Temporal aspects of anti-heparin-PF4 antibodies in heparin-induced thrombocytopenia.
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Biomedical subjects
Publications and source records attributed to Fiona Newall.
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INTRODUCTION: The use of oral anticoagulant therapy is increasing in children. Managing anticoagulant therapy in children presents unique challenges, including poor venous access. The advent of point-of-care (POC) monitoring of anticoagulant therapy offers a potential solution to this challenge. This paper reviews the published literature relating to POC monitoring of oral anticoagulant therapy in children. MATERIALS AND METHODS: A Medline search was conducted and identified key publications. Papers were reviewed with respect to their objectives, populations and POC device investigated. Study limitations were identified. RESULTS: Five publications and one abstract were identified, reporting studies using five different POC monitors. Three studies had a strong clinical management focus. Outcome measures assessed included target therapeutic range achievement and frequency of adverse events. Correlation between POC and laboratory-based results ranged from 0.83 to 0.96. Home monitoring and self-management using POC monitors were both reported to be preferred compared to standard laboratory testing. CONCLUSIONS: POC monitoring of oral anticoagulant therapy in children offers considerable advantages. The reviewed literature would suggest such monitoring can be performed accurately and reliably. The impact of quality control issues, such as calibration of thromboplastin ISI in POC devices, has not been explored in a paediatric population. Further studies are needed to clarify such issues and confirm the safety, reliability and efficacy of POC monitoring of oral anticoagulant therapy in children, including its home monitoring and self-management programs.
AIM: The epidemiology of venous thromboembolism in children has likely changed since first being described a decade ago because of evolving management strategies and a greater awareness of predisposing factors for thrombosis in children. The Royal Children's Hospital commenced a 4-year prospective registry of venous thrombosis in 1999 to determine the current Australian epidemiology of venous thrombosis in infants and children. METHODS: A prospective, single-centre registry was established to determine the prevalence, aetiology, diagnostic criteria, management and outcome of venous thromboembolism in an Australian tertiary paediatric centre. RESULTS: The incidence of venous thrombosis was 8.0/10 000 hospital admissions. Fifty-eight per cent of infants and 49% of children were male. Seventy-seven per cent of venous thromboses in infants were associated with central venous cannulation compared with 47% in children. Doppler ultrasonography was the most frequently used diagnostic tool. Treatment strategies varied between age groups. The all-cause mortality rate for infants and children in this study was 8.4% (direct thrombus-related mortality 0%). Fifteen per cent of all patients demonstrated complete resolution of their venous thrombosis at discharge, with 48% demonstrating complete resolution at follow-up assessment. Fifteen per cent of patients experienced significant thrombosis-related morbidity at follow-up assessment. CONCLUSION: In this single-centre registry, venous thrombosis in infants and children occurred with greater frequency than has previously been reported and its epidemiology varied. Central venous catheterisation continues to be a common precipitant to venous thrombosis. Optimal diagnostic and treatment interventions for venous thromboembolism have not yet been determined for infants and children, despite the significant incidence of long-term sequelae.
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.
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.
INTRODUCTION: Management strategies such as self-monitoring of anticoagulant therapy have been reported with increased frequency. Whilst patient education is frequently mentioned, details regarding the educational interventions employed are scarce. This study aimed to improve the outcomes of home monitoring of warfarin therapy in children through the development and implementation of a robust intervention, based upon the PRECEDE model of education. MATERIALS AND METHODS: Participating parents had to complete an intensive education and training program. After demonstrating practical and theoretical competency, parents commenced home monitoring. Every second scheduled home INR (H-INR) required a paired INR on the same day, obtained by a trained pathology collector (C-INR). Demographic and statistical outcome data was collected. RESULTS: Parental understanding of warfarin therapy improved significantly following the educational intervention (p<0.0001). 65.5% of H-INRs and 64.4% of C-INRs were within the target range (ns). Lin's correlation coefficient between H-INRs and C-INRs was 0.949. There were no warfarin-related adverse events. CONCLUSION: This study demonstrated a significant improvement in parental knowledge following participation in a robust educational intervention. Furthermore, compared to previous reports in children, a greater level of correlation between home and hospital-based INRs was achieved by participating parents. The use of similar educational interventions may serve to improve the outcomes of similar management strategies.
Vitamin K is essential for development of normal bone density and achieving adequate peak bone mass in childhood and is thought to be important in preventing the development of osteoporosis in later life. Warfarin, a vitamin K antagonist, is being used with greater frequency in children. The long-term effect of warfarin on bone density of children is not known. We performed a case control study survey of bone density in children on long-term warfarin (n=17, average duration of warfarin treatment 8.2 y) compared with randomly selected controls (n=321). There was a marked reduction in bone mineral apparent density of lumbar spine between patients and controls [patients 0.10 g/cm3; 95% confidence interval (CI), 0.93-0.11 g/cm3, controls 0.12 g/cm3; 95% CI, 0.11-0.12 g/cm3, p<0.001). The lumbar spine areal bone mineral density Z-score of patients was reduced compared with controls [patients, -1.96 (95% CI, -2.52 to -1.40). This difference persisted after adjustment for age and body size. The etiology for the reduced bone density is likely to be multifactorial, however, screening of children on long-term warfarin for reduced bone density should be considered.
Significant research has been directed into defining best-practice anticoagulant management of thromboembolic events and optimal strategies for determining the safety and efficacy of therapy. Similarly, improved patient outcomes have been realised through the development of novel management strategies such as self-monitoring and self-management. Considerably, less energy has been directed towards developing and evaluating the best mechanisms for delivery of patient education. This is in spite of the fact that numerous confounders to stable therapy confront warfarinised patients on a daily basis. That patients requiring warfarin therapy should be educated with respect to that therapy has never been questioned. However, relatively little attention appears to have been paid to the development of robust models of patient education in the setting of oral anticoagulant therapy. This paper reviews the current literature with respect to warfarin education interventions before recommending strategies that may facilitate determination of the impact educating patients about warfarin therapy has upon clinical outcomes.
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This paper reports the outcome of a research protocol aimed at optimising warfarin monitoring in a tertiary pediatric centre. The Thrombotest INR was the standard monitoring test employed to manage oral anticoagulant therapy in children at the Royal Children's Hospital (RCH), Melbourne. This study compares the results of this standard method to the novel CoaguChek INR monitor and the "gold standard" technique of venous INR sampling. The objectives were to determine 1) if point-of-care techniques of measuring the INR (Thrombotest and CoaguChek) are accurate and reliable compared to INR results obtained from venous sampling, processed in an accredited laboratory, and 2) if INR results generated by POC devices can be safely used to manage oral anticoagulant therapy in children. 18 children (10 females and 8 males) participated in the study. Ages ranged from 9 months to 21 years (Mean 11.9 years; SD 5.03 years). The agreement between CoaguChek and venous INR measurements (r = 0.885) was shown to be higher compared to Thrombotest and venous INR (r = 0.700). Compared to the venous INR, values obtained with Coaguchek and Thrombotest crossed into or out of the therapeutic range in 25% and 36% of cases respectively. In 88% of the CoaguChek cases and 57% Thrombotest cases, the difference from the venous result was less than 0.5. The CoaguChek method of INR monitoring is a more accurate and reliable method compared to Thrombotest, in the pediatric population tested, and can be safely used to manage oral anticoagulant therapy in children.
Several authors have reported a link between childhood stroke and inherited thrombophilia in recent years. The impact of such a relationship on management and outcome is yet to be determined, as is the potential cost-benefit ratio associated with the performance of thrombophilic screening in children presenting with ischemic stroke. We present a case that highlights the need for clinical and radiologic examinations to remain the definitive criteria used to diagnose stroke in children. The diagnosis should not be influenced by the finding of a thrombophilic marker.
OBJECTIVE: To determine whether warfarin can be safely administered to children who require long-term total parenteral nutrition (TPN), for the purpose of preventing central venous access device (CVAD)-related thrombosis. METHODS: A prospective cohort study was conducted of 8 children with short-gut syndrome or small intestinal anomalies. All patients received oral anticoagulant therapy (warfarin) managed by the hematology department at a tertiary pediatric center. Data collected included demographic details, nutritional intake, age, weight, history of deep vein thrombosis, number and functional duration of CVADs, warfarin requirements, and adverse event rates. RESULTS: A total of 15.2 warfarin years were studied prospectively. The target therapeutic range was achieved 51.1% of time. The mean dose of warfarin required to achieve the target therapeutic range (international normalized ratio) of 2.0 to 3.0 was 0.33 mg/kg/d. The mean duration between warfarin monitoring tests was 6.6 days. The median vitamin K intake per patient was 0.367 mg/kg/d (range: 0.018-2.85 mg/kg/d). Before commencing anticoagulant therapy, the mean CVAD duration was 160.9 days. Concomitant warfarin therapy was associated with a mean CVAD duration of 351.7 days. There were no major bleeding events, and no clinical extension of thrombosis was observed. CONCLUSIONS: This is the first published study to report uniform warfarin prophylaxis for CVADs in children. Warfarin therapy can be administered safely in children who require long-term TPN. Warfarin prophylaxis seems to prolong CVAD survival.
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