Inhibition of Factor Xa in Prothrombinase Is Enhanced by Covalent Linkage of Antithrombin to Heparin.
Bibliographic record
Abstract
Abstract Prothrombinase is the surface-bound complex in which factor Xa (Xa) converts prothrombin to thrombin in vivo. Studies have shown that Xa within prothrombinase is resistant to inhibition by antithrombin + heparin (AT+H). Previously we found that, unlike AT+H, a covalent conjugate of AT and H (ATH) was able to neutralize fibrin-bound thrombin. In this study, AT+H and ATH were compared in their reaction with Xa in prothrombinase. Mixtures of CaCl2, PCPS vesicles, factor Va (Va) and prothrombin in TSP buffer were combined with either AT+H or ATH. Following addition of Xa, time samples were neutralized with Na2EDTA + polybrene + substrate (S-2222) and residual Xa activity measured. Second order rate constants (k2) were calculated from plots of activity versus time. Results were compared to those in corresponding experiments with Xa alone. Inhibition of Xa in prothrombinase by AT+H had a k2 (x 108 M−1min−1) of 0.688 +/− 0.030. Conversely, free Xa neutralization by AT+H was significantly more rapid (k2 = 1.53 +/− 0.35, p = 0.041). ATH reaction with prothrombinase Xa proceeded at a rate that was insignificantly different from that with Xa alone (2.36 +/− 0.31 and 2.83 +/− 0.83, respectively) and similar to AT+H reaction with free Xa. Varying concentrations of prothrombinase components showed similar effects. We conclude that covalently linked complexes of AT + H undergo unhindered reaction with Xa in prothrombinase, while non-covalently linked AT+H encounters resistance. It is possible that ATH may effectively prevent plasma thrombin generation by neutralization of Xa in prothrombinase and thus may prohibit feedback activation of coagulation.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".