Beyond platelet activation: dysregulated lipid metabolism in defining risk and pathophysiology of VITT
Background: VITT has emerged as a rare but serious adverse event linked primarily to adenoviral vector COVID-19 vaccinations, such as ChAdOx1-S (Oxford/AstraZeneca) vaccination. The syndrome is characterized by thrombosis with thrombocytopenia, elevated D-dimer, and pathologic platelet factor 4 anti...
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Elsevier
2025-01-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2475037925000019 |
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| author | Hannah Stevens James D. McFadyen Natalie A. Mellett David J. Lynn Thy Duong Corey Giles Jane James Rochelle Botten Georgina Eden Miriam Lynn Paul Monagle Peter J. Meikle Sanjeev Chunilal Karlheinz Peter Huyen Tran |
| author_facet | Hannah Stevens James D. McFadyen Natalie A. Mellett David J. Lynn Thy Duong Corey Giles Jane James Rochelle Botten Georgina Eden Miriam Lynn Paul Monagle Peter J. Meikle Sanjeev Chunilal Karlheinz Peter Huyen Tran |
| author_sort | Hannah Stevens |
| collection | DOAJ |
| description | Background: VITT has emerged as a rare but serious adverse event linked primarily to adenoviral vector COVID-19 vaccinations, such as ChAdOx1-S (Oxford/AstraZeneca) vaccination. The syndrome is characterized by thrombosis with thrombocytopenia, elevated D-dimer, and pathologic platelet factor 4 antibodies within 42 days of vaccination. Objectives: Despite dysregulated lipid metabolism underpinning many thrombotic conditions, the role of lipid alterations in VITT remains unexplored. Here, we examined the plasma lipidome of patients with VITT and compared it with those following ChAdOx1-S vaccination and with unprovoked venous thromboembolism (VTE) to understand the role of lipids in VITT pathophysiology. Methods: This was a multicenter, prospective cohort study evaluating plasma lipidomics in newly diagnosed VITT samples, which were compared with both healthy controls following ChAdOx1-S vaccination and with unprovoked VTE. Results: Comparison with ChAdOx1-S controls reveals a distinct lipid signature in VITT, characterized by elevations in phosphatidylserine and ceramide species, alongside reductions in several plasmalogens and acylcarnitine species. Notably, similarities between VITT lipid profiles and insulin resistance phenotypes suggest potential metabolic susceptibility. While few significant associations were found between VITT and VTE, an inverse correlation with several acylcarnitine species was demonstrated. Given the known anticoagulant role of acylcarnitine species, these findings suggest a plausible mechanistic pathway elevating the thrombotic potential of VITT above that of standard VTE. Conclusion: These findings underscore the important role of lipid metabolism in VITT pathophysiology and highlight the complex interplay between lipids, coagulation, and pathologic thrombosis. |
| format | Article |
| id | doaj-art-c0494d4a08484e678d98446bc42e47a4 |
| institution | DOAJ |
| issn | 2475-0379 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj-art-c0494d4a08484e678d98446bc42e47a42025-08-20T02:43:39ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-01-019110267710.1016/j.rpth.2025.102677Beyond platelet activation: dysregulated lipid metabolism in defining risk and pathophysiology of VITTHannah Stevens0James D. McFadyen1Natalie A. Mellett2David J. Lynn3Thy Duong4Corey Giles5Jane James6Rochelle Botten7Georgina Eden8Miriam Lynn9Paul Monagle10Peter J. Meikle11Sanjeev Chunilal12Karlheinz Peter13Huyen Tran14Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Haematology, Alfred Hospital, Melbourne, Victoria, Australia; Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, Victoria, Australia; Correspondence Hannah Stevens, Alfred Hospital, Baker Heart and Diabetes Institute, 99 Commercial Road, Melbourne, VIC 3004, Australia.Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Haematology, Alfred Hospital, Melbourne, Victoria, Australia; Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, Victoria, Australia; Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne, Victoria, AustraliaMetabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, AustraliaSouth Australian Health and Medical Research Institute, Adelaide, South Australia, Australia; Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, AustraliaMetabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, AustraliaBaker Department of Cardiometabolic Health, University of Melbourne, Parkville, Victoria, Australia; Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, AustraliaSouth Australian Health and Medical Research Institute, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research Institute, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research Institute, Adelaide, South Australia, AustraliaSouth Australian Health and Medical Research Institute, Adelaide, South Australia, Australia; Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, AustraliaDepartment of Paediatrics, University of Melbourne, Parkville, Victoria, Australia; Haematology Research, Murdoch Children’s Research Institute, Parkville, Victoria, Australia; Department of Haematology, Royal Children’s Hospital, Melbourne, Victoria, Australia; Kids Cancer Centre, Sydney Children’s Hospital, Randwick, New South Wales, AustraliaBaker Department of Cardiometabolic Health, University of Melbourne, Parkville, Victoria, Australia; Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Baker Department of Cardiovascular Research, Translation and Implementation, La Trobe University, Bundoora, Victoria, AustraliaDepartment of Haematology, Monash Health, Clayton, Victoria, Australia; School of Clinical Sciences, Monash Health, Monash University, Clayton, Victoria, AustraliaAtherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, Victoria, Australia; Department of Cardiology, Alfred Hospital, Melbourne, Victoria, AustraliaDepartment of Haematology, Alfred Hospital, Melbourne, Victoria, Australia; Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne, Victoria, AustraliaBackground: VITT has emerged as a rare but serious adverse event linked primarily to adenoviral vector COVID-19 vaccinations, such as ChAdOx1-S (Oxford/AstraZeneca) vaccination. The syndrome is characterized by thrombosis with thrombocytopenia, elevated D-dimer, and pathologic platelet factor 4 antibodies within 42 days of vaccination. Objectives: Despite dysregulated lipid metabolism underpinning many thrombotic conditions, the role of lipid alterations in VITT remains unexplored. Here, we examined the plasma lipidome of patients with VITT and compared it with those following ChAdOx1-S vaccination and with unprovoked venous thromboembolism (VTE) to understand the role of lipids in VITT pathophysiology. Methods: This was a multicenter, prospective cohort study evaluating plasma lipidomics in newly diagnosed VITT samples, which were compared with both healthy controls following ChAdOx1-S vaccination and with unprovoked VTE. Results: Comparison with ChAdOx1-S controls reveals a distinct lipid signature in VITT, characterized by elevations in phosphatidylserine and ceramide species, alongside reductions in several plasmalogens and acylcarnitine species. Notably, similarities between VITT lipid profiles and insulin resistance phenotypes suggest potential metabolic susceptibility. While few significant associations were found between VITT and VTE, an inverse correlation with several acylcarnitine species was demonstrated. Given the known anticoagulant role of acylcarnitine species, these findings suggest a plausible mechanistic pathway elevating the thrombotic potential of VITT above that of standard VTE. Conclusion: These findings underscore the important role of lipid metabolism in VITT pathophysiology and highlight the complex interplay between lipids, coagulation, and pathologic thrombosis.http://www.sciencedirect.com/science/article/pii/S2475037925000019lipidomicsmass spectrometryplatelet activationthrombosis |
| spellingShingle | Hannah Stevens James D. McFadyen Natalie A. Mellett David J. Lynn Thy Duong Corey Giles Jane James Rochelle Botten Georgina Eden Miriam Lynn Paul Monagle Peter J. Meikle Sanjeev Chunilal Karlheinz Peter Huyen Tran Beyond platelet activation: dysregulated lipid metabolism in defining risk and pathophysiology of VITT Research and Practice in Thrombosis and Haemostasis lipidomics mass spectrometry platelet activation thrombosis |
| title | Beyond platelet activation: dysregulated lipid metabolism in defining risk and pathophysiology of VITT |
| title_full | Beyond platelet activation: dysregulated lipid metabolism in defining risk and pathophysiology of VITT |
| title_fullStr | Beyond platelet activation: dysregulated lipid metabolism in defining risk and pathophysiology of VITT |
| title_full_unstemmed | Beyond platelet activation: dysregulated lipid metabolism in defining risk and pathophysiology of VITT |
| title_short | Beyond platelet activation: dysregulated lipid metabolism in defining risk and pathophysiology of VITT |
| title_sort | beyond platelet activation dysregulated lipid metabolism in defining risk and pathophysiology of vitt |
| topic | lipidomics mass spectrometry platelet activation thrombosis |
| url | http://www.sciencedirect.com/science/article/pii/S2475037925000019 |
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