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In Vitro Thrombogenicity Assessment of Blood-Contacting Materials Using Platelet and Coagulation Activation Molecular Biomarkers

Catalog of Regulatory Science Tools to Help Assess New Medical Devices

This regulatory science tool (RST) is a benchtop test method for performing material-mediated thrombogenicity assessment of blood-contacting medical devices and materials using molecular biomarkers to characterize platelet and coagulation activation in a single set of tests.

Technical Description

This tool provides detailed information on how to perform an in vitro material-mediated thrombogenicity test that can be used to evaluate relative thrombogenic potentials of blood-contacting medical devices and materials using platelet and coagulation activation molecular biomarkers. This tool also demonstrates the effects of different molecular biomarkers on test sensitivity in differentiating test material’s thrombogenic potentials. The markers include beta-thromboglobulin (β-TG) and platelet factor 4 (PF4) for the platelet activation assessment, and thrombin-antithrombin (TAT) complex for the coagulation activation assessment. 

This RST provides an alternate method to perform thrombogenicity assessment currently done through  two FDA recognized standards (ASTM F2382 -18 for partial thromboplastin time [PTT] assay and ASTM F2888-19 for platelet and leukocyte count [PLC] assay) that assess the effects of medical device materials on coagulation and platelets, respectively. Instead of two separate tests prescribed in these standards, our RST allows for assessing these thrombogenicity endpoints in a single set of tests with the same blood and test samples. 

Intended Purpose 

This in vitro test tool can be used for the design, development, and safety evaluation of blood-contacting medical devices in various stages of product development. This RST may be useful if the user intends to use a single test to assess the endpoints for two markers.  This RST does not replace the current ASTM F2382 and F2888 standards. 

Testing

The usage of this tool has been evaluated in a study published in the following article “Molecular Biomarkers for In Vitro Thrombogenicity Assessment of Medical Device Materials” by Patel et.al. [3] 

Limitations

The technical limitations of the RST are described in the peer-reviewed publication “Molecular Biomarkers for In Vitro Thrombogenicity Assessment of Medical Device Materials” by Patel et.al [3]. Briefly, while we demonstrated these molecular biomarkers may be very useful in screening and selection of materials for blood-contacting medical devices based on their relative thrombogenicity potentials, the material-mediated tests presented in this study were not performed under clinically relevant blood flow conditions and cannot be used to assess device thrombogenicity related to blood flow through and around the devices caused by the device geometry. 

Supporting Documentation

A detailed description of this tool is provided in the user manual.

Relevant standards and publications include:

  1. ASTM F2382-18: Standard Test Method for Assessment of Circulating Blood-Contacting Medical Device Materials on Partial Thromboplastin Time (PTT). ASTM International, West Conshohocken, PA; 2018.
  2. ASTM F2888-19: Standard Practice for Platelet Leukocyte Count—An In-Vitro Measure for Hemocompatibility Assessment of Cardiovascular Materials. ASTM International, West Conshohocken, PA; 2019.
  3. Patel M, Parrish A, Serna III C, Jamiolkowski MA, Srinivasan K, Malinauskas RA, et al. Molecular Biomarkers for In Vitro Thrombogenicity Assessment of Medical Device Materials. Journal of Biomedical Materials Research: Part B - Applied Biomaterials. 2024; https://doi.org/10.1002/jbm.b.35491, Published online Sep 2024.

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