John K. Wu

Errors involving pediatric patients receiving chemotherapy: A literature review

A review of mishaps involving pediatric patients receiving anticancer chemotherapy was undertaken in order to assist intervention. Although the case literature is too sparse to provide definite recommendations, suggestions for management are made in the event of an error with a high risk (based on the case literature) of life-threatening toxicities. It is recommended that all incidents be reported in the literature in order to provide a basis for devising standard treatment protocols. It is also suggested that studies using animal models continue to be done in order to provide more experimental data about toxicities and potentially beneficial rescue therapies.

Immunogenicity, efficacy and safety of Nuwiq® (human-cl rhFVIII) in previously untreated patients with severe haemophilia A—Interim results from the NuProtect Study

Nuwiq® (Human‐cl rhFVIII) is a fourth generation recombinant FVIII, produced in a human cell line, without chemical modification or protein fusion. No inhibitors developed in studies with Nuwiq® in 201 previously treated patients with haemophilia A (HA). The immunogenicity, efficacy and safety of Nuwiq® in previously untreated patients (PUPs) with severe HA are being assessed in the ongoing NuProtect study.

Prevalence of Vitamin D Deficiency Varies Widely by Season in Canadian Children and Adolescents with Sickle Cell Disease

Sickle cell disease (SCD) is an inherited disorder caused by a variant (rs334) in the β-globin gene encoding hemoglobin. Individuals with SCD are thought to be at risk of vitamin D deficiency. Our aim was to assess serum 25-hydroxyvitamin D (25OHD) concentrations, estimate deficiency prevalence, and investigate factors associated with 25OHD concentrations in children and adolescents with SCD attending BC Children’s Hospital in Vancouver, Canada. We conducted a retrospective chart review of SCD patients (2–19 y) from 2012 to 2017. Data were available for n = 45 patients with n = 142 25OHD measurements assessed using a EUROIMMUN analyzer (EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany). Additional data were recorded, including age, sex, and season of blood collection. Linear regression was used to measure associations between 25OHD concentration and predictor variables. Overall, mean ± SD 25OHD concentration was 79 ± 36 nmol/L; prevalence of low 25OHD concentrations (<30, <40, and <75 nmol/L) was 5%, 17% and 50%, respectively. Mean 25OHD concentrations measured during Jul–Sep were higher (28 (95% confidence interval CI: 16–40) nmol/L higher, P < 0.001) compared to Jan–Mar. Vitamin D deficiency rates varied widely by season: Based on 25OHD <30 nmol/L, prevalence was 0% in Oct–Dec and 6% in Jan–Mar; based on <40 nmol/L, prevalence was 0% in Oct–Dec and 26% in Jan–Mar.

The Clinical Impact of Copy Number Variants in Inherited Bone Marrow Failure Syndromes

Inherited bone marrow failure syndromes comprise a genetically heterogeneous group of diseases with hematopoietic failure and a wide array of physical malformations. Copy number variants were reported in some inherited bone marrow failure syndromes. It is unclear what impact copy number variants play in patients evaluated for a suspected diagnosis of inherited bone marrow failure syndromes. Clinical and genetic data of 323 patients from the Canadian Inherited Marrow Failure Registry from 2001 to 2014, who had a documented genetic work-up, were analyzed. Cases with pathogenic copy number variants (at least 1 kilobasepairs) were compared to cases with other mutations. Genotype-phenotype correlations were performed to assess the impact of copy number variants. Pathogenic nucleotide-level mutations were found in 157 of 303 tested patients (51.8%). Genome-wide copy number variant analysis by single-nucleotide polymorphism arrays or comparative genomic hybridization arrays revealed pathogenic copy number variants in 11 of 67 patients tested (16.4%). In four of these patients, identification of copy number variant was crucial for establishing the correct diagnosis as their clinical presentation was ambiguous. Eight additional patients were identified to harbor pathogenic copy number variants by other methods. Of the 19 patients with pathogenic copy number variants, four had compound-heterozygosity of a copy number variant with a nucleotide-level mutation. Pathogenic copy number variants were associated with more extensive non-hematological organ system involvement (pu2009=u20090.0006), developmental delay (pu2009=u20090.006) and short stature (pu2009=u20090.04) compared to nucleotide-level mutations. In conclusion, a significant proportion of patients with inherited bone marrow failure syndromes harbor pathogenic copy number variants which were associated with a more extensive non-hematological phenotype in this cohort. Patients with a phenotype suggestive of inherited bone marrow failure syndromes but without identification of pathogenic nucleotide-level mutations should undergo specific testing for copy number variants.Blood disorders: impact of genomic structural variationCopy number variation in patients with inherited bone marrow failure syndromes (IBMFSs) is associated with more severe clinical symptoms. In addition to persistently low levels of red blood cells, white blood cells and/ or platelets, patients with IBMFSs also present varying degrees of physical malformations. Most cases are associated with single base-pair mutations in the DNA sequence, but Canadian researchers led by Yigal Dror at The Hospital for Sick Children in Toronto, have found that whole sections of the genome are deleted or repeated in an important proportion of patients. Those carrying copy number variants (CNV) presented more commonly with developmental delay, short stature and defects in more organ systems, than patients with point mutations. CNV analysis of patients with suspected IBMFSs could aid early disease evaluation and management.

Central venous line blood sampling for coagulation tests in hemodialysis patients

The presence of an indwelling central venous line (CVL) predisposes pediatric patients to thrombosis [1], especially those on long-term total parenteral nutrition [2], cancer patients, and those undergoing hemodialysis [3]. Oral anticoagulants such as warfarin are often used to prevent or treat CVL-related thrombosis. Because of the unpredictability of the anticoagulation effects of warfarin, especially in the presence of other medications, careful and frequent monitoring of coagulation is essential. The heparin used to flush CVLs, even if present in a minute amount, can cause a significant prolongation of coagulation screening tests. We describe a simple way of obtaining blood specimens, consistently free of heparin contamination, through a CVL on patients undergoing hemodialysis. All the procedures are performed on a sterile field set up around the patients CVL with the nurse masked and wearing sterile gloves. The initial 3 ml of blood from the CVL is discarded; 10 ml of non-heparinized normal saline is flushed in through the CVL; 30 ml of blood is drawn through the CVL into a clean sterile syringe without the addition of heparin. Specimens of blood are then collected through the CVL for coagulation tests. The 30 ml of blood in the syringe is then re-infused back through the CVL. The maximum duration that the non-heparinized blood is left in the syringe is seldom more than 30 s. We never had problems with blood clotting or infections with this method. The additional steps of flushing the CVL with non-heparinized normal saline and the subsequent withdrawal of 30 ml of blood before blood sampling almost eliminate any problem with heparin contamination. The reinfusion of the withdrawn blood under aseptic conditions significantly decreases the blood loss in these patients. With this technique, there was no heparin contamination in 27 of 30 blood samples and minor contamination in 3 (activated partial thromboplastin time less than twice normal). We describe here a simple yet consistent way of obtaining blood specimens from CVL without heparin contamination from patients undergoing hemodialysis. With the increased realization of the risk of CVL-related thrombosis in hemodialysis patients, more patients are anticipated to be on oral anticoagulants. Our method of blood sampling would greatly facilitate this procedure and enhances the reliability of the samples obtained.