A multi-laboratory assessment of congenital thrombophilia assays performed on the ACL TOP 50 family for harmonisation of thrombophilia testing in a large laboratory network

Emmanuel J. Favaloro; Soma Mohammed; Ronny Vong; Kent Chapman; Priscilla Swanepoel; Geoff Kershaw; Nancy Cai; Sarah Just; Lynne Connelly; Timothy Brighton; Leonardo Pasalic

doi:10.1515/cclm-2021-0499

Article

A multi-laboratory assessment of congenital thrombophilia assays performed on the ACL TOP 50 family for harmonisation of thrombophilia testing in a large laboratory network

Emmanuel J. Favaloro , Soma Mohammed , Ronny Vong , Kent Chapman , Priscilla Swanepoel , Geoff Kershaw , Nancy Cai , Sarah Just , Lynne Connelly , Timothy Brighton and Leonardo Pasalic

Published/Copyright: June 14, 2021

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 59 Issue 10

Abstract

Objectives

Thrombophilia testing is commonly performed within hemostasis laboratories, and the ACL TOP 50 family of instruments represent a new ‘single platform’ of hemostasis instrumentation. The study objective was to evaluate these instruments and manufacturer reagents for utility of congenital thrombophilia assays.

Methods

Comparative evaluations of various congenital thrombophilia assays (protein C [PC], protein S [PS], antithrombin [AT], activated protein C resistance [APCR]) using newly installed ACL TOPs 550 and 750 as well as comparative assessments with existing, predominantly STAGO, instrumentation and reagents. Verification of manufacturer assay normal reference ranges (NRRs).

Results

HemosIL PC and free PS assays showed good comparability with existing Stago methods (R>0.9) and could be considered as verified as fit for purpose. HemosIL AT showed high relative bias with samples from patients on direct anti-Xa agents, compromising utility. Manufacturer NRRs for PC, PS and AT were verified with minor variance. Given the interference with direct anti-Xa agents, an alternate assay (Hyphen) was evaluated for AT, and the NRR also verified. The HemosIL Factor V Leiden (APC Resistance V) evidenced relatively poor performance compared to existing assays, and could not be adopted for use in our network.

Conclusions

This evaluation of HemosIL reagents on ACL TOP 50 family instruments identified overall acceptable performance of only two (PC, free PS) of four thrombophilia assays, requiring use of third-party reagents on ACL instruments for the other two assays (AT, APCR).

Keywords: activated protein C resistance (APCR); antithrombin; laboratory testing; protein C; protein S; thrombophilia assays; verification

Corresponding author: Emmanuel J. Favaloro, Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead 2145, NSW, Australia; Sydney Centres for Thrombosis and Haemostasis, Westmead, NSW, Australia; and School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW, Australia, Phone: +612 8890 6618, Fax: +612 9689 2331, E-mail: Emmanuel.Favaloro@health.nsw.gov.au

Acknowledgments

NSW Health Pathology is acknowledged for providing in-kind support to enable study completion. The views expressed herein are those of the authors and are not necessarily those of NSW Health Pathology.

Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Not applicable.
Ethical approval: Not Applicable. According to guidance from local Human Research Ethics Committees, formal ethical approval for this evaluation was not sought, as the evaluation represents a Quality Assurance project of method verification using patient samples in excess to needs and which would otherwise be discarded after testing and mandatory short-term storage according to local accreditation requirements.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2021-0499).

Received: 2021-04-26

Accepted: 2021-05-31

Published Online: 2021-06-14

Published in Print: 2021-09-27

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Articles in the same Issue

https://doi.org/10.1515/cclm-2021-0499

Keywords for this article

activated protein C resistance (APCR); antithrombin; laboratory testing; protein C; protein S; thrombophilia assays; verification