Pro-Coagulant Lipids in Physiological Ratios Found in the Activated Platelet Membrane Do Not Impact Clot Structure or Fibrinolysis in Purified Assays
Bibliographic record
Abstract
Bethan H Morgan,1 Laura E Farleigh Smith,1 Daniela O Costa,1 Victoria J Tyrrell,1 Josefin Ahnström,2 Peter Vincent Jenkins,3 Peter W Collins,1 Nicola J Mutch,4 Valerie B O’Donnell1 1Systems Immunity Research Institute, Cardiff University, Cardiff, UK; 2Centre for Haematology, Hammersmith Hospital Campus, Imperial College London, London, UK; 3Haemostasis Diagnosis and Research, University Hospital Wales, Cardiff, UK; 4Aberdeen Cardiovascular & Diabetes Centre, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: Bethan H Morgan, Division of Infection and Immunity, Cardiff University, Sir Geraint Evans Building, Heath Park, Cardiff, CF14 4XN, United Kingdom, Email morganb10@cardiff.ac.uk Valerie B O’Donnell, Division of Infection and Immunity, Cardiff University, Sir Geraint Evans Building, Heath Park, Cardiff, CF14 4XN, United Kingdom, Email o-donnellvb@cardiff.ac.ukPurpose: A central role for the pro-coagulant membrane comprising aminophospholipids (aPL) and enzymatically oxidized phospholipids (eoxPL) in promoting hemostasis via interaction with coagulation factor Gla domains is well established. However, little is known about their interactions with the fibrinolytic pathway, their ability to alter clot structure or to support the activated protein C (APC) pathway. Previous studies used membrane liposome compositions that differ from those expected physiologically and/or generated inconsistent findings. To address this, pro-coagulant membranes comprising physiological proportions of aPL and eoxPL will be tested for their ability to support fibrinolysis using standard assays.Methods: The impact of phospholipids on clot structure and clot lysis was tested using absorbance-based assays. To investigate the impact of PS or eoxPL on fibrinolysis, plasmin was monitored chromogenically, and clot dissolution measured in a purified lysis system activated by tissue plasminogen activator or urokinase. To determine the impact of eoxPL on APC/protein S, FVa was incubated with APC (± protein S) in a purified prothrombinase assay.Results: At the concentrations of lipids tested in our study, PS did not significantly impact clot structure or fibrinolysis. Similarly, eoxPL did not impact either fibrinolysis or activity of APC/Protein S.Conclusion: Using liposome compositions that approximate activated blood cells, we found that the pro-coagulant membrane is unlikely to influence either clot structure or fibrinolytic activity directly, beyond its well characterized role in supporting Gla dependent coagulation factors and the actions of platelet associated proteins/receptors.Keywords: phospholipids, phosphatidylserine, fibrin, plasmin, activated protein C, protein S
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".