Use of human protein C concentrates in the treatment of patients with severe congenital protein C deficiency

Protein C is one of the major inhibitors of the coagulation system that downregulate thrombin generation. Severe congenital protein C deficiency leads to a hypercoagulability state that usually presents at birth with purpura fulminans and/or severe venous and arterial thrombosis. Recurrent thrombotic events are commonly seen. From the 1990’s, several virus-inactivated human protein C concentrates have been developed. These concentrates currently constitute the therapy of choice for the treatment and prevention of clinical manifestations of severe congenital protein C deficiency. This review summarizes the available information on the use of human protein C concentrates in patients with severe congenital protein C deficiency

Adherence to treatment in adolescents with haemophilia : a qualitative study

Adolescents experience important changes in their physical, emotional, social and behavioural development. It is known that adolescents wish to be accepted by their peers, strive for independence and are prone to experiment. The challenge for adolescents with haemophilia is the need for taking responsibility for managing their illness and learning to comply with recommended treatment. This study aimed to investigate the process of adherence to treatment in adolescents with haemophilia

Antithrombin activity in children with chylothorax

Objective: To determine whether increased antithrombin loss is present in children with chylothorax after cardiac surgery. Methods: Plasma and pleural effusion samples of children with chylous and non-chylous pleural effusion were assayed for antithrombin activity. Results: Ten children with chylothorax and five children with non-chylous pleural effusion were investigated. There was statistically significant increase in mean antithrombin activity in chylous samples (32.2 ± 11.4%) compared to non-chylous samples (14.4 ± 13.9%), and significant decrease in plasma of children with chylothorax (44.6 ± 15.4%) compared to children with non-chylous pleural effusion (69.9 ± 22.4%). Seven of 10 children with chylous and none of the children without chylous developed thrombosis (p < 0.007). Conclusions: Increased loss of antithrombin is present in children with chylothorax, potentially predisposing these children to an increased risk of thrombosis. Repeated antithrombin substitution should be considered in critically ill children with chylothora

Long-term subcutaneous morphine administration after surgery in newborns

Aim: To analyze the management of newborns after major surgery receiving morphine subcutaneously and to identify possible side effects. Methods: Morphine was administered via a subcutaneous catheter (Insuflon®) in 20 newborns after major surgery. Side effects like hypotension, pain during morphine administration and local infection were noted. Morphine dose was adjusted according to the hospital guidelines with the Neonatal Infant Pain Score (NIPS) and the Finnegan withdrawal score. Results: Surgery was performed at the median age of 38 5/7weeks (range: 32 1/7-49 5/7weeks). Before starting subcutaneous morphine administration, patients received intravenous morphine for a median of two weeks (range sixdays to sevenweeks). All patients showed good pain relief with no severe side effects. Three patients reacted with crying to the first dose of subcutaneous morphine. No other side effects occurred. Conclusion: Subcutaneous application of morphine with the Insuflon® catheter is an alternative to intravenous treatment of postoperative pain in neonates. In this small group pain relief was good and side effects were harmles

Geometry and dimensions of the pulmonary artery bifurcation in children and adolescents: assessment in vivo by contrast-enhanced MR-angiography

We sought to establish normal values for the diameters of the main (MPA), right (RPA), and left (LPA) pulmonary arteries and for the angles describing the geometry of the pulmonary artery bifurcation in children by using contrast-enhanced magnetic resonance angiography (CE-MRA). CE-MRA was performed in 69 children without cardiovascular disease. The median age was 10±4.9years (range 2-20), weight 37.4±18.5kg (10-82), body surface area (BSA) 1.18±0.4m2 (0.48-2.07). The pulmonary artery diameters and angles were measured at standardized sites and projections. Regression analysis of diameters and angles in relation to BSA demonstrated linear relationship between the cross-sectional diameters of the pulmonary arteries and the square root of BSA (BSA0.5). Normalized mean diameters were for the MPA 17.6±5.1mm/m2, origin of RPA 13.1±2.9mm/m2, origin of LPA 14.2±2.9mm/m2. The MPA showed a mean antero-posterior inclination of 33°±8° and a lateral leftward angulation of 18°±5°. The mean angle of the bifurcation was 99.5°±10.3°. Both side branches showed a supero-inferior course of the proximal segments, steeper for the RPA (7.7°±6.5°) than for the LPA (2.1°±7.8°). Normative curves in relation to BSA are presented for all measurements. This study provides normative values by CE-MRA for the main pulmonary artery and its side branches in children during somatic growth. These data can be used for identifying pulmonary arteries anomalies in children, and evaluate the need and the modality for treatmen

Enoxaparin therapy for arterial thrombosis in infants with congenital heart disease

Objective: To investigate efficacy and safety of enoxaparin for catheter-related arterial thrombosis in infants with congenital heart disease. Design: Prospective observational study. Setting: Pediatric Intensive Care and Cardiology Unit at the University Children's Hospital of Zurich. Patients: Acohort of 32 infants aged 0-12 months treated with enoxaparin for catheter-related arterial thrombosis from 2002 to 2005. Measurements: Dose requirements of enoxaparin, resolution of thrombosis by Doppler ultrasound, and bleeding complications. Results: Catheter-related arterial thrombosis was located in the iliac/femoral arteries in 31 (97%) infants and aorta in 1 infant, and was related to indwelling catheters and cardiac catheterization in 17 (53%) and 15 (47%) cases, respectively. Newborns required increased doses of enoxaparin to achieve therapeutic anti-FXa levels (mean 1.62 mg/kg per dose) compared with infants aged 2-12 months (mean 1.12 mg/kg per dose; p = 0.0002). Complete resolution of arterial thrombosis occurred in 29 (91%) infants at amean of 23 days after initiation of enoxaparin therapy. Partial or no resolution was observed in 1 (3%) and 2 (6%) infants, respectively, at amean follow-up time of 4.3 months. Bleeding complications occurred in 1 (3%) infant. Conclusion: Enoxaparin is efficient and safe for infants with congenital heart disease and catheter-related arterial thrombosis, possibly representing avalid alternative to the currently recommended unfractionated hepari

Estimation of Nuwiq® (simoctocog alfa) activity using one-stage and chromogenic assays-Results from an international comparative field study.

BACKGROUND Accurate determination of coagulation factor VIII activity (FVIII:C) is essential for effective and safe FVIII replacement therapy. FVIII C can be measured by one-stage and chromogenic substrate assays (OSAs and CSAs, respectively); however, there is significant interlaboratory and interassay variability. AIMS This international comparative field study characterized the behaviour of OSAs and CSAs used in routine laboratory practice to measure the activity of Nuwiq® (human-cl rhFVIII, simoctocog alfa), a fourth-generation recombinant human FVIII produced in a human cell line. METHODS FVIII-deficient plasma was spiked with Nuwiq® or Advate® at 1, 5, 30 and 100 international units (IU)/dL. Participating laboratories analysed the samples using their routine procedures and equipment. Accuracy, inter- and intralaboratory variation, CSA:OSA ratio and the impact of different OSA and CSA reagents were assessed. RESULTS Forty-nine laboratories from 9 countries provided results. Mean absolute FVIII:C was comparable for both products at all concentrations with both OSA and CSA, with interproduct ratios (Nuwiq® :Advate® ) of 1.02-1.13. Mean recoveries ranged from 97% to 191% for Nuwiq® , and from 93% to 172% for Advate® , with higher recoveries at lower concentrations. Subgroup analyses by OSA and CSA reagents showed minor variations depending on reagents, but no marked differences between the two products. CSA:OSA ratios based on overall means ranged from 0.99 to 1.17 for Nuwiq® and from 1.01 to 1.17 for Advate® . CONCLUSIONS Both OSAs and CSAs are suitable for the measurement of FVIII:C of Nuwiq® in routine laboratory practice, without the need for a product-specific reference standard

Best Practice Recommendations for the Diagnosis and Management of Children With Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS; Multisystem Inflammatory Syndrome in Children, MIS-C) in Switzerland.

Background: Following the spread of the coronavirus disease 2019 (COVID-19) pandemic a new disease entity emerged, defined as Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C). In the absence of trials, evidence for treatment remains scarce. Purpose: To develop best practice recommendations for the diagnosis and treatment of children with PIMS-TS in Switzerland. It is acknowledged that the field is changing rapidly, and regular revisions in the coming months are pre-planned as evidence is increasing. Methods: Consensus guidelines for best practice were established by a multidisciplinary group of Swiss pediatric clinicians with expertise in intensive care, immunology/rheumatology, infectious diseases, hematology, and cardiology. Subsequent to literature review, four working groups established draft recommendations which were subsequently adapted in a modified Delphi process. Recommendations had to reach &gt;80% agreement for acceptance. Results: The group achieved agreement on 26 recommendations, which specify diagnostic approaches and interventions across anti-inflammatory, anti-infectious, and support therapies, and follow-up for children with suspected PIMS-TS. A management algorithm was derived to guide treatment depending on the phenotype of presentation, categorized into PIMS-TS with (a) shock, (b) Kawasaki-disease like, and (c) undifferentiated inflammatory presentation. Conclusion: Available literature on PIMS-TS is limited to retrospective or prospective observational studies. Informed by these cohort studies and indirect evidence from other inflammatory conditions in children and adults, as well as guidelines from international health authorities, the Swiss PIMS-TS recommendations represent best practice guidelines based on currently available knowledge to standardize treatment of children with suspected PIMS-TS. Given the absence of high-grade evidence, regular updates of the recommendations will be warranted, and participation of patients in trials should be encouraged

Management of Venous Thromboembolism in Children: Current Recommendations and Therapeutic Options

Venous thromboembolism has an increasing significance in the pediatric patient population. Due to the lack of well-designed pediatric clinical trials, recommendations for the treatment of venous thromboembolic events in children have low evidence and are mainly extrapolated from adult guidelines. This review summarizes and compares recommendations for the treatment of several venous thromboembolic events in children from CHEST, ASH, and the UK guidelines