Presenters: Sean Platton (Consultant Biomedical Scientist) and Peter Baker (Clinical Scientist and the Laboratory Lead for Haemostasis)

Measurement of heparin, direct oral anti-coagulants and other non-coumarin anti-coagulants and their effects on haemostasis assays: A British Society for Haematology Guideline

This guideline aims to update healthcare professionals working in the UK on the measurement of anti-coagulants (other than coumarins) currently licensed for use in the UK, and their effects on laboratory assays (Table 1). It provides recommendations based on the body of literature produced since the previous guidance published in 2014.1 Direct factor (F)XIa- and direct FXIIa-inhibiting anti-coagulants are at various stages of development but not yet licensed, so are not discussed in this guideline.2 The recent guidelines from the International Society of Thrombosis and Haemostasis Scientific Standardization Committee (ISTH/SSC) on the nomenclature to be used when describing non-vitamin K anti-coagulation3 are followed.

Some anti-coagulants, such as unfractionated heparin (UFH) and argatroban, have been in clinical use for decades. Laboratory monitoring to guide dose adjustments has been with the widely available activated partial thromboplastin time (APTT). However, the COVID-19 pandemic highlighted the wide variability in the sensitivity of different APTT reagents in patients with acute illness, emphasising the need for accessible and cost-effective anti-FIIa and anti-FXa assays for routine monitoring.

The introduction of specific anti-FIIa or anti-FXa-based assays has provided a means to quantitate plasma drug concentrations of the newer fixed-dose FIIa inhibitors (FIIaI) and FXa inhibitors (FXaI). When used according to licence, monitoring these direct oral anti-coagulants (DOACs) is not required, but measuring drug concentration can add value in some circumstances (Table 2). As neither drug concentration nor dose-adjustment based on the measured concentration has yet been shown to affect efficacy or safety, it is incorrect to refer to a therapeutic range. In this manuscript, the term ‘expected range’ is used to acknowledge this limitation.

There are many reports in the literature about the effects of anti-coagulants on measurable parameters of haemostasis. Lack of awareness of these effects, which are variable depending on anti-coagulant, timing of sampling and reagents, can cause confusion and delay diagnosis and care. Table 3 gives a broad overview of the types of impact on laboratory assays that may be seen.

All assays described must be used in accordance with requirements of ISO15189.