Acquired Functional Coagulation Inhibitors: Review on Epidemiology, Results of a Wet-Workshop on Laboratory Detection, and Implications for Quality of Inhibitor Diagnosis

Myriam Dardikh; Piet Meijer; Felix van der Meer; Emmanuel J. Favaloro; Bert Verbruggen

doi:10.1055/s-0032-1321490

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2012; 38(06): 613-621
DOI: 10.1055/s-0032-1321490

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Acquired Functional Coagulation Inhibitors: Review on Epidemiology, Results of a Wet-Workshop on Laboratory Detection, and Implications for Quality of Inhibitor Diagnosis

Authors

Myriam Dardikh

¹Department of Laboratory Medicine, Laboratory of Haematology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Piet Meijer

²ECAT Foundation, Leiden, The Netherlands
Felix van der Meer

³Department of Thrombosis and Haemostasis, University Medical Centre Leiden, Leiden, The Netherlands
Emmanuel J. Favaloro

⁴Department of Haematology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, New South Wales, Australia
Bert Verbruggen

²ECAT Foundation, Leiden, The Netherlands

Abstract

The accurate detection and quantification of coagulation inhibitors remains a challenging problem for most diagnostic laboratories. Prolonged screening assays and abnormal results of mixing tests with normal plasma may indicate the presence of such inhibitors. Yet, the presence of lupus anticoagulant, heparin, and potential contamination of plasma with therapeutically active antithrombotic drugs has to also be ruled out. This review covers the epidemiology of acquired functional coagulation inhibitors, and reports the results of a wet-workshop, organized by the External Quality Control for Assays and Test (ECAT) Foundation, on laboratory detection of such inhibitors. The aim of the workshop was to investigate, within groups of experts from dispersed professional laboratories, the quality of inhibitor detection and the difficulties encountered during the analytical process. In this workshop 8 samples representing varying milieu were tested by 10 groups of participants from 20 different countries. Workshop participants were asked to report the results of all investigations performed and to provide a likely diagnosis and/or a conclusion of the hemostasis abnormality represented by the test samples. Generally, the sensitivity of inhibitor detection was high but the differential diagnosis of the type of inhibitors identified was unsatisfactory, as many false-positive and false-negative results were observed. The most remarkable observation was the lack of a clear step-by-step analysis of the nature of an inhibitor once a positive mixing test had been detected. The possible consequences of these observations for the appropriate diagnosis and clinical management of patients are outlined. A diagnostic algorithm for the differential diagnosis and confirmation of acquired coagulation inhibitors is presented.

Keywords

coagulation inhibitors - diagnostic algorithm for inhibitor testing - antiphospholipid antibodies - lupus anticoagulants

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References

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