Comparison of animal and human blood for in vitro dynamic thrombogenicity testing of biomaterials

Jamiolkowski, Megan A.; Patel, Mehulkumar; Golding, Madelyn D.; Malinauskas, Richard A.; Lu, Qijin

doi:10.1111/aor.14366

Comparison of animal and human blood for in vitro dynamic thrombogenicity testing of biomaterials

Journal Article · Sat Jul 30 04:00:00 EDT 2022 · Artificial Organs

DOI:https://doi.org/10.1111/aor.14366· OSTI ID:2425618

^[1]; ^[1]; Golding, Madelyn D. ^[1]; ^[1]; ^[1]

Center for Devices and Radiological Health U.S. Food and Drug Administration Silver Spring Maryland USA

Abstract Background

To determine suitable alternatives to human blood for in vitro dynamic thrombogenicity testing of biomaterials, four different animal blood sources (ovine, bovine, and porcine blood from live donors, and abattoir porcine blood) were compared to fresh human blood.

Methods

To account for blood coagulability differences between individual donors and species, each blood pool was heparinized to a donor‐specific concentration immediately before testing in a dynamic flow loop system. The target heparin level was established using a static thrombosis pre‐test. For dynamic testing, whole blood was recirculated at room temperature for 1 h at 200 ml/min through a flow loop containing a single test material. Four materials with varying thrombotic potentials were investigated: latex (positive control), polytetrafluoroethylene (PTFE) (negative control), silicone (intermediate thrombotic potential), and high‐density polyethylene (HDPE) (historically thromboresistant). Thrombus weight and surface area coverage on the test materials were quantified, along with platelet count reduction in the blood.

Results

While donor‐specific heparin levels varied substantially from 0.6 U/ml to 7.0 U/ml among the different blood sources, each source was able to differentiate between the thrombogenic latex and the thromboresistant PTFE and HDPE materials (p < 0.05). However, only donor ovine and bovine blood were sensitive enough to differentiate an increased response for the intermediate thrombotic silicone material compared to PTFE and HDPE.

Conclusions

These results demonstrated that multiple animal blood sources (particularly donor ovine and bovine blood) may be suitable alternatives to fresh human blood for dynamic thrombogenicity testing when appropriate control materials and donor‐specific anticoagulation levels are used.

Research Organization:: Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

DOE Contract Number:: SC0014664

OSTI ID:: 2425618

Journal Information:: Artificial Organs, Journal Name: Artificial Organs Journal Issue: 12 Vol. 46; ISSN 0160-564X

Publisher:: Wiley

Country of Publication:: United States

Language:: English

References (31)

Interspecies differences in coagulation profile Siller-Matula, Jolanta M.; Plasenzotti, Roberto; Spiel, Alexander Thrombosis and Haemostasis, Vol. 100, Issue 09 https://doi.org/10.1160/TH08-02-0103	journal	January 2008
Thrombogenicity Testing of Medical Devices in a Minimally Heparinized Ovine Blood Loop Grove, Kent; Deline, Steve M.; Schatz, Tim F. Journal of Medical Devices, Vol. 11, Issue 2 https://doi.org/10.1115/1.4035724	journal	May 2017
Preclinical Evaluation of the Thrombogenicity and Endothelialization of Bare Metal and Surface-Coated Neurovascular Stents Krajewski, S.; Neumann, B.; Kurz, J. American Journal of Neuroradiology, Vol. 36, Issue 1 https://doi.org/10.3174/ajnr.A4109	journal	September 2014
An In Vitro Blood Flow Loop System for Evaluating the Thrombogenicity of Medical Devices and Biomaterials Jamiolkowski, Megan A.; Hartung, Matthew C.; Malinauskas, Richard A. ASAIO Journal, Vol. 66, Issue 2 https://doi.org/10.1097/MAT.0000000000000958	journal	February 2020
Comparison of catheter thrombogenicity in a modified chandler loop model using goat blood Olsen, Aaron L.; Long, Michael Journal of Biomedical Materials Research Part A, Vol. 106, Issue 12 https://doi.org/10.1002/jbm.a.36509	journal	September 2018
Dacron® vs. PTFE as bypass materials in peripheral vascular surgery – systematic review and meta-analysis Roll, Stephanie; Müller-Nordhorn, Jacqueline; Keil, Thomas BMC Surgery, Vol. 8, Issue 1 https://doi.org/10.1186/1471-2482-8-22	journal	December 2008
Hemocompatibility testing according to ISO 10993-4: Discrimination between pyrogen- and device-induced hemostatic activation Stang, Katharina; Krajewski, Stefanie; Neumann, Bernd Materials Science and Engineering: C, Vol. 42 https://doi.org/10.1016/j.msec.2014.05.070	journal	September 2014
Comparison of porcine and human coagulation by thrombelastometry Kessler, Ulf; Grau, Tamar; Gronchi, Fabrizio Thrombosis Research, Vol. 128, Issue 5 https://doi.org/10.1016/j.thromres.2011.03.013	journal	November 2011
Neurovascular Rescue Cunningham, Edwin J.; Fiorella, David; Masaryk, Thomas J. Seminars in Vascular Surgery, Vol. 18, Issue 2 https://doi.org/10.1053/j.semvascsurg.2005.04.007	journal	June 2005
Blood Banking and Transfusion Medicine Challenges During the COVID-19 Pandemic Ngo, Andy; Masel, Debra; Cahill, Christine Clinics in Laboratory Medicine, Vol. 40, Issue 4 https://doi.org/10.1016/j.cll.2020.08.013	journal	December 2020
Thrombogenicity assessment of Pipeline Flex, Pipeline Shield, and FRED flow diverters in an in vitro human blood physiological flow loop model Girdhar, Gaurav; Andersen, Arielle; Pangerl, Elizabeth Journal of Biomedical Materials Research Part A, Vol. 106, Issue 12 https://doi.org/10.1002/jbm.a.36514	journal	September 2018
Bleeding and Thrombosis in Patients With Continuous-Flow Ventricular Assist Devices Eckman, Peter M.; John, Ranjit Circulation, Vol. 125, Issue 24 https://doi.org/10.1161/CIRCULATIONAHA.111.040246	journal	June 2012
Guide wire thrombus formation during trans-femoral TAVI Wiper, Andrew; Hashmi, Izhar; Srivastava, Vivek Cardiovascular Revascularization Medicine, Vol. 15, Issue 6-7 https://doi.org/10.1016/j.carrev.2014.04.001	journal	September 2014
Adhesive Properties of Platelets from Different Animal Species Pelagalli, A.; Belisario, M. A.; Tafuri, S. Journal of Comparative Pathology, Vol. 128, Issue 2-3 https://doi.org/10.1053/jcpa.2002.0615	journal	February 2003
Biomaterial testing for covered stent membranes: Evaluating thrombosis and restenosis potential Weaver, Jason D.; Ku, David N. Journal of Biomedical Materials Research Part B: Applied Biomaterials, Vol. 100B, Issue 1 https://doi.org/10.1002/jbm.b.31927	journal	September 2011
Shear Stress‐Induced Total Blood Trauma in Multiple Species Chan, Chris H. H.; Pieper, Ina Laura; Robinson, Christian R. Artificial Organs, Vol. 41, Issue 10 https://doi.org/10.1111/aor.12932	journal	July 2017
An in vitro model for preclinical testing of thrombogenicity of resorbable metallic stents Walker, Emily K.; Nauman, Eric A.; Allain, Jean Paul Journal of Biomedical Materials Research Part A, Vol. 103, Issue 6 https://doi.org/10.1002/jbm.a.35348	journal	October 2014
Haemodilution-induced changes in coagulation and effects of haemostatic components under flow conditions Ogawa, S.; Ohnishi, T.; Hosokawa, K. British Journal of Anaesthesia, Vol. 111, Issue 6 https://doi.org/10.1093/bja/aet229	journal	December 2013
Species Variability in Platelet Aggregation Response to Different Agonists Pelagalli, A.; Lombardi, P.; d'Angelo, D. Journal of Comparative Pathology, Vol. 127, Issue 2-3 https://doi.org/10.1053/jcpa.2002.0570	journal	October 2002
On the Use of the Platelet Activity State Assay for the In Vitro Quantification of Platelet Activation in Blood Recirculating Devices for Extracorporeal Circulation Consolo, Filippo; Valerio, Lorenzo; Brizzola, Stefano Artificial Organs, Vol. 40, Issue 10 https://doi.org/10.1111/aor.12672	journal	January 2016
In-vitro study of species-specific coagulation differences in animals and humans using rotational thromboelastometry (ROTEM) Lechner, Raimund; Helm, M.; Müller, M. Journal of the Royal Army Medical Corps, Vol. 165, Issue 5 https://doi.org/10.1136/jramc-2018-001092	journal	December 2018
A novel approach to extraction of a large thrombus on the intraventricular guide‐wire during transcatheter aortic valve replacement Chin, Thomas; Priyesh, Padmanabhan; Islam, Ashequl M. Catheterization and Cardiovascular Interventions, Vol. 89, Issue 3 https://doi.org/10.1002/ccd.26113	journal	September 2015
In Vitro Thrombogenicity Testing of Artificial Organs Paul, R.; Marseille, O.; Hintze, E. The International Journal of Artificial Organs, Vol. 21, Issue 9 https://doi.org/10.1177/039139889802100910	journal	September 1998
Nonthrombogenic Approaches to Cardiovascular Bioengineering Li, Song; Henry, Jeffrey J. D. Annual Review of Biomedical Engineering, Vol. 13, Issue 1 https://doi.org/10.1146/annurev-bioeng-071910-124733	journal	August 2011
In Vitro Shear Stress‐Induced Platelet Activation: Sensitivity of Human and Bovine Blood Lu, Qijin; Hofferbert, Bryan V.; Koo, Grace Artificial Organs, Vol. 37, Issue 10 https://doi.org/10.1111/aor.12099	journal	June 2013
Preclinical Device Thrombogenicity Assessments: Key Messages From the 2018 FDA, Industry, and Academia Forum jamiolkowski, megan a.; snyder, trevor a.; perkins, ina laura ASAIO Journal, Vol. 67, Issue 2 https://doi.org/10.1097/MAT.0000000000001226	journal	August 2020
In vitro hemocompatibility studies of drug-loaded poly-(l-lactic acid) fibers Nguyen, K. T.; Su, S. -H.; Sheng, A. Biomaterials, Vol. 24, Issue 28 https://doi.org/10.1016/S0142-9612(03)00451-4	journal	December 2003
The optimal incubation time for in vitro hemocompatibility testing: Assessment using polymer reference materials under pulsatile flow with physiological wall shear stress conditions Blok, Sjoerd Leendert Johannes; van Oeveren, Willem; Engels, Gerwin Erik Journal of Biomedical Materials Research Part B: Applied Biomaterials, Vol. 107, Issue 7 https://doi.org/10.1002/jbm.b.34326	journal	January 2019
Sheep, pig, and human platelet-material interactions with model cardiovascular biomaterials Goodman, Steven L. Journal of Biomedical Materials Research, Vol. 45, Issue 3 https://doi.org/10.1002/(SICI)1097-4636(19990605)45:3<240::AID-JBM12>3.0.CO;2-C	journal	June 1999
Comparing techniques: the use of recalcified plasma in comparison with citrated plasma alone and in combination with thrombin in ultrastructural studies Pretorius, E.; Oberholzer, H. M.; van der Spuy, W. J. Hematology, Vol. 16, Issue 6 https://doi.org/10.1179/102453311X13127324303515	journal	November 2011
Platelet Adhesion to Foreign Surfaces Under Controlled Conditions of Whole Blood flow Grabowski, E. F.; Didisheim, P.; Lewis, J. C. ASAIO Journal, Vol. 23, Issue 1 https://doi.org/10.1097/00002480-197700230-00040	journal	January 1977

Similar Records

Effect of Temperature on Thrombogenicity Testing of Biomaterials in an In Vitro Dynamic Flow Loop System

Journal Article · Sat Dec 31 23:00:00 EST 2022 · ASAIO Journal · OSTI ID:2425650

In Vitro Thrombogenicity Testing of Biomaterials in a Dynamic Flow Loop: Effects of Length and Quantity of Test Samples

Journal Article · Tue Jul 25 00:00:00 EDT 2023 · Journal of Medical Devices · OSTI ID:2425710

Reduced thrombogenic characteristics of expanded polytetrafluoroethylene and polyurethane arterial grafts after heparin bonding

Journal Article · Sat Dec 31 23:00:00 EST 1983 · Surgery; (United States) · OSTI ID:6221561

Related Subjects

Engineering
Transplantation

Comparison of animal and human blood for in vitro dynamic thrombogenicity testing of biomaterials

Citation Formats

References (31)

Similar Records

Related Subjects