Elevated von Willebrand factor levels in multiple myeloma: dysregulated mechanisms of both secretion and clearance

We read with great interest the recent publication by Ghansah et al whose work demonstrating increased thrombin generation and differential sensitivity to activated protein C (APC) in samples from patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) is an important addition to our growing understanding of the critical factors behind the high rate of thrombosis in MM.1 In particular, we noted that these authors also found raised von Willebrand Factor (VWF) antigen and Factor VIII (FVIII) levels in patients with newly diagnosed MM and, to a lesser extent in patients with MGUS. However, they concluded that the biological mechanisms underpinning raised VWF:Ag levels in MM and MGUS remain unresolved with the authors suggesting endothelial damage may be a key contributing factor. In fact, following on from the work of Ghansah et al, here, we show for the first time that not only is VWF synthesis increased in MM but that VWF circulatory clearance is also reduced in this disease. Furthermore, we also report the novel finding of raised VWF propeptide in precursor MM disease, incorporating both MGUS and smouldering MM (SM), which strengthens the evidence of a hypercoagulable profile in these premalignant conditions.</div

Elevated von Willebrand factor levels in multiple myeloma: dysregulated mechanisms of both secretion and clearance

We read with great interest the recent publication by Ghansah et al whose work demonstrating increased thrombin generation and differential sensitivity to activated protein C (APC) in samples from patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) is an important addition to our growing understanding of the critical factors behind the high rate of thrombosis in MM.1 In particular, we noted that these authors also found raised von Willebrand Factor (VWF) antigen and Factor VIII (FVIII) levels in patients with newly diagnosed MM and, to a lesser extent in patients with MGUS. However, they concluded that the biological mechanisms underpinning raised VWF:Ag levels in MM and MGUS remain unresolved with the authors suggesting endothelial damage may be a key contributing factor. In fact, following on from the work of Ghansah et al, here, we show for the first time that not only is VWF synthesis increased in MM but that VWF circulatory clearance is also reduced in this disease. Furthermore, we also report the novel finding of raised VWF propeptide in precursor MM disease, incorporating both MGUS and smouldering MM (SM), which strengthens the evidence of a hypercoagulable profile in these premalignant conditions.</div