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  • Aptamer Inhibition of Von Willebrand Factor Provides Thrombolytic Efficacy and Decreased Stroke Burden without an Increased Risk of Intracranial Hemorrhage

    Final Number:
    118

    Authors:
    D. L. Dornbos III; H. Harris; S. Gnyawali; N. Musgrave; H. Vaccaro; D. Wheeler; S. Talentino; A. Huttinger; N. Venetos; C. Jones; J. Zweier; C. Sen; C. Rink; S. M. Nimjee

    Study Design:
    Laboratory Investigation

    Subject Category:
    Basic Science

    Meeting: AANS/CNS Cerebrovascular Section 2017 Annual Meeting

    Introduction: While recombinant tissue plasminogen activator (rTPA) is the mainstay of stroke treatment, recanalization is only achieved in 25-50%. Von Willebrand Factor (VWF) inhibition has demonstrated efficacy in thrombolysis.

    Methods: Male and female adult wild-type (C57BL/6J) mice were anesthetized, and the right carotid artery was exposed. A 6-0 nylon suture was advanced within the internal carotid artery to generate vascular injury and intracranial hemorrhage (ICH). Vehicle (platelet binding buffer, n=17), rTPA (n=10) or VWF aptamer (n=14) was then intravenously administered. An MRI was obtained after 90 minutes to assess stroke and ICH volumes. Statistical analysis was performed with an unpaired t test.

    Results: Stroke volume was significantly decreased in mice treated with VWF aptamer (33.57 ± 6.743 mm3, +p<0.0001) and rTPA (48.4 ± 9.00 mm3, *p<0.01) compared to vehicle (73.54 ± 3.31 mm3)(Figure 1A). ICH volumes in mice treated with rTPA (1.88 ± 0.51 mm3) were significantly (^p<0.05) higher than both vehicle (1.04 ± 0.10 mm3) and VWF aptamer (0.94 ± 0.11 mm3)(Figure 1B).

    Conclusions: Aptamer inhibition of VWF has demonstrated effective thrombolysis and significantly decreases stroke burden compared to control. Furthermore, there is no increased risk of intracranial hemorrhage, an advantage this agent provides over rTPA and current intravenous anti-platelet therapies.

    Patient Care: By providing a safe anti-platelet drug with efficacy in thrombolysis, this treatment strategy provides a novel approach in stroke and thrombus prevention. Unlike current standards of care, such as rTPA and GP-2b-3a inhibitors, the VWF aptamer does not carry an increased risk of intracranial hemorrhage.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of VWF inhibition in thrombolysis. 2) Describe the safety profile of VWF inhibition without an increased risk of ICH. 3) Discuss potential clinical applications of this novel anti-platelet treatment.

    References:

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