Cross-sectional assessment of haemostatic profile and hepatic dysfunction in Fontan patients.

BACKGROUND: Fontan-associated liver disease is accompanied by a hypercoagulable state. While hepatic dysfunction in Fontan patients is common, its relationship with haemostatic changes and clinical outcomes in this patient population remains unclear. OBJECTIVE: To correlate liver dysfunction and haemostatic profiles with clinical outcomes in the Fontan population. PATIENTS/METHODS: Patients were enrolled in a multicentre, cross-sectional study in Australia and New Zealand. Hepatic structure and function were assessed using serum-based calculations (Fibrotest and model for end-stage liver disease excluding international normalised ratio scores). Haemostatic profiles were assessed by Thrombin Generation. Platelet function was assessed via Platelet Factor 4 (PF4) and P-selectin (P-SEL). Clinical outcomes were obtained from the Australian and New Zealand Fontan Registry. RESULTS: Seventy-three patients participated in the study (mean age 18.9±8.5 years with a mean of 13.5±6.9 years post-Fontan). The Endogenous Thrombin Potential (ETP) for patients who suffered thrombotic events (TE) (1366.4±66.2 nM/min) was higher compared with patients with major bleeding events (1011.1±138.4 nM/min) (p=0.03). Except for a negative correlation between Fibrotest-score and PF4 (p=0.045), PF4 and P-SEL concentrations did not correlate with markers of hepatic dysfunction or structural abnormality. CONCLUSIONS: Increased ETP is associated with TE during clinical follow-up after Fontan. This study reinforces that hepatic dysfunction may contribute to the derangement of coagulation factors, impacting the individual risk of haemostatic complications for the Fontan population.

Whole blood flow cytometry protocol for the assessment of platelet phenotype, function, and cellular interactions.

Platelets are a key component of the hemostatic system and their roles in inflammation via interactions with leukocytes have also gained attention in recent years. Changes in platelet phenotype and function can cause bleeding and/or thrombosis and, as such, monitoring platelet-specific changes is crucial to assessing hemostasis in the clinical setting. Currently, available platelet function tests such as platelet aggregometry and thromboelastography require a large volume of blood, which is a major limitation for the pediatric population. Whole blood flow cytometric analysis of platelets is increasingly utilized in recent years, primarily due to the sensitivity of this method, but also because it only requires a small amount of blood with minimal sample manipulation. We have developed a whole blood flow cytometry methodological approach that enables the assessment of platelet phenotype, function, and their interactions with monocytes and neutrophils.

Clinical thresholds for diagnosing iron deficiency: comparison of functional assessment of serum ferritin to population based centiles.

Low serum ferritin is diagnostic of iron deficiency, yet its published lower cut-off values are highly variable, particularly for pediatric populations. Lower cut-off values are commonly reported as 2.5th percentiles, and is based on the variation of ferritin values in the population. Our objective was to determine whether a functional approach based on iron deficient erythropoiesis could provide a better alternative. Utilizing 64,443 ferritin test results from pediatric electronic health records, we conducted various statistical techniques to derive 2.5th percentiles, and also derived functional reference limits through the association between ferritin and erythrocyte parameters: hemoglobin, mean corpuscular volume, mean cell hemoglobin concentration, and red cell distribution width. We find that lower limits of reference intervals derived as centiles are too low for clinical interpretation. Functional limits indicate iron deficiency anemia starts to occur when ferritin levels reach 10 µg/L, and are largely similar between genders and age groups. In comparison, centiles (2.5%) presented with lower limits overall, with varying levels depending on age and gender. Functionally-derived limits better reflects the underlying physiology of a patient, and may provide a basis for deriving a threshold related to treatment of iron deficiency and any other biomarker with functional outcomes.

Development and Validation of the Warfarin-Aspirin Bleeding Assessment Tool (WA-BAT) in Children.

Bleeding assessment tools (BATs) aim to screen and estimate bleeding risk in patients with inherited bleeding disorders. However, the use of BAT as a standardized measure for comparing bleeding in patients on long-term thromboprophylaxis has not yet been validated. We developed a self-administrable BAT to assess bleeding in patients undergoing long-term thromboprophylaxis with aspirin or warfarin. Eligible participants were invited to complete the warfarin-aspirin -BAT (WA-BAT) online. The WA-BAT was readministered a number of weeks later to determine intrarater reliability. The WA-BAT showed substantial intrarater reliability and assesses major and minor bleeding associated with long-term warfarin or aspirin use.

Thrombophilia testing in a tertiary paediatric hospital: Indications, outcomes and appropriateness.

AIM: The association between inherited thrombophilia and thrombotic disease in children is unclear. As a result, whether expensive thrombophilia tests are indicated in children is a contentious issue. This retrospective study aimed to assess the appropriateness of thrombophilia testing and the associated cost of inappropriate testing at a tertiary paediatric hospital. METHODS: We conducted a search for thrombophilia tests ordered at the Royal Children's Hospital between 1 January 2011 and 31 December 2013. Using pathology and clinical records, we collected data relating to demographics, clinical data, indications, requesting departments and impact on patient management. RESULTS: Over the 3-year period, 3867 tests were ordered for 613 patients costing the hospital $102 579. Tests were most commonly ordered by gastroenterology on patients receiving liver transplants, by neurology as part of the stroke protocol, and by cardiology and cardiac surgery for patients anticoagulated on heparin infusions. Testing for thrombosis-related indications was relatively uncommon. Thrombophilia testing only directly affected management in one-third of patients. Overall, 70% of thrombophilia tests ordered were considered appropriate. However, some departments were found to have rates of inappropriate testing in excess of 50%. CONCLUSION: With improvements in thrombophilia testing practices at the Royal Children's Hospital AU$29 645.40 could be saved over 3 years. While there are improvements to be made in this area, in the overall context of the hospital's pathology testing budget, review of other areas such as inappropriate use of low-cost, high-volume tests may be of greater value in reducing the cost of pathology testing.

Quality of life assessment in children commencing home INR self-testing.

INTRODUCTION: Management of oral anticoagulant therapy (OAT) in children is complex and frequent testing of the International Normalised Ratio (INR) is a significant burden. This study evaluates the impact of a home INR self-testing (home ST) program on the quality of life (QoL) of children and their families. The aim of the study was to determine if participation in a home ST program improves QoL for children requiring long-term OAT and their families. MATERIALS AND METHODS: Children aged eight to 18 years requiring long-term OAT and parents of children participated. Quantitative methods comprised three validated QoL questionnaires; the anticoagulation specific PAC QL©, the PedsQL™ and the PedsQL FIM™. Questionnaires were completed before commencing home ST and 6-12 months later. Qualitative methods consisted of open-ended questions which participants answered when completing the questionnaires for the second time. Results of INRs tested at home were collected. RESULTS: Fifty-five parents and 35 children participated. The percentage of time the children's INRs were in their target therapeutic range was 71.3. Parents reported statistically significant improvements in QoL for themselves (mean increase 6.9), their family (mean increase 8.6) and their child (mean increase 11.1) following the commencement of home ST (difference p≤0.003 on all questionnaires). The children did not report a statically significant improvement in QoL. CONCLUSION: Parents reported significant improvement for their child's QoL, their QoL and the families' function following commencement of home ST. Children did not report a significant improvement in their QoL, but clearly identified satisfaction with home ST.

The economic costs of routine INR monitoring in infants and children--examining point-of-care devices used within the home setting compared to traditional anticoagulation clinic monitoring.

INTRODUCTION: The use of point-of-care (POC) devices within the home for routine INR monitoring has demonstrated reliability, safety and effectiveness in the management of infants and children requiring long-term warfarin therapy. However, a comprehensive cost-analysis of using this method of management, compared to attending anticoagulation clinics has not been reported. The aim of this study was to compare the estimated societal costs of attending anticoagulation clinics for routine INR monitoring to using a POC test in the home. MATERIALS AND METHODS: This study used a comparative before-and-after design that included 60 infants and children managed via the Haematology department at a tertiary paediatric centre. Each participant was exposed to both modes of management at various times for a period of ≥3 months. A questionnaire, consisting of 25 questions was sent to families to complete and return. Data collected included: the frequency of monitoring, mode of travel to and from clinics, total time consumed, and primary carer's income level. RESULTS: The home monitoring cohort saved a total of 1 hour 19 minutes per INR test compared to attending anticoagulation clinics and had a cost saving to society of $66.83 (AUD) per INR test compared to traditional care; incorporating health sector costs, travel expenses and lost time. CONCLUSIONS: The traditional model of care requires a considerable investment of time per test from both child and carer. Home INR monitoring in infants and children provides greater societal economic benefits compared to traditional models.

HEEADSSS assessment for adolescents requiring anticoagulation therapy.

The care of adolescents with complex chronic illness needs to be developmentally appropriate to encourage adherence, knowledge retention and self-management. There has been an increase in the number of adolescents requiring long-term or lifelong anticoagulation therapy, related to either an underlying illness or idiopathic deep vein thrombosis. The burden of anticoagulant therapy, the associated risks and the required lifestyle changes can significantly impact on psychosocial well-being in the adolescent patient. This review identifies issues pertinent to adolescent anticoagulation management and discusses strategies to support optimal management. The HEEADSSS (Home, Education and employment, Eating, Activities with peers, Drugs, Sexual activity, Suicide and depression, and Safety) framework was used to provide guidance in undertaking a psychosocial assessment of adolescents requiring anticoagulant therapy in conjunction with a structured education strategy. Adolescent anticoagulant management strategies employing developmentally appropriate assessment and education will likely result in improved therapeutic outcomes for the patient and potentially facilitate transition to adult-based care.