Abstract
Despite great efforts in stroke research, disability and recurrence rates in ischaemic
stroke remain unacceptably high. To address this issue, one potential target for novel
therapeutics is the glycoprotein von Willebrand factor (vWF), which increases in thrombogenicity
especially under high shear rates as it bridges between vascular sub-endothelial collagen
and platelets. The rationale for vWF as a potential target in stroke comes from four
bodies of evidence. (1) Animal models which recapitulate the pathogenesis of stroke
and validate the concept of targeting vWF for stroke prevention and the use of the
vWF cleavage enzyme ADAMTS13 in acute stroke treatment. (2) Extensive epidemiologic
data establishing the prognostic role of vWF in the clinical setting showing that
high vWF levels are associated with an increased risk of first stroke, stroke recurrence
or stroke-associated mortality. As such, vWF levels may be a suitable marker for further
risk stratification to potentially fine-tune current risk prediction models which
are mainly based on clinical and imaging data. (3) Genetic studies showing an association
between vWF levels and stroke risk on genomic levels. Finally, (4) studies of patients
with primary disorders of excess or deficiency of function in the vWF axis (e.g. thrombotic
thrombocytopenic purpura and von Willebrand disease, respectively) which demonstrate
the crucial role of vWF in atherothrombosis. Therapeutic inhibition of VWF by novel
agents appears particularly promising for secondary prevention of stroke recurrence
in specific sub-groups of patients such as those suffering from large artery atherosclerosis,
as designated according to the TOAST classification.
Keywords
stroke prevention - von Willebrand factor - high shear rates - individualized treatment
