Acute ischemic stroke (AIS)
AIS is the largest thrombotic indication worldwide, affecting 17 million people per year. Since the late 90s, AIS patients are treated with recombinant tPA (tissue plasminogen activator) to recanalize the occluded blood vessel. tPA becomes less effective when administered later after symptom onset. Consequently, administration >4.5 hours after onset is avoided as efficacy is outweighed by the unavoidable bleeding risk that comes with tPA therapy.
The reasons for the limited efficacy of tPA are still largely unclear. However, tPA requires the availability of fibrin in order to degrade thrombi. In AIS, thrombi often originate from vessel damage elsewhere, after which thrombi-parts dislodge, embolize and occlude arteries in the brain. These thrombi always contain VWF, but the presence of fibrin is uncertain and varies between cases. We and others therefore suggest that degrading VWF in addition to fibrin forms an attractive strategy to treat thrombosis in stroke.