Abdelrahman Zamzam1, Muzammil H Syed1, Margaret L Rand2,3, Krishna Singh4, Mohamad A Hussain1, Shubha Jain5, Hamzah Khan5, Subodh Verma6, Mohammed Al-Omran1, Rawand Abdin7, Mohammad Qadura1. 1. Division of Vascular Surgery, St. Michael's Hospital, Toronto, Ontario, Canada. 2. Department of Laboratory Medicine and Pathobiology, Biochemistry and Pediatrics, University of Toronto, Toronto, Ontario, Canada. 3. Division of Haematology/Oncology & Translational Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada. 4. Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. 5. Department of Surgery, University of Toronto, Toronto, Ontario, Canada. 6. Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada. 7. Division of Cardiac Surgery, St. Michael's Hospital, Toronto, Canada.
Abstract
OBJECTIVE: Peripheral artery disease patients have been shown to be more susceptible to thrombotic events compared to non-peripheral artery disease patients. Therefore, the aim of this study was to investigate the coagulation profile in peripheral artery disease patients with chronic limb threatening ischemia, moderate peripheral artery disease patients with claudication, and non-peripheral artery disease controls. METHODS: Chronic limb threatening ischemia patients were matched to peripheral artery disease patients with claudication and non-peripheral artery disease controls in a 1:1:1 ratio. Each patient had their cytokines, markers of thrombin generation, coagulation factors, natural anti-coagulants, fibrinolysis, and endothelial injury markers assessed. RESULTS: Markers of thrombin activation, thrombin Fragments F1 + 2 (Frag 1 + 2), and thrombin-anti-thrombin complex were found to be significantly elevated in all peripheral artery disease and chronic limb threatening ischemia patients relative to non-peripheral artery disease controls. Similarly, relative to non-peripheral artery disease controls, inflammatory markers including C-reactive protein, soluble platelet factor 4, and neutrophil gelatinase-associated lipocalin were also found to be significantly upregulated in chronic limb threatening ischemia patients, but not in peripheral artery disease patients with claudication. Furthermore, our data demonstrated significant increases in markers of endothelial injury in chronic limb threatening ischemia patients relative to non-peripheral artery disease controls. Finally, decreases in natural anti-coagulants (protein C and protein S) and coagulation factors FIX, FXI, and FXII were also observed in chronic limb threatening ischemia patients when compared with non-peripheral artery disease controls. CONCLUSIONS: Our data suggest that in relation to non-peripheral artery disease controls, chronic limb threatening ischemia patients are more hypercoagulable. However, peripheral artery disease patients with claudication appear to have similar levels of circulating procoagulant markers as non-peripheral artery disease patients. This may explain the increased risk of thrombotic events observed in chronic limb threatening ischemia patients.
OBJECTIVE:Peripheral artery diseasepatients have been shown to be more susceptible to thrombotic events compared to non-peripheral artery diseasepatients. Therefore, the aim of this study was to investigate the coagulation profile in peripheral artery diseasepatients with chronic limb threatening ischemia, moderate peripheral artery diseasepatients with claudication, and non-peripheral artery disease controls. METHODS: Chronic limb threatening ischemia patients were matched to peripheral artery diseasepatients with claudication and non-peripheral artery disease controls in a 1:1:1 ratio. Each patient had their cytokines, markers of thrombin generation, coagulation factors, natural anti-coagulants, fibrinolysis, and endothelial injury markers assessed. RESULTS: Markers of thrombin activation, thrombin Fragments F1 + 2 (Frag 1 + 2), and thrombin-anti-thrombin complex were found to be significantly elevated in all peripheral artery disease and chronic limb threatening ischemia patients relative to non-peripheral artery disease controls. Similarly, relative to non-peripheral artery disease controls, inflammatory markers including C-reactive protein, soluble platelet factor 4, and neutrophil gelatinase-associated lipocalin were also found to be significantly upregulated in chronic limb threatening ischemia patients, but not in peripheral artery diseasepatients with claudication. Furthermore, our data demonstrated significant increases in markers of endothelial injury in chronic limb threatening ischemia patients relative to non-peripheral artery disease controls. Finally, decreases in natural anti-coagulants (protein C and protein S) and coagulation factors FIX, FXI, and FXII were also observed in chronic limb threatening ischemia patients when compared with non-peripheral artery disease controls. CONCLUSIONS: Our data suggest that in relation to non-peripheral artery disease controls, chronic limb threatening ischemia patients are more hypercoagulable. However, peripheral artery diseasepatients with claudication appear to have similar levels of circulating procoagulant markers as non-peripheral artery diseasepatients. This may explain the increased risk of thrombotic events observed in chronic limb threatening ischemia patients.
Authors: José Miguel Rivera-Caravaca; Anny Camelo-Castillo; Inmaculada Ramírez-Macías; Pablo Gil-Pérez; Cecilia López-García; María Asunción Esteve-Pastor; Esteban Orenes-Piñero; Antonio Tello-Montoliu; Francisco Marín Journal: Int J Mol Sci Date: 2021-07-01 Impact factor: 5.923