Aspirin resistance in infants with shunt-dependent congenital heart disease.

INTRODUCTION: Patients with cyanotic heart disease are at an increased risk of developing thrombosis. Aspirin has been the mainstay of prophylactic anticoagulation for shunt-dependent patients with several reports of prevalent aspirin resistance, especially in neonates. We investigate the incidence of aspirin resistance and its relationship to thrombotic events and mortality in a cohort of infants with shunt-dependent physiology. METHODS: Aspirin resistance was assessed using the VerifyNow™ test on infants with single-ventricle physiology following shunt-dependent palliation operations. In-hospital thrombotic events and mortality data were collected. Statistical analysis was performed to evaluate the effect of aspirin resistance on in-hospital thrombotic events and mortality risk. RESULTS: Forty-nine patients were included with 41 of these patients being neonates. Six patients (12%) were aspirin resistant. A birth weight < 2500 grams was a significant factor associated with aspirin resistance (p = 0.04). Following a dose increase or additional dose administration, all patients with initial aspirin resistance had a normal aspirin response. There was no statistically significant difference between aspirin resistance and non-resistance groups with respect to thrombotic events. However, a statistically significant incidence of in-hospital mortality in the presence of thrombotic events was observed amongst aspirin-resistant patients (p = 0.04) in this study. CONCLUSION: Low birth weight was associated with a higher incidence of aspirin resistance. Inadequate initial dosing appears to be the primary reason for aspirin resistance. The presence of both thrombotic events and aspirin resistance was associated with significantly higher in-hospital mortality indicating that these patients warrant closer monitoring.

Variability of antithrombotics use in patients with hypoplastic left heart syndrome and its variants following first- and second-stage palliation surgery: a national report using the National Pediatric Cardiology Quality Improvement Collaborative registry.

Purpose Patients with hypoplastic left heart syndrome and its variants following palliation surgery are at risk for thrombosis. This study examines variability of antithrombotic practice, the incidence of interstage shunt thrombosis, and other adverse events following Stage I and Stage II palliation within the National Pediatric Cardiology Quality Improvement Collaborative registry. METHODS: We carried out a multicentre, retrospective review using the National Pediatric Cardiology Quality Improvement Collaborative registry including patients from 2008 to 2013 across 52 surgical sites. Antithrombotic medications used at Stage I and Stage II discharge were evaluated. Variability of antithrombotics use at the individual patient level and intersite variability, incidence of shunt thrombosis, and other adverse events such as cardiac arrest, seizure, stroke, and need for cardiac catheterisation intervention in the interstage period were identified. Antithrombotic strategies for hybrid Stage I patients were evaluated but they were excluded from the variability and outcomes analysis. RESULTS: A total of 932 Stage I and 923 Stage II patients were included in the study: 93.8% of Stage I patients were discharged on aspirin and 4% were discharged on no antithrombotics, and 77% of Stage II patients were discharged on aspirin and 17.5% were discharged on no antithrombotics. Only three patients (0.2%) presented with interstage shunt thrombosis. The majority of patients who died during interstage or required shunt dilation and/or stenting were discharged home on aspirin. CONCLUSION: Aspirin is the most commonly used antithrombotic following Stage I and Stage II palliation. There is more variability in the choice of antithrombotics following Stage II compared with Stage I. The incidence of interstage shunt thrombosis and associated adverse events was rare.

Increased enoxaparin dosing is required for obese children.

Weight-based dosing for enoxaparin is recommended in the 2008 American College of Chest Physicians (ACCP) guidelines for venous thromboembolism (VTE) prophylaxis. Enoxaparin 0.5 mg/kg per dose administered subcutaneously every 12 hours is recommended for this indication in children. There is no established upper dosing limit of enoxaparin for prophylaxis in children, and the US Food and Drug Administration-approved enoxaparin dose for adults for VTE prophylaxis is 30 mg subcutaneously every 12 hours or 40 mg subcutaneously daily. Therefore, we assumed that the upper limit for children is 40 mg subcutaneously daily. We reviewed 3 cases of obese adolescent boys who required large doses of enoxaparin to achieve the ACCP-recommended anti-factor Xa range of 0.1 to 0.3 IU/mL for the prevention of VTE. All 3 patients required doses of enoxaparin that are higher than that recommended for adults for VTE prophylaxis: patient A (BMI: 105.9) required >0.28 mg/kg per dose, patient B (BMI: 95.7) required 0.15 mg/kg per dose, and patient C (BMI: 29.9) required 0.49 mg/kg per dose. The desired anti-factor Xa range was achieved when enoxaparin was administered every 12 hours in each patient with no reported episodes of VTE. One patient had minor bruising, but no other adverse events were noted. Because of the variability in dose requirements and unpredictability in patient responses demonstrated in our 3 adolescents, prospective studies are needed to provide definitive recommendations on dosing of enoxaparin for VTE prophylaxis in this subset of obese pediatric patients.