Newly Published
Perioperative Medicine  |   January 2020
Comparison of Neonatal and Adult Fibrin Clot Properties between Porcine and Human Plasma
Author Notes
  • From the Joint Department of Biomedical Engineering, North Carolina State University and The University of North Carolina at Chapel Hill, Raleigh, North Carolina (K.A.N., S.N., A.K., S.S., A.C.B.); the Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina (K.A.N., A.C.B.); and the Department of Anesthesiology, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia (N.A.G.).
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • Part of this work has been presented at the American Heart Association’s Vascular Discovery 2019 Scientific Sessions in Boston, Massachusetts, May 15, 2019.
    Part of this work has been presented at the American Heart Association’s Vascular Discovery 2019 Scientific Sessions in Boston, Massachusetts, May 15, 2019.×
  • Submitted for publication July 8, 2019. Accepted for publication January 3, 2020.
    Submitted for publication July 8, 2019. Accepted for publication January 3, 2020.×
  • Correspondence: Address correspondence to Dr. Brown: Biomedical Partnership Center Building, 1001 William Moore Drive, Office 26, Raleigh, North Carolina 27606. aecarso2@ncsu.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Coagulation and Transfusion / Hematologic System / Pediatric Anesthesia
Perioperative Medicine   |   January 2020
Comparison of Neonatal and Adult Fibrin Clot Properties between Porcine and Human Plasma
Anesthesiology Newly Published on January 30, 2020. doi:https://doi.org/10.1097/ALN.0000000000003165
Anesthesiology Newly Published on January 30, 2020. doi:https://doi.org/10.1097/ALN.0000000000003165
Abstract

Editor’s Perspective:

What We Already Know about This Topic:

  • Neonatal fibrinogen exists in a fetal form until maturation and is structurally and functionally distinct from adult fibrinogen

  • Replacement of neonatal fibrinogen with adult fibrinogen after cardiopulmonary bypass may lead to inconsistent efficacy in treating postcardiopulmonary bypass bleeding

  • The hemostatic system of pigs is similar to that of humans

What This Article Tells Us That Is New:

  • Fibrinogen concentration and functionality in plasma collected from piglets paralleled those observed in plasma collected from human neonates

  • Fibrin network structure was highly aligned in both neonatal species and highly branched in adults of both species

  • Fibrin network stiffness and degradation patterns in both neonatal species were substantially similar as they were in adults of both species

  • The ex vivo addition of several procoagulant therapies augmented fibrin network properties of diluted piglet plasma

Background: Recent studies suggest that adult-specific treatment options for fibrinogen replacement during bleeding may be less effective in neonates. This is likely due to structural and functional differences found in the fibrin network between adults and neonates. In this investigation, the authors performed a comparative laboratory-based study between immature and adult human and porcine plasma samples in order to determine if piglets are an appropriate animal model of neonatal coagulopathy.

Methods: Adult and neonatal human and porcine plasma samples were collected from the Children’s Hospital of Atlanta and North Carolina State University College of Veterinary Medicine, respectively. Clots were formed for analysis and fibrinogen concentration was quantified. Structure was examined through confocal microscopy and cryogenic scanning electron microscopy. Function was assessed through atomic force microscopy nanoindentation and clotting and fibrinolysis assays. Lastly, novel hemostatic therapies were applied to neonatal porcine samples to simulate treatment.

Results: All sample groups had similar plasma fibrinogen concentrations. Neonatal porcine and human plasma clots were less branched with lower fiber densities than the dense and highly branched networks seen in adult human and porcine clots. Neonatal porcine and human clots had faster degradation rates and lower clot stiffness values than adult clots (stiffness [mmHg] mean ± SD: neonatal human, 12.15 ± 1.35 mmHg vs. adult human, 32.25 ± 7.13 mmHg; P = 0.016; neonatal pig, 10.5 ± 8.25 mmHg vs. adult pigs, 32.55 ± 7.20 mmHg; P = 0.015). The addition of hemostatic therapies to neonatal porcine samples enhanced clot formation.

Conclusions: The authors identified similar age-related patterns in structure, mechanical, and degradation properties between adults and neonates in porcine and human samples. These findings suggest that piglets are an appropriate preclinical model of neonatal coagulopathy. The authors also show the feasibility of in vitro model application through analysis of novel hemostatic therapies as applied to dilute neonatal porcine plasma.