It is well known that drug responses differ among patients with regard to dose requirements, efficacy, and adverse drug reactions (ADRs). The differences in drug responses are partially explained by genetic variation. This paper highlights some examples of areas in which the different responses (dose, efficacy, and ADRs) are studied in children, including cancer (cisplatin), thrombosis (vitamin K antagonists), and asthma (long-acting β2 agonists). For childhood cancer, the replication of data is challenging due to a high heterogeneity in study populations, which is mostly due to all the different treatment protocols. For example, the replication cohorts of the association of variants in TPMT and COMT with cisplatin-induced ototoxicity gave conflicting results, possibly as a result of this heterogeneity. For the vitamin K antagonists, the evidence of the association between variants in VKORC1 and CYP2C9 and the dose is clear. Genetic dosing models have been developed, but the implementation is held back by the impossibility of conducting a randomized controlled trial with such a small and diverse population. For the long-acting β2 agonists, there is enough evidence for the association between variant ADRB2 Arg16 and treatment response to start clinical trials to assess clinical value and cost effectiveness of genotyping. However, further research is still needed to define the different asthma phenotypes to study associations in comparable cohorts. These examples show the challenges which are encountered in pediatric pharmacogenomic studies. They also display the importance of collaborations to obtain good quality evidence for the implementation of genetic testing in clinical practice to optimize and personalize treatment.

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.

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