Investigating the experience of parents who have given their infants enoxaparin at home.

INTRODUCTION: Enoxaparin is a common anticoagulant used in infants for the prevention and treatment of thrombosis. When administered with the purpose of treating a thrombosis, the duration of treatment is six to twelve weeks. Enoxaparin must be injected subcutaneously, either by direct injection or via an indwelling subcutaneous catheter (Insuflon™). Once discharged from hospital, parents/caregivers of infants and small children take responsibility for the safe preparation and administration of the enoxaparin which can be difficult and confronting. Whilst there is documented evidence about the benefits of targeted education for warfarin anticoagulation and the impact this has on the quality of life for children and their families, this has not been investigated in a cohort of children requiring enoxaparin anticoagulation. We therefore explored the educational needs of parents whose infants require enoxaparin anticoagulation after discharge to inform future practice to optimise delivery of care as well as improve patient safety and outcomes. MATERIALS & METHODS: A qualitative, descriptive methodology was employed using focus groups to generate rich descriptive data. RESULTS: Our results show that parents were traumatised by the process of managing their infant's enoxaparin, and that they may benefit from a formal, more structured educational program to facilitate this treatment in the future. CONCLUSION: It is recognised that enoxaparin therapy in infants may be a traumatic experience for parents and caregivers. The availability of an educational resource for families to refer to once discharged, as well as ongoing communication with the treating medical team is vital.

Anticoagulant prophylaxis and therapy in children: current challenges and emerging issues.

This review is aimed at describing the unique challenges of anticoagulant prophylaxis and treatment in children, and highlighting areas for research for improving clinical outcomes of children with thromboembolic disease. The evidence presented demonstrates the challenges of advancing the evidence base informing optimal management of thromboembolic disease in children. Recent observational studies have identified risk factors for venous thromboembolism in children, but there are few interventional studies assessing the benefit-risk balance of using thromboprophylaxis in risk-stratified clinical subgroups. A risk level-based framework is proposed for administering mechanical and pharmacological thromboprophylaxis. More research is required to refine the assignment of risk levels. The anticoagulants currently used predominantly in children are unfractionated heparin, low molecular weight heparin, and vitamin K antagonists. There is a paucity of robust evidence on the age-specific pharmacology of these agents, and their efficacy and safety for prevention and treatment of thrombosis in children. The available literature is heterogeneous, reflecting age-specific differences, and the various clinical settings for anticoagulation in children. Monitoring assays and target ranges are not well established. Nevertheless, weight-based dosing appears to achieve acceptable outcomes in most indications. Given the limitations of the classical anticoagulants for children, there is great interest in the direct oral anticoagulants (DOACs), whose properties appear to be particularly suitable for children. All DOACs currently approved for adults have Pediatric Investigation Plans ongoing or planned. These are generating age-specific formulations and systematic dosing information. The ongoing pediatric studies still have to establish whether DOACs have a positive benefit-risk balance in the various pediatric indications and age groups.

Anti-activated factor II assay for monitoring unfractionated heparin in children: results of the HEARTCAT study.

Essentials Unfractionated heparin has variable effects in children and therefore, monitoring is essential. A randomized controlled trial substudy investigating an anti-IIa assay in children was conducted. Anti-IIa values are lower in younger children, an effect more pronounced at low-dose heparin. Heparin effect on Xa and IIa is not equal, particularly in infants and after high-dose heparin. SUMMARY: Background Unfractionated heparin (UFH) is used for the prophylaxis and treatment of thrombosis in children. Laboratory monitoring of UFH is needed to prevent over-anticoagulation or under-anticoagulation. Objectives To investigate the association between UFH dose and UFH effect as monitored with the anti-activated factor II (FIIa) assay, the relationship between anti-FIIa and anti-activated factor X (FXa) effects, and the influence of patient age and other factors on UFH effect. Patients and methods This was a randomized controlled trial in children during cardiac catheterization, comparing high-dose UFH (100 units kg-1 bolus) with low-dose UFH (50 units kg-1 bolus). Blood samples were drawn at baseline, and after 30 min, 60 min, and 90 min. For the purpose of this study, 49 children and 117 blood samples were evaluated. Results The anti-FIIa assay discriminated well between high-dose and low-dose UFH. Multiple regression demonstrated significant influences of UFH dose and age on anti-FIIa levels. Younger children had lower anti-FIIa levels than older children, an effect that was more pronounced with low-dose UFH. Anti-FXa/anti-FIIa ratios were equal with low-dose UFH. However, anti-FXa levels were relatively increased over anti-FIIa levels in infants and after high-dose UFH bolus administration. Conclusion The UFH effect on anti-FIIa levels is lower in infants than in older children. This influence of age appears to be dose-dependent, being more pronounced with low-dose UFH. Anti-FXa and anti-FIIa levels are not equal, particularly in infants and after high-dose UFH. Monitoring UFH solely with anti-FXa assays may not be sufficient in children, and the anti-FIIa assay may provide important complementary information.

Inhalational use of antithrombotics in humans: Review of the literature.

INTRODUCTION: Off label use of anticoagulants is common. The association between fibrin deposition in the lungs and primary lung disease, injury or prematurity affords a strong theoretical basis for the potential benefit of antithrombotic therapies administered directly to the lung tissue. This review offers a critical appraisal of current evidence related to the inhalational administration of antithrombotic therapy in humans. MATERIALS AND METHODS: An interrogation of 2 databases across a 13 year period of time was undertaken using key words selected a priori. Identified publications were categorized according to the following themes: 1. Inhaled antithrombotic therapy in healthy subjects 2. Inhaled antithrombotic therapy for vascular thromboprophylaxis 3. Inhaled antithrombotic therapy in smoke inhalation and lung injury 4. Inhaled antithrombotic therapy in asthma or allergy 5. Inhaled antithrombotic therapy for plastic bronchitis post-Fontan surgery 6. Inhaled antithrombotic therapy for other indications. RESULTS: 33 articles were identified consistent with the inclusion criteria developed for this review. Unfractionated heparin, LMWH, activated protein C and thrombolytic agents have been administered via the respiratory track, with asthma and smoke inhalation/lung injury being the most frequently investigated clinical scenarios described. All studies reported had significant methodological limitations. CONCLUSIONS: The safety and clinical utility of inhaled antithrombotic therapies have not been adequately investigated to support the generation of any firm evidence. This review highlights where inhaled antithrombotic therapies have shown promise and importantly, the further research required to confirm mechanism of action and a definitive risk: benefit profile.

'I don't want to hurt him.' Parents' experiences of learning to administer clotting factor to their child.

To explore the experiences and educational needs of parents learning to use an Implanted Central Venous Access Device (IVAD) to administer clotting factor to their child with haemophilia. Parents of children with haemophilia who had learnt to administer clotting factor via IVAD attended focus groups to discuss their experiences of the learning process. Data were transcribed and analyzed thematically. Parents described distress and trauma in dealing with the diagnosis and treatment of their child's haemophilia. It was within this context that parents began the IVAD education process. Four major themes emerged from the data: dealing with fear and anxiety; a supportive learning environment; establishing a ritual and empowerment and liberation. Parents identified a supportive learning environment as their critical need rather than a specific learning process. In addition, the concept of ritual emerged both as a mechanism for increasing the child's comfort with the procedure and as a valuable learning tool for their parents. This study highlights the importance of consulting consumers to understand their experience of illness and their educational needs. Patient and family education programs should not be limited to the provision of information, but must establish and incorporate the needs of the learner.

Age-related plasma reference ranges for two heparin-binding proteins--vitronectin and platelet factor 4.

This study was conducted to establish age-related reference ranges for two heparin-binding proteins--vitronectin and platelet factor 4 (PF4)--and to determine if the quantitative values of these proteins may contribute to the reported age-dependent effect of unfractionated heparin (UFH). Plasma samples were obtained from healthy children aged between 1 month and 16 years and from healthy adult volunteers. Two commercial kits were used to measure plasma vitronectin and PF4 levels. Results were reported as mean and boundaries including 95% of the population. Plasma vitronectin levels for children aged 1-5 years were significantly higher compared with adults. Plasma PF4 levels for infants <1 year of age were significantly lower compared with adults. The differences between reference values for both proteins in all other age-groups were not statistically significant. This study for the first time has established age-related reference ranges for vitronectin and PF4. In establishing these ranges, the quantitative values of these proteins do not appear to be the major contributory cause for the age-dependent variation in UFH effect. Future studies are required to evaluate the possible impact of age-dependent differences in binding between heparin-binding proteins and UFH.

Refinement and feasibility testing of a manual micro-method for protamine titration.

Current clinical recommendations for unfractionated heparin (UFH) therapy suggest target APTT ranges should reflect heparin concentrations of 0.2-0.4 IU/ml by protamine titration or 0.35-0.7 IU/m by an anti-Xa assay. Historically, performance of a manual protamine titration assay has been labour intensive and required a large plasma sample. However, recent studies have described difficulties with standardizing anti-Xa assays and demonstrated poor correlation of anti-Xa assays in children. This study aimed to refine and test the feasibility of a modified protamine titration assay using 100 microl of plasma. The resultant method produced reliable and repeatable results in adult plasma pools spiked with UFH. The feasibility of this method was proven by testing of in vivo heparinised samples obtained from children. This protamine titration method may offer an alternative to anti-Xa assays for clinical monitoring of children on heparin therapy, and will enhance clinical studies investigating paediatric-specific management of UFH therapy.

A survey of pediatric cardiology nurses' understanding of warfarin therapy.

Children with underlying cardiac defects represent the largest cohort of pediatric patients requiring oral anticoagulant therapy. This study aimed to determine how much pediatric cardiology nurses understood about warfarin therapy, given their role as patient educators. Surveys were sent to four Australian pediatric hospitals that provided inpatient cardiac services. Data are presented descriptively, with relationship between variables analyzed using linear regression analysis. Forty-one completed questionnaires were received from 94 registered nurses. The majority of nurses held an undergraduate degree in nursing and were classified as senior registered nurses. Nurses did not demonstrate a good understanding of warfarin therapy. Knowledge deficits were identified across a broad spectrum of areas, with only 30% of nurses reporting that they felt equipped to provide families with education regarding oral anticoagulant therapy. Nurses regularly provide patients with education regarding medication regimes; however, the effectiveness of that education is rarely evaluated. This study suggests that pediatric nurses working with patients who are often prescribed oral anticoagulant therapy have significant knowledge deficits about anticoagulant therapy. The impact of this lack of knowledge on the effectiveness of patient education has not been evaluated, but it is unlikely to be helpful.

Arterial ischaemic stroke in children.

OBJECTIVE: Arterial ischaemic stroke (AIS) in childhood is a serious disorder about which little is published. The aim of this study is to determine the epidemiology and outcome of AIS in Australian children. METHODS: Cases of childhood AIS occurring at the Royal Children's Hospital, Melbourne 1993-2001, were identified by medical record search using International Classification of Disease Codes. Information was collected on demographics, risk factors, arterial distribution, results of thrombophilic testing, management and outcome. RESULTS: During the 8 years of review 95 patients presented with 98 cases of AIS calculating an incidence of 1.8 per 100000 children per year. Children less than 12 months of age represented greater than one third of all cases. Identifiable risk factors were present in 64% of cases with congenital heart disease the major risk factor. Thrombophilic testing was incomplete with initial abnormalities present in 18% of cases tested. The estimated stroke-related mortality was 8.4%. Of the patients who survived and who had follow-up details available, 78% had a neurological deficit. Twenty-six patients (26%) received anticoagulation. There was no statistically significant association between treatment with anticoagulation and normal neurological outcome. CONCLUSION: AIS is over-represented in children under 12 months of age and results in death or residual neurological impairment in the majority of cases. Further prospective studies are needed to identify risk factors for poor outcome. The recently established Australian and New Zealand Stroke and Thrombophilia Registry should provide important information on clinical and laboratory based risk factors and create a basis for international clinical trials to improve the outcome of childhood AIS.

Cerebral sinus venous thrombosis in children.

OBJECTIVE: Cerebral sinus venous thrombosis (cerebral SVT) is rare in children. Information on clinical characteristics, radiological findings and outcome is emerging. METHODS: Cases of cerebral SVT diagnosed between 1995 and 2001 were identified by a computer-assisted search using International Classification of Disease codes. Medical records were reviewed to collect information on clinical presentation, investigations, treatment and outcome. RESULTS: Sixteen cases of cerebral SVT were identified. All cases presented in association with head and neck pathology. The majority of cases presented with symptoms of raised intracranial pressure and focal neurological signs. Magnetic resonance imaging identified all cases of cerebral SVT whilst CT scanning failed to demonstrate the diagnosis in two cases. Management with anticoagulation was associated with radiological resolution of the thrombosis and normal neurological outcome. Long-term follow up demonstrated neurological deficits in greater than 40% of patients. CONCLUSION: Cerebral SVT in children is associated with significant residual neurological morbidity. Prospective studies to identify predictors of outcome and effective management interventions are required.

Heparin-induced thrombocytopenia in children.

OBJECTIVE: To audit the frequency of heparinoid (standard heparin and low molecular weight heparin) use in a tertiary paediatric hospital, and to determine the occurrence of heparin-induced thrombocytopenia (HIT). METHODS: A 1-week cross-sectional audit of all heparinoids given to inpatients at a tertiary paediatric hospital was undertaken and a retrospective medical record review of all suspected HIT cases at the tertiary paediatric centre over a 2-year period was carried out. RESULTS: One hundred and sixteen patients received heparinoid medications over a 7-day period. An average of 29 children received heparin daily. The retrospective medical record review identified four patients with suspected HIT over a 2-year period. Two patients developed thrombotic complications, which were fatal in one patient. CONCLUSION: Heparin is used frequently in paediatric tertiary hospitals, yet the occurrence of HIT in children is much lower than that reported in adults. Improved laboratory techniques could facilitate improved screening and diagnosis of this serious adverse drug reaction.

Post-thrombotic syndrome.

Post-thrombotic syndrome (PTS) is a potentially disabling complication occurring in up to 67% of adult patients following deep venous thrombosis (DVT). PTS has recently been recognised in children. We present three cases of symptomatic PTS in children, which occurred following the use of central venous lines (CVLs). In two cases, no symptoms of acute thrombosis were noted. The cases highlight the clinical presentation of this syndrome. A review of the literature revealed two reports describing PTS occurring in children following DVT with an estimated incidence of 7-12%. It is concluded that PTS is an important complication of DVT in children. The clinical findings of pain, swelling, and brawny induration are similar to adult patients. The effect on growing limbs is not known. Paediatricians should be aware of the potential of PTS in all children who are at risk of DVT, including patients with malignancy, congenital heart disease, and children who have had previous CVLs, even in the absence of documented acute DVT.