Sophie Jones

Assessing outcome measures of oral anticoagulation management in children

The complexities of managing oral anticoagulation therapy in children have been well described and various management strategies have been designed to optimise clinical outcomes within this challenging population. To date, outcome measurements used within paediatric studies investigating oral anticoagulant management have focused upon achieving therapeutic range and examining the incidence of medication-related adverse events. Whilst the reporting of such data is a priority, the relatively small number of children participating in clinical studies of oral anticoagulant management and the difficulties associated with conducting multi-centre interventional trials in such populations limit the ability of researchers to measure the significance of interventions made. This review examines current methods of reporting outcomes for paediatric oral anticoagulation management and identifies how the inclusion of quality of life as an outcome measure may strengthen the methodology of research aimed at measuring the impact of management interventions within the field of paediatric oral anticoagulant therapy.

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 carers 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

HEEADSSS assessment for adolescents requiring anticoagulation therapy

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.

Recommendations for point-of-care home International Normalized Ratio testing in children on vitamin K antagonist 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.

Central venous catheter‐related thrombosis and thromboprophylaxis in children: a systematic review and meta‐analysis: discussion

*Pediatrics, Stollery Childrens Hospital, University of Alberta, Edmonton, AB, Canada; and †Clinical Hematology, Royal Children’s Hospital,Department of Pediatrics, University of Melbourne, Melbourne, Victoria, AustraliaTo cite this article: Bauman ME, Bruce A, Jones S, Newall F, Massicotte MP, Monagle P. Recommendations for point-of-care home interna-tional normalized ratio testing in children on vitamin K antagonist therapy. J Thromb Haemost 2013; 11: 366–8.

Commencement of warfarin therapy in children following the Fontan procedure

1 Vidal E, Sharathkumar A, Glover J, Faustino EV. Central venous catheter-related thrombosis and thromboprophylaxis in children: a systematic review and meta-analysis. J Thromb Haemost 2014; 12: 1096–109. 2 Jones S, Ignjatovic V, Monagle P, Newall F. Central venous catheter-related thrombosis and thromboprophylaxis in children: a systematic review and meta-analysis: comment. J Thromb Haemost 2015; 13: 159–64. 3 Male C, Kuhle S, Mitchell L. Diagnosis of venous thromboembolism in children. Semin Thromb Hemost 2003; 29: 377–90. 4 Mitchell LG, Andrew M, Hanna K, Abshire T, Halton J, Anderson R, Cherrick I, Desai S, Mahoney D, McCuster P, Wu J, Dahl G, Chait P, de Veber G, Lee KJ, Mikulis D, Ginsberg J, Way C. A prospective cohort study determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line who are treated with L-asparaginase: results of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study. Cancer 2003; 97: 508–16. 5 Kulkarni K, Halton J, Spavor M, Israels SJ, Abish S, Yong J, Yasui Y, Mitchell LG. Increased requirement for central venous catheter replacement in paediatric oncology patients with deep venous thrombosis: a multicentre study. Thromb Haemost 2015; 113: 434–5. 6 Kuhle S, Spavor M, Massicotte P, Halton J, Cherrick I, Dix D, Mahoney D, Bauman M, Desai S, Mitchell LG. Prevalence of post-thrombotic syndrome following asymptomatic thrombosis in survivors of acute lymphoblastic leukemia. J Thromb Haemost 2008; 6: 589–94. 7 van Ommen CH, Ottenkamp J, Lam J, Brennickmeier M, Heijmans HS, Buller HR, Peters M. The risk of postthrombotic syndrome in children with congenital heart disease. J Pediatr 2002; 141: 582–6. 8 Polen E, Weintraub M, Stoffer C, Jaffe DH, Burger A, RevelVilk S. Post-thrombotic syndrome after central venous catheter removal in childhood cancer survivors: a prospective cohort study. Pediatr Blood Cancer 2015; 62: 285–90. 9 Kuhle S, Eulmesekian P, Kavanagh B, Massicotte P, Vegh P, Mitchell LG. A clinically significant incidence of bleeding in critically ill children receiving therapeutic doses of unfractionated heparin: a prospective cohort study.Haematologica 2007; 92: 244–7. 10 Massicotte P, Julian JA, Gent M, Shields K, Marzinotto V, Szechtman B, Chan AK, Andrew M. An open-label randomized controlled trial of low molecular weight heparin for the prevention of central venous line-related thrombotic complications in children: the PROTEKT trial. Thromb Res 2003; 109: 101–8. 11 Mitchell LG, Goldenberg NA, Male C, Kenet G, Monagle P, Nowak-Gottl U. Definition of clinical efficacy and safety outcomes for clinical trials in deep venous thrombosis and pulmonary embolism in children. J Thromb Haemost 2011; 9: 1856–8.

Safety and Efficacy Outcomes of Home and Hospital Warfarin Management Within a Pediatric Anticoagulation Clinic.

INTRODUCTION Following the Fontan procedure, children require lifelong anticoagulant therapy to minimise the risk of thrombosis. Factors influencing the management of warfarin therapy in children post-Fontan procedure are poorly understood. This study investigated factors affecting warfarin therapy stability and time to reach target therapeutic range, in children post-Fontan procedure. MATERIALS AND METHODS Medical histories of children who had undergone Fontan procedures between 1st June 2008 and 1st June 2010 were retrospectively audited. Variables of interest included dietary intake, activity level, gastro-intestinal function, presence of intercostal catheters and antibiotic therapy requirements. Time of warfarin commencement, attainment of a therapeutic International Normalized Ratio (INR) and dosing of warfarin were of particular interest. RESULTS Decreased warfarin dosage, compared to the clinical practice guidelines, was seen in all children. Antibiotic requirement correlated with an increased hospital length of stay in post-Fontan patients. Requirement for maintenance fluids and immobility lead to a further decrease in the warfarin dose received. CONCLUSIONS This study presents previously unknown information about the trajectory of warfarin therapy in children post-Fontan procedure. Results contribute to our understanding of the factors that impact warfarin stability in this population. This evidence together with continued research may aid to improve the clinical management of children post-Fontan procedure by reducing the time required to attain target INRs and, potentially length of hospital stay.

Recommendations for the development of a dedicated pediatric anticoagulation service: communication from the SSC of the ISTH.

The complexity of managing children with chronic disease has led to an increase in the use of long-term warfarin therapy. Time in therapeutic range (TTR) is the preferred method for determining efficacy and stability of warfarin management. This study aimed to determine the TTR achievement and incidence of adverse events among pediatric warfarin patients managed by an anticoagulation clinic over 12 months and to compare TTR achievement between patients self-testing (PST) at home and those monitored using routine methods. International normalized ratio (INR) results reported for 2012 for children currently having their warfarin therapy managed by a dedicated pediatric anticoagulation clinic were analyzed. Warfarin-related adverse events were recorded. A total of 164 patients were included. In total, 93 children performed PST and 71 children tested their INR at a hospital or pathology service. TTR achievement for the cohort was 67.1% (95% confidence interval, 64.4-69.7). A total of 69.2% of INR tests conducted at home were within the TTR compared with 64.3% of INR tests conducted at a hospital or pathology service (P=0.07). One major bleeding event occurred and there was 1 thrombotic episode. PST demonstrated noninferior warfarin stability compared with routine methods. Routine outcome evaluation of pediatric anticoagulation management within single institutions is necessary to confirm the success of such programs.

Anticoagulation of cardiomyopathy in children

F . NEWALL ,*†‡§¶ S . JONES ,*§¶ M. BAUMAN,** A . BRUCE ,** M. P . MASS ICOTTE** and P . MONAGLE ,*§¶ FOR THE SUBCOMMITTEE ON PER INATAL AND PAEDIATR IC HAEMOSTAS IS *Clinical Haematology Department, Royal Children’s Hospital; †Nursing Research Department, Royal Children’s Hospital, Parkville; ‡Department of Nursing, The University of Melbourne; §Department of Paediatrics, The University of Melbourne; ¶Haematology Research Group, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia; and **Pediatrics Department, Stollery Children’s Hospital, University of Alberta,Edmonton, AB, Canada

Recommendations for measuring health-related quality of life in children on anticoagulation

OBJECTIVES Cardiomyopathy is a common cause of heart failure in children. Thrombosis is a potential significant secondary complication. Thus warfarin is recommended by the American College of Chest Physicians for the treatment of children with cardiomyopathy despite the lack of published evidence to support its use. METHODS A retrospective clinical audit to estimate the rates of major bleeding and incidence of thromboembolism associated with oral anticoagulant therapy (warfarin) for primary thromboprophylaxis in a cohort of children with cardiomyopathy. Relevant outcomes including thrombosis and major haemorrhage were defined a priori according to internationally accepted definitions. RESULTS 36 children (35.9 warfarin years) were examined, with 25% taking warfarin for greater than 1year. Primary reasons for discontinuation of warfarin therapy were cardiac transplantation (n=7), transition to VAD (n=1), improved cardiac function (n=17), transfer of care (n=3), change to aspirin (n=2). The mean age at starting warfarin was 5.4years (range 0.2-15.2). The most common Target Therapeutic Range (TTR) for warfarin therapy was 2.0 - 3.0. TTR achievement was normally distributed and occurred in a mean 48.5% of all INR tests. There were zero warfarin related adverse events, including thrombosis or haemorrhage. CONCLUSION The low rate of TTR achievement is consistent with previously reported TTR achievement rates for infants. In addition the low rate of TTR achievement was likely influenced by the clinical profile of this complicated condition in children. Nonetheless, this data shows that the clinical outcomes for this cohort are acceptable and warfarin therapy can be safe in children with cardiomyopathy.