ORIGINAL RESEARCH article
Front. Vet. Sci.
Sec. Comparative and Clinical Medicine
Volume 12 - 2025 | doi: 10.3389/fvets.2025.1571683
This article is part of the Research TopicComparative Coagulation Profiles and Clot Function in Veterinary Medicine: Unravelling Species-Specific Hemostatic Mechanisms and Fibrin Meshwork StructuresView all 5 articles
Tissue plasminogen activator modified thromboelastography identifies fibrinolysis resistance in dogs with immune-mediated hemolytic anemia
Provisionally accepted
- 1Cornell University, Ithaca, United States
- 2BluePearl Pet Hospital Westside Atlanta, Atlanta, GA, United States
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Immune-mediated hemolytic anemia (IMHA) is an important immunologic disorder in dogs that is associated with high mortality rates, frequently due to thromboembolism. Multiple factors contribute to the pathophysiology of thrombosis in IMHA including intravascular tissue factor expression, platelet activation, and neutrophil extracellular trap (NET) formation. It was hypothesized that dogs with IMHA have impaired fibrinolysis that can be detected using a modified viscoelastic assay and that biomarkers of NET formation are associated with this hypofibrinolysis. Twenty 20 dogs with non-associative IMHA were enrolled and paired thromboelastography (TEG) assays with and without additional tissue plasminogen activator (tPA) performed. A panel of hemostasis tests including measurement of plasma thrombin-activatable fibrinolysis inhibitor (TAFI) activity, active plasminogen activator inhibitor-1 (PAI-1), and concentrations of cell-free DNA (cfDNA) and nucleosomes were also performed. Dogs with IMHA had hypercoagulable TEG tracings, increased TAFI activity and frequently displayed fibrinolysis resistance defined as minimal lysis in tPA augmented TEG assays. Increased concentrations of cfDNA, nucleosomes and active PAI-1 in dogs with IMHA compared to healthy controls were identified. These observations support the hypothesis that hypofibrinolysis is a common feature of IMHA in dogs. Increased plasma active PAI-1 concentrations and TAFI activities might contribute to the observed hypofibrinolysis. The combined hypercoagulability and hypofibrinolysis observed supports recent recommendations to provide thromboprophylaxis to all dogs with IMHA. These findings also suggest that NETosis might contribute to the common prothrombotic imbalance of IMHA in dogs.
Keywords: immunothrombosis, neutrophil extracellular traps, Nucleosomes, cell-free DNA, thrombin-
Received: 05 Feb 2025; Accepted: 19 May 2025.
Copyright: © 2025 Goggs, Davis and Brooks. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Robert Goggs, Cornell University, Ithaca, United States
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