An international study on activated partial thromboplastin time prolongation. Part 1: Analytical results

Josep Miquel Bauça; Éva Ajzner; Janne Cadamuro; Andreas Hillarp; Ann Helen Kristoffersen; Piet Meijer; Working Group on the Postanalytical Phase of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

doi:10.1016/j.cca.2022.08.024

An international study on activated partial thromboplastin time prolongation. Part 1: Analytical results

Clin Chim Acta. 2022 Oct 1:535:167-173. doi: 10.1016/j.cca.2022.08.024. Epub 2022 Aug 27.

Authors

Josep Miquel Bauça¹, Éva Ajzner², Janne Cadamuro³, Andreas Hillarp⁴, Ann Helen Kristoffersen⁵, Piet Meijer⁶; Working Group on the Postanalytical Phase of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Affiliations

¹ Department of Laboratory Medicine, Hospital Universitari Son Espases, Palma, Spain. Electronic address: pepmiquel@gmail.com.
² Central Laboratory, András Jósa University Hospital, Nyíregyháza, Hungary.
³ Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria.
⁴ Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
⁵ Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway; Norwegian Organization for Quality Improvement of Laboratory Examinations (Noklus), Haraldsplass Deaconess Hospital, Bergen, Norway.
⁶ ECAT Foundation (External Quality Control for Assays and Tests), Voorschoten, Netherlands.

PMID: 36041550
DOI: 10.1016/j.cca.2022.08.024

Abstract

Background: Unexpected prolongation of first-line coagulation tests, including activated partial thromboplastin time (APTT), should trigger further work-up by performing mixing tests to elucidate the underlying cause, direct further specific testing and clarify their possible clinical impact. The aim of our study was to assess whether methodological diversity has any impact on the APTT mixing test results and their interpretation.

Material and methods: Two lyophilized plasma samples (case 1: heparin contamination [0.5 IU/mL]; case 2: factor VIII deficiency [0.13 IU/mL]) and their respective fictional clinical cases were sent to European laboratories for APTT measurement and performance of mixing tests. Participants were surveyed about the methodology (reagents, analytical platform, reference ranges), APTT results, mixing test conditions, their classification (normal, equivocal, prolonged) and categorization of the sample (factor deficiency, presence of inhibitor, anticoagulant, unknown).

Results: A total of 269 responses were included. For case 1, all participants reported a prolonged APTT, and 91% obtained no correction in the mixing test, without differences among reagents or analytical platforms. Only 15% of them selected the presence of an anticoagulant as the single cause for the prolongation. For case 2, 99% of participants reported a prolonged APTT, while some heterogeneity in the mixing test results was found. Eighty-six percent of participants selected factor deficiency as the cause for APTT prolongation.

Conclusions: Most European laboratories obtained valid results for APTT and the subsequent mixing tests, despite using different methodologies. However, their classification could be improved. Therefore, more training and periodic evaluations are recommended to harmonize protocols and ensure proper result classification and categorization.

Keywords: APTT reagents; Activated partial thromboplastin time; Coagulation tests; Laboratory diagnosis; Mixing test.