Paul P. T. Brons

Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A

Neutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding pattern. Identification of high-risk patients is hampered by lack of data that take exposure days to therapeutic factor VIII concentrates into account. In the INSIGHT study, we analyzed the association between F8 mutation and inhibitor development in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL). This analysis included 1112 nonsevere hemophilia A patients from 14 centers in Europe and Australia that had genotyped at least 70% of their patients. Inhibitor risk was calculated as Kaplan-Meier incidence with cumulative number of exposure days as the time variable. During 44 800 exposure days (median, 24 exposure days per patient; interquartile range [IQR], 7-90), 59 of the 1112 patients developed an inhibitor; cumulative incidence of 5.3% (95% confidence interval [CI], 4.0-6.6) after a median of 28 exposure days (IQR, 12-71). The inhibitor risk at 50 exposure days was 6.7% (95% CI, 4.5-8.9) and at 100 exposure days the risk further increased to 13.3% (95% CI, 9.6-17.0). Among a total of 214 different F8 missense mutations 19 were associated with inhibitor development. These results emphasize the importance of F8 genotyping in nonsevere hemophilia A.

Health-related quality of life in children and emotional reactions of parents following completion of cancer treatment

Completing therapy is one of the major transitions in care in the practice of pediatric oncology and, therefore, deserves special consideration. The purpose of the study was to investigate health‐related quality of life (HRQOL) of pediatric patients, and emotional reactions of their parents, shortly after the end of successful treatment.

Anaphylaxis from Passive Transfer of Peanut Allergen in a Blood Product

Anaphylactic transfusion reactions from passive transfer of IgE have been documented, but a case is now reported in which the eliciting factor was a food allergen in peanuts ingested by blood donors before donation.

Longitudinal assessment of health-related quality of life in preschool children with non-CNS cancer after the end of successful treatment

The aim of the study was to access Health Related Quality of Life (HRQoL) in preschool cancer survivors during the first 3 years of continuous remission after the end of successful treatment, and to identify predictors of HRQoL.

Practice guidelines for the diagnosis and management of microcytic anemias due to genetic disorders of iron metabolism or heme synthesis

During recent years, our understanding of the pathogenesis of inherited microcytic anemias has gained from the identification of several genes and proteins involved in systemic and cellular iron metabolism and heme syntheses. Numerous case reports illustrate that the implementation of these novel molecular discoveries in clinical practice has increased our understanding of the presentation, diagnosis, and management of these diseases. Integration of these insights into daily clinical practice will reduce delays in establishing a proper diagnosis, invasive and/or costly diagnostic tests, and unnecessary or even detrimental treatments. To assist the clinician, we developed evidence-based multidisciplinary guidelines on the management of rare microcytic anemias due to genetic disorders of iron metabolism and heme synthesis. These genetic disorders may present at all ages, and therefore these guidelines are relevant for pediatricians as well as clinicians who treat adults. This article summarizes these clinical practice guidelines and includes background on pathogenesis, conclusions, and recommendations and a diagnostic flowchart to facilitate using these guidelines in the clinical setting.

Health-related quality of life after completion of successful treatment for childhood cancer†

Previous studies have assessed health‐related quality of life (HRQOL) during several treatment stages in children with cancer, but there is limited knowledge about HRQOL shortly after completing therapy. This study determined HRQOL of children with cancer shortly after the end of successful treatment compared with normative values.

Participation and risk-taking behaviour in sports in children with haemophilia.

Summary.  The aim of this study was to investigate participation in sports activities and risk‐taking behaviour in children with haemophilia and the relationship to personal and health related factors. Ninety‐nine children (mean age 12.6 years) completed questionnaires regarding participation in sports and physical education, medication, health related quality of life, and perceived motor competence. Furthermore, weight, height, active range of motion, pain, and muscle strength were assessed. Based on a risk exposure factor (REF) we defined subgroups with low, medium, and high risk when participating in sport. Most children participate in sport five times a week (mean 140 min per week), and little absence during school sports was reported. In general, prophylaxis was not tailored to sport activities. Boys with haemophilia preferred other sports than their Dutch contemporaries. The top‐5 being soccer, swimming, tennis, gymnastics, and cardio‐fitness for the former; soccer, gymnastics, tennis, hockey, and swimming for the latter. Significant differences between the low risk group and both other groups were found for sport intensity, total energy expenditure (EE) and average risk factor (ARF), however the medium and high‐risk groups did not differ in ARF. REF and sport participation increased associated with increasing interest in athletic and motor activities. No significant differences were found between REF groups regarding age, Z‐BMI, Z‐AROM, Z‐Muscle force, and the presence of painful joints. As in normal peers motivation to participate in sport depends upon the enthusiasm and interest, in children with haemophilia choice of sports differs, probably related to sport advice.

Psychosocial indicators of health-related quality of life in children with cancer 2 months after end of successful treatment.

The purpose of the study was to identify psychosocial correlates of Health-Related Quality of Life (HRQoL) in pediatric cancer patients after completion of cancer treatment. Multiple regression analyses were performed to predict self-reported HRQoL of 52 patients aged 8 to 15 years, and parent-reported HRQoL of 54 patients aged 1 to 5 years. Cognitive coping, family functioning, parental emotional reactions, communication about the disease, and several medical variables were included in the regression models. Better HRQoL was especially associated with more positive expectations of the further course of the disease and less frequent parental asking after disease-related emotions of the child. Interventions should include “positive thinking” as a coping strategy. Several other psychosocial variables were indicative of better HRQoL but further research is needed to confirm and to understand the relationship between psychosocial variables and HRQoL.

A novel hemostasis assay for the simultaneous measurement of coagulation and fibrinolysis

Abstract Thrombin and plasmin are the key enzymes involved in coagulation and fibrinolysis. A novel hemostasis assay (NHA) was developed to measure thrombin and plasmin generation in a single well by a fluorimeter. The NHA uses two fluorescent substrates with non-interfering fluorescent excitation and emission spectra. The assay was tested in vitro using modulators like heparin, hirudin, epsilon-aminocaproic acid, gly-pro-arg-pro peptide and reptilase and validated by measurement of prothrombin fragment 1+2 and plasmin-alpha2-antiplasmin levels. Intra- and inter-assay coefficients of variation were <9% and 6–25%, respectively. Interplay between coagulation and fibrinolysis was demonstrated by the effect of tissue-type plasminogen activator on thrombin generation and by the different responses of activated protein C and thrombomodulin on fibrinolysis. The last responses showed the linkage between coagulation and fibrinolysis by thrombin activatable fibrinolysis inhibitor. In conclusion, this strategy allows detection of coagulation, fibrinolysis and their interplay in a single assay.

The influence of patient reported outcomes on the discussion of psychosocial issues in children with cancer

This study investigates the effect of using patient reported outcomes (PROs) about health‐related quality of life (HRQOL) in clinical practice on the type and amount of psychosocial topics discussed during a paediatric oncology consultation.