CO044 | QUALITY AND SAFETY OF VITAMIN K ANTAGONIST TREATMENT IN PEDIATRIC PATIENTS: A RETROSPECTIVE CLINICAL AUDIT FROM A SINGLE CENTER

C. Ambaglio¹, T. Zollner¹, G. Cuni¹, S. Bolognini¹, C. Ticozzi¹, F. Schieppati¹, E. Galimberti¹, O.C. Cretu¹, V. Brusegan¹, F. Zunino¹, F. Duca², M. Marchetti¹, A. Falanga^1|2, L. Barcella¹ | ¹Immunohematology and Transfusion Medicine, Department of Transfusion Medicine and Hematology, ERN-EuroBloodNet - European Reference Network in Rare Hematological Diseases, ASST Papa Giovanni XXIII, Bergamo, Italy; ²School of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy

Background and aims. The knowledge of the quality and safety of vitamin K antagonists in pediatric patients is limited. In children the time-in-therapeutic-range (TTR) achievement has been reported between 39% and 81%, while warfarin-related major bleeding rates range from 0.5% to 1.7% per year.
Methods. A retrospective clinical audit has been conducted to evaluate the characteristics and rates of bleeding in long-term follow-up and identify possible hemorrhagic risk factors. All patients used a point-of-care device for INR determination. The TTR is calculated using the Rosendaal method. TTR > 65% has been considered optimal. Major bleeding refers to the ISTH definition. Patients are in anticoagulation for mechanical valve replacement (group A, 8 patients), other post-surgical congenital cardiopathies, mainly Fontan surgery (group B, 48 patients), and thrombotic disease (group C, 3 patients). Grade 1, 2, and 3 types of bleeding according to the CTCAE classification occurred in our population. No grade 4 and 5 events were observed. We evaluated age, suboptimal TTR, indication for anticoagulation in relation to quality of INR control, and type of bleeding. Among grade 3 bleeds, only two could be classified as major. Associations between categorical variables were assessed using Pearson’s chi-square test. All statistical analyses were performed using SPSS version 21.0 (IBM Corporation), and a two-tailed p-value < 0.05 was considered statistically significant.
Results. Included were 59 consecutive patients (45 male, 14 female, median age 11), actively in follow-up at our outpatient service for vitamin K antagonists (VKA) monitoring. Median duration of follow-up was 6 years (range 10-0.5). The median TTR percentage was 63.3%, and the mean value was 65.1%. Nine patients received pediatric formulations of warfarin; 3 patients received acenocumarol, while 47 commercial tablets of warfarin were given. There were 8 cases with at least one grade 1 bleeding event, 8 cases with grade 2, and 8 with grade 3 bleeding events. With a total follow-up of 375 person-years, the incidence rate of all hemorrhagic events was 0.064 per person-year (6.4% per year). The major bleeding event rate was 0.005 per person-year (0.5% per year). No significant correlation has been found between TTR and age; grade 1 and grade 2 bleeding and age; non-optimal TTR; type of indication; grade 3 events and age; and non-optimal TTR. Group B indication correlates to less probability of grade 3 bleeding (p=0.014), while patients with prosthetic heart valve replacement have a higher risk of grade 3 bleeding (p=0.034) despite a median TTR of 83%.
Conclusions. Our data confirm good INR control when considering TTR and incidence of major bleeding among pediatric patients. Among all types of hemorrhage, the highest risk of events requiring medical intervention was observed in patients with mechanical prosthetic heart valves.