PB0544 Management of Inherited Antithrombin Deficiency in Pregnancy and Puerperium: Single Center Experience
Bibliographic record
Abstract
Background: Heparin binds thrombin and fibrin and promotes the formation of a ternary heparin-thrombin-fibrin complex that protects thrombin from inhibition by antithrombin.Polyphosphate ( polyP) is a procoagulant polyanion released from activated platelets that, like heparin, binds thrombin and fibrin(ogen).Aims: To determine whether polyP promotes thrombin binding to fibrin, thereby forming a ternary complex that protects thrombin from inhibition by antithrombin.Methods: The polyP-fibrinogen interaction was quantified using surface plasmon resonance, whereas the binding of thrombin to fibrin in the absence or presence of polyP or heparin was quantified by measuring thrombin activity in clot supernatants.The protection of bound thrombin from inhibition by the antithrombin-heparin complex was evaluated by monitoring thrombin activity, while the procoagulant activity of fibrin-bound thrombin was quantified by incubation with FITC-fibrinogen and monitoring fibrin accretion.Results: PolyP binds fibrinogen with a Kd of 108 nM.PolyP and heparin promote thrombin binding to fibrin clots by 48% and 30%, respectively (Figure ).Thrombin binds fibrin with a Kd of 5.6 µM in the absence of a polyanion; the affinity is 3-and 14-fold higher in the presence of polyP or heparin, respectively (Table ).The heparin-catalyzed rate of thrombin inhibition by antithrombin is 14-fold lower in the presence of fibrin than in its absence.In contrast, with polyP, the rate of inhibition is 3-fold faster with fibrin than without it.Whereas fibrin-bound thrombin promotes fibrin accretion in the presence of heparin, there is no promotion of fibrin accretion in the presence of polyP.Image: Effect of polyP and unfractionated heparin in thrombin binding to fibrin clot.Conclusion(s): Like heparin, polyP binds thrombin and fibrin(ogen) and promotes thrombin binding to fibrin.Whereas thrombin assembled within the heparin-thrombin-fibrin complex is protected from inhibition by antithrombin and is procoagulant, thrombin within the polyP-thrombinfibrin is not.These findings identify important differences in the mechanisms and consequences of polyanion interactions with thrombin and fibrin.
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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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 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".