Longitudinal evaluation of serum markers of endothelial cell dysfunction and haemostasis in treated antiphospholipid syndrome and healthy pregnancies
Bibliographic record
Abstract
Antiphospholipid syndrome (APS) pregnancies are characterised by placental insufficiency leading to recurrent fetal deaths and pre-eclampsia, placental abruption and/or maternal thrombotic events. In vitro antiphospholipid antibodies (aPLs) can produce endothelial cell activation (ECA). We hypothesised that the placental dysfunction seen in APS pregnancies was related to ECA in the maternal circulation which may predispose to poor placentation with failed endovascular trophoblast invasion into the maternal spiral arteries of the placental bed. Resultant decidual vasculopathy, characteristic of growth restricted and pre-eclamptic pregnancies, may lead to the above pregnancy complications. We collected clinical data and sequential blood samples from 22 primary APS pregnancies and 22 control pregnancies. All APS pregnancies received aspirin and low molecular weight (LMW) heparin (Fragmin). Three APS women with previous cerebral thrombotic events, who developed cerebral symptoms on LMW heparin, were prescribed warfarin from the 2nd trimester. The control pregnancies were untreated. We measured the following markers of haemostatic activation and ECA by ELISA: prothrombin fragments 1+2 (PF 1+2), D-dimers, plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (tPA) and soluble intercellular adhesion molecule (sol-ICAM) and soluble thrombomodulin (sTM), a marker of endothelial cell damage. Statistical analysis was conducted on logged values (log-normal distribution) and results presented as geometric means. The gestational ages were rounded into 4-week groups to allow analysis of repeated measures using generalised estimating equations (GEE). Clinical outcome: All control pregnancies were uncomplicated. In the APS group, there were 3 cases of intra-uterine growth restriction of the fetuses, 1 case of placental abruption, 2 women developed pre-eclampsia and there were 4 preterm deliveries. Of the maternal complications 5 women developed transient ischaemic attacks (TIAs) but not completed cerebral events and one woman developed thrombotic microangiopathy in pregnancy. There was no difference in the levels of ICAM or PAI-1 whether analysed by direct comparison, effect of treatment or according to outcome; t-PA levels were significantly higher in APS group (p=0.002); sTM levels were significantly lower in the APS group (p=0.02); PF 1+2 levels increased during pregnancy, increased less in the APS group (not statistically significant p=0.08) but was significantly lower in those receiving warfarin and in the group with maternal complications (p=0.018). D-dimer levels were significantly lower in those receiving warfarin (p=0.042). Conclusion: There is no evidence of generalised ECA in treated APS pregnancies compared to healthy controls. Levels of fibrinolytic activity were higher in APS pregnancies. A significant number of patients (23%) had TIAs on heparin but those that switched to warfarin had no further events. This may be because warfarin had a significantly greater effect on suppressing coagulation activation than LMW heparin
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".