Altered platelet lipidome in bleeding patients with unexplained platelet function defects
In patients with a mild to moderate bleeding disorder (MBD) and abnormal light transmission aggregometry (LTA), a platelet function defect (PFD) is suspected. However, in many patients with PFD, the underlying mechanism remains elusive. Given the essential role of lipids in platelet signaling, plat...
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| Format: | Article |
| Language: | English |
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Ferrata Storti Foundation
2025-07-01
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| Series: | Haematologica |
| Online Access: | https://haematologica.org/article/view/12187 |
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| author | Bianca de Jonckheere Dino Mehic Dominik Kopczynski Anita Pirabe Waltraud Schrottmaier Anna Schmuckenschlager Cristina Coman Tim Dreier Helmuth Haslacher Alexander Tolios Cihan Ay Ingrid Pabinger Johanna Gebhart Robert Ahrends Alice Assinger |
| author_facet | Bianca de Jonckheere Dino Mehic Dominik Kopczynski Anita Pirabe Waltraud Schrottmaier Anna Schmuckenschlager Cristina Coman Tim Dreier Helmuth Haslacher Alexander Tolios Cihan Ay Ingrid Pabinger Johanna Gebhart Robert Ahrends Alice Assinger |
| author_sort | Bianca de Jonckheere |
| collection | DOAJ |
| description |
In patients with a mild to moderate bleeding disorder (MBD) and abnormal light transmission aggregometry (LTA), a platelet function defect (PFD) is suspected. However, in many patients with PFD, the underlying mechanism remains elusive. Given the essential role of lipids in platelet signaling, platelet lipid profiles in MBD patients with unexplained PFD may provide valuable diagnostic and mechanistic insights. This study investigated platelet lipidomes in patients with PFD of unknown cause from the Vienna Bleeding Biobank (VIBB), a prospective cohort study. Using a standardized lipidomics workflow, we analyzed platelets from 27 patients and 19 age- and sex-matched controls and found that sex-specific lipid shifts emerged exclusively within the patient cohort, with greater deviations in females. Furthermore, lipid alterations correlated with impaired platelet aggregation and were predictive of responses to ADP and TRAP-6 stimuli in LTA experiments. Baseline and stimulated platelet analyses in a female subgroup showed intrinsic lipidomic changes, including upregulated polyunsaturated triacylglycerols (PUFA-TGs), acylcarnitines (CAR)s, and reduced lysophosphatidylethanolamines (LPEs). This study emphasizes lipidomic profiling as a promising diagnostic tool for unexplained platelet dysfunction and highlights TGs, CARs, and LPEs as potential therapeutic targets. Further research into lipid-driven platelet regulation may advance personalized treatments and improve clinical outcomes for patients with MBD.
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| format | Article |
| id | doaj-art-a0f06e28dffd4c8785ea64505af7d0e9 |
| institution | Matheson Library |
| issn | 0390-6078 1592-8721 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Ferrata Storti Foundation |
| record_format | Article |
| series | Haematologica |
| spelling | doaj-art-a0f06e28dffd4c8785ea64505af7d0e92025-07-24T19:50:43ZengFerrata Storti FoundationHaematologica0390-60781592-87212025-07-01999110.3324/haematol.2025.287698Altered platelet lipidome in bleeding patients with unexplained platelet function defectsBianca de Jonckheere0Dino Mehic1Dominik Kopczynski2Anita Pirabe3Waltraud Schrottmaier4Anna Schmuckenschlager5Cristina Coman6Tim Dreier7Helmuth Haslacher8Alexander Tolios9Cihan Ay10Ingrid Pabinger11Johanna Gebhart12Robert Ahrends13Alice Assinger14Institute of Analytical Chemistry, University of Vienna, Vienna, Austria; Vienna Doctoral School in Chemistry, University of Vienna, ViennaInstitute of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria; Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, ViennaInstitute of Analytical Chemistry, University of Vienna, ViennaInstitute of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, ViennaInstitute of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, ViennaInstitute of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, ViennaInstitute of Analytical Chemistry, University of Vienna, ViennaClinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, ViennaDepartment of Laboratory Medicine, Medical University of Vienna, ViennaDepartment of Transfusion Medicine and Cell Therapy, Medical University of Vienna, ViennaClinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, ViennaClinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, ViennaClinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, ViennaInstitute of Analytical Chemistry, University of Vienna, ViennaInstitute of Vascular Biology and Thrombosis Research, Centre of Physiology and Pharmacology, Medical University of Vienna, Vienna In patients with a mild to moderate bleeding disorder (MBD) and abnormal light transmission aggregometry (LTA), a platelet function defect (PFD) is suspected. However, in many patients with PFD, the underlying mechanism remains elusive. Given the essential role of lipids in platelet signaling, platelet lipid profiles in MBD patients with unexplained PFD may provide valuable diagnostic and mechanistic insights. This study investigated platelet lipidomes in patients with PFD of unknown cause from the Vienna Bleeding Biobank (VIBB), a prospective cohort study. Using a standardized lipidomics workflow, we analyzed platelets from 27 patients and 19 age- and sex-matched controls and found that sex-specific lipid shifts emerged exclusively within the patient cohort, with greater deviations in females. Furthermore, lipid alterations correlated with impaired platelet aggregation and were predictive of responses to ADP and TRAP-6 stimuli in LTA experiments. Baseline and stimulated platelet analyses in a female subgroup showed intrinsic lipidomic changes, including upregulated polyunsaturated triacylglycerols (PUFA-TGs), acylcarnitines (CAR)s, and reduced lysophosphatidylethanolamines (LPEs). This study emphasizes lipidomic profiling as a promising diagnostic tool for unexplained platelet dysfunction and highlights TGs, CARs, and LPEs as potential therapeutic targets. Further research into lipid-driven platelet regulation may advance personalized treatments and improve clinical outcomes for patients with MBD. https://haematologica.org/article/view/12187 |
| spellingShingle | Bianca de Jonckheere Dino Mehic Dominik Kopczynski Anita Pirabe Waltraud Schrottmaier Anna Schmuckenschlager Cristina Coman Tim Dreier Helmuth Haslacher Alexander Tolios Cihan Ay Ingrid Pabinger Johanna Gebhart Robert Ahrends Alice Assinger Altered platelet lipidome in bleeding patients with unexplained platelet function defects Haematologica |
| title | Altered platelet lipidome in bleeding patients with unexplained platelet function defects |
| title_full | Altered platelet lipidome in bleeding patients with unexplained platelet function defects |
| title_fullStr | Altered platelet lipidome in bleeding patients with unexplained platelet function defects |
| title_full_unstemmed | Altered platelet lipidome in bleeding patients with unexplained platelet function defects |
| title_short | Altered platelet lipidome in bleeding patients with unexplained platelet function defects |
| title_sort | altered platelet lipidome in bleeding patients with unexplained platelet function defects |
| url | https://haematologica.org/article/view/12187 |
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