Age-Dependent Heterogeneity in the Efficacy of Prophylaxis With Enoxaparin Against Catheter-Associated Thrombosis in Critically Ill Children: A Post Hoc Analysis of a Bayesian Phase 2b Randomized Clinical Trial.

Abstract

OBJECTIVES:

We explored the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against central venous catheter-associated deep venous thrombosis in critically ill children.

DESIGN:

Post hoc analysis of a Bayesian phase 2b randomized clinical trial.

SETTING:

Seven PICUs.

PATIENTS:

Children less than 18 years old with newly inserted central venous catheter.

INTERVENTIONS:

Enoxaparin started less than 24 hours after insertion of central venous catheter and adjusted to anti-Xa level of 0.2-0.5 international units/mL versus usual care.

MEASUREMENTS AND MAIN RESULTS:

Of 51 children randomized, 24 were infants less than 1 year old. Risk ratios of central venous catheter-associated deep venous thrombosis with prophylaxis with enoxaparin were 0.98 (95% credible interval, 0.37-2.44) in infants and 0.24 (95% credible interval, 0.04-0.82) in older children greater than or equal to 1 year old. Infants and older children achieved anti-Xa level greater than or equal to 0.2 international units/mL at comparable times. While central venous catheter was in situ, endogenous thrombin potential, a measure of thrombin generation, was 223.21 nM.min (95% CI, 8.78-437.64 nM.min) lower in infants. Factor VIII activity, a driver of thrombin generation, was also lower in infants by 45.1% (95% CI, 15.7-74.4%). Median minimum platelet count while central venous catheter was in situ was higher in infants by 39 × 103/mm3 (interquartile range, 17-61 × 103/mm3). Central venous catheter:vein ratio was not statistically different. Prophylaxis with enoxaparin was less efficacious against central venous catheter-associated deep venous thrombosis at lower factor VIII activity and at higher platelet count.

CONCLUSIONS:

The relatively lesser contribution of thrombin generation on central venous catheter-associated thrombus formation in critically ill infants potentially explains the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin.

• Authors: E Vincent S Faustino, Leslie J Raffini, Sheila J Hanson, Jill M Cholette, Matthew G Pinto, Simon Li, Sarah B Kandil, Marianne E Nellis, Veronika Shabanova, Cicero T Silva, Joana A Tala, Tara McPartland, Philip C Spinella, for the CRETE Trial Investigators and the Pediatric Critical Care Blood Research Network (BloodNet) of the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI), CRETE Trial Investigators: Clinical Coordinating Center:, and, Data Coordinating Center:, and, Outcomes Adjudication Committee:, and, Data and Safety Monitoring Board:, and, Independent Safety Monitor:, and, Children’s Hospital Wisconsin:, and, Dell Children’s Medical Center:, and, Maria Fareri Children’s Hospital:, and, St. Louis Children’s Hospital:, and, University of Rochester Golisano Children’s Hospital:, and, Weill Cornell Medical Center:, and, and Yale-New Haven Children’s Hospital:, and, for the CRETE Trial Investigators and the Pediatric Critical Care Blood Research Network (BloodNet) of the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI) and CRETE Trial Investigators: Clinical Coordinating Center: and and and Data Coordinating Center: and and and Outcomes Adjudication Committee: and and and Data and Safety Monitoring Board: and and and Independent Safety Monitor: and and and Children’s Hospital Wisconsin: and and and Dell Children’s Medical Center: and and and Maria Fareri Children’s Hospital: and and and St. Louis Children’s Hospital: and and and University of Rochester Golisano Children’s Hospital: and and and Weill Cornell Medical Center: and and and and Yale-New Haven Children’s Hospital: and and
• Journal: Critical care medicine (Crit Care Med) Vol. 49 Issue 4 Pg. e369-e380 (04 01 2021) ISSN: 1530-0293 [Electronic] United States
• PMID: 33566465 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Chemical References

• Anticoagulants
• Enoxaparin

Topics

• Anticoagulants (therapeutic use)
• Catheterization, Central Venous (adverse effects)
• Child
• Child, Preschool
• Critical Illness (therapy)
• Enoxaparin (therapeutic use)
• Female
• Humans
• Infant
• Male
• Outcome Assessment, Health Care
• Pre-Exposure Prophylaxis (statistics & numerical data)
• Thrombosis (prevention & control)
• Venous Thrombosis (prevention & control)