European Medical Journal Nephrology (Jul 2021)
Von Willebrand Factor and ADAMTS13 in COVID-19 and Beyond: A Question of Balance
Abstract
von Willebrand factor (VWF) is a large, adhesive, multimeric protein involved in haemostasis. The larger the size (or number of VWF multimers), the greater the functionality of the protein. A deficiency or defect in VWF can lead to von Willebrand disease (VWD) and cause bleeding, whereas an increase in VWF may cause thrombosis. ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), sometimes called VWF-cleaving protease, is primarily responsible for controlling the size of VWF. Although a deficiency of ADAMTS13 may be caused by many factors, the most severe deficiency (<10% of normal levels) arises in thrombotic thrombocytopenic purpura, which is characterised by the presence of ultra-large VWF and resulting thrombosis. The relative levels of both VWF and ADAMTS13 can be described by either the VWF/ADAMTS13 ratio or the ADAMTS13/VWF ratio, depending on author preference. Typically, this reflects VWF antigen levels and ADAMTS13 activity. The normal ratio, where both VWF and ADAMTS13 are in balance, is close to unity (or 1.0). In VWD, the VWF/ADAMTS13 ratio approaches zero, whereas in thrombotic thrombocytopenic purpura the ADAMTS13/VWF ratio approaches zero. Recent evidence has emerged that COVID-19, which may be accompanied by high prothrombotic risk, could be characterised in some patients as expressing an imbalance of VWF and ADAMTS13, or a high VWF/ADAMTS13 ratio, in a clinical picture resembling a secondary thrombotic microangiopathy. The current narrative review discusses the so-called VWF/ADAMTS13 axis in COVID-19 and beyond.
