Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-25T16:13:39.005Z Has data issue: false hasContentIssue false

Establishment of prophylactic enoxaparin dosing recommendations to achieve targeted anti-factor Xa concentrations in children with CHD

Published online by Cambridge University Press:  01 March 2018

Emily N. Israel*
Affiliation:
Department of Pharmacy, Riley Hospital for Children at Indiana University Health, Indianapolis, IN, USA Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafayette, IN, USA
Christopher A. Thomas
Affiliation:
Department of Pharmacy, Riley Hospital for Children at Indiana University Health, Indianapolis, IN, USA
Christopher W. Mastropietro
Affiliation:
Section of Pediatric Cardiac Intensive Care, Riley Hospital for Children at Indiana University Health, Indianapolis, IN, USA Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA
*
Author for correspondence: E. N. Israel, Department of Pharmacy Practice, Purdue University College of Pharmacy, 640 Eskenazi Avenue, Indianapolis, IN 46202, USA. Tel: 317 880 5409; E-mail: [email protected]

Abstract

Background

Enoxaparin may be used to prevent central venous catheter-related thrombosis in patients with CHD. We aimed to determine whether current enoxaparin dosing regimens effectively achieve anti-factor Xa concentrations within prophylactic goal ranges in this patient population.

Methods

We implemented a formal protocol aimed at reducing central venous catheter-related thrombosis in children with CHD in January, 2016. Standard empiric prophylactic enoxaparin dosing regimens were used – for example, 0.75 mg/kg/dose every 12 hours for patients <2 months of age and 0.5 mg/kg/dose every 12 hours for patients ⩾2 months of age – with anti-factor Xa goal range of 0.25–0.49 IU/ml. Patients <2 years of age who received enoxaparin and had at least one valid steady-state anti-factor Xa measurement between 25 January, 2016 and 31 August, 2016 were retrospectively reviewed.

Results

During the study period, 47 patients had 186 anti-factor Xa concentrations measured, of which 20 (11%) were above and 112 (60%) were below the prophylactic goal range. Anti-factor Xa concentrations within the goal range were ultimately achieved in 31 patients. Median dose required to achieve anti-factor Xa concentrations within the prophylactic range was 0.89 mg/kg/dose (25, 75%: 0.75, 1.11) for patients <2 months (n=23 patients) and 0.79 mg/kg/dose (25, 75%: 0.62, 1.11) for patients ⩾2 months (n=8 patients).

Conclusions

Enoxaparin doses required to achieve prophylactic anti-factor Xa concentrations in young children with CHD were consistently higher than the currently recommended prophylactic dosing regimens. Further study is needed to determine whether dose titration to achieve prophylactic anti-factor Xa concentrations is effective in preventing central venous catheter-related thrombosis.

Type
Original Articles
Copyright
© Cambridge University Press 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Giglia, TM, Massicotte, MP, Tweddell, JS, et al. Prevention and treatment of thrombosis in pediatric and congenital heart disease: a scientific statement from the American Heart Association. Circulation 2013; 128: 26222703.Google Scholar
2. Jacobs, ML, Pourmoghadam, KK. Thromboembolism and the role of anticoagulation in the Fontan patient. Pediatr Cardiol 2007; 28: 457464.Google Scholar
3. Manlhiot, C, Brandão, LR, Kwok, J, et al. Thrombotic complications and thromboprophylaxis across all three stages of single ventricle heart palliation. J Pediatr 2012; 161: 513519.Google Scholar
4. Monagle, P, Karl, TR. Thromboembolic problems after the Fontan operation. Semin Thorac Cardiovasc Surg 2002; 5: 3647.Google Scholar
5. Monagle, P, Chan, AKC, Goldenberg, NA, et al. Antithrombotic therapy in neonates and children: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (Suppl): e737Se7801.Google Scholar
6. Murphy, L, Mastropietro, CW. Contemporary epidemiology of catheter-related thrombosis in the pediatric cardiac ICU. Crit Care Med 2016; 44 (Suppl): 205.CrossRefGoogle Scholar
7. Diab, YA, Ramakrishnan, K, Ferrell, B, et al. IV versus subcutaneous enoxaparin in critically ill infants and children: Comparison of dosing, anticoagulation quality, efficacy, and safety outcomes. Pediatr Crit Care Med 2017; 18: e207e214.Google Scholar
8. Raffini, L, Trimarchi, T, Beliveau, J, et al. Thromboprophylaxis in a pediatric hospital: a patient-safety and quality-improvement initiative. Pediatrics 2011; 127: e1326e1332.Google Scholar
9. Hanson, SJ, Punzalan, RC, Arca, MJ, et al. Effectiveness of clinical guidelines for deep vein thrombosis prophylaxis in reducing the incidence of venous thromboembolism in critically ill children after trauma. J Trauma Acute Care Surg 2012; 72: 12921297.Google Scholar
10. Andrew, M, Paes, R, Milner, M, et al. Development of the human coagulation system in the healthy premature infant. Blood 1988; 5: 16511657.Google Scholar
11. Schloemer, NJ, Abu-Sultaneh, S, Hanson, SJ, et al. Higher doses of low-molecular-weight heparin (enoxaparin) are needed to achieve target anti-Xa concentrations in critically ill children. Pediatr Crit Care Med 2014; 15: e294e299.Google Scholar
12. Sanchez de Toledo, J, Gunawardena, S, Munoz, R, et al. Do neonates, infants and young children need a higher dose of enoxaparin in the cardiac intensive care unit? Cardiol Young 2010; 20: 138143.Google Scholar
13. Massicotte, P, Julian, JA, Gent, M, et al. An open-label randomized controlled trial of low molecular weight heparin for the prevention of central venous line-related thrombotic complications in children: the PROTEKT trial. Thromb Res 2003; 109: 101108.Google Scholar
14. Schroeder, AR, Axelrod, DM, Silverman, NH, et al. A continuous heparin infusion does not prevent catheter-related thrombosis in infants after cardiac surgery. Pediatr Crit Care Med 2010; 11: 489495.Google Scholar
15. Schwartz, GJ, Munoz, A, Schneider, MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009; 20: 629637.Google Scholar
16. Mitchell, LG, Goldenberg, NA, Male, C, et al. Perinatal and Paediatric Haemostasis Subcommittee of the SSC of the ISTH: definition of clinical efficacy and safety outcomes for clinical trials in deep venous thrombosis and pulmonary embolism in children. J Thromb Haemost 2011; 9: 18561858.Google Scholar
17. Andrade-Campos, MM, Montes-Limón, AE, Fernandez-Mosteirin, N, et al. Dosing and monitoring of enoxaparin therapy in children: experience in a tertiary care hospital. Blood Coagul Fibrinolysis 2013; 24: 194198.Google Scholar