Measurement uncertainty in the VWF-ADAMTS13 axis: the challenges of adding a calculated measurand in the haemostasis laboratory

: Laboratory derived, calculated parameters are ubiquitous and support clinical decision making throughout medicine. In doing so, they present measurands as inputs to a new measurement result. The balance between von Willebrand factor (VWF) and a disintegrin and metalloproteinase with a thrombospondin type I motif, member 13 (ADAMTS13) is one such calculated parameter that has garnered significant interest in a wide range of clinical disorders. The extent to which this balance is deranged is variable and it appears from published literature to be dependent on the clinical presentation of the patient. Inflammatory conditions and disorders of the liver apparently show the largest imbalance, no doubt due to an additional contribution of reduced synthesis of ADAMTS13 in hepatic stellate cells. Haematological and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients show a mid-range increase larger than those seen in cardiac disorders. The transition of a useful biomarker in the research setting to one that is standardised and used for clinical decision making is dependent on a number of factors. This includes standardisation of methodology, reporting, traceability and calibration. Importantly, recognising that the ratio is a useful result, in addition to the VWF and ADAMTS13 results individually, shows that calculation of the ratio gives additional benefits in disease specific scenarios. Taken together these factors are major contributors to the measurement uncertainty (MU) of final results. For results to be clinically useful, and transferable within and between patients MU must be minimised. This review hopes to raise discussion of contributors to MU estimation and their importance when considering the balance of VWF an ADAMTS13 in a wide range of clinical disorders.