Cross-Sectional Comparison to Siblings and Peers

Objectives. To investigate self-reported health-related quality of life (HrQoL) in children and adolescents with chronic medical conditions compared with siblings/peers. Methods. Group 1 (6 treatment centers) consisted of 74 children/adolescents aged 8–16 years with hereditary bleeding disorders (HBD), 12 siblings, and 34 peers. Group 2 (one treatment center) consisted of 70 children/adolescents with stroke/transient ischemic attack, 14 siblings, and 72 peers. HrQoL was assessed with the “revised KINDer Lebensqualitätsfragebogen” (KINDL-R) questionnaire. Multivariate analyses within groups were done by one-way ANOVA and post hoc pairwise single comparisons by Student’s -tests. Adjusted pairwise comparisons were done by hierarchical linear regressions with individuals nested within treatment centers (group 1) and by linear regressions (group 2), respectively. Results. No differences were found in multivariate analyses of self-reported HrQoL in group 1, while in group 2 differences occurred in overall wellbeing and all subdimensions. These differences were due to differences between patients and peers. After adjusting for age, gender, number of siblings, and treatment center these differences persisted regarding self-worth () and friend-related wellbeing (). Conclusions. In children with HBD, HrQoL was comparable to siblings and peers. In children with stroke/TIA HrQoL was comparable to siblings while peers, independently of relevant confounder, showed better self-worth and friend-related wellbeing

Health-Related Quality of Life in Children and Adolescents with Hereditary Bleeding Disorders and in Children and Adolescents with Stroke: Cross-Sectional Comparison to Siblings and Peers

Objectives. To investigate self-reported health-related quality of life (HrQoL) in children and adolescents with chronic medical conditions compared with siblings/peers. Methods. Group 1 (6 treatment centers) consisted of 74 children/adolescents aged 8-16 years with hereditary bleeding disorders (HBD), 12 siblings, and 34 peers. Group 2 (one treatment center) consisted of 70 children/adolescents with stroke/transient ischemic attack, 14 siblings, and 72 peers. HrQoL was assessed with the "revised KINDer Lebensqualitatsfragebogen" (KINDL-R) questionnaire. Multivariate analyses within groups were done by one-way ANOVA and post hoc pairwise single comparisons by Student's t-tests. Adjusted pairwise comparisons were done by hierarchical linear regressions with individuals nested within treatment centers (group 1) and by linear regressions (group 2), respectively. Results. No differences were found in multivariate analyses of self-reported HrQoL in group 1, while in group 2 differences occurred in overall wellbeing and all subdimensions. These differences were due to differences between patients and peers. After adjusting for age, gender, number of siblings, and treatment center these differences persisted regarding self-worth (p =.0040) and friend-related wellbeing (p <.001). Conclusions. In children with HBD, HrQoL was comparable to siblings and peers. In children with stroke/TIA HrQoL was comparable to siblings while peers, independently of relevant confounder, showed better self-worth and friend-related wellbeing

Health-Related Quality of Life in Children and Adolescents with Hereditary Bleeding Disorders and in Children and Adolescents with Stroke: Cross-Sectional Comparison to Siblings and Peers

Objectives. To investigate self-reported health-related quality of life (HrQoL) in children and adolescents with chronic medical conditions compared with siblings/peers. Methods. Group 1 (6 treatment centers) consisted of 74 children/adolescents aged 8-16 years with hereditary bleeding disorders (HBD), 12 siblings, and 34 peers. Group 2 (one treatment center) consisted of 70 children/adolescents with stroke/transient ischemic attack, 14 siblings, and 72 peers. HrQoL was assessed with the "revised KINDer Lebensqualitatsfragebogen" (KINDL-R) questionnaire. Multivariate analyses within groups were done by one-way ANOVA and post hoc pairwise single comparisons by Student's t-tests. Adjusted pairwise comparisons were done by hierarchical linear regressions with individuals nested within treatment centers (group 1) and by linear regressions (group 2), respectively. Results. No differences were found in multivariate analyses of self-reported HrQoL in group 1, while in group 2 differences occurred in overall wellbeing and all subdimensions. These differences were due to differences between patients and peers. After adjusting for age, gender, number of siblings, and treatment center these differences persisted regarding self-worth (p =.0040) and friend-related wellbeing (p <.001). Conclusions. In children with HBD, HrQoL was comparable to siblings and peers. In children with stroke/TIA HrQoL was comparable to siblings while peers, independently of relevant confounder, showed better self-worth and friend-related wellbeing

Inherited thrombophilia in children with venous thromboembolism and the familial risk of thromboembolism: an observational study

Screening for inherited thrombophilia (IT) is controversial; persons at high risk for venous thromboembolism (VTE) who benefit from screening need to be identified. We tested 533 first-and second-degree relatives of 206 pediatric VTE patients for IT (antithrombin, protein C, protein S, factor V G1691A, factor II G20210A) and determined the incidence of symptomatic VTE relative to their IT status. The risk for VTE was significantly increased among family members with, versus without, IT (hazard ratio ‫؍‬ 7.6; 95% confidence interval [CI], 4.0-14.5; P &lt; .001) and highest among carriers of antithrombin, protein C, or protein S deficiency (hazard ratio ‫؍‬ 25.7; 95% CI, 12.2-54.2; P &lt; .001). Annual incidences of VTE were 2.82% (95% CI, 1.63%-4.80%) among family members found to be carriers of antithrombin, protein C, or protein S deficiency, 0.42% (0.12%-0.53%) for factor II G202010A, 0.25% (0.12%-0.53%) for factor V G1691A, and 0.10% (0.06%-0.17%) in relatives with no IT. Given the high absolute risk of VTE in relatives with protein C, protein S, and antithrombin deficiency, we suggest screening for these forms of hereditary thrombophilia in children with VTE and their relatives. Interventional studies are required to assess whether thromboembolism can be prevented in this highrisk population. (Blood. 2012;120(7): 1510-1515

High-throughput microfluidic blood testing to phenotype genetically linked platelet disorders: an aid to diagnosis

Linking the genetic background of patients to a bleeding diathesis and altered platelet function is still challenging. We aimed to assess how the multiparameter microspot-based measurement of thrombus formation under flow can identify patients with a platelet bleeding disorder. For this purpose, we studied 16 patients, presenting with bleeding and/or albinism and a suspected platelet dysfunction, as well as 15 relatives. Genotyping of patients revealed a novel biallelic pathogenic variant in RASGRP2 (splice site c.240-1G&amp;gt;A), abrogating CalDAG-GEFI expression; a compound heterozygosity (c.537del, c.571A&amp;gt;T) in P2RY12, affecting P2Y12 signaling; and heterozygous variants of unknown significance in the P2RY12 and HPS3 genes. Other patients had confirmed Hermansky-Pudlak syndrome type 1 or 3. In 5 patients, no genetic variant was found. Platelet functions were assessed by routine laboratory measurements. Blood samples from all subjects and day controls were screened for blood cell counts and microfluidic outcome on six surfaces (48 parameters), in comparison to a reference cohort of healthy subjects. Differential analysis of the microfluidic data showed that key parameters of thrombus formation were compromised for the 16 index patients. Principal component analysis resulted in separate clusters of patients versus heterozygous family members plus control subjects. Clusters further segregated by inclusion of hematological values and laboratory measurements. Subject ranking indicated an overall impairment in thrombus formation for the patients carrying a (likely) pathogenic variant of the genes, but not for the asymptomatic relatives. Together, our results indicate the advantage of testing for multiparametric thrombus formation in this patient population