Central venous access device-related infections in patients with haemophilia.

AIMS: Fully implantable central venous access devices (CVADs) can offer long-term reliable venous access to facilitate regular factor replacement therapy in haemophilia. However, CVAD-related infection remains a major deterrent to the optimal use of CVAD in this population. This report represents the first review of CVAD use in haemophilia in Australia and aims to examine the rate of complications including CVAD-related infections. METHODS: A retrospective review of medical records was conducted of all haemophilic patients with fully implantable CVADs at the Royal Children's Hospital (RCH), Melbourne, between 1 June 1992 and 30 June 2009. CVAD-related bloodstream infection was defined based on the guidelines from the Centre of Disease Control and Victoria National Nosocomial Infection Surveillance. To further enhance identification of CVAD-related infection in this study, a third criterion of 'suspected infection' was added by the authors. RESULTS: Eighty-one CVADs in 56 patients were managed at the RCH during this time period resulting in a combined study period of 94 756 CVAD days. Median age at first CVAD insertion = 2.16 years (range 0.66 to 13.98 years). CVADs were inserted predominantly due to difficult venous access and prophylaxis initiation (70.4%). Median life-span of a CVAD was 1227 days, equivalent to 3.36 years (n = 50; range 0.22 to 9.44 years). Fifty-seven CVAD-related infections occurred in 37 CVADs (46.3%) in 29 patients (51.8%). Overall incidence of confirmed CVAD-related bloodstream infection = 0.42 per 1000 CVAD days (95% confidence interval (CI): 0.31 to 0.58 per 1000 CVAD days) and indicate better performance compared with the published benchmark of 0.66 per 1000 CVAD days (0.44 to 0.97 per 1000 CVAD days). The incidence of both confirmed (criteria 1, 2) and suspected (criterion 3) CVAD-related infection is 0.60 per 1000 CVAD days (95% CI: 0.46 to 0.78), which is comparable to the international benchmark. The majority of CVAD-related infections (73.7%) were successfully treated with intravenous antimicrobials without necessitating CVAD removal. Klebsiella pneumoniae was the most common organism found in positive blood cultures. CONCLUSION: CVAD-related infection in this Australian population was comparable to rates described in the medical literature. Ongoing surveillance for infection rates is important to provide an up-to-date assessment of risks associated with CVAD use in this population.

Developmental haemostasis. Impact for clinical haemostasis laboratories.

Developmental haemostasis is a concept, now universally accepted, introduced by Andrew et al. in the late 1980's. However, coagulation analysers and reagents have changed significantly over the past 15 years. Coagulation testing is known to be sensitive to changes in individual reagents and analysers. We hypothesised that the reference ranges developed by Andrew et al. may not be appropriate for use in a modern coagulation laboratory. Our study was designed to determine whether a current day coagulation testing system (STA Compact analyser and Diagnostica Stago reagent system) was sensitive to age-related changes in coagulation assays. This is the first large scale study since Andrew et al. to determine the age associated numerical changes in coagulation proteins. Our results confirm the concepts of developmental haemostasis elucidated by Andrew et al. However, our results clearly demonstrate that the absolute values of reference ranges for coagulation assays in neonates and children vary with analyser and reagent systems. The results confirm the need for coagulation laboratories to develop age-related reference ranges specific to their own testing systems. Without this, accurate diagnosis and management of neonates and children with suspected bleeding or clotting disorders is not possible. Finally we present age related reference ranges for D-dimers, TFPI, and endogenous thrombin potential, previously not described.

Age-related differences in heparin response.

INTRODUCTION: Major physiological differences in the coagulation system throughout childhood, compared to adults, are well documented. However, the impact of this on anticoagulant drugs is unknown. This study aimed to determine whether heparin therapeutic range determination is affected by the age of plasma donors and whether age-specific therapeutic ranges for heparin therapy may need to be considered in the clinical setting. MATERIALS AND METHODS: Plasma samples were obtained from healthy children and adults, and pooled into age-specific pools. These were spiked with different concentrations of heparin and APTT; Anti-Factor Xa and Anti-Factor IIa were measured using standard techniques. The experiments were repeated using three separate plasma pools, and results expressed as means with standard deviations. RESULTS AND CONCLUSIONS: The results show clear age-related differences in APTT for the same Anti-Factor Xa heparin concentration. The differences were more pronounced in younger children, with higher APTT for same Anti-Factor Xa. The Anti-Factor IIa activity of heparin for a given Anti-Factor Xa activity also differed between age-specific plasma pools. This study suggests that when using heparin in children, basic assumptions about the drug mechanism of action and implications for therapeutic ranges need to be considered.

Early phase II trial of human rotavirus vaccine candidate RV3.

A naturally attenuated, human neonatal strain, rotavirus vaccine candidate RV3, was tested in a limited phase II randomized double-blind controlled trial. Doses of 1 ml, containing placebo or 6.5 x 10(5) fluorescent cell forming units (fcfu) of virus in AGMK cells, were given at 3, 5 and 7 months of age. Limited replication in the small intestine is implied by the lack of virus excretion, and by the occurrence of an immune response in only 46% of the infants. However, those who developed an immune response were partially protected against rotavirus disease during the subsequent winter epidemic (protective efficacy 54%), supporting observations of protection induced by natural infection by this strain. Protection appeared to be heterotypic. Further trials are warranted, employing strategies to increase immunogenicity of this human rotavirus candidate vaccine.