Comparison of Neonatal and Adult Fibrin Clot Properties between Porcine and Human Plasma

• Type of Material: Article
• Authors: Kimberly A Nellenbach, North Carolina State University; Seema Nandi, North Carolina State University; Alexander Kyu, North Carolina State University; Supriya Sivadanam, North Carolina State University; Nina Guzzetta, Emory University; Ashely C Brown, North Carolina State University
• Language: English
• Date: 2020-05-01
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1097/ALN.0000000000003165
• Title of Journal or Parent Work: ANESTHESIOLOGY
• Volume: 132
• Issue: 5
• Start Page: 1091
• End Page: 1101
• Grant/Funding Information: This work was supported by the American Heart Association 16SDG29870005, the National Science Foundation DMR-1847488, the Department of Defense CDMRP W81XWH-15-1-0485, and the National Institutes of Health R01HL130918-01A1.
• Keywords: Anesthesiology; COAGULATION SYSTEM; PIG; OUTCOMES; RISK; CHILDREN; MODEL; Science & Technology; Life Sciences & Biomedicine; ARTERIAL

Abstract

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. (ANESTHESIOLOGY 2020; 132:1091-101).