Familial neurofibromatosis type 1 associated with an overgrowth syndrome resembling Weaver syndrome.

The simultaneous occurrence of familial neurofibromatosis type 1 (NF1) and an overgrowth syndrome resembling Weaver syndrome was observed in two related cases (a mother and her son). NF1 was confirmed by molecular genetic analysis showing a large deletion at 17q11.2, encompassing the entire NF1 gene. The other symptoms in the two cases were similar to the features reported in Weaver syndrome. Although the combination of NF1 and an overgrowth syndrome resembling Weaver syndrome in this family may be fortuitous, we favour the hypothesis that the deletion of the entire gene has caused this combined phenotype. Possible pathogenetic mechanisms are discussed. The observation suggests a relation between NF1 with an extraordinarily large gene deletion and a Weaver(-like) syndrome. This warrants investigation for deletions in the 17q11.2 region in Weaver(-like) syndrome patients.     

The group medical appointment (GMA) in haemophilia and von Willebrand's disease: a new development in outpatient paediatric care

Summary. The Group Medical Appointment (GMA) is a novel consultation form in which patients undergo individual consultations in each other’s presence. To compare participants’ experiences with GMA and Individual Medical Appointments (IMA), the usual standard of care, our team recently implemented the GMA for children aged 0–18 years with haemophilia or von Willebrand’s disease. Participants’ experiences with GMA were measured using a standardized QUOTE‐questionnaire. Of 100 addressed families, 53 participated in GMA. Of these 53 families, 38 parents (72%) and 14 adolescents (82%) filled in the questionnaire about the GMA. Patients not on prophylaxis were defined as less experienced and patients on prophylaxis, as experienced. Although parents were satisfied with both GMA and IMA (median score 8.0 vs. 9.0 of 10), a significant difference was demonstrated between less experienced and experienced parents. After GMA, less experienced parents were significantly more satisfied (median score 8.0 vs. 5.0; P‐value 0.006), felt more social support (82% vs. 30%; P‐value 0.005) and reported additional learning effects with regard to disease and treatment (64% vs. 0%; P‐value <0.001) than experienced parents. None of the less experienced parents reported privacy problems during GMA compared with 40% of experienced parents. In adolescents an identical trend was reported. Sixty‐six per cent of parents would join a GMA in the future and 87% would recommend a GMA to others. The GMA is a valuable addition in haemophilia and von Willebrand care, especially for less experienced patients. It leads to improved satisfaction, social support and improved information.     

Product type and the risk of inhibitor development in nonsevere haemophilia A patients: a case‒control study

Inhibitor development is a major complication of treatment with factor VIII concentrates in nonsevere haemophilia A. It has been suggested that plasma-derived factor VIII (FVIII) concentrates elicit fewer inhibitors than recombinant FVIII concentrates, but studies in severe haemophilia A patients have shown conflicting results. We designed a case‒control study to investigate the clinical and genetic risk factors for inhibitor development in nonsevere haemophilia A patients. We investigated whether the type of FVIII concentrate was associated with inhibitor development in nonsevere haemophilia A patients. This nested case‒control study includes 75 inhibitor patients and 223 controls, from a source population of the INSIGHT study, including all nonsevere haemophilia A patients (FVIII:C 2–40%) that were treated with FVIII concentrates in 33 European and one Australian centre. Cases and controls were matched for date of birth and cumulative number of exposure days (CED) to FVIII concentrate. A conditional logistic regression model was used to calculate unadjusted and adjusted odds ratios. No increased risk for inhibitor development was found for any type of FVIII concentrate; either when comparing recombinant FVIII concentrates to plasma-derived FVIII concentrates (adjusted odds ratio 0·96, 95% confidence interval (CI) 0·36–2·52) or for specific types of FVIII concentrates.     

Quality of life and behavioral functioning in Dutch pediatric patients with hereditary spherocytosis

The objective of this study was to evaluate health-related quality of life (HRQoL) and behavioral functioning in pediatric patients with hereditary spherocytosis (HS). A cross-sectional study was conducted in 132 Dutch children and adolescents with HS and aged 8–18 years of whom 48 underwent splenectomy prior to the study. HRQoL was assessed using the KIDSCREEN-27, and behavioral functioning was evaluated using the strength and difficulties questionnaire (SDQ). Scores of pediatric patients with HS were compared to a Dutch norm population. Additionally, the effects of three factors were assessed: fatigue, self-image, and parents’ perceived vulnerability (measured with the checklist individual strength, the self-perception profile for children and adolescents, and the child vulnerability scale). Both unsplenectomised and splenectomised pediatric patients reported lower HRQoL on the domain physical well-being (KIDSCREEN-27) compared to Dutch peers. For behavioral functioning, parents of both groups reported more emotional problems (SDQ) compared to the norm population. Pediatric patients with lower scores on physical well-being experienced more fatigue. The patients’ perceived social acceptance and parents’ perceived vulnerability appeared as determinants of emotional problems. Conclusion: Pediatric patients in the current study generally report few complaints, and the results suggest that these patients overall have a strong ability to cope with HS. Despite these few complaints, fatigue and parents’ perceived vulnerability seem to be important determinants for lower HRQoL and more emotional problems. Therefore, screening on these factors could serve as an addition to the treatment of HS, to help pediatric patients who are at risk for lower HRQoL or more emotional problems.     

Perioperative replacement therapy in haemophilia B: An appeal to “B” more precise

Introduction

Haemophilia B is caused by a deficiency of coagulation factor IX (FIX) and characterized by bleeding in muscles and joints. In the perioperative setting, patients are treated with FIX replacement therapy to secure haemostasis. Targeting of specified FIX levels is challenging and requires frequent monitoring and adjustment of therapy.

Aim

To evaluate perioperative management in haemophilia B, including monitoring of FIX infusions and observed FIX levels, whereby predictors of low and high FIX levels were assessed.

Methods

In this international multicentre study, haemophilia B patients with FIX < 0.05 IU mL^?1 undergoing elective, minor or major surgical procedures between 2000 and 2015 were included. Data were collected on patient, surgical and treatment characteristics. Observed FIX levels were compared to target levels as recommended by guidelines.

Results

A total of 255 surgical procedures were performed in 118 patients (median age 40 years, median body weight 79 kg). Sixty percent of FIX levels within 24 hours of surgery were below target with a median difference of 0.22 IU mL^?1 [IQR 0.12‐0.36]; while >6 days after surgery, 59% of FIX levels were above target with a median difference of 0.19 IU mL^?1 [IQR 0.10‐0.39]. Clinically relevant bleeding complications (necessity of a second surgical intervention or red blood cell transfusion) occurred in 7 procedures (2.7%).

Conclusion

This study demonstrates that targeting of FIX levels in the perioperative setting is complex and suboptimal, but although this bleeding is minimal. Alternative dosing strategies taking patient and surgical characteristics as well as pharmacokinetic principles into account may help to optimize and individualize treatment.