed retrospectively and grouped into two epochs for analysis. In Epoch 1 from January 2008 to June 2012, each patient received a standard dose of heparin and coagulation profiles normalised passively after liver transplantation. In Epoch 2 from July 2012 to December 2018, an anticoagulation protocol was introduced to promote normalisation of anticoagulant factor levels after liver transplantation. Each patient received: an intraoperative dose of antithrombin concentrate (1000 IU for 0-30 kg, 2000 IU for 30-60 kg) after implantation of the liver and two additional doses 24 hours apart to replace antithrombin III (AT-III); 20ml/kg/day of fresh frozen plasma for three days to replace Protein C (PC) and Protein S (PS), continued thereafter until the patient maintained PC and PS levels above 50% without support; and unfractionated heparin (10-20 U/kg/h) for one week. HAT was defined as thrombus or occlusion of hepatic artery as diagnosed by doppler ultrasound, CT angiogram or laparotomy.
Results: A total of 181 transplant events involving 173 patients were included in this study. Over the first seven postoperative days, mean AT-III level was 54.8% in Epoch 1 and significantly higher at 101.5% in Epoch 2 (P<0.001). Likewise, mean PC activity level was 45.7% in Epoch 1 and was significantly higher at 59.4% in Epoch 2 (P<0.001). Mean free PS level was 56.2% in Epoch 1 and was significantly higher at 76.5% in Epoch 2 (P<0.001). HAT incidence was 9.8% in Epoch 1 and 3.1% in Epoch 2. Incidence of postoperative bleeding complications was 37.3% in Epoch 1 and significantly lower at 20.8% in Epoch 2 (P=0.02).
Conclusion: A novel anticoagulation protocol significantly increased anticoagulant factor levels in the first seven days following liver transplantation in children, which correlated to a reduction in the incidence of HAT and bleeding complications.
[1] Hepatic Artery Thrombosis
[2] Liver Transplantation
[3] Pediatric
[4] Antithrombin
[5] Protein C
[6] Protein S
