Decreased Concentrations of Heparinoids Are Required to Inhibit Thrombin Generation in Plasma from Newborns and Children Compared to Plasma from Adults due to Reduced Thrombin Potential
Bibliographic record
Abstract
Thrombin generation is decreased and delayed in plasma from newborns and children compared to adults. We hypothesized that lower doses of heparinoid anticoagulants are required to give similar thrombin generation in newborn (umbilical cord) and child plasmas compared to that of adults. Thrombin generation was performed in either the absence or presence of unfractionated heparin (UFH), low molecular weight heparin (LMWH) or a covalent antithrombin-heparin complex (ATH). After contact activation and recalcification of each plasma, thrombin activity was measured by periodic sub-sampling into chromogenic substrate. UFH inhibited thrombin generation to a greater extent compared to LMWH in all plasmas. Cord plasma was more sensitive to inhibition and displayed a greater difference in the effectiveness of UFH compared to LMWH than other plasmas. Lower concentrations of UFH and LMWH were required to inhibit thrombin generation in cord and child plasmas compared to adult plasma. In comparison, ATH strongly inhibited thrombin generation in all 3 plasmas. Similar peak thrombin concentrations were observed at lower ATH concentrations (0.1 U/mL) compared to either UFH (0.25 U/mL) or LMWH (0.25 U/mL). As with UFH and LMWH, cord plasma was more sensitive to inhibition by ATH than the other plasmas and lower ATH concentrations inhibited thrombin generation in cord and child plasmas compared to adult plasma. Decreased thrombin generation with heparinoids in cord and child plasmas compared to adult plasma coincided with decreased rates of prothrombin consumption and increased proportion of thrombin-alpha2-macroglobulin inhibitor complexes. In summary, lower doses of UFH, LMWH or ATH result in similar peak thrombin generation in newborn and child plasmas compared to adult plasma. Cord plasma was the most sensitive to inhibition, with ATH being more effective than UFH or LMWH.
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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 | 0.002 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".