Reagent and Instrument Variability

From Odetta Hanna, Coagulation Applications Specialist at Sekisui Diagnostics: I was wondering if you could help me locate references or resources to support a statement that I made for Method Comparison: Coagulation: Interpretation of results. I am writing a method comparison procedure and I referenced CLSI EP09-A3. However, I cannot locate any specific supporting documentation for the statements listed below. The second bullet highlighted in red, is the one I need the most help with.

Thank you for any help that you can provide.

• Method verification studies are not a measure of the accuracy of either reagent or instrument. The purpose is not to prove that two systems are identical, but to indicate the degree of consistency or the strength of association between the differing results obtained with the different systems. The systems define the relationship between two procedures.
• Each reagent formulation has a different sensitivity to deficiencies of the coagulation pathway and different results can be expected for some patients. Instruments may also respond differently due to variability in their clot detection or their calculation of results. This does not mean that one answer is correct and the other incorrect. In these instances, the only comparison that can be made is the relationship of the results to their normal reference range.
• PT INR calculations cannot be used to compare all PT results. The INR calculation is only valid when used on samples drawn from patients stabilized on oral anticoagulant therapy who are on no other medications and have no concomitant coagulopathies. The INR value may be misleading when the patient is in the induction phase of anticoagulant therapy of it the patient has an underlying coagulation pathway deficiency.
• PT and APTT are screening tests and evaluate reactions involving multiple clotting factors. The multiplicity of factors affecting the results must always be considered when interpreting method verification studies.

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  Thank you, Odetta. Vandiver JW, Vondracek TG. Antifactor Xa levels versus activated partial thromboplastin time for monitoring unfractionated heparin. Pharmacotherapy 2012;32:546–58 focuses on the varying sensitivities of the partial thromboplastin time (PTT) reagents to unfractionated heparin therapy, whereas you are looking for factor deficiencies, however it is a good starting point for discussion and perhaps some responses from participants. Geo