Key result
Rapid 4F-PCC reversal enables safe IVT and full functional recovery in warfarin-associated stroke cases.
Why the study?
Warfarin remains the only approved anticoagulant for patients with mechanical heart valve prostheses, and INR determines eligibility for intravenous thrombolysis in acute ischemic stroke, but data on rapid reversal of warfarin anticoagulation followed by IVT are limited.
Does rapid reversal of warfarin with four-factor prothrombin complex concentrate followed by intravenous thrombolysis improve functional recovery and prevent bleeding in acute ischemic stroke patients with mechanical heart valves and an INR > 1.7?
Case Report (n=2)
Yes
Does rapid reversal of warfarin with four-factor prothrombin complex concentrate followed by intravenous thrombolysis improve functional recovery and prevent bleeding in acute ischemic stroke patients with mechanical heart valves and an INR > 1.7?
Urgent reversal of warfarin anticoagulation with four-factor prothrombin complex concentrate followed by intravenous thrombolysis may be a feasible off-label therapeutic option for acute ischemic stroke in selected patients with mechanical heart valves and elevated INR.
May support 4F-PCC reversal before IVT in select warfarin patients; extends case reports but leaves open prospective safety trials.
Background Acute ischemic stroke (IS) frequently occurs in patients receiving oral anticoagulant (OAC) therapy. Although warfarin has largely been replaced by direct oral anticoagulants in routine clinical practice, it remains the only approved anticoagulant for certain indications, particularly in patients with mechanical heart valve protstheses. In these patients, the international normalized ratio (INR) is the key determinant of eligibility for intravenous thrombolysis (IVT). We present a potentially effective therapeutic strategy involving rapid reversal of warfarin anticoagulation with four-factor prothrombin complex concentrate (4F-PCC) followed by IVT. Methods We report two patients with similar clinical presentations who were receiving long-term warfarin therapy because of a mechanical aortic valve replacement. 76-year-old man with AIS had complete paralysis of the right lower limb, paresis of the right upper limb, and right central facial palsy. INR was 3.2. The second patient was a 76-year-old woman with dysarthria, left central facial palsy and left-sided hemiparesis. Her admission INR was 1.91. In both patients, CT angiography did not demonstrate arterial occlusion suitable for endovascular therapy. Results In both patients, four-factor prothrombin complex concentrate (4F-PCC) was administered to achieve rapid normalization of the INR. This was immediately followed by standard IVT. Both patients experienced marked neurological improvement, with no hemorrhagic or thromboembolic complications. At the 3-month follow-up, both had achieved complete functional recovery without residual neurological deficits. In conclusion, it can be stated that the chosen procedure led to an excellent clinical outcome in accordance with previously published cases, in the absence of other standard options for recanalization therapy.
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Neumann et al. (2026) conducted a case report in Acute ischemic stroke in patients with mechanical heart valves on warfarin and INR > 1.7 (n=2). Four-factor prothrombin complex concentrate (4F-PCC) followed by intravenous thrombolysis (IVT) was evaluated on Neurological recovery and absence of hemorrhagic/thromboembolic complications at 3 months. Urgent reversal of warfarin anticoagulation with 4F-PCC followed by IVT resulted in complete functional recovery (mRS of 0) at 3 months without hemorrhagic or thromboembolic complications in two patients.
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