ArticlePloS one2011
Warfarin anticoagulation exacerbates the risk of hemorrhagic transformation after rt-PA treatment in experimental stroke: therapeutic potential of PCC.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Antithrombotic Agents for tPA-Induced Cerebral Hemorrhage: A Systematic Review and Meta-Analysis of Preclinical Studies.Journal of the American Heart Association · 2020Pooled it
- Mechanism of exacerbation of traumatic brain injury under warfarin anticoagulation in male mice.PloS one · 2024Article
- Exploring Contraindications for Thrombolysis: Risk of Hemorrhagic Transformation and Neurological Deterioration after Thrombolysis in Mice with Recent Ischemic Stroke and Hyperglycemia.Journal of clinical medicine · 2022Article
- Recanalisation therapies for acute ischaemic stroke in patients on direct oral anticoagulants.Journal of neurology, neurosurgery, and psychiatry · 2021Review
- Hemostasis functions are associated with hemorrhagic transformation in non-atrial fibrillation patients: a case-control study.BMC neurology · 2021Article
- Article
- [Direct oral anticoagulants and acute stroke : Insights into translational research studies].Der Nervenarzt · 2017Review
- Risk of long-term anticoagulation under sustained severe arterial hypertension: A translational study comparing warfarin and the new oral anticoagulant apixaban.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- Article
- Hemorrhagic Transformation after Tissue Plasminogen Activator Reperfusion Therapy for Ischemic Stroke: Mechanisms, Models, and Biomarkers.Molecular neurobiology · 2015Review
- Rivaroxaban does not increase hemorrhage after thrombolysis in experimental ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2014Article
- Reversal of Vitamin K Antagonist Therapy by Prothrombin Complex Concentrate before Thrombolysis for Acute Stroke.Cerebrovascular diseases extra · 2013Article
- Mixed cerebrovascular disease and the future of stroke prevention.Translational stroke research · 2012Article
- Vascular protection to increase the safety of tissue plasminogen activator for stroke.Current pharmaceutical design · 2012Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOral anticoagulant therapy (OAT) with warfarin is the standard of stroke prevention in patients with atrial fibrillation. Approximately 30% of patients with cardioembolic strokes are on OAT at the time of symptom onset. We investigated whether warfarin exacerbates the risk of thrombolysis-associated hemorrhagic transformation (HT) in a mouse model of ischemic stroke.
methods62 C57BL/6 mice were used for this study. To achieve effective anticoagulation, warfarin was administered orally. We performed right middle cerebral artery occlusion (MCAO) for 3 h and assessed functional deficit and HT blood volume after 24 h.
resultsIn non-anticoagulated mice, treatment with rt-PA (10 mg/kg i.v.) after 3 h MCAO led to a 5-fold higher degree of HT compared to vehicle-treated controls (4.0±0.5 µl vs. 0.8±0.1, p<0.001). Mice on warfarin revealed larger amounts of HT after rt-PA treatment in comparison to non-anticoagulated mice (9.2±3.2 µl vs. 2.8±1.0, p<0.05). The rapid reversal of anticoagulation by means of prothrombin complex concentrates (PCC, 100 IU/kg) at the end of the 3 h MCAO period, but prior to rt-PA administration, neutralized the exacerbated risk of HT as compared to sham-treated controls (3.8±0.7 µl vs. 15.0±3.8, p<0.001).
conclusionIn view of the vastly increased risk of HT, it seems to be justified to withhold tPA therapy in effectively anticoagulated patients with acute ischemic stroke. The rapid reversal of anticoagulation with PCC prior to tPA application reduces the risk attributed to warfarin pretreatment and may constitute an interesting therapeutic option.
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