Development and implementation of an expert rule set for automated reflex testing and validation of routine coagulation tests in a large pathology network

Abstract

Introduction Haemostasis laboratories play a critical role in diagnosis and treatment of individuals with bleeding or thrombotic disorders. Routine coagulation assays such as prothrombin time (PT)/ international normalized ratio (INR), and activated partial thromboplastin time (APTT), are used in monitoring of anticoagulant therapy, as provided for treatment/prevention of thromboembolic disease, and also inform on potential haemostasis dysfunction. Increasing pressure is applied on clinical laboratories to improve response (test turnaround) times, reduce error rates and standardize policies. To this end, we describe our experience with the development and implementation of an automated process for reflex testing and validation of routine coagulation test results in a large pathology network compromising 27 laboratories. Methods Custom‐built expert rules were created to perform reflex testing and fully automate routine test validation. These rules were developed/implemented over a 15‐month period, including 6 months for development/ testing and 9 months for training/implementation of >100 personnel at 27 sites. Results These rules have enabled adherence of standardized pre‐analytical (sample integrity) checks, automated reflex decisions, automated verification and overall alignment of network practices. In addition, clinically significant results are immediately referred to haematologists. We report an improvement in test turnaround times, also reflecting savings in operator time. Conclusion The process was generally well received and generally beneficial to most laboratories in the network.

Should multiple factor dilutions be performed for all patient coagulation factor assays? Let the debate begin!

“…This algorithm essentially reflects our current approach, as also based on an expert autoverification process. 14,15 For part B, we assert that assessment of parallelism should progress only for investigation of abnormal factor test results, and only in cases where anticoagulant status is identified as "none." As an alternative to parallelism assessment, laboratories could instead perform specific investigations for factor inhibitors, LA, or presence of anticoagulant, as in part differentially informed by findings of part A.…”

Coagulation mixing studies: Utility, algorithmic strategies and limitations for lupus anticoagulant testing or follow up of abnormal coagulation tests

“…Mixing tests may utilize different mixtures of patient + normal plasma, but generally a mixture of 1:1 (or 50:50; i.e., equal volumes) is applied . The mixture of patient + normal plasma is subjected to the same test(s) that showed the initially abnormal patient test result (Figure ).…”

“…This is the option recommended by the CLSI guidelines for investigation of LA, and is also easy to adopt for mixing studies in general. Indeed, this is the option that our laboratory decided to adopt when we developed our complex set of rules for auto‐validation of routine coagulation tests . The main advantage is that the method is easy to apply and verify, and does not require generation of alternate methods or cut‐off values requiring additional verification.…”

“…Nevertheless, since it is feasible that such patients will have a clinically significant defect (until proven otherwise), it is usually incumbent on the laboratory/patient carer/clinician to investigate and potentially explain the abnormality. Different laboratories and clinicians may have different strategies for such patient test follow up, but algorithmic reflex testing, potentially including mixing studies, provides one standard and logical approach to facilitate discovery, if permitted by the local regulatory environment and fiscal contraints . Some of the routine tests themselves (Table ) may form part of an algorithmic follow up (eg, an abnormal PT and APTT may cause reflex testing of fibrinogen and/or TT and/or D‐dimer) .…”

“…Different laboratories and clinicians may have different strategies for such patient test follow up, but algorithmic reflex testing, potentially including mixing studies, provides one standard and logical approach to facilitate discovery, if permitted by the local regulatory environment and fiscal contraints . Some of the routine tests themselves (Table ) may form part of an algorithmic follow up (eg, an abnormal PT and APTT may cause reflex testing of fibrinogen and/or TT and/or D‐dimer) . Note that individual test sensitivities for anticoagulants including DOACs is impacted by the reagent and instrument combination in use, and should be confirmed by each laboratory.…”