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Bleeding and thrombotic complications of pediatric liver transplant.

ABSTRACT: BACKGROUND:Pediatric patients undergoing liver transplant are at significant risk for bleeding and thrombotic complications due to the complex nature of rebalanced hemostasis in patients with liver disease. METHODS/OBJECTIVES:We reviewed records of 92 pediatric liver and multivisceral transplant cases at Duke University Medical Center between January 2009 and December 2015. The goal was to define the nature and incidence of bleeding and thrombotic complications in this cohort and define potential risk factors. RESULTS:There were 24 major bleeding events in 19 transplants (incidence 20.7%) and 30 thrombotic events in 23 transplants (incidence 25%). Five of the 10 retransplantations were for vascular thrombotic complications. Thirty-day mortality was 4.9%, and three of these four deaths were due to vascular thrombosis. No bleeding events led to retransplantation or mortality. Prophylactic aspirin was associated with decreased risk of thrombosis without increased bleeding. Prophylactic heparin did not increase bleeding risk. Laboratory assays predicted events poorly, apparently failing to capture the nuanced and dynamic interplay between pro- and anticoagulant factors in the posttransplant patient. CONCLUSIONS:Both bleeding and thrombosis are frequent in this population, but only thrombotic complications contributed to retransplantation and mortality. A standardized approach to coagulation testing and antithrombotic therapy may be useful in predicting and reducing adverse outcomes. Alternative approaches to monitoring hemostasis need to be prospectively investigated in this complex patient population.

SUBMITTER: Borst AJ

PROVIDER: S-EPMC5867241 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Bleeding and thrombotic complications of pediatric liver transplant.

Borst Alexandra J AJ Sudan Debra L DL Wang Laura A LA Neuss Michael J MJ Rothman Jennifer A JA Ortel Thomas L TL

Pediatric blood & cancer 20180119 5

<h4>Background</h4>Pediatric patients undergoing liver transplant are at significant risk for bleeding and thrombotic complications due to the complex nature of rebalanced hemostasis in patients with liver disease.<h4>Methods/objectives</h4>We reviewed records of 92 pediatric liver and multivisceral transplant cases at Duke University Medical Center between January 2009 and December 2015. The goal was to define the nature and incidence of bleeding and thrombotic complications in this cohort and ...[more]

PMID: 29350493

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Project description:End stage liver disease (ESLD) is associated with significant thrombotic complications. In this study, we attempted to determine if patients with ESLD, due to oncologic or autoimmune diseases, are susceptible to thrombosis to a greater extent than patients with ESLD due to other causes.In this retrospective study, we analyzed the UNOS database to determine the incidence of thrombotic complications in orthotopic liver transplant (OLT) recipients with autoimmune and oncologic conditions. Between 2000 and 2012, 65,646 OLTs were performed. We found 4,247 cases of preoperative portal vein thrombosis (PVT) and 1,233 cases of postoperative vascular thrombosis (VT) leading to graft failure.Statistical evaluation demonstrated that patients with either hepatocellular carcinoma (HCC) or autoimmune hepatitis (AIC) had a higher incidence of PVT (p = 0.05 and 0.03 respectively). Patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and AIC had a higher incidence of postoperative VT associated with graft failure (p < 0.0001, p < 0.0001, p = 0.05 respectively). Patients with preoperative PVT had a higher incidence of postoperative VT (p < 0.0001). Multivariable logistic regression demonstrated that patients with AIC, and BMI ≥40, having had a transjugular intrahepatic portosystemic shunt, and those with diabetes mellitus were more likely to have preoperative PVT: odds ratio (OR)(1.36, 1.19, 1.78, 1.22 respectively). Patients with PSC, PBC, AIC, BMI ≤18, or with a preoperative PVT were more likely to have a postoperative VT: OR (1.93, 2.09, 1.64, 1.60, and 2.01, respectively).Despite the limited number of variables available in the UNOS database potentially related to thrombotic complications, this analysis demonstrates a clear association between autoimmune causes of ESLD and perioperative thrombotic complications. Perioperative management of patients at risk should include strategies to reduce the potential for these complications.

Project description:In patients with acute liver failure (ALF), elevated prothrombin time and thrombocytopenia can fuel a perception of a bleeding tendency. However, the incidence, site, risk factors, and clinical significance of bleeding complications have not been quantified in a large cohort of patients with ALF. We studied 1,770 adult patients enrolled in the ALF Study Group Registry between 1998 and 2016. Bleeding complications and blood component transfusions were collected for 7 days after admission. The relationship of bleeding complications to 21-day mortality was assessed. Despite a median international normalized ratio of 2.7 and platelet count of 96?×?109 /L on admission, bleeding complications were observed in only 187 patients (11%), including 173 spontaneous and 22 postprocedural bleeding episodes. Eighty-four percent of spontaneous bleeding episodes were from an upper gastrointestinal source and rarely resulted in red blood cell transfusion. Twenty patients experienced an intracranial bleed; half of these occurred spontaneously and half after intracranial pressure monitor placement, and this was the proximate cause of death in 20% and 50%, respectively. Bleeders and patients who received red blood cell transfusions were more acutely ill from extrahepatic organ system failure but not from hepatocellular failure. Consistent with this observation, bleeding complications were associated with lower platelet counts but not higher international normalized ratio. Transfusion of any blood component was associated with nearly 2-fold increased death or need for liver transplantation at day 21, but bleeding complications were the proximate cause of death in only 5% of cases. CONCLUSIONS:Despite a perceived bleeding diathesis, clinically significant bleeding is uncommon in patients with ALF; bleeding complications in patients with ALF are markers of severe systemic inflammation rather than of coagulopathy and so portend a poor prognosis. (Hepatology 2018;67:1931-1942).

Project description:Hepatic steatosis develops after liver transplantation (LT) in 30% of adults, and nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in nontransplanted children. However, posttransplant steatosis has been minimally studied in pediatric LT recipients. We explored the prevalence, persistence, and association with chronic liver damage of hepatic steatosis in these children. In this single-center study of pediatric patients transplanted 1988-2015 (n?=?318), 31% of those with any posttransplant biopsy (n?=?271) had???1 biopsy with steatosis. Median time from transplant to first biopsy with steatosis was 0.8 months (interquartile range [IQR], 0.3-6.5 months) and to last biopsy with steatosis was 5.5 months (IQR, 1.0-24.5 months); 85% of patients with steatosis also had for-cause biopsies without steatosis. All available for-cause biopsies were re-evaluated (n?=?104). Of 9 biopsies that could be interpreted as nonalcoholic steatohepatitis (NASH)/borderline NASH, with steatosis plus inflammation or ballooning, 8 also had features of cholestasis or rejection. Among 70 patients with surveillance biopsies 3.6-20.0 years after transplant, only 1 overweight adolescent had a biopsy with NAFLD (grade 1 steatosis, mild inflammation, no ballooning or fibrosis)-despite a 30% prevalence of overweight/obesity in the cohort and 27% with steatosis on previous for-cause biopsy. Steatosis on preceding for-cause biopsy was not associated with portal (P?=?0.49) or perivenular fibrosis (P?=?0.85) on surveillance biopsy. Hepatic steatosis commonly develops early after transplant in children and adolescents, but it rarely persists. Biopsies that did have steatosis with NASH characteristics were all for-cause, mostly in patients with NAFLD risk factors and/or confounding causes of liver damage. Prospective studies that follow children into adulthood will be needed to evaluate if and when hepatic steatosis presents a longterm risk for pediatric LT recipients. Liver Transplantation 23 957-967 2017 AASLD.

Project description:BackgroundPrediction of thrombotic and bleeding risk is important to optimize antithrombotic therapy after percutaneous coronary intervention.Methods and resultsWe developed the prediction rules for thrombotic and bleeding events separately in Japanese patients. Derivation and validation cohorts consisted of 4778 patients from CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) registry cohort 2 and 4669 patients from RESET (Randomized Evaluation of Sirolimus-Eluting Versus Everolimus-Eluting Stent Trial) and NEXT (Nobori Biolimus-Eluting Versus Xience/Promus Everolimus-Eluting Stent Trial). Primary thrombotic and bleeding events were a composite of myocardial infarction, definite or probable stent thrombosis or ischemic stroke, and GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) moderate or severe bleeding. The prediction rule for thrombosis assigned 2 points for severe chronic kidney disease, atrial fibrillation, peripheral vascular disease, and anemia and 1 point for age ?75 years, heart failure, diabetes mellitus, and chronic total occlusion. The prediction rule for bleeding assigned 2 points for thrombocytopenia, severe chronic kidney disease, peripheral vascular disease, and heart failure and 1 point for prior myocardial infarction, malignancy, and atrial fibrillation. In derivation and validation cohorts, area under the curve was 0.68 and 0.64, respectively, for thrombosis and 0.66 and 0.66, respectively, for bleeding. In the validation cohort, a high thrombosis risk score (?4, n=682) was associated with higher 3-year incidence of thrombotic events than a score that was intermediate (2-3, n=1178) or low (0-1, n=2809) (7.6%, 3.7%, versus 2.4%, respectively; P<0.0001). A high bleeding risk score (?3, n=666) was associated with higher incidence of bleeding than scores that were intermediate (1-2, n=1802) or low (0, n=2201) (8.8%, 4.1%, versus 2.3%, respectively; P<0.0001). Among 682 patients at high thrombotic risk, only 39 (5.7%) had low bleeding risk, whereas 401 (58.8%) had high bleeding risk with very high incidence of bleeding (11.6%).ConclusionsCREDO-Kyoto thrombotic and bleeding risk scores demonstrated modest accuracy in stratifying thrombotic and bleeding risks; however, a large proportion of patients at high thrombotic risk also had high bleeding risk.

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Bleeding and thrombotic complications of pediatric liver transplant.

Publications

Bleeding and thrombotic complications of pediatric liver transplant.

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