Evaluation of a Urin-based Point-of-Care Testing Device for Direct Oral Anticoagulants in Patients With Acute Ischemic or Hemorrhagic Stroke

Stroke is the second leading cause of death worldwide and the most common cause of acquired disability in adulthood. During the acute phase of ischemic brain infarction, the goal of therapy is the rapid re-opening of the occluded vessel through recanalization procedures. This aims to restore blood flow to the penumbra, the tissue surrounding the infarct core with reduced blood supply, and prevent irreversible damage. Established approaches include systemic thrombolysis (intravenous thrombolysis, IVT) using Actilyse® (rt-PA), which is the only approved and proven effective therapy available within the first 4.5 hours. Mechanical thrombectomy (endovascular thrombectomy, EVT) has also been employed in recent years for highly selected patients with large vessel occlusion. However, this treatment requires interdisciplinary center structures and specialized imaging-based patient selection. Nonetheless, these patients also clearly benefit from prior or concomitant IVT, making it the foundation of stroke care in Germany and worldwide for decades.

The rate of patients eligible for IVT treatment remains improvable, stabilizing around 20% of all acute cerebral ischemia patients, depending on the center and region. Various reasons contribute to this, but among the primary causes for not considering IVT (besides contraindications such as delayed or unknown symptom onset window) is the growing fraction of patients (about 8%) who are on oral anticoagulation or cannot receive IVT due to the lack of exclusion thereof (e.g., in patients with altered consciousness or aphasia). Current estimates suggest that nearly 2 million people in Germany require oral anticoagulation, with an increasing trend.

Current Problem:

The availability of oral anticoagulation options includes Vitamin K antagonists (e.g., Marcumar) and direct oral anticoagulants (DOACs). DOACs are classified into two subgroups based on their mechanism: Factor IIa inhibitors (e.g., Dabigatran) and Factor Xa inhibitors (e.g., Apixaban, Rivaroxaban, Edoxaban). For stroke treatment, it's crucial to know the presence and extent of anticoagulation because it significantly increases the risk of bleeding under additional IVT, rendering IVT contraindicated or requiring immediate hemostatic therapy in the event of bleeding. While reliable and rapid anticoagulation assessment is possible with Vitamin K antagonists using point-of-care (PoC) devices (e.g., CoaguCheks®), this is more challenging for DOAC patients.

The accurate determination or exclusion of anticoagulation is therapeutically relevant since it affects the administration of substance-specific antidotes like Idarucizumab (for Factor IIa inhibitors) and Andexanet alfa (for Factor Xa inhibitors). Urgently needed for DOAC patients with acute stroke symptoms, PoC devices are essential. Many of these patients, lacking the ability to assess drug levels, cannot receive IVT in a timely manner. This situation is particularly problematic when reliable information about DOAC usage is absent due to patient or caregiver inability to provide an accurate history.