VWF and myeloproliferative disorder: In particular, the highest platelet activation rate in vivo can trigger consumption of primary haemostatic factors (e.g. von Willebrand factor) that in turn can contribute to a paradoxical increase in mucosal bleeding in addition to thrombosis, as occurs in thrombocytotic myeloproliferative neoplasms, and Heyde's syndrome.27–29 Thus, it is biologically plausible that the relationship between the degree of platelet activation and bleeding could be non-linear, with bleeding associated with the extremes of U-TXM values due to severely reduced or maximally enhanced platelet function in vivo.