Clopidogrel Use in Children

doi:10.1016/j.jpeds.2005.05.006

The Journal of Pediatrics

Volume 147, Issue 5, November 2005, Pages 657-661

https://doi.org/10.1016/j.jpeds.2005.05.006 Get rights and content

Objectives

To review a pediatric experience with the antiplatelet agent clopidogrel and suggest a dosage regimen.

Study design

A retrospective chart review of all infants and children treated with clopidogrel at The Hospital for Sick Children, Toronto between January 2001 and April 2004. Clopidogrel dosages, duration of therapy, complications, and adverse effects in a pediatric population were explored.

Results

Fifteen infants and children with congenital and acquired heart disease were treated with clopidogrel (median age, 3.5 years; range, 6 weeks to 16 years). Dosages ranged from 1 to 6 mg/kg/day for periods between 1 month and 6 months. Although no thrombotic events were reported, 1 child had a bleeding complication (gastrointestinal) while on triple antithrombotic therapy. Other complications reported in adults, including rash and clinical thrombocytopenia, were not noted in this pediatric series.

Conclusions

Clopidogrel was well tolerated. We suggest a starting dose of 1 mg/kg/day for children.

Section snippets

Methods

A retrospective review of the inpatient pharmacy records was undertaken to identify children hospitalized at The Hospital for Sick Children, Toronto in whom prophylactic antiplatelet therapy with clopidogrel bisulfate (Plavix; Sanofi-Synthelabo/Bristol Myers Squibb, Canada) was administered between January 2001 and April 2004. The hospital ethics committee approved the study. Relevant clinical data were extracted from the children's hospital records, including age, sex, weight, underlying

Results

Fifteen infants and children treated with clopidogrel were identified (Table). The female to male ratio was 2:1, median age was 3.5 years (range, 6 weeks to 16 years), and mean weight was 15.0 ± 9.5 kg. Four of the 15 children were under age 1 year. Fourteen children underwent cardiac catheterization; their underlying cardiac conditions and indications for the procedure are summarized in Table. Endovascular stents were inserted in 10 children (71%). In these children, clopidogrel therapy was

Discussion

The pathophysiology of thrombosis in children with heart disease is a complex phenomenon. It may involve endothelial cell damage after surgery, stent insertion, indwelling catheterization, or endovascular procedures (eg, Fontan and Blalock-Taussig shunting).⁴ Abnormalities in blood flow patterns and polycythemia may also lead to hyperviscosity and stasis. Venous thrombus formation is usually the result of local coagulation activation combined with a disturbed balance between coagulation and

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Cited by (30)

Covered Stent Treatment of an Extracranial Internal Carotid Artery Pseudoaneurysm in a Three Year Old Child with 12 Years of Follow Up: A Case Report
2021, EJVES Vascular Forum
Citation Excerpt :
Platelet aggregation with aspirin at the standard prophylactic dose has been shown to be safe. Aspirin is the most commonly used platelet anti-aggregant in children with cardiovascular disease, although the use of clopidogrel is increasing.10 In this case, platelet anti-aggregation was started early with aspirin at a dose of 3 mg/kg/day for up to 100 mg/day, a dose that has been maintained until today.
Extracranial internal carotid artery (ICA) pseudoaneurysms in children, although uncommon, are life threatening. Covered stents are a good alternative treatment, as they avoid the risk of open surgery and preserve the ICA. Until recently, long term outcomes were unknown.
A three year old boy was hospitalised with an enlarged swelling on the left side of his neck and severe respiratory distress. He had been treated a month prior for a left deep cervical abscess, with bacteriological culture positive for Staphylococcus aureus. Computed tomography angiography (CTA) revealed a large pseudoaneurysm originating from the left ICA, approximately 2 cm above the bifurcation. A balloon expanded covered stent (Jostent Graftmaster; Abbott Vascular, Redwood City, CA, USA) was deployed via a left femoral approach, after selective angiography, to seal the carotid rupture without incident. Control angiography revealed immediate exclusion of the pseudoaneurysm and patent ICA. The bacteriological culture of the residual haematoma was negative. The child was discharged with full recovery and without neurological sequelae, under platelet anti-aggregation. He has been followed up and has remained asymptomatic for 12 years, with CTA confirmed ICA patency, without deformation or evidence of significant restenosis.
This is the first report of the long term outcome of a covered stent in a child treated at three years of age, with a 12 year follow up. The good performance of the covered stent in this case reinforces its adoption as a first line option in the treatment of extracranial ICA pseudoaneurysms in children.
What is the optimal dose of clopidogrel in pediatric patients?
2019, Anales de Pediatria
El objetivo de este estudio fue recopilar datos retrospectivos sobre la prescripción de clopidogrel y describir las condiciones de uso en la población pediátrica de un hospital de referencia de nivel terciario y evaluarlas con base en la evidencia disponible.
Estudio observacional, descriptivo y retrospectivo realizado entre marzo de 2010 y marzo de 2017. Los criterios de inclusión fueron: 100% de los pacientes menores de 18 años que fueron dados de alta de nuestro hospital con clopidogrel como tratamiento domiciliario en el período de estudio. Se recogieron los siguientes datos: datos demográficos, diagnóstico, indicación de clopidogrel, fecha de inicio y de finalización del tratamiento, presencia o ausencia de tratamiento concomitante con ácido acetilsalicílico u otros antiagregantes plaquetarios o anticoagulantes, tratamiento concomitante con inhibidores de la bomba de protones, efectividad y efectos adversos.
Un total de 11 pacientes se incluyeron en el estudio (45% hombres). La edad promedio fue de 3,1 años (rango: 1 mes-8 años). La dosis recomendada de clopidogrel fue de 0,2 mg/kg/día en todos los individuos, recibiendo tratamiento concomitante con ácido acetilsalicílico 10/11 pacientes para optimizar la terapia antiplaquetaria. Ningún niño recibió tratamiento concomitante con anticoagulantes y solo uno de ellos recibió tratamiento con inhibidores de la bomba de protones. No se observaron trastornos hemorrágicos u otros efectos adversos asociados con clopidogrel.
Según nuestra experiencia, la dosis de clopidogrel de 0,2 mg/kg/día demostró ser una estrategia segura y efectiva, independientemente de la edad del paciente. La buena tolerancia observada podría estar asociada con el ajuste de la dosis óptima para lograr la agregación plaquetaria sin aumentar el riesgo de efectos adversos.
The aim of this study was to collect retrospective data on the prescription of clopidogrel, describe the conditions of its use in the paediatric population of a tertiary referral hospital, and evaluate its use based on the current scientific evidence.
We conducted a retrospective, observational and descriptive study between March 2010 and March 2017. We included all patients under the age of 18 who were discharged from our hospital for home treatment with clopidogrel within the study period. We collected data on the following: demographic data, diagnosis, indication for clopidogrel, start and end date of treatment, presence or absence of concomitant treatment with acetylsalicylic acid or other antiplatelet or anticoagulant drugs, concomitant treatment with proton pump inhibitors, effectiveness, and adverse effects.
The study included a total of 11 patients (45% male). The mean age was 3.1 years (range, 1 month-8 years). The prescribed dose of clopidogrel was 0.2 mg/kg/day in all patients, and 10/11 patients received concomitant treatment with acetylsalicylic acid with the purpose of optimising antiplatelet therapy. None of the children received concomitant treatment with anticoagulants, and only one of them received treatment with a proton pump inhibitor. We did not find evidence of haemorrhagic complications or other adverse effects associated with clopidogrel.
Based on our experience, a clopidogrel dose of 0.2 mg/kg/day is a safe and effective treatment, regardless of the patient's age. The good tolerance observed in our study could be related to the adjustment of the optimal dose with the aim of achieving platelet aggregation without increasing the risk of adverse effects.
Efficacy and safety of clopidogrel in children with diarrhea associated hemolytic uremic syndrome
2012, Thrombosis Research
Citation Excerpt :
The optimal dose of clopidogrel is uncertain. In studies of clopidogrel use in children, the mean daily dosing regimens varied between 0.41 mg/kg and 2.3 mg/kg with some patients receiving up to 8.9 mg/kg [15–18]. Clopidogrel dosing also varied in our study population (mean 0.85 mg/kg/day).
Hemolytic uremic syndrome is a thrombotic microangiopathy. Clopidogrel, a recently developed platelet aggregation inhibitor, has not been previously reported as a treatment for this illness. Our study's objective was to explore the efficacy and safety of clopidogrel in children with diarrhea associated hemolytic uremic syndrome.
We performed a retrospective chart review of all children (≤ 18 years) hospitalized with diarrhea associated hemolytic uremic syndrome. Outcomes in clopidogrel treated children were described. In subgroup analysis, outcomes were compared to those untreated with platelet aggregation inhibitors.
Of 72 children with diarrhea associated hemolytic uremic syndrome, 88% were treated with platelet aggregation inhibitors (clopidogrel 56%, sulfinpyrazone 19%, dipyridamole 13%). The median age of clopidogrel treated children was 5 years; 40% were male. Initial median hemoglobin, platelet count, and serum creatinine were 10.1 g/dL, 53 × 10³/μL, and 2.3 mg/dL respectively. Clopidogrel (median dose 1 mg/kg/d) was given for a median of 4 days (range 1–15). Other therapies included erythropoietin (98%), red blood cell transfusions (80%), diuretics (58%), anti-hypertensive agents (45%), and dialysis (33%). The median hospital length of stay was 9 days (range 3–26). Three children had bleeding complications (epistaxis/hematemesis). The risk of chronic kidney disease was 5% and death 2.5%. In subgroup analysis, median duration of dialysis was 11 days in thirteen clopidogrel treated children compared to 21 days in five untreated patients (P = 0.04).
Children with diarrhea associated hemolytic uremic syndrome treated with clopidogrel have outcomes comparable to untreated patients. Bleeding complications may occur.
Kawasaki disease
2010, Paediatric Cardiology
Kawasaki Disease
2009, Paediatric Cardiology
Safety and Efficacy of Clopidogrel in Children with Heart Disease
2008, Journal of Pediatrics
Citation Excerpt :
This is consistent with earlier in vitro results in which, compared with platelets from adults, platelets from young children were hyporesponsive to stimuli and exhibited decreased aggregation and granule secretion.5 Adult doses extrapolated to children on the basis of weight can be life-threatening and cause increased bleeding.9-10 The optimal clopidogrel dose in infants and children is being evaluated in the Platelet Aggregation Inhibition in Children On CLOpidogrel (PICOLO) trial.
To evaluate the efficiency and safety of clopidogrel treatment in children with heart disease.
We conducted single center retrospective chart review of children with heart disease at the University Hospital, Leuven, Belgium, in whom clopidogrel was used. The indication, dosage, duration of therapy, and adverse events were examined. Clinical efficacy was defined by an absence of thrombotic events.
46 children were identified. The mean age of first clopidogrel dose was 4.9 ± 4.1 years. The study dosage ranged from 0.1 to 0.7 mg/kg/day clopidogrel. Almost all patients received concomitant aspirin therapy. No thrombotic events developed. Skin bruising developed in almost every patient, suggesting that clopidogrel has an anti-platelet effect. 2 patients who were treated with concomitant warfarin had bleeding complications (severe epistaxis and gastrointestinal bleeding). Hematological abnormalities were documented in 1 patient who received clopidogrel for 1 year; they reversed with medication cessation.
Clopidogrel therapy in a pediatric population appears to be relatively safe and effective; however, randomized, controlled prospective studies are needed to determine the true efficacy and safety of clopidogrel in children.

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: Finkelstein is supported by a fellowship grant from The Hospital for Sick Children Research Training Center. Koren is a Senior Scientist of the Canadian Institute for Health Research and holder of the Ivey Chair in Molecular Toxicology, University of Western Ontario, London, Ontario.

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Original ArticleClopidogrel Use in Children

Objectives

Study design

Results

Conclusions

Section snippets

Methods

Results

Discussion

J Am Coll Cardiol

Am Heart J

Ann Thorac Surg

Blood Cells Mol Dis

Am J Cardiol

Thromb Res

J Clin Neurosci

Thromboembolism in newborns, infants and children

Thromb Haemost

Arterial thromboembolism in the pediatric population

Semin Thromb Hemost

Original Article
Clopidogrel Use in Children