Cirrhotic children who are waitlisted for liver transplantation are prone to bleeding from ruptured esophageal varices, with Grade 2-3 varices and red signs as known risk factors. The involvement of hemostasis remains controversial due to the rebalanced coagulation during cirrhosis.
Material and methods
This was a prospective observational study involving children with portal hypertension and decompensated cirrhosis. Portal hypertension was assessed by ultrasound and endoscopy, whereas hemostasis was evaluated using dynamic parameters of thromboelastometry (ROTEM®) and platelet function analysis (Multiplate®), in addition to conventional laboratory tests. The clinical endpoint was the occurrence of upper gastrointestinal bleeding. The above-mentioned parameters were compared between children with and without bleeding using univariate statistical methods. Furthermore, an earlier developed predictive model for estimating the risk of variceal bleeding, comprising Grade 2-3 varices, red spots on upper endoscopy, and fibrinogen levels <150mg/dL, was applied to our prospective cohort.
In total, 20 children were included in the study, of which 18 exhibited biliary atresia, with a median age of 9 months (range:4-129). Six of them were classified in the bleeding group since they had upper gastrointestinal bleeding during the pre-transplant period. No statistically significant difference was noted between the two groups regarding waiting time prior to transplantation, presence and severity of esophageal varices, Factor V levels (49% vs. 70%), INR (1.8 vs. 1.5), and platelet counts (104 10e3/µL vs. 219 10e3/µL). However, significant differences were observed with respect to fibrinogen levels (109mg/dL vs. 257mg/dL, p<0.05), platelet adenosine diphosphate (ADP)-dependent platelet aggregation (103 AU/min vs. 368AU/min, p<0.05), thrombin-dependent platelet aggregation (265 AU/min vs. 558 AU/min, p<0.05), and clotting time (64 sec vs. 52 sec, p<0.05) in EXTEM analysis. The predictive model of bleeding risk was tested in our prospective cohort, yielding a predictive performance (accuracy) of 85.18% (sensitivity 90.5%, specificity 66.7%, negative predictive value [NPV] 90.5%, and positive predictive value [PPV] 66.7%).
Our study demonstrated that hemostasis is involved in the risk of bleeding from esophageal varices. Low fibrinogen levels were identified as a risk factor for bleeding in children with decompensated cirrhosis, thus suggesting the potential benefit of prophylactic fibrinogen administration in high-risk cases. In the future, the Multiplate® analysis should aid practitioners determining the risk of esophageal variceal bleeding in children with decompensated cirrhosis, and it may possibly be integrated in our predictive model.
1 Université catholique de Louvain, Cliniques universitaires Saint-Luc, Service de Gastroentérologie et Hépatologie Pédiatrique, Bruxelles, Belgique.
2 Université catholique de Louvain, Cliniques universitaires Saint-Luc, Service d’Anesthésiologie, Bruxelles, Belgique.
3 DNAlytics, Louvain-la-Neuve, Belgique.
4 Université catholique de Louvain, Cliniques universitaires Saint-Luc, Service de Biologie Hématologique, Bruxelles, Belgique.
5 Université catholique de Louvain, Cliniques universitaires Saint-Luc, Service d’Hématologie, Bruxelles, Belgique.