Abstract WP58: ADAMTS13/vWF Regulates the Efficacy of tPA in Ischemic Stroke Patients

Background: Intravenous tissue plasminogen activator (tPA), an efficacious thrombolytic, is sometimes ineffective due to various clinical factors and high clot burden. Recent animal data show that elevated von Willebrand Factor (vWF) content in thrombi may impair the recanalization efficacy of tPA, which can be improved by administering ADAMTS13 (A Disintegrin and Metalloproteinase with Thrombospondin motifs 13), a vWF-cleaving protease. In the current study, we investigated the role of ADAMTS13 and vWF in regulating the early response to tPA in ischemic stroke patients. Method: 138 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. tPA responders are defined as patients with rapid clinical improvement (NIHSS≥4) within 7 days post tPA treatment and with mRankins ≤ 2 at 3 months, while non-responders show no improvement and remain disabled (mRankins > 2) after 3 months. ADAMTS13 levels and vWF activity were measured by ELISA. Result: ADAMTS13 and vWF are inversely correlated with each other, consistent with a role of ADAMTS13 in degrading vWF multimer (Figure 1A). tPA responders demonstrated significantly elevated level of ADAMTS13 (p<0.001) and reduced vWF activity (p=0.007) as early as 12 hours post tPA treatment, while in non-responders, ADAMTS13 deficiency correlated to delayed vWF reduction after 72hr (Figure 1B). Conclusion: Our results point to a crucial role of ADAMTS13 in regulating hyperacute-stage tPA response, and suggest the potential of ADAMTS13 as an adjunct therapy to tPA. Studies in a larger patient cohort with extended time course are still ongoing.