Characteristics and quality of oral anticoagulation treatment in pediatric patients in the Netherlands based on the CAPS cohort

Abstract

To cite this article: Maagdenberg H, Bierings MB, van Ommen CH, van der Meer FJM, Appel IM, Tamminga RYJ, de Boer A, Maitland-van der Zee AH. Characteristics and quality of oral anticoagulation treatment in pediatric patients in the Netherlands based on the CAPS cohort. 2018; 16: 116-24. J Thromb Haemost Essentials• The knowledge of quality and safety of acenocoumarol and phenprocoumon use in children is limited.• We used data from a multicenter retrospective followup study in children in the Netherlands.• The quality of anticoagulation control in the first month of use was low, but improved thereafter.• No thromboembolic events occurred, however bleeding events occurred in 1-3 out of 10 patients.Summary. Background: The use of vitamin-K antagonists in pediatric patients is rare and information on the quality and safety of treatment with acenocoumarol and phenprocoumon is limited. Objectives: To assess the quality, safety and effectiveness during the first year of acenocoumarol and phenprocoumon treatment in pediatric patients in the Netherlands. Methods: The Children Anticoagulation and Pharmacogenetics Study (CAPS) was designed as a multicenter retrospective follow-up study. Patients who used acenocoumarol or phenprocoumon at an age of ≤ 18 years, were selected from four pediatric hospitals and one anticoagulation clinic in the Netherlands. The quality of treatment was assessed by calculating the percentage of time in therapeutic INR range (TTR) for the first month and for every 3 months of use during the first year of treatment. Effectiveness and safety were assessed by the number of thromboembolic and bleeding events. Results: In total, 213 patients participated, of whom 187 (155 acenocoumarol; 32 phenprocoumon) were included in this analysis. The mean TTR was 47.0% and 51.4% in the first month of use for acenocoumarol and phenprocoumon, respectively. After the first 3 months the mean TTR for both VKAs was above 64%. In 14.6% (acenocoumarol) and 31.3% (phenprocoumon) of the patients a bleeding event occurred during the first year of treatment; no thromboembolic events were reported. Conclusions: The quality of anticoagulation treatment was low during the first month of use and leaves room for improvement. After the first month it increased to an acceptable level. However, bleeding events occurred frequently during the first year.

The pediatric acenocoumarol dosing algorithm: the Children Anticoagulation and Pharmacogenetics Study

“…The doses recommended in the guidelines seem to be safe, but are not yet optimal, with percentages of time in which the INR is within the therapeutic range (time in therapeutic range [TTR]) of around⁓ 50% during the first year of treatment . Within the cohort of the Children Anticoagulation and Pharmacogenetics Study, we obtained similar results within the first 3 months of acenocoumarol use (54.6%), and higher percentages after the first 3 months of use (> 64%) .…”

A systematic review of adherence to anticoagulation regimens in pediatric patients

“…One study found the lowest TTR for target INR range of 2.0-2.5 (30%, p < .001). 35 Another study's lowest TTR was for INR target 2.5-4.0 (p = .006), 21 while the lowest TTR for the other study was for goal INR of 2.0-3.0 (p = .002). 27 Additionally, one study reported that TTR was negatively correlated with the number of INR measurements obtained in the first 9 months of therapy, as well as the number of dose adjustments in the first 12 months of therapy (p < .05).…”

“…Characteristics of the 17 included studies are shown in Table 1. [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] Seven studies collected data prospectively and the remaining 10 collected data via retrospective medical record reviews. Mean ages of the patient populations ranged from 3.7 to 14.2 years.…”

“…Of these, three found a significant relationship between older age and lower nonadherence (higher adherence). 31,35,37 No studies examining other demographic factors found a significant relationship between these variables and nonadherence. Specifically, there was no significant relationship between nonadherence and sex and/or gender (n = 2 nonsignificant findings), 27,31 race (n = 1 nonsignificant finding), 31 or socioeconomic status (n = 1 nonsignificant finding).…”

“…27 Additionally, one study reported that TTR was negatively correlated with the number of INR measurements obtained in the first 9 months of therapy, as well as the number of dose adjustments in the first 12 months of therapy (p < .05). 35 Blurring the effects of medication nonadherence and medication interactions on the INR, Faircloth et al reported that taking three or more medications that interact with warfarin was associated with an increased likelihood of having a TTR <80% (OR 10.6 [1.1-100]). 27…”