Abstract WP5: The Age Effect on tPA Response Was Regulated by ADAMTS13/vWF

Abstract

Background: Although growing evidence has suggested that elderly stroke patients can benefit from intravenous tissue plasminogen activator (tPA), impaired functional outcome and increased risk of hemorrhagic transformation have also been frequently observed in those patients after tPA treatment. By cleaving von Willebrand factor (vWF), ADAMTS13 (A Disintegrin and Metalloproteinase with Thrombospondin motifs 13) is involved in arterial thrombosis and tPA regulation. Recent studies have identified decreased ADAMTS13 activity and increased vWF levels with aging and vascular cognitive impairment, which may put elderly individuals in a prothrombotic status at baseline. We therefore hypothesized that the ADAMTS13/vWF axis may also play a role in regulating the age effect on tPA response. Method: Consecutive tPA-treated ischemic stroke patients were prospectively recruited in accordance with IRB protocol. Peripheral venous blood was sampled at 12, 24 and 72hr post tPA administration. Result: A total of 173 patients were recruited, of whom 128 were younger than 70 years and 45 were older than 70 years. Impaired tPA response (mRankins > 2 at 3 months) was observed in patients ≥70 years compared to patients <70 years. Increased age was associated with decreased ADAMTS13 level and enhanced vWF (Figure 1A and 1B). Post tPA treatment, patients <70 years old had rapid and persistently elevated ADAMTS13 levels, which may enhance thrombolysis by cleaving vWF multimers (Figure 1C). However, in patients ≥70 years old , ADAMTS13 levels was lower and also rose slowly, which may have resulted in delayed vWF degradation and impaired thrombolytic efficacy (Figure 1C). Conclusion: Our results suggest that the ADAMTS13/vWF axis may contribute to impaired tPA response in older stroke patients and that ADAMTS13 may be a potential adjunct therapy to enhance the tPA efficacy. This proof of concept data may pave the way for future clinical trials.