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Biomedical subjects

Paul Monagle

Publications and source records attributed to Paul Monagle.

29 records · Page 2Linked to original sources
PubMed2004

Thrombophilia interpretation in childhood stroke: a cautionary tale.

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.

Blood Coagulation Factors↗
PubMed2003

Thrombosis in pediatric cardiac patients.

Cardiac disease and thrombosis are intimately related in adults, but primary myocardial infarction in children is rare. Homozygous familial hyperlipidemia occurs in approximately 1 million children, and causes severe coronary artery disease during childhood. Kawasaki's disease is an acquired inflammatory disorder, which, if untreated, leads to coronary artery aneurysms and subsequent myocardial infarction. The current understanding of the pathophysiology and management of these conditions is discussed. More commonly, the relationship between cardiac disease in children and thrombosis is that children being treated for congenital structural cardiac disease develop iatrogenic thrombosis, most commonly precipitated by central venous access. The epidemiology of common treatment-induced thrombosis is described, and management guidelines presented. Finally, many cardiac surgical procedures increase the risk of thrombosis, and prophylactic antithrombotic therapy is commonly used. The current evidence for prophylaxis in different clinical situations is presented. Additional study is required in all areas to improve the outcome for children affected by cardiac disease and thrombosis.

Anticoagulants↗
PubMed2003

Fibrinolytic response to venous occlusion is decreased in patients after Kawasaki disease.

Impaired fibrinolysis is considered a sensitive marker of endothelial dysfunction. Persistent endothelial dysfunction occurs in some patients following Kawasaki disease. The aim of the present study was to assess whether impaired fibrinolysis is present in long-term survivors of Kawasaki disease. The study included 42 children with a documented history of Kawasaki disease presenting with or without coronary lesions, and 26 healthy controls. Blood samples were collected from patients and controls prior to and following venous occlusion stress testing. Significantly decreased fibrinolytic response to venous occlusion was detected in patients compared with controls due to decreased tissue plasminogen activator. In addition, patients had significantly increased plasma concentrations of plasminogen and fibrinogen, which were related to similar increases of alpha2 -macroglobulin. Decreased fibrinolytic response was found in patients with coronary aneurysms but also in those without coronary lesions. In summary, a decreased fibrinolytic response to venous occlusion may reflect persistent endothelial damage following acute Kawasaki disease, potentially predisposing these patients to accelerated atherosclerosis and cardiovascular disease in early adult life.

Adolescent↗
PubMed2003

Fibrinolytic system in adolescents: response to venous occlusion stress tests.

Recent studies indicate that the incidence of thromboembolic events is increasing as a secondary complication in children with serious underlying diseases. The mechanism to eliminate these thrombi via the thrombolytic system in children is unknown. The baseline fibrinolytic system is age dependent, with significant variation between children and adults. Adult studies would suggest that the fibrinolytic response to venous occlusion has more clinical relevance than the baseline fibrinolytic system. The aim of this study was to determine whether the fibrinolytic response to venous occlusion stress testing in healthy adolescents differs from the response in healthy adults. Healthy adolescents (13-18 y) from a school population and normal adults were recruited. Pre- and postvenous occlusion blood samples were collected using standard techniques. Plasma tissue plasminogen activator, plasminogen activator inhibitor-1, plasminogen, alpha(2)-antiplasmin, alpha(2)-macroglubulin, D-dimers, euglobulin lysis time, and fibrinogen were measured on each sample. Adolescents had significantly decreased tissue plasminogen activator antigen levels and increased plasminogen activator inhibitor-1 activity levels after venous occlusion, resulting in significantly prolonged euglobulin lysis times. The results of our study confirm developmental differences in the fibrinolytic response to venous occlusion stress testing. The age-related differences in fibrinolytic response to venous occlusion of younger children and the significance of these differences on the pathophysiology of thromboembolic events in children require further studies.

Adolescent↗
PubMed2003

Warfarin therapy in children who require long-term total parenteral nutrition.

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.

Adolescent↗
PubMed2002

Thromboembolic problems after the Fontan operation.

One of the major causes of morbidity and mortality after the Fontan operation is thromboembolic events (TE). To assess the current knowledge of TE after Fontan surgery, a comprehensive MEDLINE search of the English literature from 1971 to 2000 was conducted using the key words Fontan, univentricular heart, children, thrombosis, congenital heart disease, cavopulmonary, and palliation. Other relevant publications were identified from bibliographies of the literature retrieved. Fifty-one studies were identified and analyzed for incidence, potential morbidity and mortality, risk factors, prophylactic options, and risk/benefit ratio of prophylactic anticoagulation as relates to TE after Fontan surgery. There were 23 case reports, 13 retrospective cohort studies that included some details about TE among other reported outcomes after Fontan procedures, eight retrospective cohort studies in which TE was the primary outcome measure, and seven articles reporting cross-sectional point surveys, only three of which directly surveyed TE as an outcome. Based on an analysis of the current literature, there is insufficient evidence to make clear recommendations about optimal anticoagulant prophylaxis at this time. Multicenter randomized controlled trials comparing prophylactic antiplatelet with anticoagulation therapies are needed to provide rational scientific guidelines for future management of Fontan patients.

Anticoagulants↗