Hostname: page-component-848d4c4894-75dct Total loading time: 0 Render date: 2024-05-12T18:38:06.943Z Has data issue: false hasContentIssue false
  • English
  • Français

Low-molecular-weight heparin administered by subcutaneous catheter is a safe and effective anti-coagulation regimen in selected inpatient infants and children with complex congenital heart disease

Part of: Advanced Imaging

Published online by Cambridge University Press:  16 February 2021

Nadja Pardun Open the ORCID record for Nadja Pardun [Opens in a new window] ,
Julia Lemmer ,
Kristina Belker ,
Milka Pringsheim ,
Peter Ewert  and
Cordula M. Wolf
Nadja Pardun
Affiliation:
Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany
Julia Lemmer
Affiliation:
Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany
Kristina Belker
Affiliation:
Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany
Milka Pringsheim
Affiliation:
Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany
Peter Ewert
Affiliation:
Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany
Cordula M. Wolf*
Affiliation:
Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
*
Author for correspondence: Dr C. M. Wolf, Department of Congenital Heart Defects and Pediatric Cardiology, German Heart Center Munich, Technical University of Munich, Lazarettstrasse 36, Munich 80636, Germany. Tel: +49 89 12182877. E-mail: wolf@dhm.mhn.de
Get access Rights & Permissions [Opens in a new window]

Abstract

Background/hypothesis:

Disadvantages of intravenous therapeutic unfractionated heparin, the first-line anti-coagulant agent in children with complex congenital heart disease, include unpredictable pharmacokinetics requiring frequent phlebotomies and the need for continuous intravenous access.

Objective:

To compare efficacy and safety of low-molecular-weight heparin administered by a subcutaneous indwelling catheter with intravenous unfractionated heparin.

Materials and methods:

Clinical data from 31 inpatients prospectively enrolled to receive subcutaneous low-molecular-weight heparin were compared with those from a historical group of 44 inpatients receiving intravenous unfractionated heparin. Investigation of parents’ satisfaction by telephone survey.

Results:

The percentage of anti-factor Xa levels outside therapeutic range was lower in the subcutaneous low-molecular-weight heparin group compared with the percentage of activated partial thromboplastin times outside therapeutic range in the intravenous unfractionated heparin group (40% versus 90%, p < 0.001). Neither group had a major complication. Transient local reactions occurred in 19% of patients of the subcutaneous low-molecular-weight heparin group. The number of needle punctures and that of placement of indwelling catheters were significantly lower in the subcutaneous low-molecular-weight heparin compared with the intravenous unfractionated heparin group (p < 0.001). In total, 84.2% of parents in the subcutaneous low-molecular-weight heparin group reported a positive experience when asked about comparison with prior intravenous unfractionated heparin treatment.

Conclusion:

Subcutaneous low-molecular-weight heparin offers a safe anti-coagulation regimen for children with complex congenital heart disease providing more efficient therapeutic anti-coagulation and a reduction in needle punctures, thus causing less pain and anxiety in this children.

Keywords

Anti-coagulationlow-molecular-weight heparinsubcutaneous cathetercongenital heart disease
Type
Original Article
Information
Cardiology in the Young , Volume 31 , Issue 9 , September 2021 , pp. 1439 - 1444
Check for updates
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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

Girod, DA, Hurwitz, RA, Caldwell, RL. Heparinization for prevention of thrombosis following pediatric percutaneous arterial catheterization. Pediatr Cardiol 1982; 3: 175–180.CrossRefGoogle ScholarPubMed
Grady, RM, Eisenberg, PR, Bridges, ND. Rational approach to use of heparin during cardiac catheterization in children. J Am Coll Cardiol 1995; 25: 725–729.CrossRefGoogle ScholarPubMed
Andrew, M, Marzinotto, V, Massicotte, P, et al. Heparin therapy in pediatric patients: a prospective cohort study. Pediatr Res 1994; 35: 78–83.CrossRefGoogle ScholarPubMed
Ohuchi, H, Yasuda, K, Miyazaki, A, et al. Prevalence and predictors of haemostatic complications in 412 Fontan patients: their relation to anticoagulation and haemodynamics. Eur J Cardio-Thorac Surg 2015; 47: 511–519.CrossRefGoogle ScholarPubMed
Potter, BJ, Leong-Sit, P, Fernandes, SM, et al. Effect of aspirin and warfarin therapy on thromboembolic events in patients with univentricular hearts and Fontan palliation. Int J Cardiol 2013; 168: 3940–3943.CrossRefGoogle ScholarPubMed
Glatz, AC, Keashen, R, Chang, J, et al. Outcomes using a clinical practice pathway for the management of pulse loss following pediatric cardiac catheterization. Catheter Cardiovasc Interv 2015; 85: 111–117.CrossRefGoogle ScholarPubMed
Van de Werf, F. Inhibitors of the platelet thrombin receptor: will they live up to their promises? Circulation 2011; 123: 1833–1835.CrossRefGoogle ScholarPubMed
Andrew, M, Michelson, AD, Bovill, E, Leaker, M, Massicotte, MP. Guidelines for antithrombotic therapy in pediatric patients. J Pediatr 1998; 132: 575–588.CrossRefGoogle ScholarPubMed
Newall, F, Johnston, L, Ignjatovic, V, Monagle, P. Unfractionated heparin therapy in infants and children. Pediatrics 2009; 123: e510–e518.CrossRefGoogle ScholarPubMed
Dix, D, Andrew, M, Marzinotto, V, et al. The use of low molecular weight heparin in pediatric patients: a prospective cohort study. J Pediatr 2000; 136: 439–445.CrossRefGoogle ScholarPubMed
Albisetti, M, Andrew, M. Low molecular weight heparin in children. Eur J Pediatr 2002; 161: 71–77.CrossRefGoogle ScholarPubMed
Aslam, MS, Sundberg, S, Sabri, MN, Cooke, D, Lakier, JB. Pharmacokinetics of intravenous/subcutaneous Enoxaparin in patients with acute coronary syndrome undergoing percutaneous coronary interventions. Catheter Cardiovasc Interv 2002; 57: 187–190.CrossRefGoogle ScholarPubMed
Hirsh, J, Warkentin, TE, Raschke, R, Granger, C, Ohman, EM, Dalen, JE. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998; 114 (Suppl 5): 489S–510S.CrossRefGoogle ScholarPubMed
Prandoni, P, Lensing, AW, Buller, HR, et al. Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992; 339: 441–445.CrossRefGoogle ScholarPubMed
Belcaro, G, Nicolaides, AN, Cesarone, MR, et al. Comparison of low-molecular-weight heparin, administered primarily at home, with unfractionated heparin, administered in hospital, and subcutaneous heparin, administered at home for deep-vein thrombosis. Angiology 1999; 50: 781–787.Google ScholarPubMed
Fareed, J, Hoppensteadt, D, Walenga, J, et al. Pharmacodynamic and pharmacokinetic properties of enoxaparin: implications for clinical practice. Clin Pharmacokinet 2003; 42: 1043–1057.CrossRefGoogle ScholarPubMed
Sutor, AH, Chan, AK, Massicotte, P. Low-molecular-weight heparin in pediatric patients. Semin Thromb Hemost 2004; 30 (Suppl 1): 31–39.Google ScholarPubMed
Hirsh, J, Siragusa, S, Cosmi, B, Ginsberg, JS. Low molecular weight heparins (LMWH) in the treatment of patients with acute venous thromboembolism. Thromb Haemost 1995; 74: 360–363.Google ScholarPubMed
Hull, RD, Raskob, GE, Brant, RF, et al. Low-molecular-weight heparin versus heparin in the treatment of patients with pulmonary embolism. American-Canadian thrombosis study group. Arch Intern Med 2000; 160: 229–236.CrossRefGoogle Scholar
Massicotte, P, Adams, M, Marzinotto, V, Brooker, LA, Andrew, M. Low-molecular-weight heparin in pediatric patients with thrombotic disease: a dose finding study. J Pediatr 1996; 128: 313–318.CrossRefGoogle ScholarPubMed
Hepponstall, M, Chan, A, Monagle, P. Anticoagulation therapy in neonates, children and adolescents. Blood Cells Mol Dis 2017; 67: 41–47.CrossRefGoogle Scholar
Michaels, LA, Gurian, M, Hegyi, T, Drachtman, RA. Low molecular weight heparin in the treatment of venous and arterial thromboses in the premature infant. Pediatrics 2004; 114: 703–707.CrossRefGoogle ScholarPubMed
Moffett, BS, Lee-Kim, Y, Galati, M, et al. Population pharmacokinetics of enoxaparin in pediatric patients. Ann Pharmacother 2018; 52: 140–146.CrossRefGoogle ScholarPubMed
Bauman, ME, Belletrutti, MJ, Bajzar, L, et al. Evaluation of enoxaparin dosing requirements in infants and children. Better dosing to achieve therapeutic levels. Thromb Haemost 2009; 101: 86–92.Google ScholarPubMed
Ho, SH, Wu, JK, Hamilton, DP, Dix, DB, Wadsworth, LD. An assessment of published pediatric dosage guidelines for enoxaparin: a retrospective review. J Pediatr Hematol Oncol 2004; 26: 561–566.CrossRefGoogle ScholarPubMed
Hanas, R. Reducing injection pain in children and adolescents with diabetes: a review of indwelling catheters. Pediatr Diabetes 2004; 5: 102–111.CrossRefGoogle ScholarPubMed
Hanas, R, Ludvigsson, J. Side effects and indwelling times of subcutaneous catheters for insulin injections: a new device for injecting insulin with a minimum of pain in the treatment of insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 1990; 10: 73–83.CrossRefGoogle ScholarPubMed
Streif, W, Goebel, G, Chan, AK, Massicotte, MP. Use of low molecular mass heparin (enoxaparin) in newborn infants: a prospective cohort study of 62 patients. Arch Dis Child Fetal Neonatal Ed 2003; 88: F365–F370.CrossRefGoogle ScholarPubMed
Young, G. Anticoagulation therapies in children. Pediatr Clin North Am 2017; 64: 1257–1269.CrossRefGoogle ScholarPubMed
Young, G, Male, C, van Ommen, CH. Anticoagulation in children: making the most of little patients and little evidence. Blood Cells Mol Dis 2017; 67: 48–53.CrossRefGoogle ScholarPubMed
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: 101–108.CrossRefGoogle ScholarPubMed
Hofmann, S, Knoefler, R, Lorenz, N, et al. Clinical experiences with low-molecular weight heparins in pediatric patients. Thromb Res 2001; 103: 345–353.CrossRefGoogle ScholarPubMed
Kakkar, VV, Boeckl, O, Boneu, B, et al. Efficacy and safety of a low-molecular-weight heparin and standard unfractionated heparin for prophylaxis of postoperative venous thromboembolism: European multicenter trial. World J Surg 1997; 21: 2–8.CrossRefGoogle ScholarPubMed
Roschitz, B, Beitzke, A, Gamillscheg, A, et al. Signs of thrombin generation in pediatric cardiac catheterization with unfractionated heparin bolus or subcutaneous low molecular weight heparin for antithrombotic cover. Thromb Res 2003; 111: 335–341.CrossRefGoogle ScholarPubMed
Simonneau, G, Charbonnier, B, Decousus, H, et al. Subcutaneous low-molecular-weight heparin compared with continuous intravenous unfractionated heparin in the treatment of proximal deep vein thrombosis. Arch Intern Med 1993; 153: 1541–1546.CrossRefGoogle ScholarPubMed
van Den Belt, AG, Prins, MH, Lensing, AW, et al. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev 2004: CD001100.Google Scholar
Bontadelli, J, Moeller, A, Schmugge, M, et al. Enoxaparin therapy for arterial thrombosis in infants with congenital heart disease. Intensive Care Med 2007; 33: 1978–1984.CrossRefGoogle ScholarPubMed
Kindo, M, Gerelli, S, Hoang Minh, T, et al. Exclusive low-molecular-weight heparin as bridging anticoagulant after mechanical valve replacement. Ann Thorac Surg 2014; 97: 789–795.CrossRefGoogle ScholarPubMed
Thom, KE, Hanslik, A, Male, C. Anticoagulation in children undergoing cardiac surgery. Semin Thromb Hemost 2011; 37: 826–833.CrossRefGoogle ScholarPubMed
Hinsley, K, Evans-Langhorst, M, Porter, C, et al. Low molecular weight heparin as an anticoagulation strategy for left-sided ablation procedures. Congenit Heart Dis 2018; 13: 222–225.CrossRefGoogle ScholarPubMed
Hammerstingl, C, Tripp, C, Schmidt, H, von der Recke, G, Omran, H. Periprocedural bridging therapy with low-molecular-weight heparin in chronically anticoagulated patients with prosthetic mechanical heart valves: experience in 116 patients from the prospective BRAVE registry. J Heart Valve Dis 2007; 16: 285–292.Google ScholarPubMed
Nohe, N, Flemmer, A, Rumler, R, Praun, M, Auberger, K. The low molecular weight heparin dalteparin for prophylaxis and therapy of thrombosis in childhood: a report on 48 cases. Eur J Pediatr 1999; 158 (Suppl 3): S134–S139.CrossRefGoogle ScholarPubMed
Fanikos, J, Tsilimingras, K, Kucher, N, Rosen, AB, Hieblinger, MD, Goldhaber, SZ. Comparison of efficacy, safety, and cost of low-molecular-weight heparin with continuous-infusion unfractionated heparin for initiation of anticoagulation after mechanical prosthetic valve implantation. Am J Cardiol 2004; 93: 247–250.CrossRefGoogle ScholarPubMed
Hanas, R, Adolfsson, P, Elfvin-Akesson, K, et al. Indwelling catheters used from the onset of diabetes decrease injection pain and pre-injection anxiety. J Pediatr 2002; 140: 315–320.CrossRefGoogle ScholarPubMed
Burdick, P, Cooper, S, Horner, B, Cobry, E, McFann, K, Chase, HP. Use of a subcutaneous injection port to improve glycemic control in children with type 1 diabetes. Pediatr Diabetes 2009; 10: 116–119.CrossRefGoogle ScholarPubMed
Adolfsson, P, Ziegler, R, Hanas, R. Continuous subcutaneous insulin infusion: special needs for children. Pediatr Diabetes 2017; 18: 255–261.CrossRefGoogle ScholarPubMed
Allvin, R, Rawal, N, Saros, GB. Postoperative analgesia. Is it time to abandon intramuscular injections? Lakartidningen 2000; 97: 1687–1691.Google ScholarPubMed
Rouss, K, Gerber, A, Albisetti, M, Hug, M, Bernet, V. Long-term subcutaneous morphine administration after surgery in newborns. J Perinatal Med 2007; 35: 79–81.CrossRefGoogle ScholarPubMed
Dyer, SL, Collins, CT, Baghurst, P, Saxon, B, Meachan, B. Insuflon versus subcutaneous injection for cytokine administration in children and adolescents: a randomized crossover study. J Pediatr Oncol Nurs 2004; 21: 79–86.CrossRefGoogle ScholarPubMed
Anderson, DR, Ginsberg, JS, Brill-Edwards, P, Demers, C, Burrows, RF, Hirsh, J. The use of an indwelling Teflon catheter for subcutaneous heparin administration during pregnancy. A randomized crossover study. Arch Intern Med 1993; 153: 841–844.CrossRefGoogle ScholarPubMed
Marquez, NR, Pino, AP, Zuniga, CP. Subcutaneous catheter used for administration of low-molecular-weight-heparin in pediatrics. Rev Chil Pediatr 2014; 85: 46–51.Google Scholar
Planes, A, Vochelle, N, Mazas, F, et al. Prevention of postoperative venous thrombosis: a randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thromb Haemost 1988; 60: 407–410.Google ScholarPubMed
Supplementary material: File

Pardun et al. supplementary material

Table S1

Download Pardun et al. supplementary material(File)
File 40.9 KB
Supplementary material: File

Pardun et al. supplementary material

Table S2

Download Pardun et al. supplementary material(File)
File 46.7 KB
Supplementary material: File

Pardun et al. supplementary material

Table S4

Download Pardun et al. supplementary material(File)
File 48.7 KB
Supplementary material: File

Pardun et al. supplementary material

Table S3

Download Pardun et al. supplementary material(File)
File 42.3 KB
Supplementary material: File

Pardun et al. supplementary material

Figure S1

Download Pardun et al. supplementary material(File)
File 59.4 KB