Volume 32, No.3, 2023
Case Reports
Intra-Arterial Thrombectomy for Acute Ischemic Stroke Related to the Procoagulant Effect of Warfarin in A Patient with Atrial Fibrillation and Bioprosthetic Valve Replacement

Hsu-Tung  Huang,  1, 2 , Yi-Ting  Huang,  1, 2, 3 , Yen-Ting  Chen,  4, 5 , Lung  Chan,  1, 2, 6 , Chien-Tai  Hong,  1, 2, 6 , Chen-Chih  Chung,  1, 2, 6, 7 , 
1 Department of Neurology, Taipei Medical University Shuang Ho Hospital, New Taipei, Taiwan
2 Taipei Neuroscience Institute, Taipei Medical University, Taiwan
3 School of Nursing, College of Medicine, National Taiwan University
4 Department of Medical Imaging, Shuang-Ho Hospital, New Taipei City, Taiwan
5 Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
6 Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
7 Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
Corresponding Author:

Chen-Chih  Chung

keywords: Anticoagulant, procoagulant, stroke, thrombectomy, valvular heart disease
Abstract for case report

We report a 78-year-old male with valvular heart disease, congestive heart failure, and atrial fibrillation, who received bioprosthetic valve replacement and developed AIS related to the paradoxical procoagulant effect of warfarin. Emergent cerebral angiography with mechanical thrombectomy was performed, and recanalization was successfully achieved. After shifting warfarin to nonvitamin K oral anticoagulant (NOAC), the paradoxical procoagulant effect ameliorated.

Warfarin is a highly effective treatment for reducing the risk of cardioembolic stroke in patients with Af(6). However, patients initiating warfarin have been reported to exhibit a 71% higher risk of AIS in the first 30 days of use(1). This paradoxical procoagulant effect of warfarin is believed to be induced through blocking of the activation of clotting factors II, VII, IX, and X and the deactivation of protein C and protein S, leading to a transient hypercoagulable state(1,2). Bridging therapy with heparin or low-molecular- weight heparin can be considered when warfarin therapy is initiated; however, in the acute phase of ischemic stroke, these treatments appear to increase the risk of major bleeding without any net benefit(7,8). Nonvitamin K oral anticoagulants (NOACs), which block factors Xa and IIa and do not deactivate protein C or protein S, have proved effective and safe for the prevention of embolic events in patients with Af(7,8). However, VHD frequently coexists with Af(9), and limited data are available on the comparison of NOACs and warfarin after surgical repair for VHD with bioprosthetic valves; thus, the optimal treatment for patients with Af and VHD with bioprosthetic heart valves remains controversial(7-9). As per contemporary knowledge, our patient developed AIS in the first 14 days of warfarin use, with an INR level within the therapeutic range (therapeutic range: 2.0–3.0(7,8)), which is concordant with the onset time of warfarin-induced thrombotic events(1). Our patient had low levels of serum protein C and protein S during warfarin treatment, supporting the hypothesis of the paradoxical procoagulant effect during the initial use of warfarin. Protein C has a shorter half-life, and warfarin initially decreases protein C levels(2,5), plausibly contributing to an increased coagulation tendency at the time of the thrombotic event in our patient. Restoration of these two endogenous anticoagulants to normal levels after warfarin discontinuation also provided evidence of recovery from the paradoxical procoagulant effect induced by warfarin. Our patient received intra-arterial thrombectomy with successful recanalization and achieved complete recovery from ischemic stroke without residual sequela. Although no direct evidence exists of the benefits of endovascular intervention or tPA therapy in patients with AIS in a hypercoagulable state, Kim and Bang also reported a case with warfarin-related procoagulation and AIS that was successfully treated with thrombectomy(5). Furthermore, our case report describes a difficult and complicated clinical scenario: Our patient had Af and had recently received bioprosthetic valve replacement for VHD, had experienced severe AIS, and was ineligible for intravenous tPA therapy due to elevated INR.